diff --git "a/notes/Ghai-Essential-Pediatrics_9.txt" "b/notes/Ghai-Essential-Pediatrics_9.txt" new file mode 100644--- /dev/null +++ "b/notes/Ghai-Essential-Pediatrics_9.txt" @@ -0,0 +1,2141 @@ +ii. Compensatory increase in the rate of erythropoiesis (Table 12.10) and +iii. Features specific to particular etiologies of hemolytic anemia. +An elevated corrected reticulocyte count may be the only manifestation of mild hemolytic anemia in a well compensated child. Hemoglobin and heme released from red cells following intravascular hemolysis bind to the proteins haptoglobin and hemopexin. These protein complexes are removed from circulation. Hence, haptoglobin and hemopexin levels are low in patients with +__ _s_s_ _n_t_iat_P_ _d_ia.r cs __________________________________ +. +e t +i +_ +_ +E +e +_ + + + + + + + + + + + + + + + + + + +Fig. 12.6: Child with hemolytic anemia, showing hemolytic facies and icterus + +Table 12. 9: Laboratory signs of accelerated erythrocyte destruction +Fall in blood hemoglobin level at> 1.0 g/ dl per week Increased serum level of unconjugated bilirubin Increased urinary urobilinogen excretion +Increased serum lactate dehydrogenase Reduced haptoglobin and hemopexin Reduced glycosylated hemoglobin +Decreased erythrocyte life span (labeled with radioisotope s1cr) + +Table 12.10: Laboratory signs of accelerated eythropoiesis Peripheral blood +Polychromasia or reticulocytosis Macrocytosis +Increase in nucleated red cells +Bone marrow +Erythroid hyperplasia Iron kinetic studies +Increased plasma iron turnover Increased erythrocyte iron turnover + + +intravascular hemolytic anemia. When haptoglobin is saturated, free plasma hemoglobin can be detected. The level of indirect bilirubin is an insensitive measurement of hemolysis as it is only elevated when liver function is impaired or when hemolysis is extensive. +A peripheral smear is useful in evaluation of hemolytic anemias. It may show malarial parasites; presence of bite cells may suggest glucose 6 phosphate dehydrogenase enzyme (G6PD) deficiency. Spherocytes are seen in hereditary spherocytosis, but may also be seen post transfusion. Microcytosis with many fragmented red cells may suggest thalassemia and thrombocytopenia with + +schistocytosis (fragmented red cells) can be seen in disseminated intravascular coagulopathy or hemolytic uremic syndrome. The Coombs test is the most important initial test to perform to define the etiology of hemolysis. A positive direct antiglobin (direct Coombs) test means that the erythrocyte is coated with IgG or C3 component of complement, and is positive in most cases of immune hemolytic anemia. However, the test may be falsely negative in 2-5% cases. +Hallmarks of intravascular and extravascular hemolysis. Following intravascular hemolysis, hemoglobin is released into the plasma (hemoglobinemia). A part of the circu­ lating free hemoglobin is converted to methemoglobin, which binds with albumin to form methemalbumin that confers a brown color to plasma for several days following the hemolytic event. When the amount of hemoglobin exceeds the haptoglobin binding capacity it is excreted in the urine (hemoglobinuria). Some of this hemoglobin is reabsorbed in the proximal renal tubules; the loss of hemeladen tubular cells is seen as hemosiderinuria. Similar to intravascular hemolysis, unconjugated bilirubin, lactate dehydrogenase and reticulocyte count are elevated in extravascular hemolysis and haptoglobulin may be decreased. However, in extravascular destruction of red cells, there is no free hemoglobin or methemoglobin in the plasma; hence, hemoglobinemia, hemoglobinuria and hemosiderinuria are absent. +Specific tests such as hemoglobin electrophoresis, osmotic fragility, enzyme assays for G6PD and pyruvate kinase deficiency and assay for CDSS/59 for paroxysmal nocturnal hemoglobinuria are based on the etiology suspected (Table 12.8). + +Management +It is important to maintain fluid balance and renal output during and after acute hemolysis. Shock is managed by appropriate measures. However, blood transfusions, considered useful in acute anemia of other types, should be used cautiously when managing patients with acquired hemolytic anemias. Even with careful blood matching, transfused blood cells may undergo hemolysis, leading to an increase in the burden on excretory organs and, sometimes, thromboses. +Acute autoimmune hemolytic anemia is treated with corticosteroids (prednisone 1-2 mg/kg/day), which are tapered gradually over several months after ongoing hemolysis has resolved. Patients with chronic hemolysis require thorough investigation for etiology and treatment specific to cause. + +Hereditary Spherocytosis +Patients with hereditary spherocytosis may have one of several membrane protein defects. Many of these result in instability of spectrin and ankyrin, the major skeletal membrane proteins. The degree of skeletal membrane +Hematological Disorders - + + + +protein deficiency correlates with the degree of hemolysis. Membrane protein deficiency leads to structural changes including membrane instability, loss of surface area, abnormal membrane permeability and reduced red cell deformability. These defects are accentuated during depletion of metabolites, demonstrated as an increase in osmotic fragility after 24-hr incubation of blood cells at 37°C. Non-deformable erythrocytes are destroyed during passage through spleen. + +Laboratory findings. Patients with hereditary spherocytosis may have a mild to moderate chronic hemolytic anemia. The red cell distribution width (RDW) is increased due to the presence of spherocytes and increased reticulocytes. The MCV is decreased and MCHC increased due to cellular dehydration. + +Prese11tation. The age of presentation ranges from early childhood to adulthood. Patients chiefly present with jaundice of varying intensity. Splenomegaly is found in 75% patients. Gallstones are frequent, particularly in older patients and represent pigment calculi. + +Management. Patients require lifelong folic acid supple­ +mentation of 1-5 mg daily to prevent folate deficient due to the high turnover of red cells and accelerated erythro­ poeisis. While splenectomy does not cure the hemolytic disorder, it may reduce the degree of hemolysis. It is the treatment of choice in patients with severe hemolysis and high transfusion requirement. Splenectomy is delayed or avoided in patients with mild hemolysis. Splenectomy may diminish the risk of traumatic splenic rupture in children with splenomegaly. Splenectomy is usually performed beyond 6 yr of age following immunizations against Haemophilus influenzae type B, Streptococcal +pneumoniae and Neisseria meningitidis. Post splenectomy, +patients should receive penicillin prophylaxis, to prevent sepsis, usually up to early adulthood. +As with other hemolytic anemias, patients with here­ ditary spherocytosis are also susceptible to aplastic crisis with human parvovirus B19. This organism selectively invades erythroid progenitor cells and causes transient arrest in red cell production. Patients usually recover in 4-6 weeks. + +Abnorma/lties in Red Cell Glycofysis +Glucose is the primary metabolic substrate for erythro­ cytes. Since mature red cells do not contain mitochondria, glucose is metabolized by anerobic pathways; the two main metabolic pathways are Embden Meyerhof pump (EMP) and the hexose monophosphate shunt. The Embden Meyerhof pump pathway accounts for 90% of glucose utilization. The inability to maintain adenosine triphos­ phate impairs cellular functions, including deformability, membrane lipid turnover and membrane permeability, leading to shortened red cell life. The hexose monophos­ phate shunt is responsible for 10% of glucose metabolism. + + +This pathway generates substrates that protect red cells from oxidant injury. A defect in this shunt causes collection of oxidized hemoglobin (Heinz bodies), lipids and membrane proteins in red cells, which result in hemolysis. The reticulocyte count is raised and bone marrow shows erythroid hyperplasia. Demonstration of autohemolysis is a useful screening test; diagnosis requires specific enzyme assays. +Glucose-6-phosphate dehydrogenase deficiency Glucose-6- phosphate dehydrogenase (G6PD) deficiency is the most common red cell enzyme deficiency. It is an X­ linked recessive disease with full expression in affected males. Many variants are identified based on differences in antioxidant reserve and enzyme levels. After an oxidant exposure, hemoglobin is oxidized to methemoglobin and denatured to form intracellular inclusions also known as Heinz bodies. These Heinz bodies get attached to the red cell membrane and aggregate intrinsic membrane proteins such as band 3. Reticuloendothelial cells detect these membrane changes as antigenic sites and ingest a part of the red cell. This partly phagocytosed cell, called 'bite' cell, has a shortened half-life. +The child may present with jaundice in neonatal period. Findings during a hemolytic crisis are pallor, icterus, hemoglobinemia, hemoglobinuria and splenomegaly. Plasma haptoglobin and hemopexin are low. The peripheral blood smear shows fragmented bite cells and polychromasia. Special stains demonstrate Heinz bodies during the initial few days of hemolysis. Diagnosis of G6PD deficiency is suggested by family history, clinical findings, laboratory features and exposure to oxidants prior to the hemolytic event (Table 12.11). Confirmation of the diagnosis requires quantitative enzyme assay or molecular gene analysis. +Management consists of supportive care during the acute crisis (hydration, monitoring and transfusions if needed) along with folic acid supplementation. Coun­ seling to avoid intake of oxidant drugs (Table 12.11) is imperative. +Pyruvate kinase deficiency This is the most common enzyme defect in the Embden Meyerhof pump and is inherited in an autosomal recessive manner. Homozygotes present with splenomegaly, icterus and hemolytic anemia, but the clinical spectrum is variable. Folic acid supplementation is required to prevent megaloblastic + + +Tle 12.11: Drugs that cause oxidant stress and hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency +Sulfonamides: Sulfamethoxazole Antimalarials: Primaquine, quinine +Analgesics: Aspirin, non-steroidal anti-inflammatory drugs, phenazopyridine (pyridium) +Others: Nitrofurantoin, dapsone, methylene blue, rasburicase, toluidine blue, nalidixic acid, furazolidine, quinidine +--E-s s_n__i_l P___di_atr_i_cs __________________________________ +a +e +_ +t +e +_ +_ +_ + + +complications due to relative folate deficiency. Splenec­ tomy is considered a therapeutic option in patients with pyruvate kinase deficiency, it does not stop the hemolytic process. The reticulocyte count increases dramatically after splenectomy. + +Autoimmune Hemolytic Anemia +An autoimmune phenomenon targeting the red cells may occur in isolation, or arise as a complication of an infection (viral hepatitis B, upper respiratory tract viral infections, mononucleosis and cytomegalovirus infection), systemic lupus erythematosus (SLE) or other autoimmune syndromes, immunodeficiency states or malignancies. + +Clinical features The disease usually has an acute onset, manifested by weakness, pallor, fatigue and dark urine. Jaundice is a prominent finding and splenomegaly is common. Some cases are chronic. Clinical features may suggest an underlying disease (e.g. SLE or HIV). + +Laboratory findings The anemia is normochromic and normocytic and may vary from mild to severe. The reticulocyte count is usually increased. Spherocytes and nucleated red cells may be seen on the peripheral blood smear. Other features suggesting hemolysis include increased levels of lactic dehydrogenase, indirect and total bilirubin, aspartate aminotransferase and urinary urobili­ nogen. Intravascular hemolysis is indicated by hemo­ globinemia or hemoglobinuria. Serologic studies help define pathophysiology, plan therapeutic strategies and assess prognosis. The direct antiglobulin test is positive in almost all cases. Further evaluation allows distinction into one of three syndromes. + +Autoimmune hemolytic anemia due to warm reactive auto­ +antibodies is caused by IgG antibodies against the patient's red blood cells, with specificity for Rh-like antigen. These antibodies have maximal in vitro antibody activity at 37°C and do not require complement for activity. The condition can occur in isolation (primary), associated with immune disorders (e.g. SLE, lymphoproliferative disease, immuno­ deficiency), or with use of certain drugs (e.g. penicillin, cephalosporins) due to the 'hapten' mechanism (tight binding of drug to the red cell membrane is followed by immune destruction of cells by newly formed or pre­ existing antibodies to the drug). Extravascular destruction of the red cells by reticuloendothelial system occurs, resulting in splenomegaly. +In contrast, patients with cold reactive autoimmune +hemolytic anemia have antibodies, primarily of the IgM class, that require complement for their activity, have optimal reactivity in vitro at 4°C, and are specific to the i or I antigen on red cells. Detection of complement alone on red blood cells help make a diagnosis. While the condition is usually seen in adults, children may develop Donath Landsteiner hemolytic anemia, which is associated with an acute viral syndrome and is mediated by cold + +hemolysis. Paroxysmal cold hemoglobinuria is a related condition, usually identical to cold autoimmune hemolytic anemia, except for antigen specificity to P antigen and the evidence of in vitro hemolysis. Children may develop cold agglutinins following infections, such as mycoplasma, Epstein-Barr virus (EBV) and cytomegalovirus (CMV), in association with intravascular hemolysis. +IgG and complement associated autoimmune hemolytic anemia may occasionally occur due to warm antibody or, very rarely, due to drug associated autoimmune hemolytic anemia. + +Management Medical management of any underlying disease is important. Most patients with warm auto­ immune hemolytic anemia respond to prednisone 1 mg/ kg, given daily for 4 weeks or till hemoglobin is stable. After initial treatment, corticosteroids may be tapered slowly over 4-6 months. While use of intravenous immune globulin (!VIG) (1 g/kg/day for 2 days) may induce remission, the response is not sustained. The rate of remission with splenectomy may be as high as 50%, parti­ cularly in warm reactive autoimmune hemolytic anemia. However, this option should be considered carefully in younger patients due to a high risk of infections with encapsulated organisms. Hence, splenectomy is withheld until other treatments have been tried. In severe cases unresponsive to conventional therapy, immunosuppres­ sive agents such as cyclophosphamide, azathioprine and cyclosporine may be tried alone or in combination with corticosteroids. Danazol is effective in 50-60% of cases of chronic hemolytic anemia. Refractory cases may respond to rituximab (monoclonal antibody to B cell CD20) or to hematopoietic stem cell transplantation. +Patients with cold autoimmune hemolytic anemia and paroxysmal cold hemoglobinuria are less likely to respond to corticosteroids or intravenous immunoglobulin (IVIG). When associated with infections, these syndromes have an acute, self-limited course and supportive care is all that is necessary. Plasma exchange is effective in severe cold autoimmune (IgM) hemolytic anemia and may be helpful in severe cases because the offending antibody has an intravascular distribution. +Transfusion may be necessary because of the complication of severe anemia but should be monitored closely. In most patients, cross-match compatible blood will not be found and the least incompatible unit should be identified by the blood bank. Transfusions must be conducted carefully, beginning with a test dose. + +Prognosis In general, children with warm autoimmune hemolytic anemia are at greater risk for more severe and chronic disease with higher morbidity and mortality rates. Hemolysis and positivity of antiglobulin tests may continue for months or years. Patients with cold auto­ immune hemolytic anemia or paroxysmal cold hemo­ globinuria have acute self-limited disease. +Hematological Disorders - + + + +Suggested Reading +Gupta N, Sharma S, Seth T, et al. Rituximab in steroid refractory autoimmune hemolytic anemia. Indian J Pediatr DOI: 10.1007 /sl2098-0ll-0544-4 +Ware RE. Autoimmune hemolytic anemia. In. Orkin SH, Nathan DG, Ginsburg D, et al. (Eds.) (2009), Nathan and Oski's Hematology of In­ fancy and Childhood, (7th edn). Philadelphia, PA: Saunders Elsevier + +Thalassemias +The word thalassemia is a Greek term derived from thalassa, which means 'the sea' (referring to the Mediter­ ranean sea) and emia, which means 'related to blood'. The disease is more common in populations in the geographic belt from Southeast Asia to Africa. Thalas­ semias, caused by defects in the globin gene, are the most common monogenic disease. More than 200 mutations are described and the defects are inherited in an auto­ somal recessive manner. The carrier rates for p thalas­ semia in north Indians are reported to vary from 3-17% in different ethnic groups. + +Pathophysiology +The major hemoglobin in humans, called HbA, constitutes approximately 90% of total hemoglobin in children +beyond one year of age. A minor component, HbA2, +accounts for 2-3% of hemoglobin. The main hemoglobin in fetal life is HbF, of which only traces remain after one year. Each of these hemoglobins has two a chains that are associated with two p globin chains in HbA, o chains in +HbA2 and y globin chains in HbF. +Thalassemias are inherited disorders of hemoglobin synthesis that result from an alteration in the rate of globin chain production. A decrease in the rate of production of globins (a, p, o, y) impedes hemoglobin synthesis and creates an imbalance with normally produced globin chains. Because two types of chains (a and non-a) pair with each other at a ratio close to 1:1 to form normal hemoglobin, an excess of the normally produced type is present and accumulates in the cell as an unstable product, leading to early the destruction of the red cell. The type of thalassemia usually carries the name of the chain or chains that is not produced. The reduction may vary from a slight decrease to a complete absence. When p chains are produced at a lower rate, the thalassemia is termed P+, whereas p0 thalassemia indicates a complete absence of production of P chains from the involved allele. +Presentation +Thalassemia should be considered in the differential diagnosis of any child with hypochromic, microcytic anemia that does not respond to iron supplementation. Children with p thalassemia major usually demonstrate no symptoms until about 3-6 months of age, when p chains are needed to pair with a chains to form HbA, since y chains production is turned off. However, in some cases, the condition may not be recognized till 3-5 yr of age due to a delay in cessation of HbF production. + +Severe pallor and hepatosplenomegaly are almost always present. Icterus is usually absent, but mild to moderate jaundice may occur due to liver dysfunction from iron overload and chronic hepatitis. Symptoms of severe anemia such as intolerance to exercise, irritability, heart murmur or even signs of frank heart failure may be present. Bony abnormalities, such as frontal bossing, prominent facial bones and dental malocclusion are usually present (Fig 12.6). Ineffective erythropoiesis leads to a hypermetabolic state associated with fever and failure to thrive. Hyperuricemia may be encountered. + +Spectrum of Disease +p thalassemia trait. Patients have mild anemia, abnormal red blood cell indices and abnormal hemoglobin HPLC +results with elevated levels of HbA2, HbF or both. The +peripheral blood film exaination usually reveals marked hypochromia, microcytosis and presence of target cells. Anisocytosis, usually prominent in iron deficiency anemia, is not seen. + +Thalassemia intermedia. This condition may occur due to a compound heterozygous states, resulting in anemia of intermediate severity, which usually does not require regular blood transfusions. This is primarily a clinical diagnosis and requires monitoring of the child over time to see the clinical spectrum of disease. + +Thalassemia major. This condition is characterized by transfusion-dependent anemia, splenomegaly, bone deformities, growth retardation and hemolytic facies in untreated or inadequately treated individuals. Organomegaly is marked in patients receiving irregular or inadequate transfusion support. Examination of the peripheral blood smear shows severe hypochromia, microcytosis, marked anisocytosis, fragmented red blood cells, polychromasia, nucleated red cells and occasionally, immature leukocytes. + +Associated variants. p thalassemia may be associated with p chain structural variants. The most significant condition in this group of thalassemic syndromes is the HbE/P thalassemias. Patients with HbE/P thalassemia may present with severe symptoms identical to that of patients with p thalassemia major, or with milder course similar to that of patients with thalassemia intermedia or minor. The variation in severity can be explained because of the difference in p globin chain production, i.e. P+ or the co-inheritance of a thalassemia gene, level of HbF production and the presence of other modifying genes. +po, + +Laboratory Studies +Complete blood count and peripheral blood film examination are usually sufficient to suspect the diagnosis. In thalassemias major and intermedia, the hemoglobin +_ Ess_en_t_i_a_l P_e_d_i_ta_r_i_c_ --------------------------------- +s +- +_ +_ +_ +_ + +level ranges from 2-8 g/dl, MCV and MCH are signif­ icantly low, reticulocyte count is elevated to 5-8% and leukocytosis is usually present. A shift to the left reflects the hemolytic process. The platelet count is usually normal unless the spleen is markedly enlarged, causing hypersplenism. Peripheral blood film examination reveals marked hypochromasia and rnicrocytosis, polychromato­ philic cells, nucleated red blood cells, basophilic stippling and occasional immature leukocytes (Figs 12.7 and 12.8). High performance liquid chromatography (HPLC) for hemoglobin must be sent prior to the first blood transfusion. The test confirms the diagnosis of � thalas­ semia. Absence of HbA and elevation of HbF suggest thalassernia major; the level of HbA2 is not important for diagnosis. The presence of elevated HbA2 alone suggests the diagnosis of thalassemia trait. + + +Complications and Management +Genetic counseling is needed for the couple and their family to prevent the birth of other children with thalassemia major and prenatal testing can be used to detect thalassemia major in the fetus. Carriers are relatively easy to identify and screen. Prenatal diagnosis and genetic counseling programs have led to a dramatic reduction in the frequency of births of children with thalassemia major in many countries. +The introduction of hematopoietic stem cell transplan­ tation offers the possibility of cure in severe forms of thalassemia. However, this option is available only to a relatively small number of patients. Treatment of non­ transplanted children consists of regular blood trans­ fusions and iron-chelating agents; if both are pursued vigorously, these children survive into adulthood. Major challenges in chronic care of these children are ensuring safety of blood products and meeting the costs of life-long iron-chelating agents. +Patients with thalassemia major require medical supervision to monitor for complications and transfusion therapy. Blood transfusion should be initiated at an early age when the child is asymptomatic and attempts should be made to keep pretransfusion hemoglobin 9-10 g/ dl (to promote growth and prevent deformity). Chelation therapy to deal with the accumulated iron overload is vital to prevent iron overload and organ dysfunction. A normal diet is recommended, with supplements of folic acid and small doses of vitamins C and E. Iron supplements should not be given. Drinking tea with meals has been shown to decrease absorption of iron in the gut. +Iron overload. Iron overload is the major causes of morbidity and organ toxicity. The excessive load of iron is due to increased gastrointestinal iron absorption as well as repeated transfusions. Hence, avoidance of transfusions alone will not eliminate the iron overload problem. Patients with signs of iron overload demonstrate signs of +endocrinopathy caused by iron deposits, including + + + + + + + + + + + +, B + +Figs 12.7A and B: Peripheral smears from a transfusion dependent patient with beta thalassemia major showing marked anisopoikilo­ cytosis, microcytosis, hypochromia, polychromatophilia, nucleated red blood cells and few fragmented erythrocytes. Jenner-Giemsa x 1000 + + + + + + + + + + + + + + + + + + +Fig. 12.8: Peripheral smear from an asymptomatic patient with hemoglobin E disease, showing microcytosis, hypochromia, target cells and nucleated red blood cells. Jenner-Giemsa x 1000 +Hematological Disorders - + + + +diabetes, hypothyroidism, hypoparathyroidism, decreased +growth and lack of sexual maturation. +The simplest method for monitoring of iron status is by measurement of serum ferritin. However, the test may underestimate liver and cardiac iron. A liver biopsy or liver MRI and echocardiography may be useful in accurately assessing the iron status. A highly accurate and noninvasive tool to assess the heart iron status is the cardiac T2 magnetic resonance. + +Chelation therapy. The introduction of chelating agents capable of removing excess iron from the body has dramatically increased life expectancy. The cost, however, has resulted in poor compliance and inadequate dosing of iron chelators in many Indian patients. The optimal time to initiate chelation therapy is dictated by the amount of accumulated iron. This usually occurs after 1-2 yr of transfusions when ferritin level is about 1000-1500 µg/1. The standard till now has been deferoxamine which must be administered parenterally because of its short half-life. Prolonged subcutaneous infusion is the most effective route. A total dose of 40-60 mg/kg/ day is infused over 8-12 hours during the night for 5-6 days a week by a mechanical pump. Patients should be warned about orange discoloration of urine due to the excretion of iron­ deferoxamine complex (ferrioxamine). Higher doses of deferoxamine (6-10 g) may be administered intra­ venously, as inpatient when serious iron overload such as cardiac failure occurs. Severe toxicity may develop if chelation therapy is started prematurely. Eye exami­ nations, hearing tests and renal function tests are required to monitor the effects of deferoxine therapy. +Deferiprone is an oral chelating agent which is less effective than deferoxamine in preventing organ damage. It is administered at a dose of 75 mg/day. Since the agent may cause arthritis, neutropenia and even agranulocytosis, its administration requires careful monitoring both to prevent serious complications and to assess the adequacy of chelation. +Deferasirox is another oral chelating agent that has shown efficacy similar to parenteral agent deferoxamine in maintaining or reducing liver iron. The molecule is a tridentate ligand that binds iron with a high affinity, forming a 2:1 complex that is excreted in bile and elimi­ nated primarily via the feces. This chelator is highly selec­ tive for iron and chelates both intracellular and extra­ cellular deposits excess in the liver, heart and reticulo­ endothelial system. The recommended starting dose is 30 mg/kg/ day. It may cause skin rash, nausea, vomiting and renal and hepatic toxicity; hence, the serum creatinine, liver function tests and urine for proteinuria need to be monitored. + +Hematopoietic stem cell transplantation Hematopoie­ tic stem cell transplantation is the only known curative treatment for thalassemia. Poor outcome after hematopoietic + + +stem cell transplantation correlates with the presence of hepatomegaly, portal fibrosis and inadequate chelation prior to transplant. The event-free survival rate for patients who have all three features is 59%, compared to 90% for those who do not have these features. +Reactions. After multiple transfusions, many patients develop reactions; these may be minimized by using leukocyte filters during transfusion or by using leukocyte­ depleted packed red cells. Administration of acetaminophen and diphenhydramine hydrochloride before each transfusion minimizes febrile or allergic reactions. Rarely alloimmunization to red blood cell antigens can occur. +Infections. The major complications of blood transfusions are those related to transmission of infections such as hepatitis B and C and HIV. Hepatitis B vaccination and regular assessment of the hepatitis and HIV status are required. +Lactoferrin, a prominent component of the granules of polymorphonuclear leukocytes, is bacteristatic for many pathogens. The very high transferrin saturation attained in patients with iron overload compromise the bacterio­ static properties of this protein. Infection with Yersenia enterocolitica can occur in patients with iron overload and presents with fever and diarrhea. Treatment with trimethoprim-sulfamethoxazole and gentamicin is required. Other important infections which may occur are mucormycosis (Rhizopus oryzae) and Listeria monocytogenes. +Hypersplenism. The spleen acts as a store for nontoxic iron, protecting the body from extra iron. Hence, early removal of the spleen may be harmful. Splenectomy is justified only in hypersplenism, which is associated with excessive destruction of erythrocytes that increases the need for frequent blood transfusions, resulting in further iron accumulation. Patients who require more than 200-250 ml/kg of packed red blood cells per year to maintain hemoglobin may benefit from this procedure. This is rarely required in children receiving adequate transfusion therapy. Presplenectomy immunizations and prophylactic antibiotics have significantly decreased infections in splenectomized children. The procedure is usually delayed until the child is aged 7 yr or older. +Bone disease. The classic "hair on end" appearance of the skull, results from widening of the diploic spaces. The maxilla may overgrow, resulting in maxillary overbite and prominence of the upper incisors. These changes contribute to the classic hemolytic or 'chipmunk' facies observed in patients with thalassemia major. Osteoporosis and osteopenia may result in fractures. Such children may need treatment with calcium, vitamin D and bisphosphonates to improve bone density. +Extramedullary hematopoiesis. These occur in patients with severe anemia, e.g. thalassemias intermedia, who are not receiving transfusion therapy. The process may cause +__ _s_s_e_n_ t_i_ai_P_e_d_ ia _t-ric_________________________________ _ +s +_ +E + + +neuropathy or paralysis from compression of the spine or peripheral nerves. Compression fractures and paravertebral expansion of extramedullary masses, which behave clinically like tumors, are more frequent during the second decade of life. +Psychosocial complications. As these children are surviving into adulthood newer problems related to employment marriage and having families, as well as the stress of chronic illness will need to be addressed. + +Management of other Tha/assemic States +Patients with thalassemia intermedia require monitoring to assess the need for transfusion, as persistently low hemoglobin may retard growth. Hydroxyurea at a dose of 15-20 mg/kg/day may be used to increase HbF pro­ duction and reduce the need for transfusion support. This therapy is most effective in children with XLM1 mutation. Patients with thalassemia trait do not require medical followup after the initial diagnosis. Iron therapy should not be used unless a definite deficiency is confirmed. Genetic counseling is indicated to create awareness and +prevent thalassemia major in subsequent offspring. + +Suggested Readng +i +Nadkarni A, Gorakshakar AC, Krishnarnoorthy R, et al. Molecular +pathogenesis and clinical variability of beta thalassemia syndromes +among Indians: Am J Hematol 2001; 68:75-80 +Samaik SA. Thalassemia and related hemoglobinopathies. Indian J Pediatr 2005;72:319-24 + +Sickle Cell Anema +i +Sickle cell anemia is an autosomal recessive disease that results from the substitution of valine for glutamic acid at position 6 of the beta-globin gene. Patients who are homo­ zygous for the HbS gene have sickle cell disease. Patients who are heterozygous for the HbS gene have sickle trait. The gene frequency for sickle cell anemia in India is 4.3%, but the disease is reported chiefly from Orissa, Maha­ rashtra, Madhya Pradesh and Jharkand. Deoxygenation of the heme moiety of sickle hemoglobin leads to hydro­ phobic interactions between adjacent sickle hemoglobin (HbS) molecules that aggregate into larger polymers. Sickle red blood cells are less deformable and obstruct the microcirculation, resulting in tissue hypoxia, which further promotes sickling. These red blood cells are rapidly hemolyzed and have a life span of only 10-20 days. + +Clinical Features +Patients with sickle cell anemia can present with serious and varied manifestations. +Pain is the most common presentation of vaso-occlusive crisis. Presentation with pain suggests acute chest syndrome if pleuritic in nature and ritis or osteomyelitis if joint or bone are involved. Pul crises tend to recur, precipitated by triggers such as dehydration or fever. Shortness of breath or dyspnea suggests an acute chest syndrome, while + + +unilateral weakness, aphasia, paresthesias, visual symptoms may suggest stroke or infarct. Sudden increase in pallor, syncope or sudden pain or fullness in the left side of the abdomen mass may indicate a splenic sequestration crisis. +The usual presentations in a young child are icterus due to elevated unconjugated bilirubin, pallor and mild splenomegaly. The disease may manifest as a febrile illness since these children are prone to pneumococcal, Salmonella and other bacterial infections. Tachypnea suggests pneumonia, congestive heart failure, or acute chest syndrome, while hypoxia is common with acute chest syndrome. Children with aplastic crisis may present with congestive heart failure (CHF) due to severe anemia. Hypotension and tachycardia are signs of septic shock or sequestration crisis. Growth retardation and gallstones are common in children with sickle cell anemia. + +Types of Crisis +Vasa-occlusive crisis. A vaso-occlusive crisis occurs when the microcirculation is obstructed by sickled red blood cells resulting in ischemic injury. The major complaint is pain, usually affecting bones such as femur, tibia and lower vertebrae. Alternatively, vaso-occlusion may present as dactylitis, hand and foot syndrome (painful and swollen hands and/or feet), or an acute abdomen. The spleen may undergo auto-infarction and is often not palpable beyond 6 yr of age. Involvement of the kidney results in papillary necrosis leading to inability to concentrate urine (isosthenuria). Other presentations include acute chest syndrome, retinal hemorrhages, priapism, avascular necrosis of the femoral head and cerebrovascular accidents. + +Acute chest syndrome. This is a type of vaso-occulsive crisis that affects the lung and presents with chest pain, cough, tachypnea, dyspnea, hypoxemia, fever or a new pul­ monary infiltrate. This requires urgent admission; oxygen support, antibiotics (also should cover for mycoplasma and chlamydia), intravenous fluids, bronchodilators and use of steroids may be of benefit. +Sequestration crisis. This is due to sickled cells that block splenic outflow, leading to the pooling of peripheral blood in the engorged spleen resulting in splenic sequestration. + +Aplastic crisis. Aplastic crises can occur when the bone marrow stops producing red blood cells. This is most commonly seen in patients with infection or folate deficiency. This is usually self-limited and may follow viral infections of which parvovirus B19 is the most commonly implicated. Usually only supportive care and occasionally packed red blood cell transfusions are required. + +Infections +Affected children have increased susceptibility to encapsulated organisms (e.g. Haemophilus influenzae, +Hematological Disorders - + + + +Streptococcus pneumoniae). They are also at risk of other common infectious organisms such as Salmonella, Mycoplasma pneun10niae, Staphylococcus aureus and Escherichia coli. + +Laboratory Studies +Anemia and thrombocytosis are commonly found. +Leukocytosis occurs in patients with sickle cell anemia. However, a rise in the white blood cell count (i.e. >20,000 per mm3) with a left shift is indicative of infection. In the +peripheral smear, sickle-shaped red blood cells are found along with target cells. Presence of Howell-Jolly bodies indicates that the patient is functionally asplenic. The baseline indirect bilirubin level may be elevated because of chronic hemolysis. +If the diagnosis of sickle cell anemia has not been made, a sickling test will establish the presence of sickle hemoglobin. Hemoglobin electrophoresis is the test that can differentiate between individuals who are homozygous +or heterozygous. Hemoglobin in a homozygous patient will chiefly (80-90%) be hemoglobin SS (HbSS), while carriers will have 35-40% as HbSS. This needs to be +checked prior to blood transfusions. + +Assessment During Acute Illness +In a sick child, a type and cross-match is required for probable transfusion. A chest X-ray and X-rays of bones may be indicated in pain crisis. Blood culture should be sent. Monitoring of oxygen saturation and arterial blood gases should be ordered in patients with respiratory distress. A major drop in hemoglobin (more than 2 g/dl) from baseline indicates a splenic sequestration or aplastic crisis. Reticulocyte count and examination of spleen size will help to differentiate between these two conditions. An electrocardiogram must be performed if symptoms of chest pain and/or pulse irregularities are noted. + +Inpatient Management +Hydration and analgesia are the mainstays of treatment in a pain crisis. Narcotic analgesia is most frequently used. Hydration is corrected orally if the patient is not vomiting and can tolerate oral fluids. In severe dehydration, intravenous fluids are required. Care is taken not to overload the patient and accurate intake-output monitoring should be ensured. Blood transfusion is useful in patients in aplastic crisis and acute sequestration crisis. Oxygen supplementation is of benefit if the patient has hypoxia. Intubation and mechanical ventilation may be required in children in whom cerebrovascular accidents have occurred, or with acute chest syndrome. Exchange blood transfusions are indicated in cases of cerebrovascular accidents and acute chest syndrome. This involves replacing +the patient's red blood cells by normal donor red blood cells, decreasing HbSS to less than 30%. They may be +performed in patients with acute sequestration crisis or in + + +priapism that does not resolve after adequate hydration and analgesia. +I +Preventive Care +All children require prophylaxis with penicillin or amoxicillin, at least until 5 yr of age and should receive +immunizations with pneumococcal, meningococcal and Haemophilus influenzae B vaccines. They should receive life +long folate supplementation. Hydroxyurea is a cytotoxic agent which can increase HbF and reduce episodes of pain crises and acute chest syndrome and may be useful beyond 5 yr of age. Parents need to learn how to identify compli-cations and be informed for necessity and indications for admission. Patients need to be screened regularly for development of gallstones. Genetic counseling and testing should be offered to the family. + +Suggested Reading +Sachdeva A, Sharma SC, Yadav SP. Sickle cell disease. In: IAP Specialty series on Pediatric Hematology & Oncology 2006;77-96 +Steinberg MH. Management of sickle cell disease. N Engl J Med 1999;40:1021-30 + +Aplastic Anemia +Aplastic anemia comprises a group of disorders of the hematopoietic stem cells resulting in the suppression of one or more of erythroid, myeloid and megakaryocytic cell lines. The condition may be inherited or acquired. In developed countries, bone marrow failure due to hypoplastic or aplastic anemia affects 2-6 individuals per million populations. Although precise information is lacking, the prevalence is estimated to be higher in India. + +Etiopathogenesis +Hematopoietic stem cells may be deficient due to (i) an acquired injury from viruses, toxins or chemicals; (ii) abnormal marrow microenvironment; (iii) immuno­ logic suppression of hematopoiesis (mediated by antibodies or cytotoxic T cells); and (iv) mutations in genes +controlling hematopoiesis resulting in inherited bone marrow failure syndromes (Table 12.12). + +Clinical Features +Physical examination in case of severe anemia reveals pallor and/or signs of congestive heart failure. Ecchymoses, petechiae, gum bleeding and nose bleeds are associated with thrombocytopenia. Fever, pneumonia or sepsis may occur due to neutropenia. Inherited bone mar­ row failure syndromes, usually diagnosed in childhood or as young adults, may be associated with characteristic congenital physical anomalies, positive family history or neonatal thrombocytopenia. The child should be +evaluated for the stigmata of congenital bone marrow failure syndromes (Table 12.12; Figs 12.9 and 12.10). +However, Fanconi anemia may be present even without +any abnormal phenotypic features. History of exposure +___ _s_s_ _n_t_iai_P_ed_iat_rics __________________________________ +E +e +_ +_ +_ +_ +_ + +Table 12.12: Congenital syndromes associated with bone marrow failure + +Syndrome +Associated with pancytopenia Fanconi anemia + + +Dyskeratosis congenita + +Single lineage cytopenias + + +Inheritance + + +AR + + + +X-linked recessive, AD,AR + +Associated features + + +Absent thumbs, absent radius, microcephaly, renal anomalies, short stature, cafe au lait spots, skin pigmentation +Dystrophic nails, leukoplakia + +Risk of malignancy + + +High risk of acute myeloid leukemia, myelodysplasia, oral or liver cancer + +Skin cancer (usually squamous cell), myelodysplasia + + + +Amegakaryocytic AR thrombocytopenia +Diamond-Blackfan syndrome AD,AR (pure red cell aplasia) + + + +Thrombocytopenia absent radii AR + +AR autosomal recessive; AD autosomal dominant + + +None + +Short stature, congenital anomalies in one-third, macrocytosis, elevated fetal hemoglobin, raised adenosine deaminase +Absent radius + +None + +Leukemia, myelodysplasia, other cancers + + + +None + + + +to toxins, drugs like chloramphenicol, environmental hazards and viral infections, e.g. hepatitis B or C, suggest an acquired aplasia. + +Laboratory Studies +Hematological features of bone marrow failure include pancytopenia or bilineage involvement, noted in aplastic anemia, single cytopenia as seen in pure red cell aplasia and amegakaryocytic thrombocytopenic purpura. Single lineage cytopenias should be differentiated from transient erythroblastopenia of childhood. Peripheral blood smear reveals anemia, occasionally with macrocytosis (100,000/mm3 0 +50,000-100,000/mm3 1 <50,000/mm3 2 +(b) Elevated fibrin-related marker (soluble fibrin monomers or fibrin degradation products)* +No increase 0 Moderate increase 2 Strong increase 3 +(c) Prothrombin time +<3 sec 0 >3 but <6 sec 1 >6 sec 2 +(d) Fibrinogen level +>1 g/1 0 <1 g/1 1 +Calculate score +Score '.5: Compatible with overt DIC; repeat daily +Score <5: Suggestive of non-overt DIC; repeat in 1-2 days +* Values of D-dimer above the upper limit of normal are moderately elevated; values above 5 times the upper limit of normal are strongly increased. + +Specific indications for such therapy include the presence of arterial or large vessel venous thrombosis. These patients should continue to receive replacement therapy with heparin during continuous monitoring of platelet counts and fibrinogen levels and prothrombin, activated partial thromboplastin and thrombin time. +Novel therapies Therapy with activated protein C and tissue factor pathway inhibitor has not been shown to be beneficial in controlled trials in children. + +Suggested Reading +Levi M. Disseminated intravascular coagulation: What's new? Crit Care Clin 2005;21:449-67 +Taylor FB, Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scori11g system for disseminated i.ntravascular coagulation. Thromb Haemost 2001; 86:1327-30 + +Thrombotic Disorders +The incidence of thrombosis is lower in children than in adults, but is associated with significant morbidity and mortality. Till 6 months of age, children have lower levels of the vitamin-K dependent coagulation factors II, IX and X as compared to adults. Levels of thrombin inhibitors, such as antithrombin, heparin cofactor II, plasminogen and proteins C and S are low at birth. Protein S level approaches adult value by the age of 3-6 months, but protein C levels remains low during childhood. In newborns compared with adults, thrombin generation is delayed and decreased, probably due to low prothrombin level. The incidence of thrombosis is maximal in infancy and during adolescence. + + +Table 12.21: Types of blood component therapy, their constituents and guidelines for use Component Constituents Indication Dose Precautions + +Fresh frozen plasma (FFP) + +All coagulation factors as Coagulation factor +in normal plasma; contains deficiencies with pro-0. 7-1.0 U/ml of longed prothrombin factors II, V, VII, VIII, IX, time; thrombotic +X, XI, XII, XIII and thrombocytopenic 2.5 mg/ml fibrinogen purpura + + +15 ml/kg or 1 bag per Infuse soon after thawing; need 10 kg (constitutes ABO compatible units; may 25-30% replacement cause fluid overload +therapy for coagulation factors) + + + +Cryoprecipitate Fibrinogen 150 mg/bag, factor VIII 80-120 units/ bag, factor XIII and vWD (does not contain factor IX) + +Fibrinogen deficiency 1 bag per 5 kg will raise or consumption; factor fibrinogen levels by VIII deficiency (hemo- 70 mg/ di +philia A), vWD disease; factor XIII deficiency + + + +Random donor platelets (RDP) + +Platelets; ':5.5 x 1010 platelets per bag + + +Thrombocytopenia One unit raises platelet Infuse rapidly; do NOT +counts by 5-10,000/ refrigerate prior to transfusion mm3; 1 unit every +10 kg raises counts +by 30,000-50,000/mm3 + + + +Single donor platelets (SDP) + + +Fresh blood + +Platelets; contains at least 3 x 1011 platelets + + +All components of blood + + +Thrombocytopenia + + + +To replace acute and massive blood loss + + +One collection is equi­ valent to approxi­ mately 6 units of random platelets +Only to be used in severe trauma + + +Precautions as above + + + +Not a good source for platelets or coagulation factors +- Essential Pediatrics + + + +Clinical Evaluation +Congenital heart disease and, recent cardiac catheteri­ zation are important causes of arterial thrombosis in children. Other predisposing factors for arterial or venous thrombosis include recent surgery, trauma, use of central venous catheter, nephrotic syndrome, dehydration, sepsis and collagen vascular disorders (Table 12.22). +Limb edema, erythema and tenderness on dorsiflexion of the foot (positive Homan sign) suggest deep vein throm­ bosis. Signs of arterial thrombosis include diminished or absent peripheral pulses and cool extremities. Manifes­ +tations of pulmonary embolism include anxiety, breathlessness, pleuritic chest pain, fever, tachypnea and cough, and a high index of suspicion is required to make the diagnosis. Symptoms of central nervous system thrombosis include vomiting, lethargy, seizures or weakness in an extremity. Strokes may occur in utero; such newborns present with seizures and lethargy, while older children present with headaches or neurologic deficits such as hemiplegia. Patients with renal vein thrombosis may show flank pain and hematuria. + +Laboratory Evaluation +Many clotting factors are consumed in acute thrombosis and factor levels may be fallaciously low in the acute phase. The child should be evaluated to rule out disseminated intravascular coagulopathy with complete blood count, peripheral blood smear, prothrombin time, activated partial thromboplastin time and fibrinogen level. Levels of D-dimer indicates activity of the coagulation cascade, and is a sensitive indicator of underlying DIC. + + +Table 12.22: Factors which increase risk of thrombosis in children +Acquired conditions +Infections: Viral, bacterial sepsis Disseminated intravascular coagulation Dehydration +Central venous catheter Surgery, trauma +Cyanotic congenital heart disease Antiphospholipid antibody syndrome +Acute lymphoblastic leukemia; therapy (L-asparaginase and steroids) +Nephrotic syndrome +Inherited prothrombotic disorders +Resistance to activated protein C Factor V Leiden +Protein C deficiency Protein S deficiency Antithrombin deficiency +Prothrombin gene G20210A mutation Elevated lipoprotein (a) level +H yperhomocys teinemia + +Color Doppler shows absence of signals in thrombosed vessels and the lumen cannot be compressed with direct pressure. However, it may not be sufficiently sensitive to detect thrombosis in vessels such as subclavian veins, superior vena cava or brachiocephalic veins. Echocardiography is useful for vena caval and proximal subclavian vein thrombosis. An RI in conjunction with magnetic resonance venography is more sensitive than CT scan for the diagnosis of cerebral venous thrombosis. Chest radiography may reveal findings of pulmonary embolism which include small pleural effusions with wedge shaped pleural-based opacity of pulmonary infarction, but has poor sensitivity. Ventilation­ perfusion scanning is useful in suspected pulmonary embolism. Patients with elevated levels of D-dimer and intermediate probability of pulmonary thrombosis on perfusion scan should be screened by spiral CT. + +Management +Screening tests for hypercoagulable state should ideally be sent prior to initiating anticoagulation. Patients with respiratory distress or neurological problems should be managed in an intensive care unit. Initial therapy requires heparin (unfractionated or low molecular weight) followed by oral warfarin. Unfractionated heparin exhibits antithrombin as well as anti-Xa activity, whereas the action of low molecular weight heparin (LMWH) has primarily anti-Xa function. Close monitoring is required to prevent overdosage and risk of bleeding. The international normalized ratio (INR), is useful for monitoring oral anticoagulation with heparin and should be maintained in the range of 2 to 3. The duration of therapy depends on the risk of recurrence, which can be assessed by testing for thrombophilic states. The evaluation is best done after 3 months of the event and after stopping anticoagulants. Children with lower limb deep vein thrombosis should be fitted for compression stockings. + +Recurrent Thrombosis +Recurrent thrombosis may occur due to inadequate anticoagulation therapy. The risk of recurrence is estimated at 4-5% in patients without adverse risk factors, 17-20% for those with one predisposing condition and almost 50% with two or more risk factors. + +Suggested Reading +Saxena R, Kannan M, Chaudhry VP. Laboratory studies in coagula­ tion disorders. Indian J Pediatr 2007;74:649-55 +Tormene D, Gavasso S, Rossetto V, Simioni P. Thrombosis and thrombophilia in children: a systematic review. Sein Thromb Hemost 2006;32:724-8. + +WHITE BLOOD CELLS +Quantitative changes (more than ±2 SD) in white cell counts are the most frequently found abnormality on the +Hematological Disorders - + + +hemogram report. The differential count helps define the expanded population of cells. The percentage increase over normal range is important; very high counts are indicative of leukemoid reaction (a very high leukocyte response to infection that may be confused with leukemia) or leukemia. +The examination of the peripheral smear is very useful. The morphology of cells may reveal abnormal size, immaturity, change in nuclear-cytoplasmic ratio, inclusions and abnormal granules. Howell Jolly bodies are found with absent splenic function (asplenia, post splenec­ tomy) and toxic granulations and shift to the left suggest sepsis. Epstein-Barr virus infection results in large monocytoid cells which can be confused for blasts on peripheral smear. + +Leukocytosis +The onset and duration of illness, history of intake of medications and prior hospitalization may provide a clue to the diagnosis. + +Neutrophi/ia +Neutrophils increase in diverse conditions, like acute bacterial infections, acute blood loss, hemolysis and diabetic ketoacidosis (Table 12. 23). Cytochemical staining for leukocyte alkaline phosphatase (LAP), an enzyme found in mature neutrophils, is useful; neutrophils granules contaning LAP stain blue, resulting in a high LAP score in infections and leukemoid reaction. In chronic myeloid leukemia, neutrophils are deficient in LAP so the score is low compared to normal neutrophils. + + +Table 12.23: Common causes of neutrophilia Acute +Acute bacterial infections +Epinephrine, corticosteroids, granulocyte colony stimulating factor +Hemorrhage; hemolysis Hypoxia +Trauma, burns, exercise, heat stroke +Renal failure, diabetic ketoacidosis, hepatic failure Hodgkin lymphoma +Chronic +Chronic myeloid leukemia +Rheumatological and inflammatory diseases Hemolytic anemias; sickle cell anemia +Post-splenectomy Chronic blood loss Thyrotoxicosis +Chronic idiopathic neutrophilia +Genetic causes or syndromes +Down syndrome Asplenia +Leukocyte adhesion defects + +Monocytosis +Monocytes, the circulating tissue macrophage precursors, are important for ingestion and killing of pathogenic bacteria, e.g. Mycobacterium tuberculosis, and parasites, e.g. Leishmania. Monocytosis is noted in many infections (Table 12.24). Abnormality of macrophage activation may cause disorders like familial hemophagocytic syndrome. +I + + +Table 12.24: Causes of monocytosis +Infections: Tuberculosis, typhoid, bacterial endocarditis, +brucella, kala-azar, malaria +Autoimmune diseases: Systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, polyarteritis nodosa +Post-splenectomy neutropenia; hemolytic anemia +Malignancy: L phoma, chronic myeloid leukemia, juvenile myelomonocytic leukemia, myelodysplasia +ym +Myxedema + + +Basophilia +Basophilia is usually seen during acute hypersensitivity reactions, but may be found in chronic myeloid leukemia, Hodgkin lymphoma, varicella, hypothyroidism and while on antithyroid medications. + +Eosinophilia +Eosinophilia is noted in many allergic disorders systemic inflammatory conditions and malignancies (Table 12.25). Parasites which invade tissue are more likely to cause eosinophilia (e.g. Toxocara which causes visceral larva migrans). Sustained elevation in eosinophil count is associated with cardiac toxicity. Moderate elevation refers to an absolute eosinophil count of 1500-5000 cells/µl and severe eosinophilia is >5000 cells/µl. + +Lymphocytosis +Lymphocytosis is a common feature of many infections (Table 12.26). It is important to distinguish reactive from neoplastic lymphocytosis. + +Leukopenia +This is usually found in conjunction with pancytopenia, e.g. aplastic anemia, megaloblastic anemia, bone marrow replacement or infiltration (malignancy, Gaucher disease, osteopetrosis) and hypersplenism. + +Neutropenia +Neutropenia may occur due to increased destruction or decreased production of neutrophils, and is usually acquired (Table 12.27) Rarely, neutropenia may be congenital, occurring as cyclic neutropenia, or as a part of inherited deficit. Transient neutropenia is common with viral infections. Severe neutropenia is present when the absolute neutrophil count is below 500 cells/µl. +_ E_s_s_ _en_t_a_i_P_e_d_ia_t_rics___________________________________ +i +_ +_ + + +Table 12.25: Common causes of eosinophilia +Acute +Allergic disorders: Asthma, atopic dermatitis, urticaria, drug hypersensitivity, pemphigoid +Parasitic infestations: Toxocara, ascaris, amebiasis, strongy­ loidiasis, filaria, toxoplasmosis, trichinosis, schistosomiasis, malaria, scabies +Fungal infections: Bronchopulmonary aspergillosis, coccidio­ mycosis +Malignancy: Hodgkin lymphoma, T cell lymphoma, acute myelogenous leukemia, myeloproliferative syndrome +Hypereosinophilic syndrome + +Chronic +Allergic disorders: Pemphigus, dermatitis herpetiformis Autoimmune disorders: Inflammatory bowel disease, +rheumatoid arthritis +Myeloproliferative syndrome, hypereosinophilic syndrome Loeffler syndrome +Immunodeficiency syndromes: Hyper IgE, Wiskott Aldrich syndrome; Omenn syndrome; graft versus host reaction Miscellaneous: Thrombocytopenia with absent radii; renal +allograft rejection; Addison disease + + +Lymphopenia +Lymphopenia is noted during several infections, including viral (hepatitis, influenza) and bacterial (typhoid, tuberculosis, sepsis) illnesses. The most common infectious cause is acquired immunodeficiency syndrome (AIDS). Lymphopenia is also found in inherited immuno­ deficiency syndromes due to decreased production of B or T lymphocytes (severe combined immunodeficiency, isolated CD4+ lymphocytopenia, ataxia-telangiectasia and Wiskott-Aldrich syndrome. It may also occur after anti­ thymocyte globulin treatment for aplastic anemia, use of corticosteroids, systemic lupus erythematosus and protein losing enteropathy. + +QualitativeDefects +Qualititave defects in leukocytes may give rise to immuno­ deficiencies. The work up of most immunodeficiencies needs specialized tests for estimate of immunoglobulins, T and B lymphocyte subsets and complement and functional assays. + +Cl1ediak-Higaslzi syndrome is identified by its characteristic morphology showing giant lysosomes in the granulocytes and oculocutaneous albinism. Defects in CHSl or Lyst gene impair lysosomal trafficking, resulting in ineffective granulopoiesis, delayed degranulation and altered chemo­ taxis resulting in increased bacterial infections. In the + + +Table 12.26: Common causes of lymphocytosis +Infections: Infectious mononucleosis, infectious hepatitis, cytomegalovirus, tuberculosis, pertussis +Endocrine: Thyrotoxicosis, Addison disease Malignancy: Acute lymphoblastic leukemia, lymphoma + +Table 12.27: Common causes of neutropenia Acute +Infections: Severe sepsis; tuberculosis, Shigella, brucellosis; dengue, varicella, Epstein-Barr virus, cytomegalovirus, HN; kala-azar, malaria; rickettsia +Drugs: Sulfonamides, phenytoin, phenobarbital, penicillin, phenothiazines +Bone marrow infiltration: Leukemia, lymphoma, neuroblastoma Hypersplenism +Chemotherapy: Busulphan, cyclophosphamide, radiation +Chronic +Aplastic anemia: Acquired; inherited (Fanconi anemia) Autoimm.une diseases: Systemic lupus erythematosus, Crohn +disease, rheumatoid arthritis Vitamin B12 or folate deficiency +Bone marrow infiltration: Myelodysplasia, chronic myelogenous leukemia, chronic idiopathic neutropenia +Paroxysmal nocturnal hemoglobinuria +Inherited disorders: Cyclic neutropenia; severe congenital neutropenia; chronic benign neutropenia; Kostmann syndrome; Schwachrnan-Diamond syndrome; dyskeratosis congenita; Chediak-Higashi syndrome; glycogen storage disease type 1B +Associated with immunodeficiency: Hyper IgM syndrome; HN + + +accelerated phase, there is lymphohistiocytic infiltration of organs. + +Leukocyte adhesion defect type 1 results from deficiency of CDll and CD18 on the neutrophils, lead to defects in adhesion, chemotaxis and C3bi mediated phagocytosis. This causes delayed umbilical cord separation in the newborn and leads to repeated, severe infections and periodontitis later in life. + +Chronic granu/0111atous disease is an X-linked, (or rarely, autosomal recessive) inherited defect of the respiratory burst pathway in the granulocytes. It manifests as infections in the lungs, skin and gastrointestinal tract with S. aureus, aspergillus and Serratia marcescens, leading to formation of deep-seated granulomatous lesions. Many other primary immunodeficiencies have quantitative defects in T, B or both lymphocyte subsets with maturation or functional defects, which lead to life threatening infections. + +Otolaryngology + + + + + + + +Sandeep Samant, Grant T. Rohman, Jerome W. Thompson + + + + + + + +DISEASES OF THE EAR + +Otitis Media +Otitis media is a common early childhood infection. Anatomic features that make young children particularly susceptible to ear infections include shorter, more horizontal and compliant eustachian tubes and bacterial carriage in the adenoids. Other risk factors include expo­ sure to cigarette smoke, overcrowding, bottlefeeding, cleft palate, Down syndrome, allergy and immune dysfunction. These risk factors contribute to the pathophysiology of the two common varieties of otitis media, acute otitis media and otitis media with effusion. + +Acute Otitis Media +Acute otitis media (AOM) in children tends to have a bimodal age distribution, with children between ages 6 and 24 months and 5 to 6 yr at greatest risk. +Etiology. The most common organisms causing AOM are Streptococcus pneumoniae and Haemophilus influenzae, accounting for approximately 65% cases; 15% are caused by Moraxella catarrhalis, Streptococcus pyogenes and Staphylococcus aureus. Respiratory viruses play an important role in initiating otitis media and may be the only pathogens in some cases, since 20% of middle ear aspirates are sterile. + +Diagnosis. AOM is characterized by the rapid onset of symptoms, which may be local, e.g. otalgia or ear tugging, and/or systemic, e.g. fever or crying. Older children may report impaired hearing. History of recent upper respira­ tory tract infection is common. Otoscopic examination reveals a red and bulging tympanic membrane with redu­ ced mobility as measured by either tympanometry or insufflation through the otoscope (pneumatic otoscopy). Rupture of the drum with ear discharge (suppuration) may have already occurred, in which case the ear canal contains an opaque yellow-green or reddish-brown fluid. Cleaning of this fluid usually reveals an intact drum, as the rupture is small and closes promptly after spontaneous perforation. The diagnosis of AOM is considered certain if all of the following criteria are met: (i) rapid onset; (ii) signs of middle ear effusion; and (iii) signs and symptoms of middle ear inflammation. + +Treatment. Antimicrobial therapy is recommended. However, in some cases children may qualify for a trial of observation (Table 13.1). Amoxicillin should be the first­ line therapy for AOM. Higher doses (80-90 mg/kg/ day) may be considered where streptococcal resistance is endemic. Agents with �-lactamase resistance (e.g. amoxicillin-clavulanic acid, cefaclor, cefuroxime or newer cephalosporins) are useful second-line drugs. Initial + + + +Table 13.1: Criteria for choice of treatment or observation in children with acute otitis media + +Age Diagnosis certain <6mo Antibacterial therapy 6-23 mo Antibacterial therapy +?.24mo Antibacterial therapy if illness severe* Observation is an option if illness not severe** + + +Diagnosis uncertain Antibacterial therapy +Antibacterial therapy if illness severe* Observation is an option if illness not severe** + + +*Severe illness is defined as moderate to severe otalgia or fever ;?.39°C +*Observation is appropriate only if follow-up can be ensured; antibacterial therapy is started if symptoms persist or worsen +Adapted from guidelines of the American Academy of Pediatrics and American Academy of Family Physicians. Clinical Practice Guideline: Subcommittee on Management of Acute Otitis Media. Pediatrics 2004;113:1451-65 + +359 +-�E_s_s_ e_tn__ia_i_P_e_d_ia__t nc_·_s __________________________________ + + +antibiotic therapy should last at least 7 days. Re­ examination is indicated after 3-4 days and at 3 weeks. +Adjuvant treatment with oral and topical decongestant drugs is not necessary. Antihistaminic agents, which contribute little to the resolution of otitis media and may precipitate sinus infections due to their drying effect on mucosal secretions, are also not recommended. Tympano­ centesis (aspiration of the middle ear fluid) with a bent 18-gauge spinal needle on a syringe may provide specimen for culture in patients with complicated AOM who cannot tolerate tympanostomy tube insertion. Tympanocentesis improves otalgia but does not shorten the course of the illness. +Many children present with recurrent episodes of AOM. A child that has 4 episodes of AOM in 6 months or 6 episodes in 12 months should be considered for tym­ panostomy tube insertion. If a child requires a second set of tympanostomy tubes, concurrent adenoidectomy is considered. No benefit from concurrent tonsillectomy has been demonstrated in patients with recurrent AOM. + +Otitis Media with Effusion (OME) +Following an episode of AOM, serous or mucoid middle ear effusions may be seen. Effusions are found to persist in up to 40% of children 1 month after AOM and in 10% after 3 months. Many children with OME do not have a history of previous acute middle ear infections. Most children are asymptomatic or complain of hearing loss and ear fullness. Otalgia is not normally present. Otoscopy reveals a dull tympanic membrane with middle ear effusion (Fig. 13.1), frequently with air fluid levels or bubbles. Reduced tympanic membrane mobility on either pneumatic otoscopy or type B pattern on tympanometry confirms the diagnosis. + + + + + + + + + + + + + + + + + + + +Fig. 13.1: Otitis media with effusion. Note the dull lustreless tympanic membrane. (Courtesy: Textbook of ENT, Hazarika) + +Since over 65% of serous middle ear effusions resolve spontaneously within 3 months, newly diagnosed effusions should be observed for this period. Antibiotic adminis­ tration is not shown to resolve OME. Use of antihistamines and decongestants is not recommended. The benefit of corticosteroid administration has not been proven but a brief trial of steroids is commonly used. +If effusion persists beyond 3 months, tympanostomy tube insertion may be considered for any hearing loss >25 dB (Fig. 13.2). Other indications of tube placement in OME are speech delay, altered behavior, major sequelae such as otitic meningitis or impending cholesteatoma formation from tympanic membrane retraction. Improve­ ment in hearing and ear discomfort is immediate. Mean time before extrusion is usually between 12 and 18 months. Insertion of longterm tubes ( of T-tube design) or adenoidectomy may be considered in patients with recurrent or persistent symptomatic effusion. T-tubes have been associated with tympanic membrane perforation. Earplugs are recommended while the tubes are in place to avoid entry of water into the middle ear space. + +Chronic Suppurative Otitis Media (CSOM) +Ear drainage that persists for longer than 6 weeks is generally due to chronic inflammation of the middle ear space or mastoid air cells. Chronic suppurative otitis media (CSOM) invariably presents with tympanic membrane perforation, which allows otorrhea. CSOM most often results from neglected episodes of AOM and is therefore more common in children with inadequate access to health care. It most often occurs in the first five years of life as eustachian tube dysfunction plays a central role in the pathophysiology. +Clwlesteatoma, a sac of squamous epithelium extending from the tympanic membrane into the middle ear, also + + + + + + + + + + + + + + + + + + +Fig. 13.2: Tympanostomy tube in situ in the anteroinferior quadrant of the tympanic membrane (Courtesy, Textbook of ENT, Hazarika) +_________________________________o_t_o_,a_ry_n_o,__g o_g_y__ + + +presents with a chronically draining ear. Most cholesteatoma is acquired. It remains unclear whether a cholesteatoma arises from extension of a tympanic membrane retraction pocket, or from aberrant inward migration of normal epithelium. Rarely, it may be congenital, arising de nova through the eustachian tube by passage of neonatal epithelium. Though not malignant, cholesteatoma may cause serious compli­ cations by slow expansion and local destruction. +Etiology. The most commonly isolated organism is Pseudomonas aeruginosa; other organisms include Staphylo­ coccus aureus, Proteus spp, E. coli and anerobes. Fungi, especially Aspergillus and Candida spp., may be important. + +Diagnosis Chronic ear discharge is the hallmark of CSOM. Otoscopy reveals perforation of the tympanic membrane (Fig. 13.3). A chronically draining ear may also be seen with cholesteatoma, which is a sac of squamous epithelium extending from the tympanic membrane into the middle ear. Most cholesteatoma is acquired, although whether it arises from extension of a tympanic membrane retraction pocket, or from aberrant inward migration of the normal eardrum epithelium, remains unclear. Rarely, the choles­ teatoma may be congenital, arising de nova in the middle ear space. Though not malignant, cholesteatoma may cause serious complications by slow expansion and local destruction. These complications are discussed further in the next section. +Treatment. Medical therapy consists primarily of topical antibiotics and aural toilet. Topical quinolones appear to be effective and safe. Complicated infections and/ or any signs of systemic involvement require the use of systemic antibiotic therapy. Parents should be instructed to avoid water exposure. Secondary fungal otitis externa is a complication of topical antibiotic treatment. Otolaryn­ gology referral is necessary to rule out cholesteatoma. + + + + + + + + + + + + + + + + + + + +Fig. 13.3: Otoscopy in a child with chronic suppurative otitis media showing subtotal central perforation (Courtesy, Textbook of ENT, Hazarika) + +Surgery is usually indicated for cases of CSOM that do not respond to conservative treatment. Surgical therapy involves repair of the tympanic membrane perforation (tympanoplasty) with or without mastoidectomy. If cholesteatoma is suspected, ear exploration via mastoi­ dectomy and cholesteatoma removal is mandatory. The primary goal of surgical therapy for cholesteatoma is to create a 'safe ear' by removal of all cholesteatoma. Hearing preservation is a secondary goal. + +Complications of Otitis Media +Untreated otitis media may cause serious complications, which are classified as either intracranial or extracranial (Table 13.2). Complications of AOM are more common in young children, while complications of CSOM with or without cholesteatoma are common in older children. +The most common complication of CSOM is hearing loss, which may affect language development and school performance. The hearing loss is usually conductive and results from middle ear edema and fluid and tympanic membrane perforation. Sensorineural hearing loss may rarely occur due to direct extension of inflammatory mediators into the inner ear. + +Meningitis is the most common intracranial complication of both acute and chronic otitis media. Furthermore, AOM is the most common cause of secondary meningitis. Pneumococcal meningitis is the most common cause of acquired sensorineural hearing loss in children. The mortality rate from otitic meningitis has decreased significantly in the postantibiotic era and with the use of streptococcal vaccines. +Brain abscess is a potentially lethal complication. Unlike meningitis, which is caused more frequently by AOM, brain abscesses result almost exclusively from CSOM. Therapy with broad spectrum parenteral antibiotics is begun immediately and surgical drainage considered. Thrombosis of the sigmoid or transverse sinus is another important intracranial complication. Patients typically + + +Table 13.2: Complications of otitis media• lntracranial +Meningitis Epidural abscess +Dural venous (sigmoid sinus) thrombosis Brain abscess +Otitic hydrocephalus Subdural abscess +Extracranial +Acute coalescent mastoiditis Subperiosteal abscess +Facial nerve paralysis +Labyrinthinitis or labyrinthine fistula + +*Listed from most to least common +..E_s_s_e_ _ t_ia_i_P_e_d_ ia_ t_ ri_ cs_ _________________________________ +n +- + + +present with headache, malaise and high spiking fever in a 'picket fence' pattern. Treatment involves parenteral antibiotics and surgical drainage of the mastoid. +Acute coalescent mastoiditis. This results from the spread of infection into the mastoid bone. The entity should be differentiated from fluid effusion within mastoid air cells, which is sometimes mistakenly reported radiologically as 'mastoiditis'. Such opacification is commonly seen with AOM or OME, is readily apparent on CT and is of little clinical significance. Coalescent mastoiditis, on the other hand, presents with postauricular erythema, tenderness, and edema. The auricle is displaced inferiorly and +laterally. The CT scan shows fluid and breakdown of the wall separating the mastoid air cells. Untreated, coalescent mastoiditis may spread externally, leading to the +formation of subperiosteal or deep neck abscesses. Acute coalescent mastoiditis should initially be treated +with parenteral antibiotics directed against the afore­ mentioned pathogens associated with AOM. If mastoiditis is superimposed on a chronically draining ear, coverage should be added for gram-negative and anerobic organisms. Surgery in the form of cortical mastoidectomy with tympanostomy tube insertion is indicated for cases with poor response to parenteral antibiotic therapy, presence of an abscess or an intracranial complication or +acute mastoiditis in a chronic ear. +Other complications include labyrinthinefistula andfacial nerve paralysis. Labyrinthine fistula, in which a choleste­ +atoma has eroded into the inner ear, presents with vertigo and sensorineural hearing loss. Facial nerve paralysis secondary to otitis media is treated with appropriate antibiotics and tympanostomy tube insertion. If facial nerve paralysis is secondary to cholesteatoma, mastoi­ dectomy is indicated. + +Otitis Externa +Acute otitis externa (swimmer's ear) presents with itching, +pain and fullness. Erythema and edema of the ear canal and tenderness on moving the pinnae or tragus are diagnostic features. Otorrhea is common. Risk factors include swimming, impacted cerumen, hearing aid use, +eczema or trauma from foreign objects (hairpins or cotton swabs). The etiologic agents of otitis externa include P. aeruginosa, Staphylococcus, Proteus, E. coli, Aspergillus and Candida spp. +Treatment consists of ear canal culture, cleaning and topical antibiotic drops. Topical antibiotics have clinical cure rates up to 80%. If edema is significant, ribbon gauze or a 'wick' may be placed in the external auditory canal to stent it open for drop delivery. Oral antibiotics are reserved for failure to improve and complications. +Otomycosis or fungal otitis externa is most common in humid weather and presents with pain and pruritus. These opportunistic infections are frequently seen subsequent +to treatment of a bacterial infection. Examination reveals + +fungal spores and filaments. Aspergillus and Candida are the most common pathogens. Aural toilet and a topical antifungal (e.g. clotrimazole) are curative. +Otic furunculosis is an exquisitely painful, superficial +abscess in the outer portion of the ear canal, typically from S. aureus. Oral antistaphylococcal antibiotics and anal­ gesics bring about prompt relief. Incision and drainage +may be necessary. +Eczematous or psoriatic otitis externa describes a group of inflammatory conditions in which there is drainage, pruritis and/ or scaling of the ear canal skin. Underlying causes include contact dermatitis, atopic dermatitis and seborrheic dermatitis. +Malignant otitis externa is a rare invasive infection of the external auditory canal cartilage and bone. Immunocom­ promised children (acquired immunodeficiency syn­ +drome, leukemia, diabetes mellitus, immunosuppression after organ transplant) are at risk. Pseudomonas aeruginosa +is the most common etiology. Invasive fungal species, especially Aspergillus, are also seen. The external auditory canal is tender and facial or scalp necrosis may arise, with +or without cranial nerve abnormalities. Diagnosis is confirmed with CT and MRI scan and/ or scintigraphy for osteomyelitis of the temporal bone. Aggressive surgical +debridement and parenteral antibiotics and/ or antifungals for -6 weeks are required. Treatment response may be monitored with serial Gallium67 bone scans. + +Hearing Loss +Early detection of hearing loss in children is imperative. Unrecognized early hearing loss can impede development of speech, language and cognitive skills. Separate differen­ tial diagnoses exist for deficits of both the conductive and sensorineural components of the hearing mechanism. +Hearing loss in children can be classified as either congenital or acquired. +Conductive Hearing Loss +Any process that interferes with the conductive mechanism +of the ear canal, tympanic membrane, or ossicles may cause a conductive hearing loss. The most common pedia­ tric cause of conductive lost is otitis media with effusion and is typically of mild to moderate severity. Several congenital syndromes may also be associated with middle ear abnormalities, such as Apert, Crouzon and Treacher­ Collins syndromes. +Sensorineural Hearing Loss +Sensorineural hearing loss is caused by a lesion of the +cochlea, auditory nerve or central auditory pathway. SNHL can be acquired or congenital, both being equally common. The most common postnatal cause of acquired +sensorineural hearing loss is meningitis, while the most common prenatal cause is intrauterine infection (e.g. +TORCH infections, syphilis). Other causes of acquired +_________________________________o_t_ o_ ,a_ry_n_o_g_,o_g_y __ + + +hearing loss include prematurity, hyperbilirubinemia, perinatal hypoxia, acquired immunodeficiency syndrome, head trauma and ototoxic medications (aminoglycosides, loop diuretics). +Congenital causes of sensorineural hearing loss are of +syndromic and nonsyndromic types. Although 70% of +congenital hearing loss is nonsyndromic, over 300 genetic syndromes are associated with SNHL. Common syndromes include Pendred syndrome (euthyroid goiter), Jervell and Lange-Nielsen syndrome (prolonged QT waves, syncope), Usher syndrome (retinitis pigmentosa and blindness), Alport's syndrome, branchio-oto-renal syndrome, neuro­ fibromatosis and Waardenburg syndrome. Multiple chromosome loci and at least 65 genes associated with genetic hearing loss have been identified. Mutations in a single gene, GJB2, may be responsible for up to 50% of nonsyndromic congenital hearing loss. GJB2 encodes the protein connexin 26, which is widely expressed in cells of the inner ear. Screening tests for this mutation are available. + +Neonatal Screening +All neonates with risk factors for hearing loss should be screened with an oto-acoustic emission test or an auditory brainstem response. The use of clinical indicators to focus hearing screens will miss as many as 50% of all cases of impairment. Hence universal newborn hearing screen programs are now commonplace in the United States and Europe. The importance of neonatal screening cannot be overemphasized. Infants in whom treatment for hearing loss is initiated by 6 months of age are able to maintain language and social development in line with their phys­ ical development. This is in contrast to those whose hearing loss is identified after 6 months of age. A limitation of newborn screening is that some forms of early-onset hearing loss are not apparent at birth. A United States Joint Committee on infant hearing has identified 11 risk indicators that should prompt continued monitoring of hearing status even in the face of normal neonatal screens (Table 13.3). + +Screening in Older Children +Clinical evaluation of hearing at routine well child assess­ ments is critical for early detection of hearing impairment. Examination should include otoscopy with attention to middle ear pathology. Doubtful cases are referred for detailed audiologic evaluation so that timely intervention may begin. +Multiple techniques exist to assess hearing sensitivity and are selected based on the age and the abilities of the child. For younger children unable to understand instruc­ tions, visual-reinforcement audiometry is performed. Pure tone audiometry is possible in children older than 5 yr. Tympanometry may be performed in nearly all children to assess ear drum mobility. + + +Table 13.3: Indications for continued hearing monitoring in children with normal hearing on neonatal screening +Caregiver concern regarding hearing, speech, or develop­ mental delay +Family history of childhood hearing loss +Neonatal intensive care for >5 days or use of any of the following, regardless of duration: Extracorporeal membrane oxygenation, assisted ventilation, exposure to ototoxic antibiotic (gentamycin, tobramycin) or loop diuretics (furosemide) and hyperbilirubinemia requiring exchange transfusion +In utero infections (CMV, rubella, syphilis, herpes, toxo­ plasmosis) +Findings of a syndrome associated with hearing loss +Postnatal infection known to cause hearing loss (e.g. meningitis) +Syndromes associated with progressive hearing loss (e.g. neurofibromatosis) +Neurodegenerative disorders (e.g. Hunter syndrome, Friedreich ataxia) +Head trauma +Recurrent or persistent (�3 mo) otitis media with effusion Chemotherapy or head radiation + + +Treatment of Hearing Loss +Once diagnosed, treatment of hearing loss is based on the extent of deficit and the underlying pathology. For very mild hearing loss, treatment may consist simply of preferential seating in school. For mild to moderate conductive hearing loss, treatment options include tympanostomy tubes or, if a perforation is present, tympanoplasty. +Treatment of significant sensorineural hearing loss may require the use of hearing aids from as early as 3 months of age. The development of cochlear implants has rapidly reshaped the management of childhood hearing loss. Bilateral cochlear implantation may be considered for infants as young as 12 months of age who have a profound bilateral hearing loss and may be considered even earlier if the hearing loss is due to meningitis. If a child has never had auditory stimulus (secondary to profound congenital deafness), cochlear implantation before 6 yr of age is crucial to develop the auditory cortex for sound awareness and speech development. Sign language and deaf education programs should be considered for children who are not candidates for cochlear implantation. + +DISEASES OF THE NOSE AND SINUSES + +Rhinitis +Allergic Rhinitis +Allergic rhinitis is an inflammatory disorder characterized by sneezing, itching, nasal obstruction and clear rhino- +__ E_s_s_e_n_ _tia_i_P_e_d_i_a _tr-_s_________________________________ +i +c +_ + + +rrhea. The pathophysiology involves an IgE-mediated reaction to a specific allergen. Symptoms may be seasonal ('hay fever') or perenial. Examination reveals a pale nasal mucosa, congested nasal turbinates and mucoid rhinor­ rhea. Conjunctiva! itching and redness may be present. Inhaled allergens (e.g. pollen, spores and dust mites) are common causes. Accurate diagnosis may require demonstration of eosinophilia in a nasal smear, or the use of skin/ serologic tests to show specific IgE response to allergens. These tests establish the atopic etiology and help differentiate from other conditions with similar symptoms. Treatment includes allergen avoidance, use of topical nasal steroid sprays for prevention and oral antihistamines for symptom relief. The use of oral decongestants is controversial. Topical decongestants should also generally be discouraged as they cause rebound congestion (short­ term) and chemical rhinitis or rhinitis medicamentosa +(longterm). + +Viral Rhinitis +Viral rhinitis or common cold is the most common cause of both nasal obstruction and rhinorrhea in children. Children normally average between six and eight of these upper respiratory infections per year. Malaise, low to moderate grade fever, nasal congestion and rhinorrhea are the presenting symptoms. A number of different viruses can be responsible, including rhinovirus, influenza and adenovirus. Treatment is symptomatic and involves antipyretics, saline nasal spray. Use of oral decongestants and antihistamines are controversial. A number of deve­ loped countries recommend annual influenza vaccination in children older than 6 months. Otitis media and sinusitis are frequent complications. + +Sinusitis +Sinusitis can be classified as either acute or chronic. The ethmoid and maxillary sinuses are the earliest to develop and are the ones most commonly infected in pediatric sinusitis. The frontal sinuses may become involved only after 5-6 yr of life; isolated sphenoid disease is rare. Risk factors associated with sinusitis include recurrent upper respiratory infections, allergic rhinitis, cystic fibrosis, immunodeficiency, ciliary dyskinesia, daycare attendance and exposure to tobacco smoke. Ten-fifteen percent of upper respiratory tract infections are complicated by sinusitis. A sinus infection should be considered in any child whose cold symptoms have not resolved by 7-10 days. +Etiology. The most common isolates in acute sinus infec­ tions are 5. pneumoniae, H. influenzae and M. catarrhalis. The same bacteria are implicated in chronic sinusitis, as are 5. aureus, anerobes and occasionally fungi. The adenoid pad plays an important role in the pathophysiology of pediatric sinusitis since it may serve as a bacterial reservoir for the paranasal sinuses (Fig. 13.4). + +Diagnosis. Acute rhinosinusitis typically presents as an episode of upper respiratory infection with worsening of nasal discharge and cough 7 to 10 days after onset of symptoms. A severe URI with fever (>38.5°C) and purulent rhinorrhea also meets the diagnostic criteria for acute sinusitis. Chronic sinusitis is defined as symptoms of sinusitis lasting longer than 30 days. Nasal obstruction, malaise and headache may all be features of chronic rhinosinusitis. Imaging is not necessary and should be reserved for cases with complications and those being considered for surgery. CT scan is superior to plain X-rays for imaging of paranasal sinuses (Fig. 13.4). + +Allergic fungal sinusitis is an increasingly recognised condition in atopic, immunocompetent patients. Older children and adolescents are most commonly affected. The cause is hypersensitivity to fungal antigens. This results in the form of chronic rhinosinusitis that requires surgical intervention. + +Complications. These include orbital or intracranial spread of infection. Orbital complications most commonly result from direct extension from the ethmoids. Early orbital complications manifest as periorbital (preseptal) cellulitis. More severe complications include orbital abscess or cavernous sinus thrombosis. Ophthalmoplegia, vision loss, and toxemia indicate a life-threatening infection of the cavernous sinus. Intracranial complications (meningitis and abscesses) may also occur and are more commonly associated with frontal and sphenoid sinus infections. + + + + + + + + + + + + + + + + + + + + + + + + +Fig. 13.4: Note the air fluid level in right maxillary sinus in a patient with maxillary sinusitis (Courtesy: Textbook of ENT, Hazarika) +__________________________________o_to_1_a_ry_n__go_1og__y__ + + +Treatment. Although a significant number of acute sinusitis episodes will resolve spontaneously, treatment with antibiotics is preferred. Therapy with amoxicillin is recommended for 10-14 days. Longer courses and second­ line antibiotic agents are indicated for refractory infections. Parenteral antibiotics are necessary for sinusitis with orbital or intracranial complications. Other adjuvant mea­ sures include oral decongestants, mucolytic agents and topical nasal saline. Topical decongestants may be used in sinusitis with complications. Antihistamines are avoided due to their drying effect. +Antibiotics are also required for chronic sinusitis. As most of these patients have already failed a course of standard-dose amoxicillin, initial therapy consists of coamoxiclav, high-dose amoxicillin or cefuroxime. The duration of treatment is longer than for acute sinusitis, typically 3 to 6 weeks. Patients with penicillin allergy may be treated with a macrolide antibiotic, although there is increasing resistance of pathogens to these agents. Topical nasal steroids are occasionally useful for treatment. +Surgical intervention for acute sinusitis is limited to those with orbital or intracranial complications. Surgery may be considered for patients with chronic sinusitis who have not responded to aggressive medical management or who show anatomical obstruction after maximal medical management and extensive medical workup with allergy testing and immune evaluation. Adenoidectomy, to remove a potential bacterial reservoir for the sinuses, must be considered in younger children. The indications for endoscopic sinus surgery include patients with sinonasal polyposis, cystic fibrosis, failure to improve despite one-month course of medical therapy and any orbital or cranial complication. +Nasal Obstruction +Causes. Chronic mouth breathing in children is generally caused by blockage of nasal airflow. The site of nasal blockage is most often in the nasopharyngeal area due to adenoid hypertrophy. Intranasal causes of obstruction include allergic rhinitis, recurrent sinusitis, nasal septum deviation, turbinate hypertrophy, nasal polyps and less +commonly, neoplasms. As a rule, bilateral nasal polyps do not occur in normal children and their presence should +prompt testing for cystic fibrosis. Congenital causes of nasal airway obstruction include choanal stenosis or atresia, dermoid cysts, teratomas, encephaloceles, and pyriform aperture (bony opening to the nasal cavity in the skull) stenosis. +Diagnosis. Adenoid enlargement should be suspected in children, usually older than 2 yr, who present with nasal blockage, mouth breathing, sleep disturbance and chronic nasal discharge. Examination must rule out nasal pathology such as septal deviation or polyposis. Neonates with pyriform aperture stenosis may present with a single midline maxillary incisor. A CT scan or X-ray confirms +the diagnosis (Fig. 13.5). + + + + + + + + + + + + + + + + + + + + + + + + +Fig. 13.5: Lateral radiograph of the neck showing adenoid hypertrophy occluding the nasopharyngeal airway in a 6-yr-old boy (Courtesy, Textbook of ENT, Hazarika) +Treatment. Adenoidectomy is recommended for symptomatic younger children. Pubertal growth of the rnidface and regression of adenoid size tend to result in relief of adenoid-related nasal obstruction in children older than 9 yr. Pyriform aperture stenosis is treated with surgical drilling of the obstructing bony plates. Treatment for sinonasal polyposis includes topical and systemic steroids for limited disease and surgical intervention for larger, obstructing polyps. +Surgery on the nasal septum should be avoided in pre­ pubertal children, as it may lead to retardation in nidface growth and saddling of the nasal dorsum. A conservative operation to correct a limited portion of the septum may be justified in a particularly symptomatic child. Turbinate hypertrophy usually responds to treatment of allergy, though electrocautery may be used in refractory cases. + +Eplstaxls +Bleeding from the nose occurs frequently in children. Most pediatric epistaxis occurs in the anterior portion of the nasal septum at a confluence of arterial vessels known as Little's area (Kiesselbach plexus). Local trauma, especially nose picking, is by far the most common cause of pediatric epistaxis. Reduced ambient humidity also places the patient at risk. Examination reveals prominent vessels in Little's area that bleed promptly when touched with a cotton-tipped probe. Digital pressure by pinching the nose invariably stops the bleeding. Avoidance of nose picking, +application of an antibiotic ointment for lubrication and, +---------------------------- +Essential Pediatrics + +for refractory cases, cauterization with topical silver nitrate or electrocautery are curative. Bleeding disorders must be suspected in children with suggestive family history, a history of frequent bleeding from other sites, or any nasal bleeding which does not respond in the usual fashion. +Less frequent causes of recurrent epistaxis include juvenile nasopharyngeal angiofibroma and hereditary hemorrhagic telangiectasia. The former is a benign, vascular tumor occurring exclusively in adolescent males that can cause profuse, brisk bleeding. Hereditary telan­ giectasia also known as Osler-Weber-Rendu syndrome, is a genetic defect in blood vessel structure resulting in arteriovenous malformations. Patients may suffer from severe, recurrent epistaxis, as well as gastrointestinal bleeds and pulmonary hemorrhage. + +Choanal Atresia +Congenital failure of the nasal cavities to open into the nasopharynx is called choanal atresia. It results from failed resorption of the buccopharyngeal membrane either unilaterally or bilaterally or even partial with a severe stenosis. As neonates are obligate nasal breathers for 6 months, bilateral choanal atresia presents immediately afterbirth with respiratory distress. The affected baby cycles between silent cyanosis and crying. Suckling immediately precipitates cyanosis. Bilateral atresia can present as part of the CHARGE association, consisting of coloboma, heart abnormalities, choanal atresia, retardation of growth and development, genitourinary defects and ear anomalies. +Unilateral choanal atresia is a more indolent process and may present later in childhood with unilateral nasal discharge or blockage. Atresia typically manifests when the opposite nasal passage becomes blocked due to rhinitis or adenoid hypertrophy. + +Diagnosis. Inability to pass an 8 French catheter can aid in diagnosis. Flexible nasal endoscopy confirms the diagnosis. CT scan demonstrates the atretic plate thickness and differentiates between bony and membranous atresia. + +Treatment. Bilateral choanal atresia requires urgent management by inserting a finger in the baby's mouth and depressing the tongue down and forward away from the back of the throat. This should be replaced with a plastic oropharyngeal airway or a McGovern open-tip nipple. Failure of these measures may necessitate intubation or tracheostomy. +Treatment of choanal atresia is surgical. The two primary approaches are transpalatal and transnasal. Transnasal endoscopic repair is often attempted first as it is less invasive. Transpalatal repair, which involves removal of the posterior hard palate, is often reserved for failed endoscopic repair. Stents are placed in the nasal passages to prevent restenosis and are typically left in place for 3 to 6 weeks postoperatively. + +DISEASES OF THE ORAL CAVITY AND PHARYNX +Inflammatory Disorders +Recurrent aphthous stomatitis is a common pediatric disorder that presents as painful white ulcers of variable size on the oral mucosa. The exact etiology is unknown. The ulcers resolve spontaneously over several days. If symptomatic management does not suffice, topical steroids and rarely, systemic steroids are employed, but may require intravenous fluids for dehydration. +Herpetic stomatitis presents in children with small, painful vesicles that evolve into gray pseudomembranous mucosal ulcers. Antiviral medications may be used to hasten recovery, though the lesions usually heal spon­ taneously within 10-14 days. Once again intravenous fluids may be required. +Oral ca11didiasis (thrush) appears as small, white, curd-like lesions on the tongue and oral mucosa. In children under age 6 months or those on antibiotics, it is a benign finding. It can also be related to systemic diseases such as diabetes or immunodeficiency. Oral antifungals are effective. + +Congenital Disorders +A11kyloglossia (tongue tie) is a limitation of anterior tongue mobility caused by a congenitally short lingual frenulum. This condition is not related to speech impairment. +Cleft palate may appear with or without cleft lip and can cause serious feeding difficulties. The etiology is multi­ factorial. Treatment should include staged reconstruction of the lip and palate defects and multidisciplinary management. +Micrognathia (small mandible), if severe, may displace the tongue posteriorly and cause respiratory distress in the neonate. Congenital micrognathia is most commonly seen with the Pierre Robin sequence, in which patients also have cleft palate and glossoptosis. If the micrognathia is severe, the neonate may require tracheostomy to secure the airway. +Macroglossia may be idiopathic or associated with syn­ dromes such as Down syndrome, Beckwith-Wiedemann syndrome and neurofibromatosis. If significant, the enlarged tongue may cause drooling, speech impairment and airway obstruction. +Lingual thyroid may present as a posterior midline tongue mass and is caused by an abnormal descent of the thyroid from the tongue base in utero. It may present with neonatal respiratory distress and may be associated with a thyroglossal dust cyst. As lingual thyroid often represents the only functioning thyroid tissue, its removal may necessitate chronic thyroid hormone supplementation. + +Sore Throat +Viral pharyngitis is very common and is caused by a number of different pathogens including adenovirus, +_______________________________o_t_o1_ago_r_y1_on_g___y + + +enterovirus, coxsackievirus and parainfluenza virus. It typically presents with nonexudative pharyngeal erythema and tender cervical adenopathy. Upper respiratory complaints (rhinorrhea, nasal obstruction, cough, fever) are common. Treatment is supportive, as this is nearly always self-limited. + +Infectious mononucleosis, caused by the Epstein Barr virus, presents with sore throat, gray pharyngeal exudate and soft palate edema. Patients show significant cervical lymphadenopathy and hepatosplenomegaly. Monospot or Paul-Bunnell tests are useful screening tests (only 40% accurate) and antibody titer confirms the diagnosis. Medical treatment is supportive and may include steroids for respiratory difficulty or severe dysphagia. +Acute bacterial pharyngotonsillitis is caused by group A �-hemolytic streptococci. Less common pathogens include nongroup A streptococcus, S. aureus (Fig. 13.6), H. influ­ enzae, M. catarrhalis, diphtheria, gonococci, chlamydia and mycoplasma. Streptococcal pharyngitis presents as bil­ ateral tonsil hypertrophy and erythema with characteristic exudate. To distinguish between viral and bacterial pharyngotonsillitis, a rapid strep test should be obtained. A negative result should be confirmed by throat culture. Treatment is with a ten-day course of penicillin VK or a first-generation cephalosporin. Both suppurative and nonsuppurative complications can result from incom­ pletely treated streptococcal pharyngitis. Non-suppura­ tive complications include scarlet fever, acute rheumatic fever and poststreptococcal glomerulonephritis. Suppura­ tive complications include peritonsillar, para-pharyngeal or retropharyngeal abscesses. + + + + + + + + + + + + + + + + + + + +"lg. 13.6: Acute staphylococcal pseudomembranous tonsillitis with unilateral hypertrophy of the right tonsil. This condition has to be differentiated from other causes of white patch on the tonsil (Courtesy: +Textbook of ENT, Hazarika) + +Peritonsillar abscess typically presents with a muffled voice, trismus and decreased oral intake. Physical examination reveals a unilateral displacement of the affected tonsil towards the midline with a bulge in the peritonsillar region and uvular deviation to the opposite side. CT scan may aid in diagnosis. Treatment consists of incision and drain­ age by experienced personnel. This should be followed by a 7 1- 0 day course of oral or parenteral penicillin or clindamycin. Steroids, to reduce pain and fever, may be considered as adjunctive therapy. Immediate tonsillec­ tomy (Quinsy tonsillectomy) may be performed, but has increased hemorrhage risk. A single peritonsillar abscess is a relative indication for tonsillectomy. Patients with recurrent abscesses should always be considered for tonsil removal. +Pharyngeal injury may occur in children after falling with a pen, stick or other sharp object in the mouth. Exami­ nation reveals a puncture or laceration of the soft palate, tonsil, or pharyngeal wall. The most significant risk is a carotid injury. The presence of significant bleeding, neurologic findings or a puncture lateral to the exposed tonsil should prompt immediate consultation and evaluation with angiography. + +Adenotonsillectomy +Removal of the tonsils and adenoids is one of the most commonly performed pediatric operations. Recurrent tonsillitis is a common indication. More than 5-6 episodes of tonsillitis in a year or significant missed time from school or work should prompt consideration for tonsillectomy. Other indications include obstructive sleep apnea, suspicion of malignancy and previous peritonsllar abscess. Surgery is performed on an outpatient basis in older children. The most significant risk of tonsillectomy is postoperative hemorrhage. + +Obstructive Sleep Apnea +Obstructive sleep apnea (OSA) is characterized by episodic obstruction of airflow through the upper airway during sleep. Adenotonsillar hypertrophy is the most common cause for pediatric OSA. Congenital nasal masses may be responsible for neonatal OSA. Physiologic sequelae may include hypoxemia, hypercapnia and acidosis. The most severely affected patients may develop failure to thrive, right ventricular hypertrophy, pulmonary hypertension and cor pulmonale. +Patients with OSA present with noisy breathing, specifically stertor (sonorous upper airway breathing). Other symptoms include snoring, breath holding, or gasping during sleep, as well as enuresis. Daytime manifestations include morning headache, halitosis and behavioral disorders. Physical examination often reveals audible breathing with open mouth posture, hyponasal speech and tonsillar hyperplasia. Polysomnography (sleep study) remains the gold standard for diagnosis. +Adenotonsillectomy is considered first-line therapy in pediatric OSA. If the apnea hypopnea index is greater than +_ E_s_s_e_n_t i_ a_i_P_e_d_ i_at_r_ic_ _________________________________ +s +_ + +ten then the child should be monitored closely in the postoperative period with pulse oximetery. Surgical removal of nasal masses may be required. In the most severe cases of OSA, tracheostomy may be considered. + + +DISEASES OF THE LARYNX AND TRACHEA +Stridor +The term strider refers to excessively noisy, musical breathing and is generally due to upper airway obstruc­ tion. The relationship of strider to the respiratory cycle often provides a clue to its etiology: Inspiratory stridor suggests obstruction above the vocal cords (supraglottis), while expiratory stridor usually originates from the distal trachea (Table 13.4). Biphasic (inspiratory and expiratory) strider usually originates from a subglottic or proximal tracheal lesion. Most pediatric strider originates from supraglottic lesions. + +Table 13.4: Supraglottic compared to tracheal obstruction Supraglottic obstruction Tracheal obstruction +Inspiratory stridor Biphasic or expiratory stridor Weak cry or voice Normal cry or voice +Dyspnea is generally mild May have severe dyspnea Less pronounced cough Deep barking, brassy cough + + +Evaluation of the stridorous child should include a thorough history. Physical findings include nasal flaring and suprasternal or intercostal retractions. Chest X-rays or lateral neck films may confirm diagnoses such as retropharyngeal abscess, epiglottitis, or croup. Barium esophagram or CT may rule out extrinsic vascular compression. Flexible and rigid endoscopy is generally needed to confirm the diagnosis. There are multiple causes of pediatric airway obstruction, some of which are listed below. + +Infections +Croup (laryngotracheobronchitis) is a viral upper respiratory tract infection and often presents in children 1-5 yr of age with biphasic strider, barking cough and low-grade fever. Onset of symptoms is usually over several days. Chest X­ ray reveals a characteristic narrowing of the subglottic region known as the steeple sign (Fig. 13.7). +Most cases of croup are mild and resolve within 1 to 2 days. Conservative management should include reassurance, cool mist and oral hydration. Children with strider at rest should be hospitalized for close observation, cool mist and supplemental oxygen. Therapy with epinephrine (1:1000 in doses of 0.1-0.5 ml/kg to a maximum dose of 5 ml), gives through a nebulizer helps in relief of symptoms. A single dose of dexamethasone (0.3-0.6 mg/kg IM) reduces overall severity during first 24 hr. Recently, inhalation of budesonide in doses of 1 mg twice a day for 2 days has shown satisfactory results. + + + + + + + + + + +Fig. 13. 7: Laryngotracheobronchitis (croup). 'Steeple sign' + + +Antibiotics are indicated only if the child fails to improve or if purulent secretions are present. Coverage should be directed towards Staphylococcus and H. influenzae. + +Acute epiglottitis (often called supraglottitis), although less common than croup, typically presents with a greater degree of airway compromise. Patients typically present with acute onset (over several hours) of sore throat, marked dysphagia and high fever. Patients are often encountered leaning forward in a 'tripod' position, toxic­ appearing and drooling. Unlike croup, cough is frequently absent. Lateral neck X-ray reveals a characteristic thickening of the epiglottis ('thumbprint' sign) or other supraglottic structures. H. influenzae type B is the major etiologic organism. +If epiglottitis is suspected, rapid airway management is essential and includes intubation by skilled personnel. Instrumentation of the throat with tongue depressors is not advised as this can precipitate a fatal laryngospasm. Management includes securing the airway and broad­ spectrum IV antibiotics, e.g. coamoxiclav, ceftriaxone or cefuroxime. The incidence of epiglottitis has declined since the use of vaccines against H. influenzae. + +Bacterial tracheitis is typically seen in younger children following viral upper respiratory tract infection. The child appears toxic with a brassy cough and strider. Patients have a classic irregular tracheal wall on X-ray. Bronchos­ copy is both diagnostic and therapeutic, as the purulent tracheal secretions can be visualised, cultured and mechanically debrided. Bacterial tracheitis is a relative medical emergency, as life-threatening obstruction may develop from these tracheal secretions. The responsible pathogen is usually S. aureus. +Retropharyngeal abscess is a potential suppurative complication of bacterial pharyngitis that may present with strider. Patients often have high fever, reduced mobility of the neck and appear toxic. Complications of +_________________________________o_t_o_,a_ry_n_o,g_o__g_y__ + + +retropharyngeal abscess include spread of infection into the mediastinum. Mediastinitis is potentially fatal. Lateral neck radiograph reveals a bulge in the posterior pharyngeal wall. Treatment is by surgical drainage and broad-spectrum parenteral antibiotics. + +Congenital Causes +Laryngomalacia is the most common congenital laryngeal anomaly, accounting for up to 60% and the most common cause of infant stridor. Inspiratory stridor is the hallmark of the condition. Symptoms are typically aggravated when the child is supine or crying. Flexible endoscopy reveals partial collapse of a flaccid supraglottic airway with inspiration. If present, gastroesophageal reflux, should be managed. Laryngomalacia is generally benign and self­ limited, as most cases resolve by 18 months of age. Surgical intervention is advised for either respiratory distress or failure to thrive. +Vocal cord paralysis is the second most common congenital laryngeal anomaly. Bilateral vocal cord paralysis usually +presents with a high-pitched inspiratory stridor and cyanosis. It is usually iatrogenic by excessive stretch of the neck during vaginal delivery producing an Erb's palsy of the recurrent nerve, but can also be idiopathic. Other +causes may include Arnold-Chiari malformation, hydrocephalus or hypoxia. Unilateral vocal cord paralysis, +in contrast, may present with a mild stridor or with signs of aspiration. Iatrogenic injury during ligation of patent ductus arteriosus is a frequent cause. Tracheostomy is required to secure the airway in bilateral paralysis, though generally not in unilateral paralysis unless there is excessive aspiration. +Congenital subglottic stenosis is the third most common congenital laryngeal anomaly. It results from incomplete +recanaliza tion of the laryngotracheal tube during embryonic development. Subglottic stenosis may present as recurrent episodes of stridor and may be mislabeled as 'croup'. Many cases resolve spontaneously as the child grows, while severe cases usually require tracheostomy. Surgical excision of the stenosis may be necessary to relieve the obstruction in these cases. +Vascular ring is a great vessel anomaly that causes extrinsic compression of both the trachea and the esophagus. The child with vascular ring anomaly usually presents with dysphagia as well as stridor. Contrast swallowing studies (esophagram) or CT may reveal the diagnosis. Treatment for vascular anomalies is surgical. +Subglottic hemangioma is a benign vascular tumor that may present in the trachea. Infants usually become sympto­ matic between 3-6 months of life. Symptoms include biphasic stridor and a barking cough. Up to 50% may have concurrent cutaneous head and neck hemangiomas. Imaging may reveal asymmetric subglottic narrowing. The +diagnosis in confirmed with endoscopy. Treatment + +options include primarily oral propranolol, intralesional +steroids, CO2 laser excision, tracheostomy, and open surgical excision. +Congenital saccular cyst, laryngeal web and laryngeal atresia are rare laryngeal anomalies. They present with airway obstruction and require surgical intervention. + +Iatrogenic Causes +Acquired subglottic stenosis is the most common cause of acquired stridor. It most often results from longterm +endotracheal intubation and subsequent scar formation. Minor stenosis may be observed, while more severe stenosis may be treated by a variety of surgical methods including tracheostomy, widening of the stenosis with cartilage grafts, and excision of the stenotic segment. +Laryngeal granuloma may also result from prolonged intubation. Endoscopy reveals a vocal cord granuloma. These are often amenable to endoscopic removal. + +Neoplasms +Recurrent respiratory papilloma is the most common benign laryngeal tumor and presents with gradual airway obstruction. Endoscopy reveals single or multiple irregular, wart-like masses in the larynx or pharynx. The condition is caused by human papillomavirus; HPV types 6 and 11 are the most common. Transmission is believed to be vertical, from the passage of the fetus through an +infected birth canal. Treatment is with CO2 laser ablation or microdebrider excision of the papillomas. Adjunctive therapies include intralesional cidofovir and alpha-inter­ +feron. Multiple surgical procedures are usually necessary as the disease typically recurs. + +Foreign Body Aspiration +Foreign body aspiration should always be considered as a potential cause of stridor and airway obstruction in children. Foreign bodies most commonly aspirated are food and coins. Conforming objects such as balloons pose the greatest risk of choking death, followed by round objects such as balls or marbles. After establishing airway patency, urgent endoscopic visualization and removal by an experienced surgeon are necessary. +Hoarseness +Vocal nodules are the most common cause of hoarseness in children and are generally caused by vocal abuse. They are seen more frequently in habitually shouting or screaming children, usually boys with siblings. The severity of hoarseness fluctuates, worsening with vocal abuse and improving with rest. Endoscopy reveals small, bilateral, opposing nodules at the junction of the anterior and middle-thirds of the vocal cord. Speech therapy is usually effective in older children. Surgery is rarely +indicated. +_ E_s_s_ e_ _t_a_l_P_e _d_ia_t_r_i ___________________________________ +i +n +c +s +_ + + +Reflux laryngitis may result from gastric secretions spilling onto the larynx. Reflux has been implicated in numerous diseases of the head and neck, ranging from laryngitis and subglottic stenosis to chronic sinusitis and otitis media with effusion. Diagnosis is best established with 24 hr pH monitoring. Medical management is usually effective, though surgical fundoplication may be needed in severe cases. +Hypothyroid myxedema may occasionally cause an increase in vocal fold edema and present as hoarseness or stridor. Thyroid function tests should be conducted in the hoarse child with a clinical history suggestive of hypothyroidism. +Laryngotracheal cleft is a rare congenital defect in the posterior cricoid cartilage of the larynx. In its mildest form, children with this process may experience feeding diffi­ culty, recurrent respiratory tract infection or hoarseness. In its more severe forms, the cleft may extend inferiorly between the entire trachea and esophagus. Severe clefts usually cause significant aspiration pneumonias and are often not compatible with life. The condition may be associated with hereditary conditions such as Opitz-Frias or Pallister-Hall syndromes. Management of symptomatic clefts is surgical. + +DISEASES OF THE SALIVARY GLANDS +Infections +Bacterial parotid sialoadenitis is frequent in small children and presents with painful unilateral parotid swelling. Purulent material may be expressed from the parotid duct intraorally with parotid massage. Dehydration leads to staphylococcal overgrowth in the duct system. Treatment includes oral antibiotics as well as hydration, sialogogues, massage and warm compresses. +Viral parotitis is caused most often by the mumps virus. Patients generally present with painful parotid enlarge­ ment and fever. They may also present with an acute unilateral hearing loss or vestibular weakness. Systemic manifestations such as meningoencephalitis, pancreatitis and orchitis may also be present. +Tuberculosis is the most common granulomatous inflam­ mation of the parotid. It may be limited to the salivary glands without lung involvement. Sarcoidosis may also present with unilateral or bilateral parotid swelling. It is +usually seen with systemic symptoms and peripheral adenopathy. A variety of laboratory tests and radiological studies including chest radiograph support the diagnosis. Steroids are of value in treating xerostomia. +Human immunodeficiency virus (HIV) involvement of the parotid glands is common, presenting as bilateral intraglandular cysts. The cysts invariably recur after +aspiration. + + +Drooling +Drooling (sialorrhea) is a common, self-limited finding in young children. However, in children with neuromuscular disorders, dysphagia and poor lip closure may result in chronic drooling. If the swallowing mechanism is also abnormal, pooled secretions may allow chronic aspiration, leading to pneumonia or other complications. +Medical therapy for drooling not controlled with speech therapy consists of drying agents such as glycopyrrolate and antihistamines. Refractory cases of sialorrhea may be treated surgically with salivary gland excision; ductal ligation or rerouting; destruction of parasympathetic fibers; or some combination of the above. At present, the preferred surgical treatment is bilateral submandibular gland excision with parotid duct ligation. Tracheostomy or separation of the trachea from the upper airway is reserved for profound and life-threatening chronic aspiration. + +SuggestedReading +Diseases of the Enr +American Academy of Pediatrics and American Academy of Family +Physicians. Clinical Practice Guideline: Subcommittee on management of acute otitis media. Pediatrics 2004;113:1451-65 +Leach AJ, Morris PS. Antibiotics for the prevention of acute and chronic suppurative otitis media in children. Cocluane Database Syst Rev 2006;4:4401 +Powers JH. Diagnosis and treatment of acute otitis media: Evaluating the evidence. Infect Dis Clin N Am 2007;21:409-26 +Smith JA and Danner CJ. Complications of cluonic otitis media and cholesteatoma. Otolaryngol Clin N Am 2006;39:1237-55 +Diseases of the nose +Daniel SJ. The upper airway: Congenital malformations. Paed Resp Reviews 2006;75:5260-3 +Lusk R. Pediatric cluonic rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg 2005;14:393-6 +Diseases of the oral cavity and pharynx +Darrow DH. Surgery for pediatric sleep apnea. Otolaryngol Clin N Arn 2007;40:855-75 +Mueller OT, Callanan VP. Congenital malformations of the oral cavity. Otolaryngol Clin N Am 2007;40:141-60 +Diseases of the lary11x and trachea +Ahmad SM, Soliman A. Congenital anomalies of the larynx. Otolaryngol Clin N Am 2007;40:177-91 +Bjornson C, Russell KF, Vandermeer B, et al. Nebulized epinephrine for croup in children. Cochrane Database Syst Rev 2011;2:CD006619 +Brodsky L, Carr MM. Extraesophageal reflux in children. Curr Opin Otolaryngol Head Neck Surg 2006;14:387-92 +Knutson D, Aring A. Viral croup. Am Fam Physician 2004;69: 535-40 +Rafei K, Lichenstein R. Airway infectious disease emergencies. Pediatr Clin North Arn 2006; 53: 215-42 +Russell KF, Liang Y, O'Gormon K, et al. Glucocorticoids for croup. Cochrane Database Syst Rev 2011;1:CD001955 +Diseases of the salivary glands +Mehta D, Willging JP. Pediatric salivary gland lesions. Sernin Pediatr Surg 2006;15:76-4 + +Disorders of Respiratory System + + + + + + + +SK Kabra + + + + + + + +COMv10N RESPIRATORY SYMPTOMS Cough +After maximal inspiration, the air is suddenly released through the partially closed glottis, because of forceful contraction of the expiratory muscles. This produces a bout of cough. The cough reflex is controlled by a center in the medulla. Irritation of the pharynx, larynx, trachea, bronchi and pleura transmit the afferent impulses through the vagus +or glossophyngeal nerves. Efferent pathways are in the +nerve supply to the larynx and respiratory muscles. Cough is an important defense mechanism of the +respiratory system and helps to bring out the infected secretions from the trachea and bronchi. Cough should not be suppressed in younger children as retention of secretions in their lungs may result in atelectasis and pulmonary complications. On the other hand, persistent cough interferes with the sleep and feeding. It fatigues the child and may result in vomiting. + +Etiology +Acute cough Causes include: +i. Upper respiratory tract infection (rhinovirus, influ­ enza virus, parainfluenza, respiratory syncytial virus, adenovirus), postnasal discharge due to sinusitis (streptococci, Haemophilus influenzae or Moraxella, usually in older children), rhinitis, hypertrophied tonsils and adenoids, pharyngitis, laryngitis and tracheob ronchitis +ii. Nasobronchial allergy and asthma iii. Bronchiolitis +iv. Pneumonia and pulmonary suppuration (5. pneu­ moniae, 5. aureus, H. influenzae, Klebsiella, Chlamydia, Mycoplasma, gram-negative bacilli, viral pneumonia) +v. Measles +vi. Whooping cough and related syndromes (Bordetella pertussis, parapertussis, respiratory syncytial virus, adenovirus) + + +vii. Foreign body in the air passage viii. Empyema +Chronic and recurrent cough Causes are as follows: i. Inflammatory disorders of airway, such as: (a) +asthma; (b) infections, e.g. viral, bacterial, chlamydia, mycoplasma, tuberculosis, parasitic infections; (c) inhalation of environmental irritants such as tobacco smoke, dust; and (d) Loeffler syndrome. +ii. Suppurative lung disease, including: (a) bron­ chiectasis, (b) cystic fibrosis; (c) foreign body retained in bronchi; (d) congenital malformations, seques­ trated lobe, or bronchomalacia; and (e) immuno­ deficiency or primary ciliary dyskinesia. +iii. Anatomic lesions, tumors, tracheal stenosis or H-type tracheoesophageal fistula. +iv. Miscellaneous causes, e.g. (a) psychogenic, habit cough; (b) postnasal discharge, sinusitis; (c) gastro­ esophageal reflux disease; and (d) interstitial lung disease. + +Expectoration +Young children are not able to expectorate and usually swallow the respiratory secretions. Older children with chronic respiratory problems may be able to bring out expectoration. Common causes of expectoration are bronchiectasis due to various causes, lung abscess, bronchitis, asthma and tuberculosis. The amount and nature of expectoration may give clue about the cause of respiratory disease. Investigations such as cell count, Gram stain and culture or stain for AFB and culture help in diagnosis and guide for treatment. + +Hemoptysis +Causes of hemoptysis in children include necrotizing pneumonia, foreign body aspiration, bleeding diathesis, cavitatory tuberculosis, idiopathic pulmonary hemo­ siderosis, mitral stenosis, dilated cardiomyopathy and Goodpasture syndrome. + +371 +- Essential Pediatrics + + + +Respiratory Noises +The intensity and pitch of respiratory sounds depend on their site of origin within the respiratory tract. The pitch of the sound keeps increasing and the intensity keeps decreasing with decreasing size of the respiratory tract (Table 14.1). For example, snoring is a highly intense but low pitched sound because it results from the oropharynx. Wheeze is a high pitched, less intense sound originating from lower airway obstruction. As a rule, extrathoracic airway obstruction produce inspiratory sounds. Intra­ thoracic major airway obstruction produces inspiratory as well as expiratory sounds while distal airway obstruction predominantly produce expiratory sounds. + +Rattling +Rattling is due to excessive secretions in the pharynx or tracheobronchial tree during breathing. It is present in asthma, bronchitis and tracheobronchial stenosis. Inhalation of gastrointestinal content into the tracheobronchial tree can also result in rattling. Some normal infants may have transient rattling but prolonged rattling is pathological. + +Wheezing +Wheezing refers to high pitched whistling sounds audible without auscultation. Partial obstruction of the bronchi and bronchioles produces wheezing. Sufficient air must flow through the narrowed airway to produce the wheezing sotmd. This may be due to causes within the lumen or in the walls of the bronchi. The causes of wheezing are listed below. +Wheeze associated lower respiratory tract infec­ tion Wheezing is most often due to heightened sensitivity of the respiratory tract. Infections of the lower respiratory passages may cause bronchospasm in these patients. Attacks of wheezing are always preceded by a cold or acute respiratory disease. These are most frequent between 3 and 8 yr of age and become less frequent thereafter. These attacks are relieved by bronchodilators. + +Bronchiolitis (see page 381) Bronchial asthma (see page 382) +Tropical eosinophilia This is more frequent in adults than in children. It is an unusual form of infection with filariasis, e.g. Diroftlaria imitis, W. bancrofti, B. malayi. Clinical features simulate chronic recurrent asthma. X-ray films show fine pulmonary infiltrates with snowflake appearance. This + +should be distinguished from iliary tuberculosis. The leukocyte count shows eosinophilia. The patients are treated with diethylcarbamazine (10 mg/kg) in 3 divided doses orally for 2 to 3 weeks. Two or three spaced courses may be given. +Loeffler syndrome The pulmonary phase of migration of ascaris larvae may cause wheezing, pulmonary pro­ blems and eosinophilia. These features are characteris­ tically transient. +Inhaled foreign bodies cause unilateral localized wheeze which begin suddenly. Wheezing tends to be continuous and becomes worse with crying, during excitement and with cold. + +Rare causes These include pressure from enlarged mediastinal nodes or from anomalous left pulmonary artery compressing the right main bronchus. + +Cystic fibrosis Recurrent wheezing, productive cough and malabsorption are usual features. Some may have history of meconium ileus in the neonatal period. + +Stridor +Stridor indicates upper respiratory obstruction and is usually accompanied by hoarseness, brassy cough, dys­ pnea, chest retractions and restlessness. Stridor is frequent in infants and is often attributed to (i) small size of the larynx; (ii) loose submucous connective tissue around the glottic region; and (iii) rigid cricoid cartilage encircling the subglottic zone. +Acute stridor Acute upper airway obstruction occurring in the region of glottis which is produced by inflammation and edema may be life-threatening. The obstruction may either be supraglottic as in epiglottitis or subglottic as in infectious croup (Table 14.2). + + +Table 14.2: Stridor due to supraglottic and tracheal obstruction +Clinical features Supraglottic Trac/zeal obstruction obstruction +Strider Inspiratory and Usually expiratory and often less serious more serious +Cry Muffled Normal Dyspnea Less severe More marked +Cough Less marked Deep barking or brassy + + + +Table 14.1: Respiratory sounds Sou11d Cause Character + +Snoring Grunting +Rattling Strider +Wheeze + + +Oropharyngeal obstruction Partial closure of glottis +Secretions in trachea or bronchi Obstruction larynx or trachea +Lower airway obstruction + + +Inspiratory, low-pitched, irregular +Expiratory; occurs in hyaline membrane disease +Inspiratory, coarse; can be felt by placing hands over the chest Inspiratory; may be associated with an expiratory component +Continuous musical sound, predominantly expiratory in nature +Disorders of Respiratory System - + + + +Chronic stridor Common causes are listed below: Congenital laryngeal stridor. This is caused by flaccidity (laryngomalacia) or easy collapsibility of the aryepiglottic folds or epiglottis. This condition usually manifests by the end of the first week or during the second week afterbirth. The stridor is characteristically intermittent and is aggravated by crying or feeding. It is modified in sleep or by the change of posture. The loud inspiratory sound frightens the parents but the infant is relatively less symptomatic. Respiratory distress and chest retraction are absent or minimal. Feeding behavior and activity of the infant are generally normal. Breathing difficulty may be significant, if micrognathia and cleft palate are also associated. Congenital laryngeal stridor disappears spontaneously by the age of six months to one year. These infants are more prone to develop aspiration of feeds and frequent lung infection. +Congenital laryngeal or tracheal stenosis or web. Cry of the infant is weak and hoarse, breathing is labored and the air entry in lungs is reduced. In subglottic tracheal stenosis, the cry is unaffected and the stridor is both inspiratory and expiratory. +Laryngeal cysts or neoplasm. Angioma, papilloma, lymph­ angioma and retention cysts may be responsible for stridor. +Neurogenic stridor. Bilateral vocal cord paralysis results from brainstem injury. Unilateral paralysis is due to the involvement of the peripheral nerve. The left recurrent laryngeal nerve is more liable to injury since it has a longer course and hooks around the aorta from the front to back. +Extrinsic obstruction. Vascular rings cause intermittent stridor that becomes worse when the neck is flexed. The infant prefers to keep the head in the position of hyper­ extension. Other causes of external airway compression are mediastinal goiter, lymphangioma and thyroglossal duct cyst. Congenital goiters which cause respiratory obstruction and stridor are due to maternal intake of antithyroid drugs and iodides during pregnancy. Goiter of neonatal hypothyroidism and that due to defect in the synthesis of thyroid hormones are usually not so big as to cause stridor. +Miscellaneous causes. Stridor is common in infants with hydrocephalus and those with Down syndrome. Other causes include micrognathia and glossoptosis, macro­ glossia and diaphragmatic hernia. +Treatment The diagnosis of congenital laryngeal stridor can be established only by direct laryngoscopy. Fluoroscopy after barium swallow should be done to rule out the extrinsic causes of obstruction. Tumors and cysts require surgical excision. Corticosteroids hasten the recovery in laryngeal edema. Congenital laryngeal stridor does not require treatment. Gavage feeding is done if the respiratory distress is marked. Congenital goiter caused by the administration of antithyroid drugs or iodides to + + +the mother during pregnancy is treated with triiodo­ thyronine and Lugol's iodine. + +Dyspnea +Tachypnea refers to abnormally rapid respiration, while dyspnea means labored or difficult breathing, usually accompanied by pain and air hunger. The causes of dyspnea range from illnesses affecting the lungs, heart and musculoskeletal system. + +Epistaxis +Epistaxis or bleeding from the nose is rare in children below the age of 3 yr. It may occur due to local or systemic causes. Local causes include: (i) trauma to nose caused by nose picking, (ii) capillary malformations in the Little's area, (iii) foreign body, (iv) bleeding polyps of the septum, and (v) allergic rhinitis and nasal diphtheria. Systemic causes of epistaxis are: (i) hypertension, (ii) blood dyscrasia, (iii) emphysema, and (iv) pertussis. +Pressure on alae nasi for 10 min controls bleeding in most cases of epistaxis. In resistant cases, the nasal mucosa is plugged with gauze piece soaked in 1:10,000 solution of adrenaline hydrochloride as a temporary measure. Plugging of the nose for a prolonged period (>48 hr) should be avoided. The bleeding points should be identi­ fied and cauterized with silver nitrate solution. Nasal bleed due to systemic causes should be evaluated and treated appropriately. The child should receive treatment with iron supplements to raise hemoglobin level. Profuse bleeding is more likely to be from the posterior aspect from sphenopalatine vessels. Cauterization is ineffective in these vessels. Firm anterior and posterior packing is done. Blood dyscrasia if present should be appropriately treated. + +Suggested Reading +Kabra SK. History taking and physical examination. In: Essential Pediatric Pulmonology, 2nd edn. Ka bra SK, Lodha R (eds). Nobel Vision, New Delhi, 2010;15-22 + +INVESTIGATIONS FOR RESPIRATORY ILLNESSES + +Bronchoscopy +Bronchoscopy can be of two types, fiberoptic and rigid. Fiberoptic bronchoscopy is done under local anesthesia and sedation. This is used for diagnosis of structural abnormality of airways, diagnosis of foreign body and for obtaining bronchoalveolar lavage samples to identify cell type and infective etiology of lower respiratory tract. Rigid bronchoscopy can be used in place of fiberoptic broncho­ scopy. This is commonly used for removal of foreign bodies from airways or obtaining biopsy from airway tumors. + +Pulmonary Function Tests +Pulmonary function tests (PFT) are important tools for monitoring of a patient with chronic respiratory illness. Flow rates and lung volumes are measured. The proce- +- Essential Pediatrics + + + +dure requires cooperation of the patient. PFT may be performed in children above the age of 5-7 yr. Commonly used parameters include: forced expiratory volume in first second (FEVl), forced vital capacity (FVC), mid­ expiratory flow rate and ratio of FEVl/FVC. Normal FEVl/FVC ratio is between 0.8 and 1.0. In obstructive diseases (asthma) the ratio is reduced. In restrictive lung diseases (interstitial lung disease), the ratio of FEVl/FVC is normal but FVC is reduced below 80% of predicted. + +Blood Gas Analysis +Estimation of partial pressures of oxygen (Pa02) and carbon dioxide (PaC02) in blood along with blood pH gives a fair +estimate of pulmonary functions. Arterial blood gas analysis is useful in making a diagnosis of respiratory failure as well as for monitoring children with acute and chronic +respiratory failure. Pa02 below 60 mm Hg and PaC02 over +50 mm Hg suggest acute respiratory failure. + +Imaging +Noninvasive diagnostic methods include X-rays, most commonly used to diagnose pulmonary infections and computerized tomography scans, used for visualization of lymph nodes, tumors, bronchiectasis and pleural pathologies. + +Sweat Chloride Test +Chloride in sweat is increased in children suffering from cystic fibrosis. Sweat chloride is estimated by quantitative pilocarpine iontophoresis. Values of sweat chloride in normal children is less than 40 mEq/1. Patients with cystic fibrosis show levels more than 60 mEq/1. + +Suggested Reading +Beydon N, Davis SD, Lombardi E, et al. An official American Thoracic Society /European Respiratory Society statement: pulmonary fw1etion testing in preschool children. Am J Respir Crit Care Med 2007;175: 1304--45 +Kabra SK, Lodha R. Investigations in pulmonology. In: Essential Pediatric Pulrnonology. New Delhi, Nobel Vision 2010;23-9 +Nicolai T. The role of rigid and flexible bronchoscopy in children. Pediatr Respir Rev 2011;12:190-5 + +RESPIRATORY TRACT INFECTIONS +Common Cold or Nasopharyngitis +Common cold is a frequent illness in childhood and is usually caused by infections of the upper respiratory tract with adenoviruses, influenza, rhinovirus, parainfluenza or respiratory syncytial viruses. These are spread by droplet infection. Predisposing factors include chilling, sudden exposure to cold air and overcrowding. Rhinitis could also be due to allergy. +Clinical features include fever, thin nasal discharge and irritability. Cervical lymph nodes may enlarge. Naso­ pharyngeal congestion causes nasal obstruction and respiratory distress. The latter is more pronounced in young infants. Eustachian tube opening may be blocked + +leading to serous otitis media and congestion of tympanic membrane. In allergic rhinitis there is a clear mucoid discharge with sneezing. +Narrowing of the airway and pharyngeal irritation causes dry hacking cough. Excessive lacrirnation is due to the blocked lacrirnal ducts in the nose. Nasal discharge may become purulent, if secondarily infected especially in younger children. Purulent discharge does not necessarily mean secondary infection as it can result from shedding of epithelial and inflammatory cells resulting from viral infection itself. The illness usually lasts for three days but cold may persist up to two weeks. +Complications include otitis media, laryngitis, sinusitis, bronchiolitis, exacerbation of asthma and broncho­ pneumonia. +Differential diagnosis include the presence of foreign body which presents with unilateral serosanguineous or purulent discharge from a nostril. The intermittent use of rifrnpicin may cause flu-like syndrome in some children. Drugs like reserpine and prochlorperazine cause nasal stuffiness. Clear mucoid discharge from the nose in the first few weeks of life is called snuffles. Snufles of congenital syphilis is severe rhinitis with bilateral serosanguineous discharge commonly excoriating the upper lip and leaving fine scars. Nasal strictures may ulcerate leaving a flat nasal bridge. + +Treatment +Relieve nasal congestion. Babies sneeze and blow out the nasal discharge, if their anterior nares are tickled by the tip of a handkerchief. Nose drops of saline may give symptomatic relief. Nasal decongestants (ephedrine, xylometozoline) may cause rebound congestion. These should not be used routinely and used only in refractory cases for limited duration. Antihistaminics are best avoided in the first six months of life, but give symptomatic relief by drying up thin secretions and relieving sneezing. Nonsedating agents, e.g. loratidine and cetirizine may be used in allergic rhinitis. Terfenadine should not be prescribed in children because of potential cardiotoxicity. +Fever is controlled by antipyretics such as paracetamol (acetaminophen). Cough syrups should not be given. If the cough is suppressed in infants and young children, mucoid secretions may be retained in the bronchi and this may predispose to spasmodic cough, wheezing, atelectasis and suppuration. +Antibiotics are of little value in viral infections. These are used if the secretions become purulent, the fever continues to rise and if the child develops bronchopneumonia. There is no evidence that large doses of vitamin C are helpful. The children should be protected from sudden exposure to chills and kept warm during the winter months. + +Acute Tonsillopharyngitis +Sore throat is due to acute inflammation of the pharynx and tonsils. Most often, it is associated with the viral infections +Disorders of Respiratory System - + + + +of the upper respiratory tract such as adenovirus, influ­ enza, parainfluenza virus, enterovirus and Epstein-Barr virus. It may, however, be a prodrome of measles and rubella or may be caused by S. pyogenes especially group A beta-hemolytic streptococci. Mycoplasma pneumoniae and Candida albicans have also been incriminated. +Clinical features of tonsillopharyngitis include fever, malaise, headache, nausea and sore throat. Younger children may not complain of sore throat but often refuse to feed normally. It is difficult to distinguish the clinical syndromes due to viral or streptococcal infections. Hoarseness, cough and rhinitis are more common in viral infection. In these, the onset is gradual and there is less toxemia. In streptococcal infections, cervical lymph nodes are enlarged, the illness is acute with high fever and there is absence of nasal discharge or conjunctivitis. Tonsils are swollen and covered with exudates in both types of infections. +A possibility of acute pharyngitis due to group A beta­ hemolytic streptococci may be considered in a patient who has exudates in throat, tender enlarged cervical nodes along with absence of nasal or conjuctival congestion. Throat swab culture for group A beta-hemolytic strepto­ cocci helps in the definitive diagnosis. A rapid antigen detection test (RADT) for identification of group A beta­ hemolytic Streptococcus gives the result within 10 min and has moderate (80-90%) sensitivity and high (>95%) specificity. Enzyme immunoassays are preferred to latex agglutination tests. Testing for antistreptolysin O (ASO) and anti DNAase B antibodies is not useful. +Complications of sore throat include acute glomerulo­ nephritis, rheumatic fever, otitis media, sinusitis and peritonsillar and retropharyngeal abscesses. The infection may spread down the tracheobronchial tree to cause tracheobronchitis and pneumonia. + +Differential Diagnosis +Herpangina is an acute febrile illness due to group A Coxsackie virus. Patients have dysphagia, sore throat and papulovesicular lesions surrounded by erythema over the tongue, pharynx, anterior tonsillar pillars and soft palate. Pharynx appears congested. Diphtheria is characterized by moderate fever, severe toxemia, sore throat and membrane formation over the fauces or palate. Patients with pharyngoconjunctival fever have fever, conjunctivitis, pharyngitis and cervical lymphadenitis due to infection with adenovirus type 3. Infectious mononucleosis is characterized by lymphadenopathy, morbilliform rash, hepatosplenomegaly and sometimes, aseptic meningitis. + +Treatment +Warm saline gargles are prescribed for older children. Younger children are encouraged to sip warm tea/liquids. Paracetamol is administered for fever. Soft food such as custard or rice and lentil gruel is given because swallowing + +is painful. Oral antihistaminics, e.g. chlorpheniramine or promethazine are useful in symptomatic relief. However, routine use of cough suppressants (e.g. dextromethor­ phan, codeine) and expectorants (ambroxol, guaifensin) should be avoided. +Antibiotics are not required in patients with viral infections. Patients with documented streptococcal infec­ tion (i.e. by throat culture or RADT) should receive anti­ biotic therapy in order to decrease the duration of symp­ toms, reduce morbidity and prevent complications. Options of oral treatment include (i) penicillin V 250 mg q 8-12 hr, (ii) amoxycillin 30-40 mg/kg/day, (iii) erythro­ mycin 40-50 mg/kg/day or (iv) cephalexin 50 mg/kg/ day, given for 10 days; or (v) azithromycin 10-12 mg/ kg/day for 5 days. Where noncompliance is likely, a single intramuscular injection of benzathine penicillin (0.6-1.2 MU) may be given. Cotrimoxazole, which is commonly used for sinusitis and otitis media, is not an appropriate medication for sore throat. +The therapy for diphtheria is described in Chapter 10. + +Recurrent Sore Throat +A detailed history is obtained and physical examination conducted. Para.nasal sinuses and ears should be examined for the foci of infection. Smoky and dusty atmos­ phere should be avoided. Dampness in the environment and overcrowding predispose the child to recurrent upper respiratory tract infections. +Each episode of bacterial pharyngitis should be treated with adequate doses of antibiotics for at least 10 days. Presence of beta-lactamase producing bacteria in the pharynx may inactivate penicillin and lead to recurrent sore throat. This should be treated with amoxycillin plus clavulinic acid or clindamycin. In selected cases, penicillin prophylaxis may be administered for 3--6 months, especially if group A beta-hemolytic streptococcal infection is present. Tonsillectomy is often recommended for recurrent attacks of sore throat. It does not prevent recurrence of +pharyngeal infections. Tonsillectomy should be advised only if there are more than 5-6 episodes of tonsillitis in a year or tonsillar or peritonsillar abscess. It may reduce the incidence of infection with group A beta-hemolytic streptococcus. Tonsillectomy is recommended in diph­ theria carriers, in presence of retention cysts in tonsils or if the tonsils are a focus of infection for suppurative otitis media. There is no indication for tonsillectomy after rheumatic fever or glomerulonephritis. + +Suggested Reading +Casey JR, Pichichero ME. Metaanalysis of short course antibiotic treat­ ment for group A streptococcal tonsillopharyngitis. Pediatr Infect Dis J 2005;24:909-17 +Kabra SK, Kaur J. Upper respiratory tract infection. In: Essential Pe­ diatric Pulmonology, 2nd edn. Kabra SK, Lodha R, (eds). New Delhi, Nobel Vision 2010;49-54 +-�Es:s e n:t:ia:l�P�e:di:a:tr�ics _________________________________ +:_ :;,: +:; :;: + + +ACUTE LOWER RESPIRATORY TRACT INFECTION_ S__ _ +Acute lower respiratory tract infections are the leading cause of death in children below 5 yr of age. These include croup syndromes, bronchitis, bronchiolitis and pneu­ monia. + +Croup +The term croup is used for a variety of conditions in which a peculiar brassy cough is the main presenting feature. Inspiratory stridor, hoarseness or respiratory distress may not always be associated with croup. The diseases include acute epiglottitis, laryngitis, laryngotracheobronchitis and spasmodic laryngitis. + +Epiglottitis +Supraglottitis includes both epiglottitis and inflammatory edema of the hypopharynx. Haemophilus influenzae type B is the most frequent cause. Other microbes like pneu­ mococcus, beta-hemolytic Streptococcus and Staphylococcus +are not common etiologies. The illness usually starts with a minor upper respiratory tract illness which progresses rapidly within the course of a few hours. The child suffers from high fever and has difficulty in swallowing. The breathing becomes noisy but is generally softer than in case of laryngotracheobronchitis. The child is not able to phonate and often sits up leaning forwards with his neck extended and saliva dribbling from his chin which appears to be thrust forwards. The accessory muscles of respiration are active and there is marked suprasternal and subcostal retraction of the chest. As the child becomes fatigued, the stridor diminishes. The diagnosis of epiglottitis is made by a cautious direct laryngoscopy, wherein the epiglottis appears angry red and swollen. Injudicious attempt to +examine the throat may, rarely, cause death by sudden reflex spasm of the larynx. It is therefore prudent not to force a child, panting for breath, to lie down for throat +examination or to send him to the radiology department for an urgent X-ray film if the clinical diagnosis is other­ wise obvious. In case these procedures are considered essential, the equipment and personnel for respiratory resuscitation should always be readily available. + +Laryngitis and Laryngotracheobronchitis +(Infectious croup) +These conditions are nearly always caused by viral infections, usually with parainfluenza type l. Other viruses incriminated include respiratory syncytial and parainfluenza types 2 and 3, influenza virus, adenovirus and rhinovirus. Bacterial etiology or bacterial super­ infection are unusual. In infectious croup, the onset of the illness is more gradual. Usually, there is a mild cold for a few days before the child develops a brassy cough and mild inspiratory stridor. As the obstruction increases, the stridor becomes more marked and the suprasternal and +sternal recession with respiration become manifest. The + + +child becomes restless and anxious with fast breathing due to increasing hypoxemia. Eventually cyanosis appears. As the obstruction worsens, breath sounds may become inaudible and stridor may apparently decrease. This may unfortunately be misinterpreted as clinical improvement by an unwary physician. +Spasmodic Croup +It occurs in children between the age of 1 and 3 yr. There is sometimes no preceding coryza. The child wakes up suddenly in the early hours of the morning with brassy cough and noisy breathing. The symptoms improve within a few hours. The illness may recur on subsequent days. The course is generally benign and patients recover completely. The cause is unknown. Humidification of the room in which the child is nursed is all that is necessary. +Differential Diagnosis +The syndromes of croup should be distinguished from each other and also from the croup associated with +diphtheria in which a membrane is seen on laryngoscopy or occasionally with measles. Rarely the croup may result from angioneurotic edema. A retropharyngeal abscess +may cause respiratory obstruction. Aspiration of a foreign body is an important cause of obstruction. It may be rarely confused with wheezing in asthma. + +Management +A child with epiglottitis needs hospitalization. Humidified oxygen should be administered by hood. Face masks are not well tolerated by these children. As oxygen therapy masks cyanosis, a careful watch should be kept for impend­ ing respiratory failure. Sedatives should not be given. Unnecessary manipulation of the patient may induce laryngeal spasm. Fluids should be administered for +adequate hydration of the patient by intravenous route. Antibiotics such as cefotaxime or ceftriaxone 100 mg/kg/ +day is recommended in patients with epiglottitis, but not in laryngotracheobronchitis or laryngitis. Endotracheal intubation or tracheostomy may be indicated if the response to antibiotics is not adequate and obstruction is worsening. A child with acute laryngotracheobronchitis should be assessed for severity of illness on basis of general appearance, stridor (audible with or without stethoscope), oxygen saturation and respiratory distress (Table 14.3). Mild cases can be managed on ambulatory basis with symptomatic treatment for fever and encouraging the child to take liquids orally. Parents may be explained about the progression of diseases and to bring the child back to +hospital in case of worsening of symptoms. +A patient with moderately severe illness may need +hospitalization and treatment with nebulised epinephrine (1:1000 in doses of 0.1-0.5 ml/kg to a maximum dose of 5 +ml administered through nebulizer for immediate relief of symptoms. While epinephrine acts rapidly to decrease +vascular permeability, airway edema and improves +Disorders of Respiratory System -- + +Table 14.3: Assessment of severity of acute laryngotracheobronchitis + + +General appearance + +Stridor + +Respiratory distress + +Cyanosis +Oxygen saturation in room air + + +Mild +Happy, feeds well, interested in surroundings +Stridor on coughing; no stridor at rest +No distress + +Absent >92% + +Moderate +Irritable but can be comforted by parents +Stridor at rest; worsens when agitated +Tachypnea and chest retractions +Absent >92% + + +Severe +Restless or agitated or altered sensorium +Stridor at rest; worsens when agitated +Marked tachypnea with chest retractions +May be present <92% + + + +airflow, the action is temporary and repeat administration may be necessary at 2--4 hr. Recent studies have shown that a single intramuscular dose of dexamethasone (0.3-0.6 mg/kg) reduces disease severity in the first 24 hr with decreased need of intubation and adrenaline nebulization and shortened duration of hospital stay. Inhalation of budesonide in doses of 1 mg twice a day for two days is useful. +Severe croup may need hospitalization, preferably in intensive care, with oxygen inhalation and need for steroids (similar to moderate severity). Worsening distress may need short term ventilation. + +Suggested Reading +Bjornson C, Russell KF, Vandermeer B, Duree T, Klassen TP, Johnson DW. Nebulized epinephrine for croup in children. Cochrane Database Syst Rev 2011;2:CD006619 +Knutson D, Aring A. Viral croup. Arn Fam Physician 2004;69: 535-40 Russell KF, Liang Y, O'Gorman K, Johnson DW, Klassin TP. Gluco­ +corticoids for croup. Cochrane Database Syst Rev 2011; (1): CD001955 + +Pneumonia +Pneumonia may be classified anatomically as lobar or lobular pneumonia, bronchopneumonia and interstitial pneumonia. Pathologically, there is a consolidation of alveoli or infiltration of the interstitial tissue with inflam­ matory cells or both. + +Etiology +Viral pneumonia caused by respiratory syncytial virus, influenza, parainfluenza or adenovirus may be responsi­ ble for about 40% of the cases. In over two-thirds of the cases, common bacteria cause pneumonia. In the first 2 months, the common agents include gram-negative bacteria such as Klebsiella, E. coli and gram-positive organisms like pneumococci and staphylococci. Between 3 months and 3 yr common pathogens include S. pneumoniae, H. infiuenzae and staphylococci. After 3 yr of age, common bacterial pathogens include pneumococci and staphy­ lococci. Gram-negative organisms cause pneumonia in early infancy, severe malnutrition and immunocompro­ rnised children. +Atypical organisms including Chlamydia and Myca­ plasma spp. may cause community acquired pneumonia + + +in adults and children. Pneurnocystis jiroveci, histo­ plasmosis and coccidioidomycosis may cause pneumonia in immunocomprornised children. +Other causes of pneumonia include ascaris, aspiration of food, oily nose drops, liquid paraffin and kerosene poisoning. The etiology remains unknown in one-third of cases of pneumonia. + +Clinical Features +Risk factors for pneumonia include low birth weight, malnutrition, vitamin A deficiency, lack of breastfeeding, passive smoking, large family size, family history of bronchitis, advanced birth order, crowding, young age and air pollution. Indoor air pollution is one of the major risk factor for acute lower respiratory tract infection in children in developing countries. Onset of pneumonia may be insidious starting with upper respiratory tract infection or may be acute with high fever, dyspnea and grunting respiration. Respiratory rate is always increased. Rarely, pneumonia may present with symptoms of acute abdominal emergency. This is attributed to referred pain from the pleura. Apical pneumonia may be associated with meningismus and convulsions. In these patients the +cerebrospinal fluid is always clear. +On examination, there is flaring of alae nasi, retraction of the lower chest and intercostal spaces. Signs of consolidation are present in lobar pneumonia. + +Pneumococcal Pneumonia +Respiratory infections due to S. pneumoniae are transmitted by droplets and are more common in the winter months. Overcrowding and diminished host resistance predis­ poses the children to infection with pneumococci. Bacteria multiply in the alveoli and an inflammatory exudate is formed. Scattered areas of consolidation occur, which coalesce around the bronchi and later become lobular or lobar in distribution. There is no tissue necrosis. Pathological process passes from the stage of congestion to red and gray hepatization before the final stage of resolution. +Clinicalfeatures. Incubation period is 1 to 3 days. The onset is abrupt with headache, chills, cough and high fever. Cough is initially dry but may be associated with thick +___ _s s__e t_i_ai_P_e_d_i_at_r_ic___________________________________ +s +n +_ +E +_ + + +rusty sputum. Child may develop pleuritic chest pain. Respiration is rapid. In severe cases there may be grunting, chest indrawing, difficulty in feeding and cyanosis. Percussion note is impaired, air entry is diminished, crepitations and bronchial breathing may be heard over areas of consolidation. Bronchophony and whispering pectoriloquy may be observed. Meningismus may be present in apical pneumonia. +Diagnosis. The diagnosis is based on history, physical examination, X-ray findings of lobar consolidation (Fig. 14.1) and leukocytosis. Bacteriological confirmation is difficult; sputum is examined by Gram staining and culture. Blood culture may be positive in 5-10% of cases. Demonstration of polysaccharide antigen in urine and blood do not have sufficient specificity for confirming pneumococcal pneumonia as it may be also be positive in children with colonization in throat. +Treatment. Antibiotic therapy may be empiric while awaiting confirmation of etiology. While the treatment of choice for pneumococcal pneumonia is penicillin (penicillin V 250 mg q 8-12 hr orally, penicillin G 0.5 MU/ kg/day IV or procaine penicillin 0.6 MU IM daily, for 7 days), amoxycillin (30-40 mg/kg/ day for 7 days) with or without clavulanic acid is a useful alternative. +The need for oxygen administration should be guided by signs of respiratory distress (rapid breathing, chest retractions, nasal flare), presence of cyanosis or hypoxernia on pulse oximetry. Patients may be dehydrated, and require IV fluids. Fever should be managed with para­ cetamol. + +Staphylococcal Pneumonia +Staphylococcal pneumonia occurs in infancy and child­ hood. The pulmonary lesion may be primary infection of + + + + + + + + + + + + + + + + + + + +Fig. 14.1: Consolidation of right upper lobe due to infection with Sreptococcus pneumoniae + + +the parenchyma; or may be secondary to generalized staphylococcal septicemia. It may be a complication of measles or influenza; other risk factors include cystic fibrosis, malnutrition and diabetes. +In infants, the pneumonic process is diffuse initially, but soon the lesions suppurate, resulting in bronchoalveolar destruction. The illness is characterized by the formation of multiple pneumatoceles. The pneumatoceles fluctuate in size and finally resolve and disappear within a period of few weeks to months. Staphylococcal abscesses may erode into the pericardium causing purulent pericarditis. Empyema in a child below two yr of age is nearly always secondary to staphylococcal infections. +Clinical manifestations. The illness usually follows upper respiratory tract infection, pyoderma or a purulent disease. The patient is toxic and sick looking. Cyanosis may be present. Progression of the symptoms and signs is rapid. Pulmonary infection may occasionally be complicated by disseminated disease, with metastatic abscesses in joints, bone, muscles, pericardium, liver, mastoid or brain. +Diagnosis. The diagnosis of staphylococcal pneumonia is suspected in a newborn or an infant with respiratory infection who has evidence of staphylococcal infection elsewhere in the body. The characteristic complications of pyopneumothorax and pericarditis are highly suggestive. Pneumatoceles are present in X-ray films (Fig. 14.2), characteristically in pneumonia due to staphylococci or Klebsiella. These pneumatoceles persist as thin walled asymptomatic cysts for several weeks. Staphylococci can be cultured from the blood. +Treatment. The child should be hospitalized and isolated to prevent the spread of resistant staphylococci to the other patients. Fever is controlled with antipyretics; intravenous fluids may be required. Oxygen is administered to relieve dyspnea and cyanosis. + + + + + + + + + + + + + + + + + +Fig. 14.2: Staphylococcal pneumonia. Note multiple pneumatoceles (arrow) +Disorders of Respiratory System - + + + +Empyema is aspirated and the pus is sent for culture and sensitivity. Prompt antibiotic therapy should be initiated +with coamoxiclav, or a combination of cloxaclin and a third­ generation cephalosporin, e.g. ceftriaxone. If the patient does not show improvement in symptoms within 48 hr, therapy +with vancomycin, teicoplanin or linezolid may be necessary. Therapy should continue till all evidence of the disease disappears both clinically and radiologically, which usually takes 2 weeks in uncomplicated cases. Therapy is continued for 4--6 weeks in patients with empyema or pneumothorax. Following initial IV therapy, the remaining course may be completed with oral antibiotics. +Complications. Pneumatoceles do not require specific measures. Empyema and pyopneumothorax are treated by intercostal drainage under water seal or low pressure aspiration. Metastatic abscesses require surgical drainage. Significant pleural thickening that prevents complete expansion of the underlying lung may require decor­ tication. Early thoracoscopic drainage of empyema helps prevent pleural thickening. Installation of streptokinase or urokinase in pleural cavity or loculated pleural effusion may also be useful. +Haemophilus Pneumonia +Haemophilus influenzae infections occur usually between the age of three months and three years and are nearly always associated with bacteremia. Infection usually begins in the nasopharynx and spreads locally or through the blood­ +stream. Most nasophyngeal infections are mild and confer immunity from subsequent serious illness after the early +months of life. As the infants have transplacentally transferred antibodies during the first 3 to 4 months of life, infections are relatively less frequent during this period. +Clinical features. The onset of the illness is gradual with nasopharyngeal infection. Certain viral infections such as +those due to influenza virus act synergistically with H. influenzae. The child has moderate fever, dyspnea, grunt­ +ing respiration and retraction of the lower intercostal spaces. +Complications include bacteremia, pericarditis, empyema, meningitis and polyarthritis. +Treatment. Haemophilus infection is treated with ampicillin at a dose of 100 mg/kg/day or coamoxiclav. Cefotaxime (100 mg/kg/day) or ceftriaxone (50-75 mg/kg/day) are recommended in seriously ill patients. +Streptococcal Pneumonia +Infection of the lungs by group A beta hemolytic strep­ tococci is secondary to measles, chickenpox, influenza or whooping cough. Group B streptococcal pneumonia is an important cause of respiratory distress in newborns. Pathologically it causes interstitial pneumonia, which may be hemorrhagic. Tracheobronchial mucosa may be ulcerated and lymph nodes enlarged. Serosanguineous or +thinly purulent pleural effusion is frequently associated. + +Clinical feature. The onset is abrupt with fever, chills, dyspnea, rapid respiration, blood streaked sputum, cough and extreme prostration. Signs of bronchopneumonia are generally less pronounced, as the pathology is usually interstitial. X-ray film shows interstitial pneumonia, seg­ mental involvement, diffuse peribronchial densities or an effusion. +Complications. Thin serosanguineous or purulent empyema is a usual complication. Pulmonary suppuration is less frequent. Ten percent of the patients have bacteremia. When pneumatoceles are present, the condition mimics staphylococcal pneumonia. +Treatment. Therapy for streptococcal pneumonia is carried out as outlined for pneumococcal pneumonia. The response is gradual but recovery is generally complete. Empyema is treated by closed drainage with indwelling intercostal tube. +Primary Atypical Pneumonia +The etiological agent of primary atypical pneumonia is Mycoplasma pneumoniae. The disease is transmitted by droplet infection, chiefly in the winter months. The illness is +uncommon in children below the age of four yr, although subclinical and mild infections are reported in infants. +Primary atypical pneumonia involves the interstitial tissue with round cell infiltration. The alveolar septae are edematous and mucosa of the broncl1ioles is inflamed and ulcerates. Obstruction of the terminal bronchioles causes emphysema and atelectasis. Pleura may show patchy fibrinous exudates. +Clinical features. Following an incubation period of 12-14 days, patients have malaise, headache, fever, sore throat, myalgia and cough. Cough is dry at first but later associated with mucoid expectoration, which may be blood streaked. Dyspnea is unusual. There are very few physical signs, except mild pharyngeal congestion, cervical lymphadenopathy and few crepitations. Hemolytic anemia may be seen. +X-ray findings are more extensive than suggested by the physical findings. Poorly defined hazy or fluffy exudates radiate from the hilar regions. Enlargement of the hilar lymph nodes and pleural effusion are reported. Infiltrates involve one lobe, usually the lower. +Diagnosis. It is difficult to distinguish Mycoplasma pneu­ monia from viral or rickettsial pneumonia. The leucocyte +count is usually normal. Cold agglutinins are elevated in many patients. M. pneumoniae may be cultured from the +pharynx and sputum. The diagnosis is made rapidly by demonstration of IgM antibody by ELISA during the acute stage. IgG antibodies are seen on a complement fixation test after one week of illness. +Treatment. Patients are treated with macrolide antibiotics (erythromycin, azithromycin or clarithromycin) or tetra­ +cycline (for older children) for 7 to 10 days. +- Essential Pediatrics ------------------ +- +- +- +- +- + + +Chlamydia Pneumoniae +It may cause pneumonia in young infants. Clinical features include spasmodic cough. A history of purulent conjunc­ tivitis during early neonatal period may be present. + +Pneumonia Due to Gram-negative Organisms +The etiological agents are E. coli, Klebsiella and Pseudomonas. These organisms affect small children ( <1 yr of age) or +children with malnutrition and deficient immunity. Pseudomonas may colonize airways of patients with cystic +fibrosis and causes recurrent pulmonary exacerbations. The clinical features are similar, but patients can be very sick. Signs of consolidation are minimal, particularly in infants. Constitutional symptoms are more prominent than +respiratory distress. X-ray shows unilateral or bilateral consolidation. Infection with E. coli or Klebsiella pneumoniae +may be associated with pneumatoceles. + +Treatment. Intravenous use of third generation cephalo­ sporins (cefotaxime or ceftriaxone, 75-100 mg/kg/ day) +with or without an aminoglycoside is recommended for +10 to 14 days. Ceftazidime or piperacillin-tazobactam are effective in patients with Pseudomonas infection. + +Viral Pneumonias +Respiratory syncytial virus is the most important cause in infants under 6 months of age. At other ages, influenza, parainfluenza and adenoviruses are common. The bronchial tree or alveoli are involved resulting in extensive interstitial pneumonia. Features of consolidation are usually not present. Radiological signs consist of perihilar and peribronchial infiltrates. + +Ingestion of Aliphatic Hydrocarbons +Kerosene exerts its toxic effects on the lungs and the central nervous system. It is poorly absorbed from the gastro­ +intestinal tract. Milk and alcohol promote its absorption. It has low viscosity and less surface tension, and therefore, +diffuses quickly from the pharynx into the lungs. Administration of oil apparently decreases its absorption from the gastrointestinal tract but is not recommended. Clinical features of hydrocarbon pneumonia include cough, dyspnea, high fever, vomiting, drowsiness and coma. Physical signs in lungs are minimal. X-ray film of the chest shows ill defined homogeneous or patchy opacities; occasionally features resemble rniliary mottling. +Vomiting is not induced. Gastric lavage is usually avoided to prevent inadvertent aspiration. The patient is kept on oxygen. The routine use of antibiotics and/or corticosteroids is not recommended. + +Loeffler Syndrome +Larvae of many nematodes, during their life cycle, enter +the portal circulation, liver and then through the hepatic + + +vein and inferior vena cava into the heart and lungs. In the lungs, the larvae penetrate the capillaries, enter the alveoli, plug the bronchi with mucus and eosinophilic material due to allergic reaction. There are fleeting patchy pulmonary infiltrations. Some cases may be due to drug reaction to aspirin, penicillin, sulfonamide or irnipramine. +Clinical features include cough, low fever, feeling unwell and scattered crepitations. There is eosinophilia and X-ray lungs shows pulmonary infiltrates of varying size, which superficially resemble miliary tuberculosis. Treatment is symptomatic. + +Suggested Reading +Bradley JS, Byington CL, Shah SS, et al. Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. The manage­ ment of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infec­ tious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis 2011; 53:617-30 +Harris M, Clark J, Coote N, et al. British Thoracic Society Standards of Care Committee. British Thoracic Society guidelines for the manage­ ment of community acquired pneumonia in children: Update 2011. Tho­ rax 2011;66 SIII-3 +Kabra SK, Lodha R, Pandey RM. Antibiotics for community-acquired pneumonia in children. Cochrane Database Syst Rev 2010; 3:CD004874 Sarthi M, Lodha R, Kabra SK. Pneumonia. Indian J Pediatrics 2009;76: +Sll-7 + +Acute Respiratory Tract Infection (ARTI) Control Program +Acute lower respiratory tract infection (LRTI) is a leading +cause of mortality in children below 5 yr of age. The etio­ logical agent is bacterial in 50-60% children. The common bacteria causing LRTI in preschool children include H. infiuenzae, S. pneumoniae and staphylococci. All these +agents are sensitive to antibacterials like cotrimoxazole. Hence, judicious use of cotrimoxazole in children suffering from LRTI may prevent death due to pneumonia. World Health Organization (WHO) has recommended certain criteria for diagnosis of pneumonia is children at primary +health care level for control of LRTI deaths in developing countries where the infant mortality is more than 40 / 1000 +live births. Clinical criteria for diagnosis of pneumonia include rapid respiration with or without difficulty in +respiration. Rapid respiration is defined as respiratory rate of more than 60, 50 or 40 per minute in children below 2 +months of age, 2 months to 1 yr, and 1 to 5 yr of age, respectively. Difficulty in respiration is defined as lower chest indrawing. +The World Health Organization recommends that, in a primary care setting, if a child between 2 months and 5 yr of age presents with cough he should be examined for +rapid respiration, difficulty in breathing, presence of cyanosis or difficulty in feeding (Table 14.4). If the respiration is normal and there is no chest indrawing and difficulty in feeding, the patient is assessed to be having +an upper respiratory tract infection and can be managed +Disorders of Respiratory System - + + +Table 14.4: WHO clinical classification for treatment in children aged 2 mo to 5 yr with cough or dificult breathing + +Signs, symptoms +Cough or cold +No fast breathing, chest indrawing or indicators of severe illness +Increased respiratory rate <2 mo-old: �60 per min +2-12 mo-old: �50 per min 12-60 mo-old: �40 per min +Chest indrawing +Cyanosis, severe chest indrawing, inability to feed + + +Classification No pneumonia \ No newline at end of file