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Pediatrics_Nelson. Drug reactions to penicillins and cephalosporins are the most common allergic drug reactions encountered in the pediatric population. Approximately 6% to 10% of children are labeled as penicillin allergic. Risk factors for drug reactions include previous drug exposure, increasing age (>20 years of age), parenteral or topical administration, higher dose, intermittent Type IV reaction (delayed, cell-mediated) Contact dermatitis from topical antihistamine Drug-drug interactions Torsades de pointes arrhythmia from terfenadine with erythromycin Idiosyncratic Hemolytic anemia in a patient with G6PD deficiency after primaquine therapy Intolerance Tinnitus after a single, small dose of aspirin Adapted from Riedl MA, Casillas AM: Adverse drug reactions: types and treatment options, Am Fam Physician 68(9):1781−1790, 2003. G6PD, Glucose-6-phosphate dehydrogenase.


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Pediatrics_Nelson. Adapted from Riedl MA, Casillas AM: Adverse drug reactions: types and treatment options, Am Fam Physician 68(9):1781−1790, 2003. G6PD, Glucose-6-phosphate dehydrogenase. repeated exposure, and a genetic predisposition of slow drug metabolism. An atopic background does not predispose an individual to the development of drug reactions but may indicate a greater risk of serious reaction. Allergic reactions can be classified as immediate (anaphylactic) reactions, which occur within 60 minutes of drug administration; accelerated reactions, which begin l to 72 hours after drug administration; and late reactions, which occur after 72 hours. The most common form of adverse drug reaction is cutaneous. Accelerated reactions are usually dermatologic or serum sickness reactions. Late reactions include desquamating dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and serum sickness.


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Pediatrics_Nelson. Skin testing protocols are standardized for penicillin and are well described for other agents, such as local anesthetics, muscle relaxants, vaccines, and insulin. Positive skin testing to such reagents confirms the presence of antigen-specific IgE and supports the diagnosis of a type I hypersensitivity reaction in the appropriate clinical setting.


Pediatrics_Nelson

Pediatrics_Nelson. The broadest experience with managing adverse drug reactions is with penicillin. Penicillin allergy should be evaluated when the individual is well and not in acute need of treatment. Penicillin skin testing is helpful for IgE-mediated reactions because of its negative predictive value; only 1% to 3% of patients with negative skin tests have a reaction, which is mild, when re-exposed to penicillin. Skin testing for penicillin should be performed using the major determinant, penicilloyl polylysine (available as Pre-Pen), and minor determinants, which include penicillin G, penicilloate, and penilloate. Skin testing to penicillin does not predict non-IgE-mediated reactions. For patients with a history consistent with serum sickness or desquamative-type reactions, skin testing should not be performed, and penicillin should be avoided indefinitely.


Pediatrics_Nelson

Pediatrics_Nelson. The risk of a child who has reacted positively to penicillinskin testing suffering an allergic reaction to a cephalosporinantibiotic is less than 2%. It is believed that the first-generation cephalosporins (e.g., cephalexin) are more likely thansecond-generation (e.g., cefuroxime) or third-generation (cefpodoxime) cephalosporins to be cross-reactive. This is dueto the chemical similarity of side chains of the β-lactam ringbetween penicillin and first-generation cephalosporins.


Pediatrics_Nelson

Pediatrics_Nelson. If penicillin skin testing is positive, penicillin should be avoided, and an alternative antibiotic should be used. If there is a definite need for penicillin, desensitization can be accomplished by administration of increasing amounts of drug over a short time in a hospital setting. The exact mechanism of desensitization is unclear; however, it is thought to render mast cells unresponsive to the drug. To maintain desensitization, the drug must be given at least twice daily. If the drug is stopped for longer than 48 hours, the patient is no longer desensitized, and the same protocol must be repeated before repeated antibiotic use.


Pediatrics_Nelson

Pediatrics_Nelson. For other antibiotics, the relevant allergenic determinants produced by metabolism or degradation are not well defined. Skin testing to the native antibiotic in nonirritating concentrations can be performed. A negative response does not exclude allergy; however, a positive response suggests the presence of IgE-mediated allergy. In the case of a negative skin test response, a graded challenge or test dose may be administered, depending on the clinical history of the reaction. Patients who have experienced Stevens-Johnson syndrome, toxic epidermal necrolysis, or serum sickness should not be challenged. Anaphylaxis is the most serious complication of allergic drug reactions and can result in death (see Chapter 81). Most drug reactions do not seem to be allergic in nature. Repeated, intermittent exposure during childhood or early adulthood contributes to an increased incidence of adverse drug reactions in adults.


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Pediatrics_Nelson. Avoidance of the suspect drug is paramount. A MedicAlert bracelet with appropriate information should be worn. One of the most common concerns in regard to allergic drug reactions is cross-reactivity between penicillin and cephalosporins. In children with a history of penicillin allergy, it is important to determine whether they are truly allergic by skin testing to penicillin, using the major and minor determinants. If the penicillin skin test is negative, there is not an increased risk of an allergic reaction to cephalosporins. A positive penicillin skin test leads to an alternate non-cross-reacting antibiotic, a graded challenge to the required cephalosporin under appropriate monitoring, or desensitization to the required cephalosporin.


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Pediatrics_Nelson. For children with a history of a cephalosporin allergy who require another cephalosporin, two approaches may be considered: a graded challenge with a cephalosporin that does not share the same side chain determinant, or skin testing with the same or a different cephalosporin. A positive response suggests the presence of IgE-mediated allergy, and the value of a negative test is unknown. Skin testing with cephalosporins has not been standardized or validated. Bieber T: Atopic dermatitis, N Engl J Med 58:483–1494, 2008 Greenberger P, Grammer L: Northwestern University allergy-immunology syllabus 2012: residents and students, Allergy Asthma Proc 33(3), 2012 Greer FR, Sicherer SH, Burks AW: Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods and hydrolyzed formulas, Pediatrics 121:183–191,


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Pediatrics_Nelson. Leung DYM, Sampson HA, Geha RS, et al: Pediatric Allergy: Principles and Practice, ed 2, St Louis, 2010, Elsevier National Heart, Lung, and Blood Institute and National Asthma Education and Prevention Program: Expert panel report 3: guidelines for the diagnosis and management of asthma. Full report 2007. NTH Publication No. 08–4051. Bethesda, MD, 2007, U.S. Department of Health and Human Services. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm National Heart, Lung, and Blood Institute and National Asthma Education and Prevention Program: Expert panel report 3: guidelines for the diagnosis and management of asthma. Summary report 2007. NTH Publication No. 08–5846. Bethesda, MD, 2007, U.S. Department of Health and Human Services. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthsumm.pdf Shearer WT, Leung DYM: 2010 primer on allergic and immunologic diseases, J Allergy Clin Immunol 125:S1–S2, 2010


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Pediatrics_Nelson. Shearer WT, Leung DYM: 2010 primer on allergic and immunologic diseases, J Allergy Clin Immunol 125:S1–S2, 2010 Sicherer SH: Understanding and Managing Your Child’s Food Allergies, Baltimore, 2006, Johns Hopkins University Press Williams HC: Atopic dermatitis, N Engl J Med 352:2314–2324, 2005 Wood RA: Food Allergies for Dummies, Hoboken, NJ, 2007, Wiley Hilary M. Haftel


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Pediatrics_Nelson. Baltimore, 2006, Johns Hopkins University Press Williams HC: Atopic dermatitis, N Engl J Med 352:2314–2324, 2005 Wood RA: Food Allergies for Dummies, Hoboken, NJ, 2007, Wiley Hilary M. Haftel The rheumatic diseases (collagen vascular or connective tissue diseases) of childhood are characterized by autoimmunity and inflammation, which may be localized or generalized. The classic rheumatic diseases of children include juvenile idiopathic arthritis (JIA), formerly called juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), and juvenile dermatomyositis (JDM). Vasculitis is a component of many rheumatic diseases. Musculoskeletal pain syndromes are a set of overlapping conditions characterized by poorly localized pain involving the extremities. Scleroderma, Behçet syndrome, and Sjögren syndrome are rare in childhood. The differential diagnosis of rheumatologic disorders typically includes infections, postinfectious processes, and malignancies (Table 86-1).


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Pediatrics_Nelson. The history can identify symptoms that reflect the source of the inflammation, including whether it is localized or systemic. Symptoms of systemic inflammation tend to be nonspecific. Fever, caused by cytokine release, can take many forms. A hectic fever, without periodicity or pattern, is commonly found in vasculitides such as Kawasaki disease but also occurs in children with underlying infection. Certain illnesses, such as systemic-onset JIA, produce a patterned fever with regular temperature spikes once or twice a day. Other rheumatic illnesses cause low-grade fevers. Charting the child’s fever pattern, particularly in the absence of antipyretics, is useful. Rashes occur in many forms (see Table 86-1). Other systemic symptoms (malaise, anorexia, weight loss, and fatigue) can vary from mild to debilitating.


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Pediatrics_Nelson. Symptoms of localized inflammation vary depending on the involved site. Arthritis, or inflammation of the synovium (synovitis), leads to joint pain, swelling, and impaired ability to use the affected joint. Morning stiffness or gelling is described. The child may be slow to arise in the morning and may have a limp. Children may refrain from usual activities and athletics. Enthesitis is inflammation at the insertion of a ligament to a bone. Serositis, inflammation of serosal lining such as pleuritis, pericarditis, or peritonitis, gives rise to chest pain, shortness of breath, or abdominal pain. Myositis,inflammation of the muscle, may lead to symptoms of muscle pain, weakness, or difficulty performing tasks of daily living. Vasculitis, inflammation of the blood vessels, leads to nonspecific symptoms of rash (petechiae, purpura) and edema when small vessels deep in the papillary dermis are involved; involvement of medium-sized vessels results in a circumscribed tender nodule.


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Pediatrics_Nelson. A thorough history and physical examination is frequently sufficient to narrow the differential diagnosis and elicit the diagnosis. The child’s overall appearance, evidence of growth failure, orfailure to thrive may point to a significant underlying inflammatory disorder. The head and neck examination may showevidence of mucosal ulceration, seen in diseases such as SLE. The eye examination may show pupillary irregularity and synechiae from uveitis or the conjunctivitis of Kawasaki disease.Diffuse lymphadenopathy may be found and is nonspecific. Therespiratory and cardiac examinations may show pericardial orpleural friction rubs, indicating serositis. Splenomegaly or hepatomegaly raises suspicion of activation of the reticuloendothelial system that occurs in systemic-onset JIA or SLE.


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Pediatrics_Nelson. The joint examination is crucial for the diagnosis of arthritis and may identify evidence of joint swelling, effusion, tenderness, and erythema from increased blood flow. Joint contractures may be seen. The joint lining, or synovium, may be thickened from chronic inflammation. Activation of epiphyseal growth plates in an area of arthritis can lead to localized bony proliferation and limb length discrepancies. Conversely inflammation at sites of immature growth centers may lead to maldevelopment of bones, such as the carpals or tarsals, resulting in crowding, or the temporomandibular joints, resulting in micrognathia. A rash or evidence of underlying skin disorders, such as skin thickening from scleroderma or sclerodactyly, may be noted. Chronic Raynaud phenomenon may result in nail-fold capillary changes, ulceration, or digital tuft wasting.


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Pediatrics_Nelson. The rheumatic diseases of childhood encompass a heterogeneous group of diseases with a shared underlying pathogenesis: disordered functioning of the immune system leading to inflammation directed against native proteins, with secondary increases in numbers of activated lymphocytes, inflammatory Monarticular, Yes 50% No Yes Yes Yes — Eye disease Uveitis/retinitis Iridocyclitis (rare in No Conjunctivitis, No No Conjunctivitis, uveitis systemic) Pathogenesis Autoimmune Autoimmune Group A Borrelia Acute lymphoblastic N. gonorrhoeae Unknown streptococcus burgdorferi leukemia ANA, Antinuclear antibody; ASO, antistreptolysin-O titer; CCP, cyclic citrullinated protein; NSAID, nonsteroidal anti-inflammatory drug; TNF, tumor necrosis factor; WBC, white blood cell.


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Pediatrics_Nelson. ANA, Antinuclear antibody; ASO, antistreptolysin-O titer; CCP, cyclic citrullinated protein; NSAID, nonsteroidal anti-inflammatory drug; TNF, tumor necrosis factor; WBC, white blood cell. Coombs-positive hemolytic anemia Immune neutropenia Immune thrombocytopenia Thrombosis (anticardiolipin, antiphospholipid, lupus anticoagulant) Immune lymphopenia Antimitochondrial (primary biliary cirrhosis, SLE) Antimicrosomal (chronic active hepatitis, SLE) Antithyroid (thyroiditis, SLE) Antineutrophil cytoplasmic antibody (ANCA-cytoplasmic) (granulomatosis with polyangiitis) ANCA-perinuclear (microscopic polyangiitis) Anti-CCP (rheumatoid positive JIA) Single-stranded DNA (nonspecific, indicates inflammation) Double-stranded DNA (SLE, renal disease) DNA-histone (drug-induced SLE) Sm (Smith) (SLE, renal, CNS) RNP (ribonucleoprotein) (SLE, Sjögren syndrome, scleroderma, polymyositis, MCTD)


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Pediatrics_Nelson. Ro (Robert: SSA) (SLE, neonatal lupus-congenital heart block, Sjögren syndrome) La (Lane: SSB) (SLE, neonatal lupus [congenital heart block], Sjögren syndrome) Jo-1 (polymyositis, dermatomyositis) Scl-70 (systemic sclerosis) Centromere (CREST; limited scleroderma) PM-Scl (scleroderma, UCTD) Adapted from Condemi J: The autoimmune disease, JAMA 268:2882–2892, 1992. ANCA, Antineutrophil cytoplasmic antibody; CCP, cyclic citrullinated protein; CNS, central nervous system; CREST syndrome, calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, telangiectasia; MCTD, mixed connective tissue disease; SLE, systemic lupus erythematosus; SSA, Sjögren syndrome antigen A; SSB, Sjögren syndrome antigen B; UCTD, undifferentiated connective tissue disease.


Pediatrics_Nelson

Pediatrics_Nelson. cytokines, and circulating antibodies. This antibody production can be nonspecific, or it can be targeted against specific native proteins, leading to subsequent disease manifestations (Table 86-2). Although immune system hyperactivity may be self-limited, the hallmark of most rheumatic diseases of childhood is chronicity, or the perpetuation of the inflammatory process, which can lead to long-term disability. Although rheumatic diseases sometimes present with nonspecific symptoms, especially early in the course, over time a characteristic set of symptoms and physical findings can be elicited. In conjunction with carefully chosen confirmatory laboratory tests, an appropriate differential diagnosis is made, and eventually the correct diagnosis and treatment plan is developed.


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Pediatrics_Nelson. Most rheumatologic diagnoses are established by clinicalfindings and fulfillment of classification criteria. Laboratorytesting should be judicious and based on a differential diagnosisrather than random screening in search of a diagnosis. Laboratory tests confirm clinical diagnoses rather than develop them. Evidence of an underlying systemic inflammation may be indicated by elevated acute phase reactants, especially the erythrocyte sedimentation rate, but also the white blood cell count, platelet count, and C-reactive protein. The complete blood count may demonstrate a normochromic, normocytic anemia of chronic disease. These laboratory findings are nonspecific for any particular rheumatologic diagnosis. Certain laboratory tests may help confirm a diagnosis, such as autoantibody production in SLE or muscle enzyme elevation in JDM, or identify increased risk for complications, such as uveitis in a patient with JIA with a positive antinuclear antibody.


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Pediatrics_Nelson. Radiologic studies should focus on areas of concern identified by history or physical examination. Radiography of jointsin patients with arthritis on examination may be beneficial,but radiographic abnormalities may lag far behind the clinicalexamination. Tests with greater sensitivity, such as bone scan,computed tomography scan, and magnetic resonance imaging,may be useful when trying to differentiate between synovitisand traumatic soft tissue injury. Magnetic resonance imagingmay also be useful to identify evidence of central nervous system involvement with SLE or for evidence of myositis with JDM. Henoch-Schönlein purpura (HSP) is a vasculitis of unknown etiology characterized by inflammation of small blood vesselswith leukocytic infiltration of tissue, hemorrhage, and ischemia.The immune complexes associated with HSP are predominantlycomposed of IgA.


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Pediatrics_Nelson. HSP is the most common systemic vasculitis of childhood and cause of nonthrombocytopenic purpura, with an incidence of 13 per 100,000 children. It occurs primarily in children 3 to 15 years of age, although it has been described in adults. HSP is slightly more common in boys than girls and occurs more frequently in the winter than in the summer months. Available @ StudentConsult.com


Pediatrics_Nelson

Pediatrics_Nelson. Available @ StudentConsult.com HSP is characterized by rash, arthritis, and, less frequently, gastrointestinal or renal vasculitis. The hallmark of HSP is palpable purpura, caused by small vessel inflammation in the skin leading to extravasation of blood into the surrounding tissues, frequently with IgA deposition. The rash is classically found in dependent areas: below the waist, on the buttocks, and lower extremities (Fig. 87-1). The rash can begin as small macules or urticarial lesions but rapidly progresses to purpura with areas of ecchymosis. The rash also can be accompanied by edema, particularly of the calves and dorsum of the feet, scalp, and scrotum or labia. HSP occasionally is associated with encephalopathy, pancreatitis, and orchitis.


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Pediatrics_Nelson. Arthritis occurs in 80% of patients with HSP and is most common in the lower extremities, particularly the ankles and knees. The arthritis is acute and very painful with refusal to bear weight. Joint swelling can be confused with peripheral edema seen with the rash of HSP. Gastrointestinal involvement occurs in about one half of affected children and most typically presents as mild to moderate crampy abdominal pain, thought to be due to small vessel involvement of the gastrointestinal tract leading to ischemia. Less commonly, significant abdominal distention, bloody diarrhea, intussusception, or abdominal perforation occurs and requires emergent intervention. Gastrointestinal involvement is typically seen during the acute phase of the illness. It may precede the onset of rash.


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Pediatrics_Nelson. One third of children with HSP develop renal involvement, which can be acute or chronic. Although renal involvement is mild in most cases, acute glomerulonephritis manifested by hematuria, hypertension, or acute renal failure can occur. Most cases of glomerulonephritis occur within the first few months of presentation, but rarely patients develop late renal disease, which ultimately can lead to chronic renal disease, including renal failure. Figure 87-1 Rash of Henoch-Schönlein purpura on the lower extremities of a child. Note evidence of both purpura and petechiae.


Pediatrics_Nelson

Pediatrics_Nelson. Figure 87-1 Rash of Henoch-Schönlein purpura on the lower extremities of a child. Note evidence of both purpura and petechiae. Erythrocyte sedimentation rate, C-reactive protein, and white blood cell count are elevated in patients with HSP. The platelet count is the most important test, because HSP is characterized by nonthrombocytopenic purpura with a normal, or even high, platelet count, differentiating HSP from other causes of purpura that are associated with thrombocytopenia such as autoimmune thrombocytopenia, systemic lupus erythematosus, or leukemia. A urinalysis screens for evidence of hematuria. A serum blood urea nitrogen and creatinine should be obtained to evaluate renal function. Testing the stool for blood may identify evidence of gut ischemia. Any question of gut perforation requires radiologic investigation.


Pediatrics_Nelson

Pediatrics_Nelson. The diagnosis of HSP is based on the presence of two of four criteria (Table 87-1), which provides 87.1% sensitivity and 87.7% specificity for the disease. The differential diagnosis includes other systemic vasculitides (Table 87-2) and diseases associated with thrombocytopenic purpura, such as idiopathic thrombocytopenic purpura and leukemia. Therapy for HSP is supportive. A short-term course of non-steroidal anti-inflammatory drugs can be administered for the acute arthritis. Systemic corticosteroids usually are reserved for children with gastrointestinal disease and provide significant relief of abdominal pain. A typical dosing regimen is prednisone, 1 mg/kg/day for 1 to 2 weeks, followed by a taper schedule. Recurrence of abdominal pain as corticosteroids are weaned may necessitate a longer course of treatment. Acute nephritis typically is treated with corticosteroids but may require more aggressive immunosuppressive therapy.


Pediatrics_Nelson

Pediatrics_Nelson. Most cases of HSP are monophasic, lasting 3 to 4 weeks andresolving completely. The rash can wax and wane, however, for1 year after HSP. Parents should be warned regarding possiblerecurrences. The arthritis of HSP does not leave any permanent joint damage; it does not typically recur. Gastrointestinalinvolvement can lead to temporary abnormal peristalsis thatposes a risk of intussusception, which may be followed by complete obstruction or infarction with bowel perforation. Any child Palpable purpura Raised, palpable hemorrhagic skin lesions in the absence of thrombocytopenia Bowel angina Diffuse abdominal pain or the diagnosis of bowel ischemia Diagnostic biopsy Histologic changes showing granulocytes in the walls of arterioles or venules; IgA deposits in vessel wall Pediatric age group Age <20 years at onset of symptoms *The diagnosis of Henoch-Schönlein purpura is based on the presence of two of four criteria.


Pediatrics_Nelson

Pediatrics_Nelson. Pediatric age group Age <20 years at onset of symptoms *The diagnosis of Henoch-Schönlein purpura is based on the presence of two of four criteria. Granulomatosis with polyangiitis (formerly known as Wegener granulomatosis) Polyarteritis nodosa Churg-Strauss syndrome Microscopic polyangiitis Henoch-Schönlein purpura Serum sickness (e.g., drug-related) Vasculitis associated with infections with a recent history of HSP who presents with acute abdominalpain, obstipation, or diarrhea should be evaluated for intussusception. Renal involvement rarely may lead to renal failure.


Pediatrics_Nelson

Pediatrics_Nelson. The prognosis of HSP is excellent. Most children have complete resolution of the illness without any significant sequelae. Patients with HSP renal disease (elevated blood urea nitrogen, persistent high-grade proteinuria) are at highest risk for long-term complications, such as hypertension or renal insufficiency, particularly if the initial course was marked by significant nephritis. There is a long-term risk of progression to end-stage renal disease in less than 1% of children with HSP. The rare patients who develop end-stage renal disease may require renal transplantation. HSP may recur in the transplanted kidney. Kawasaki disease (KD) is a vasculitis of unknown etiology that is characterized by multisystem involvement and inflammation of small to medium-sized arteries with resulting aneurysm formation.


Pediatrics_Nelson

Pediatrics_Nelson. Kawasaki disease (KD) is a vasculitis of unknown etiology that is characterized by multisystem involvement and inflammation of small to medium-sized arteries with resulting aneurysm formation. KD is the second most common vasculitis of childhood. It is more common in children of Asian descent. It has been described in variable frequency in all parts of the world; the highest frequency is in Japan. KD most commonly occurs in children younger than 5 years of age, with a peak between 2 to 3 years, and is rare in children older than 7 years. The incidence in the United States is approximately 6 per 100,000 children who are younger than 5 years of age. A seasonal variability has been described with a peak between February and May, but the disease occurs throughout the year. The clinical course of KD can be divided into three phases, each with its own unique manifestations. Aneurysmal involvement of the coronary arteries is the most important manifestation of KD.


Pediatrics_Nelson

Pediatrics_Nelson. The clinical course of KD can be divided into three phases, each with its own unique manifestations. Aneurysmal involvement of the coronary arteries is the most important manifestation of KD. Available @ StudentConsult.com Lymphadenopathy Fever Without a Source Fever of Unknown Origin


Pediatrics_Nelson

Pediatrics_Nelson. The acute phase of KD, which lasts 1 to 2 weeks, is marked by sudden onset of a high, hectic fever (>40 °C) without an apparent source. The onset of fever is followed by conjunctival erythema; mucosal changes, including dry, cracked lips and a strawberry tongue; cervical lymphadenopathy; and swelling of the hands and feet (Fig. 88-1). Conjunctivitis is bilateral, bulbar, and nonsuppurative. Cervical lymphadenopathy is found in 70% of children and should be greater than 1.5 cm in diameter for the purposes of diagnosis. A rash, which can vary in appearance, occurs in 80% of children with KD and may be particularly accentuated in the inguinal area and on the chest. Extreme irritability is prominent, especially in infants. Abdominal pain and hydrops of the gallbladder, cerebrospinal fluid pleocytosis, sterile pyuria, and arthritis, particularly of medium-sized to large joints, may occur. Carditis in the acute phase may be manifested by tachycardia, shortness of breath, or overt congestive


Pediatrics_Nelson

Pediatrics_Nelson. sterile pyuria, and arthritis, particularly of medium-sized to large joints, may occur. Carditis in the acute phase may be manifested by tachycardia, shortness of breath, or overt congestive heart failure. Giant coronary artery aneurysms, which are rare but occur most commonly in very young children, can appear during this phase.


Pediatrics_Nelson

Pediatrics_Nelson. The subacute phase, which lasts until about the fourth week, is characterized by gradual resolution of fever (if untreated) and other symptoms. Desquamation of the skin, particularly of the fingers and toes, appears at this point. The platelet count, previously normal or slightly depressed, increases to a significant degree (often >1 million/mm3). This phase heralds the onset of coronary artery aneurysms, which may also appear in the convalescent phase and pose the highest risk of morbidity and mortality. Risk factors for development of coronary artery aneurysms include prolonged fever, prolonged elevation of inflammatory parameters such as the erythrocyte sedimentation rate (ESR), age younger than 1 year or older than 6 years, and male gender. Figure 88-1 Facial features of Kawa-saki disease with (A) morbilliform rash and nonsuppurative conjunctivitis and (B) red, chapped lips. AB


Pediatrics_Nelson

Pediatrics_Nelson. Figure 88-1 Facial features of Kawa-saki disease with (A) morbilliform rash and nonsuppurative conjunctivitis and (B) red, chapped lips. AB The convalescent phase begins with the disappearance of clinical symptoms and continues until the ESR returns to normal, usually 6 to 8 weeks after the onset of illness. Beau lines of the fingernails may appear during this phase.


Pediatrics_Nelson

Pediatrics_Nelson. It is particularly important to exclude other causes of fever, notably infection. It is appropriate to obtain blood and urine culturesand to perform a chest x-ray. In the acute phase, inflammatory parameters are elevated, including white blood cell count, C-reactive protein, and the ESR, which can be profoundlyelevated (often >80 mm/hr). Platelet counts may be inappropriately low or normal. A lumbar puncture, if performed toexclude infection, may reveal pleocytosis. Tests of hepatobiliary function may be abnormal. Greatly elevated platelet countsdevelop during the subacute phase. The development of coronary artery aneurysms is monitored by performing two-dimensional echocardiograms, usually during the acute phase, at 2 to3 weeks, and again at 6 to 8 weeks. More frequent echocardiograms and, potentially, coronary angiography are indicated forpatients who develop coronary artery abnormalities.


Pediatrics_Nelson

Pediatrics_Nelson. The diagnosis of KD is based on the presence of fever for more than 5 days without an identifiable source and the presence of four of five other clinical criteria (Table 88-1). The diagnosis of incomplete (atypical) KD, which occurs more commonly in infants, is made when fever is present for at least 5 days even if only two or three clinical criteria are present, particularly in the presence of coronary artery aneurysms. The diagnosis of KD should be considered in infants younger than 6 months of age with fever for at least 7 days even if no other criteria are present. Because many of the manifestations of KD are found in other illnesses, many diagnoses must be considered and excluded before the diagnosis of KD can be established (Table 88-2). Intravenous immunoglobulin (IVIG) is the mainstay of therapy for KD, although the mechanism of action is unknown. Fever of >5 days’ duration associated with at least four* of the following five changes:


Pediatrics_Nelson

Pediatrics_Nelson. Fever of >5 days’ duration associated with at least four* of the following five changes: One or more changes of the mucous membranes of the upper respiratory tract, including pharyngeal injection, dry fissured lips, injected lips, and “strawberry” tongue One or more changes of the extremities, including peripheral erythema, peripheral edema, periungual desquamation, and generalized desquamation Polymorphous rash, primarily truncal Cervical lymphadenopathy >1.5 cm in diameter Disease cannot be explained by some other known disease process. *A diagnosis of Kawasaki disease can be made if fever and only three changes are present in conjunction with coronary artery disease documented by two-dimensional echocardiography or coronary angiography.


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Pediatrics_Nelson. Coronary artery thrombosis Peripheral artery aneurysm Coronary artery aneurysms Myocardial infarction Myopericarditis Heart failure Hydrops of gallbladder Aseptic meningitis Irritability Arthritis Sterile pyuria (urethritis) Thrombocytosis (late) Diarrhea Pancreatitis Peripheral gangrene A single dose of IVIG (2 g/kg over 12 hours) results in rapiddefervescence and resolution of clinical illness in most patients and, more important, reduces the incidence of coronary artery aneurysms. Aspirin is initially given in anti-inflammatory doses (80 to 100 mg/kg/day divided every 6hours) in the acute phase. Once the fever resolves, aspirin isreduced to antithrombotic doses (3 to 5 mg/kg/day as a single dose) and given through the subacute and convalescentphases, usually for 6 to 8 weeks, until follow-up echocardiography documents the absence or resolution of coronary artery aneurysms.


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Pediatrics_Nelson. Up to 10% of children with KD initially fail to respondsatisfactorily to IVIG therapy. Most of these patients respondto retreatment with IVIG, but an alternative preparation ofIVIG may be required. Corticosteroids or infliximab arerarely used in KD, as opposed to other vasculitides, but mayhave a role during the acute phase if active carditis is apparent or for children with persistent fever after two doses ofIVIG. Most cases resolve without sequelae. Myocardial infarction has been documented, most likely caused by stenosis of a coronary artery at the site of an aneurysm. Coronary artery aneurysms found on autopsy in older children following sudden cardiac death may have been due to past KD. Other complications are listed in Table 88-3.


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Pediatrics_Nelson. IVIG reduces the prevalence of coronary artery disease from 20% to 25% in children treated with aspirin alone to 2% to 4% in children treated with IVIG and aspirin. Other than the risk of persistent coronary artery aneurysms, KD has an excellent prognosis.


Pediatrics_Nelson

Pediatrics_Nelson. The chronic arthritides of childhood include several types, the most common of which is juvenile idiopathic arthritis (JIA), formerly called juvenile rheumatoid arthritis (JRA). The classification of JIA includes several other types of juvenile arthritis, such as enthesitis-related arthritis and psoriatic arthritis. The etiology of this autoimmune disease is unknown. The common underlying manifestation of this group of illnesses is the presence of chronic synovitis, or inflammation of the joint synovium. The synovium becomes thickened and hypervascular with infiltration by lymphocytes, which also can be found in the synovial fluid along with inflammatory cytokines. The inflammation leads to production and release of tissue proteases and collagenases. If left untreated, the inflammation can lead to tissue destruction, particularly of the articular cartilage and, eventually, the underlying bony structures.


Pediatrics_Nelson

Pediatrics_Nelson. JIA is the most common chronic rheumatologic disease of childhood, with a prevalence of 1:1000 children. The disease has two peaks, one at 1 to 3 years and one at 8 to 12 years, but it can occur at any age. Girls are affected more commonly than boys, particularly with the oligoarticular form of the illness. Available @ StudentConsult.com


Pediatrics_Nelson

Pediatrics_Nelson. Available @ StudentConsult.com JIA can be divided into several subtypes, depending on the number of joints involved (less than five versus five or more), thepresence of sacroiliac involvement, and the presence of systemicfeatures, each with particular disease characteristics (Table 89-1).Although the onset of the arthritis is slow, the actual joint swelling is often noticed acutely by the child or parent, such as after anaccident or fall, and can be confused with trauma (even thoughtraumatic effusions are rare in children). The child may developpain and stiffness in the joint that limit use, but rarely refuses touse the joint at all. Morning stiffness and gelling also can occur inthe joint and, if present, can be followed in response to therapy.


Pediatrics_Nelson

Pediatrics_Nelson. On physical examination, signs of inflammation are present,including joint tenderness, erythema, and effusion (Fig. 89-1).Joint range of motion may be limited because of pain, swelling,or contractures from lack of use. In children, because of the Table 89-1 Features of Juvenile Idiopathic Arthritis Subgroups FEATURE OLIGOARTICULAR POLYARTICULAR SYSTEMIC ONSET SPONDYLOARTHROPATHIES No. joints <5 ≥5 Varies, usually ≥5 Varies Types of joints Medium to large (also small in extended Small to medium Small to medium Medium to large, including sacroiliac joints Extra-articular None None Systemic features Enthesopathy, psoriasis, bowel manifestations RF positivity + (in older children with early-onset RA) ANA, Antinuclear antibody; RA, rheumatoid arthritis; RF, rheumatoid factor. Figure 89-1 An affected knee in a patient with oligoarticular juve-nile idiopathic arthritis. Note sizeable effusion, bony proliferation, and flexion contracture.


Pediatrics_Nelson

Pediatrics_Nelson. Figure 89-1 An affected knee in a patient with oligoarticular juve-nile idiopathic arthritis. Note sizeable effusion, bony proliferation, and flexion contracture. presence of an active growth plate, it may be possible to findbony abnormalities of the surrounding bone, causing bonyproliferation and localized growth disturbance. In a lowerextremity joint, a leg length discrepancy may be appreciable ifthe arthritis is asymmetric.


Pediatrics_Nelson

Pediatrics_Nelson. All children with chronic arthritis are at risk for chronic iridocyclitis or uveitis. There is an association between human leukocyte antigens (HLAs) (HLA-DR5, HLA-DR6, and HLA-DR8) and uveitis. The presence of a positive antinuclear antibody identifies children with arthritis who are at higher risk for chronic uveitis. Although all children with JIA are at increased risk, the subgroup of children, particularly young girls, with oligoarticular (less than five affected joints) JIA and a positive antinuclear antibody are at highest risk, with an incidence of uveitis of 80%. The uveitis associated with JIA can be asymptomatic until the point of visual loss, making it a primary treatable cause of blindness in children. It is crucial for children with JIA to undergo regular ophthalmologic screening with a slit-lamp examination to identify anterior chamber inflammation and to initiate prompt treatment of any active disease.


Pediatrics_Nelson

Pediatrics_Nelson. Oligoarticular JIA is defined as the presence of arthritis in fewer than five joints within 6 months of diagnosis. This is the most common form of JIA, accounting for approximately 50% of cases. Oligoarticular JIA presents in young children, with a peak at 1 to 3 years and another peak at 8 to 12 years. The arthritis is found in medium-sized to large joints; the knee is the most common joint involved, followed by the ankle and the wrist. It is unusual for small joints, such as the fingers or toes, to be involved, although this may occur. Neck and hip involvement also is uncommon. Children with oligoarticular JIA may be otherwise well without any evidence of systemic inflammation (fever, weight loss, or failure to thrive) or any laboratory evidence of systemic inflammation (elevated white blood cell count or erythrocyte sedimentation rate). A subset of these children later develops polyarticular disease (called extended oligoarthritis).


Pediatrics_Nelson

Pediatrics_Nelson. Polyarticular JIA describes children with arthritis in five or more joints within the first 6 months of diagnosis and accounts for about 40% of cases. Children with polyarticular JIA tend to have symmetric arthritis, which can affect any joint but typically involves the small joints of the hands, feet, ankles, wrists, and knees. The cervical spine can be involved, leading Extra-articular manifestations Systemic symptoms Enthesopathy Psoriasis, nail Bowel symptoms (systemic-onset JRA) ANA, Antinuclear antibody; IBD, inflammatory bowel disease; JAS, juvenile ankylosing spondylitis; JIA, juvenile idiopathic arthritis; PSA, poststreptococcal arthritis; RF, rheumatoid factor.


Pediatrics_Nelson

Pediatrics_Nelson. ANA, Antinuclear antibody; IBD, inflammatory bowel disease; JAS, juvenile ankylosing spondylitis; JIA, juvenile idiopathic arthritis; PSA, poststreptococcal arthritis; RF, rheumatoid factor. to fusion of the spine over time. In contrast to oligoarticular JIA, children with polyarticular disease can present with evidence of systemic inflammation, including malaise, low-grade fever, growth retardation, anemia of chronic disease, and elevated markers of inflammation. Polyarticular JIA can present at any age, although there is a peak in early childhood. There is a second peak in adolescence, but these children differ by the presence of a positive rheumatoid factor (and anti-CCP antibody) and most likely represent a subgroup with true adult rheumatoid arthritis; the clinical course and prognosis are similar to the adult entity.


Pediatrics_Nelson

Pediatrics_Nelson. A small subgroup of patients (approximately 10%) with juvenile arthritis does not present with onset of arthritis but rather with preceding systemic inflammation. This form of JIA, thought to be an autoinflammatory disease, manifests with a typical recurring, spiking fever, usually once or twice per day, which can occur for several weeks to months. This is accompanied by a rash, typically morbilliform and salmon-colored. The rash may be evanescent and occur at times of high fever only. Rarely the rash can be urticarial in nature. Internal organ involvement also occurs. Serositis, such as pleuritis and pericarditis, occurs in 50% of children. Pericardial tamponade rarely may occur. Hepatosplenomegaly occurs in 70% of children. Children with systemic-onset JIA appear sick; they have significant constitutional symptoms, including malaise and failure to thrive. Laboratory findings show the inflammation, with elevated erythrocyte sedimentation rate, C-reactive protein, white blood cell


Pediatrics_Nelson

Pediatrics_Nelson. constitutional symptoms, including malaise and failure to thrive. Laboratory findings show the inflammation, with elevated erythrocyte sedimentation rate, C-reactive protein, white blood cell count, and platelet counts and anemia. The arthritis of JIA follows the systemic inflammation by 6 weeks to 6 months. The arthritis is typically polyarticular in nature and can be extensive and resistant to treatment, placing these children at highest risk for long-term disability.


Pediatrics_Nelson

Pediatrics_Nelson. The spondyloarthropathies describe a group of arthritides that include inflammation of the axial skeleton and sacroiliac joints and enthesitis, or inflammation of tendinous insertions. These include juvenile ankylosing spondylitis, psoriatic arthritis, and the arthritis of inflammatory bowel disease. This group of diseases can also present with peripheral arthritis and can be initially classified in other subgroups. It is only later, when the patient develops evidence of sacroiliac arthritis, psoriasis, or gastrointestinal disease, that the diagnosis becomes clear (Table 89-2). Other important features of this group include the frequent presence of HLA-B27 and the need for earlier treatment with tumor necrosis factor (TNF) blockers.


Pediatrics_Nelson

Pediatrics_Nelson. Most children with oligoarticular JIA have no laboratory abnormalities. Children with polyarticular and systemic-onset disease commonly show elevated acute phase reactants and anemia of chronic disease. In all pediatric patients with joint or bone pain, a complete blood count should be performed to exclude leukemia, which also can present with limb pain (see Chapter 155). All patients with oligoarticular JIA should have an antinuclear antibody test to help identify those at higher risk for uveitis. Older children and adolescents with polyarticular disease should have a rheumatoid factor performed to identify children with early onset adult rheumatoid arthritis.


Pediatrics_Nelson

Pediatrics_Nelson. Diagnostic arthrocentesis may be necessary to exclude suppurative arthritis in children who present with acute onset of monarticular symptoms. The synovial fluid white blood cell count is typically less than 50,000 to 100,000/mm3 and should be predominantly lymphocytes, rather than neutrophils seen with suppurative arthritis. Gram stain and culture should be negative (see Chapter 118). The most common radiologic finding in the early stagesof JIA is a normal bone x-ray. Over time, periarticular osteopenia, resulting from decreased mineralization, is mostcommonly found. Growth centers may be slow to develop,whereas there may be accelerated maturation of growth platesor evidence of bony proliferation. Erosions of bony articularsurfaces may be a late finding. If the cervical spine is involved,fusion of C1-4 may occur, and atlantoaxial subluxation maybe demonstrable.


Pediatrics_Nelson

Pediatrics_Nelson. The diagnosis of JIA is established by the presence of arthritis, the duration of the disease for at least 6 weeks, and exclusion of other possible diagnoses. Although a presumptive diagnosis of systemic-onset JIA can be established for a child during the systemic phase, a definitive diagnosis is not possible until arthritis develops. Children must be younger than 16 years of age at time of onset of disease; the diagnosis of JIA does not change when the child becomes an adult. Because there are so many other causes of arthritis, these disorders need to be excluded before providing a definitive diagnosis of JIA (Table 89-3). The acute arthritides can affect the same joints as JIA but have a shorter time course.


Pediatrics_Nelson

Pediatrics_Nelson. The treatment of JIA focuses on suppressing inflammation, preserving and maximizing function, preventing deformity, and preventing blindness. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first choice in the treatment of JIA. Naproxen, sulindac, ibuprofen, indomethacin, and others have been used successfully. Systemic corticosteroid medications, such as prednisone and prednisolone, should be avoided in all but the most extreme circumstances, such as for severe systemic-onset JIA with internal organ involvement or for significant active arthritis leading to the inability to ambulate. In this circumstance, the corticosteroids are used as bridging therapy until other medications take effect. For patients with a few isolated inflamed joints, intra-articular corticosteroids may be helpful.


Pediatrics_Nelson

Pediatrics_Nelson. Second-line medications, such as hydroxychloroquine and sulfasalazine, have been used in patients whose arthritis is not completely controlled with NSAIDs alone. Methotrexate, given either orally or subcutaneously, has become the drug of choice for polyarticular and systemic-onset JIA, which may not respond to baseline agents alone. Methotrexate can cause bone marrow suppression and hepatotoxicity; regular monitoring can minimize these risks. Leflunomide, with a similar adverse effect profile to methotrexate, has also been used. Biologic agents that inhibit TNF-α and block the inflammatory cascade, including etanercept, infliximab, and adalimumab, are effective in the treatment of JIA. The risks of these agents are greater, however, and include serious infection and, possibly, increased risk of malignancy. Anakinra, an interleukin-1 receptor antagonist, is very beneficial in the treatment of the systemic features of systemic-onset JIA.


Pediatrics_Nelson

Pediatrics_Nelson. Complications with JIA result primarily from the loss of function of an involved joint secondary to contractures, bony fusion, or loss of joint space. Physical and occupational therapies, professionally and through home programs, are crucial to preserve and maximize function. More serious complications stem from associated uveitis; if left untreated, it can lead to serious visual loss or blindness. The prognosis of JIA is excellent, with an overall 85% complete remission rate. Children with oligoarticular JIA uniformly tend to do well, whereas children with polyarticular disease and systemic-onset disease constitute most children with functional disability. Systemic-onset disease, a positive Juvenile idiopathic arthritis Systemic lupus erythematosus Juvenile dermatomyositis Scleroderma with arthritis Leukemia Lymphoma Sickle cell disease Thalassemia Malignant and benign tumors of bone, cartilage, or synovium Metastatic bone disease Hemophilia


Pediatrics_Nelson

Pediatrics_Nelson. Leukemia Lymphoma Sickle cell disease Thalassemia Malignant and benign tumors of bone, cartilage, or synovium Metastatic bone disease Hemophilia Rickets/metabolic bone disease Lysosomal storage diseases Heritable disorders of collagen rheumatoid factor, poor response to therapy, and the presence of erosions on x-ray all connote a poorer prognosis. The importance of physical and occupational therapy cannot be overstated because when the disease remits, the physical limitations remain with the patient into adulthood.


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Pediatrics_Nelson. Systemic lupus erythematosus (SLE) is a multisystem disorder of unknown etiology characterized by a production of large amounts of circulating autoantibodies. This antibody production may be due to loss of T-lymphocyte control on B-lymphocyte activity, leading to hyperactivity of B lymphocytes, which leads to nonspecific and specific antibody and autoantibody production. These antibodies form immune complexes that become trapped in the microvasculature, leading to inflammation and ischemia. Although SLE affects primarily women of childbearing age, approximately 5% of cases present in childhood, mainly around puberty. SLE is rare in children younger than 9 years of age. Although there is a female predominance of this disease in adolescence and adulthood, there is an equal gender distribution in children. The overall prevalence of SLE in the pediatric population is 10 to 25 cases per 100,000 children.


Pediatrics_Nelson

Pediatrics_Nelson. Patients with SLE can present either in an abrupt fashion with fulminant disease or in an indolent manner (Tables 90-1 and 90-2). Nonspecific symptoms are common but can be quite profound and may include significant fatigue and malaise, low-grade fever, and weight loss.


Pediatrics_Nelson

Pediatrics_Nelson. Skin disease can be a prominent finding, occurring in up to 95% of patients. A raised, erythematous rash on the cheeks, called a malar butterfly rash, is common (Fig. 90-1). This rash also can occur across the bridge of the nose, on the forehead, and on the chin. Photosensitivity can be problematic, particularly during the summer months. Both of these rashes improve with appropriate therapy. The rash of discoid lupus, by contrast, is an inflammatory process that leads to disruption of the dermal-epidermal junction, resulting in permanent scarring and loss of pigmentation in the affected area. If discoid lupus occurs in the scalp, permanent alopecia ensues because of loss of hair follicles. Raynaud phenomenon, although not specific for SLE, and livedo reticularis also can occur.


Pediatrics_Nelson

Pediatrics_Nelson. Mouth and nasal sores resulting from mucosal ulceration are a common complaint in patients with SLE and can lead to ulceration and perforation of the nasal septum. Because of reticuloendothelial system stimulation, lymphadenopathy and splenomegaly are common findings in SLE. In particular, axillary lymphadenopathy can be a sensitive indicator of disease activity. Serositis can be seen, with chest pain and pleural or pericardial friction rubs or frank effusion. Renal involvement is one of the most serious manifestations of SLE and is common in pediatric SLE, occurring in 50% to 70% of children. Renal disease may range from microscopic Malar butterfly rash Discoid lupus Photosensitivity Oral and nasopharyngeal ulcers Nonerosive arthritis (more than two joints with effusion and tenderness) Pleuritis or pericarditis (serositis) Seizures or psychosis in absence of metabolic toxins or drugs Cellular casts (RBC, granular, or tubular)


Pediatrics_Nelson

Pediatrics_Nelson. Cellular casts (RBC, granular, or tubular) Hemolytic anemia with reticulocytosis or Leukopenia (<4000 on two occasions) or Lymphopenia (<1500 on two occasions) or Thrombocytopenia (<100,000/mm3) Evidence of presence of antiphospholipid antibodies IgG or IgM anticardiolipin antibodies or Lupus anticoagulant or False-positive VDRL for >6 mo Positive ANA in absence of drugs known to induce lupus ANA, Antinuclear antibody; RBC, red blood cell; VDRL, Venereal Disease Research Laboratory. *These are the 1997 revised criteria for diagnosing systemic lupus erythematosus (SLE). A patient must have 4 of the 11 criteria to establish the diagnosis of SLE. These criteria may be present at the same or at different times during the patient’s illness. Additional, less specific diagnostic manifestations are noted in Table 90-2. proteinuria or hematuria to gross hematuria, nephrotic syndrome, and renal failure. Hypertension or the presence of edema suggests lupus renal disease.


Pediatrics_Nelson

Pediatrics_Nelson. proteinuria or hematuria to gross hematuria, nephrotic syndrome, and renal failure. Hypertension or the presence of edema suggests lupus renal disease. Arthralgias and arthritis are common. The arthritis is rarely deforming and typically involves the small joints of the hands; any joint may be involved. Myalgias or frank myositis, with muscle weakness and muscle fatigability, may occur. SLE can affect the central nervous system (CNS), leading to a myriad of symptoms ranging from poor school performance and difficulty concentrating, to seizures, psychosis, and stroke. Testing for SLE is performed to establish the diagnosis, determine prognosis, and monitor response to therapy. Althoughnonspecific, a positive antinuclear antibody is found in more than 97% of patients with SLE, usually at high titers.Because of its high sensitivity, a negative antinuclear antibodyhas a high negative predictive value for SLE. The presence of Myositis, myalgia Arthralgia


Pediatrics_Nelson

Pediatrics_Nelson. Myositis, myalgia Arthralgia Figure 90-1 Malar butterfly rash on teenage boy with systemic lupus erythematosus. Note erythema on cheeks and chin, sparing the nasolabial folds. antibodies to double-stranded DNA should raise suspicionfor SLE because these antibodies are present in most patientswith SLE and are found almost exclusively in the disease. Titers of anti-double-stranded DNA antibodies are quantifiable and vary with disease activity. Antibodies directed against Sm (Smith) are specific to SLE but are found in onlyapproximately 30% of persons with SLE, limiting its clinical utility. Antibodies to Ro (SSA) and La (SSB) also can befound in patients with SLE, but they also occur in patientswith Sjögren syndrome. Likewise patients with SLE can haveantibodies directed against phospholipids, which also can beseen in other rheumatologic diseases and in primary antiphospholipid syndrome.


Pediatrics_Nelson

Pediatrics_Nelson. These antibodies lead to an increased risk of arterial and venous thrombosis and can be detected by the presence of anticardiolipin antibodies, a false-positive Venereal Disease Research Laboratory (VDRL) test, or a prolonged activated partial thromboplastin time.


Pediatrics_Nelson

Pediatrics_Nelson. Hematologic abnormalities also are prevalent in patients with SLE. Leukopenia, primarily manifest as lymphopenia, is common. Thrombocytopenia and anemia of chronic disease may be found. Rarely patients with SLE develop Coombspositive autoimmune hemolytic anemia. Excessive antibody production can lead to polyclonal hypergammopathy with an elevated globulin fraction in the serum. Excessive circulating antibodies and immune complexes also lead to the consumption of complement proteins, with low levels of C3 and C4 and decreased complement function as measured by CH50. Effective therapy returns the low complement levels to normal. This is one way to monitor therapy except in patients with familial deficiency in complement components, which, itself, predisposes to SLE.


Pediatrics_Nelson

Pediatrics_Nelson. Urinalysis may show hematuria and proteinuria, identifying patients with lupus nephritis. Serum blood urea nitrogen and creatinine evaluate renal function. Hypoalbuminemia and hypoproteinemia may be present. Elevation of muscle enzymes may be a clue for the presence of myositis. Elevated cerebrospinal fluid (CSF) protein and an elevated IgG-to-albumin ratio when comparing CSF with serum (IgG index) can indicate antibody production in the CSF and help diagnose SLE affecting the CNS. CNS lupus has a specific pattern on gadolinium-enhanced magnetic resonance imaging.


Pediatrics_Nelson

Pediatrics_Nelson. Because SLE is a multisystem disease, it can be difficult to diagnosis early in the disease course. Suspicion must be high in patients who present with diffuse symptoms, particularly adolescent girls. Many of the clinical manifestations of SLE are found in other inflammatory illnesses and during acute or chronic infection. Criteria have been developed for the diagnosis of SLE (see Table 90-1). The presence of 4 of 11 of these criteria has 98% sensitivity and 97% specificity for SLE.


Pediatrics_Nelson

Pediatrics_Nelson. Corticosteroids have been the mainstay of treatment for SLE for decades. Initial use of pulse methylprednisolone and high-dose oral prednisone (up to 2 mg/kg) frequently is required, followed by cautious tapering to minimize recurrence of symptoms. Nonsteroidal anti-inflammatory drugs have been used to treat the arthralgias and arthritis associated with SLE. Hydroxychloroquine is used not only for the treatment of lupus skin disease, such as discoid lupus, but as maintenance therapy. Hydroxychloroquine treatment results in longer periods of wellness between flares of disease as well as decreased numbers of flares.


Pediatrics_Nelson

Pediatrics_Nelson. Corticosteroids and hydroxychloroquine frequently are not sufficient therapies for lupus nephritis or cerebritis. Cyclophosphamide is effective for the worst forms of lupus nephritis, with significant improvements in outcome and decreased rates of progression to renal failure. CNS lupus responds to cyclophosphamide. For patients who are not able to tolerate the tapering of corticosteroids, the use of steroid-sparing agents, such as azathioprine, methotrexate, or mycophenolate mofetil, may be indicated. Patients with SLE should be counseled to wear sun block and avoid sun exposure because exposure to the sun precipitates flares of the disease. Because of this prohibition,patients benefit from calcium and vitamin D supplementation to reduce the risk of osteoporosis that may result from prolonged corticosteroid use. Early treatment of hyperlipidemiato decrease long-term cardiovascular complications is alsoindicated.


Pediatrics_Nelson

Pediatrics_Nelson. Long-term complications include avascular necrosis secondary to corticosteroid use, infections, and myocardial infarction. Adult patients with SLE develop accelerated atherosclerosis, not only because of prolonged corticosteroid use but also due to the underlying disease. All patients with SLE should be counseled regarding their weight and maintaining an active lifestyle to reduce other cardiac risk factors. Outcomes for SLE have improved significantly over the past several decades and depend largely on the organ systems that are involved. Worse prognoses are seen in patients with severe lupus nephritis or cerebritis, with risk of chronic disability or progression to renal failure. With current therapy for the disease and the success of renal transplantation, however, most patients live well into adulthood.


Pediatrics_Nelson

Pediatrics_Nelson. The etiology of juvenile dermatomyositis (JDM) is unknown. It is characterized by activation of T and B lymphocytes, leading to vasculitis affecting small vessels of skeletal muscle, with immune complex deposition and subsequent inflammation of blood vessels and muscle. JDM may follow infections, allergic reactions, or sun exposure, but no causal relationship has been shown. JDM is a rare disease, with an incidence of less than 0.1:100,000 children. JDM can occur in all age groups with a peak incidence between 4 to 10 years. The disease is slightly more common in girls than boys. Dermatomyositis tends to present in a slow, progressive fashion, with insidious onset of fatigue, malaise, and progressive muscle weakness, accompanied by low-grade fevers and rash. Some children present in an acute fashion, however, with rapid onset of severe disease.


Pediatrics_Nelson

Pediatrics_Nelson. The muscle disease of JDM primarily affects the proximal muscles, particularly the hip and shoulder girdles, and the abdominal and neck muscles. Children have difficulty climbing steps, getting out of chairs, and getting off the floor. The patient may have a positive Gower sign. In severe cases, the patient is not able to sit up from a supine position or even liftthe head off the examination table (see Chapter 182). If muscles of the upper airway and pharynx are involved, the patient’s voice will sound nasal and the patient may have difficulty swallowing.


Pediatrics_Nelson

Pediatrics_Nelson. A classic JDM rash occurs on the face and across the cheeks but also can be found on the shoulders and back (shawl sign). Patients may have heliotrope discoloration of the eyelids. Scaly, red plaques (Gottron papules) classically are found across the knuckles but can be found on the extensor surfaces of any joint. Patients may have periungual erythema and dilated nail-fold capillaries. Less commonly, patients develop cutaneous vasculitis, with inflammation, erythema, and skin breakdown. Rash typical of dermatomyositis Symmetric proximal muscle weakness Elevated muscle enzymes (ALT, AST, LDH, CPK, and aldolase) EMG abnormalities typical of dermatomyositis (fasciculations, needle insertion irritability, and high-frequency discharges) Positive muscle biopsy specimen with chronic inflammation


Pediatrics_Nelson

Pediatrics_Nelson. ALT, Alanine aminotransferase; AST, aspartate aminotransferase; CPK, creatine phosphokinase; EMG, electromyography; LDH, lactate dehydrogenase. *To make a definitive diagnosis of dermatomyositis, four of five criteria are required. At some point, 15% of patients with JDM develop arthritis, commonly affecting small joints, but any joint may be involved. Raynaud phenomenon, hepatomegaly, and splenomegaly may also occur. Many patients with JDM have no evidence of systemic inflammation (normal blood count and erythrocyte sedimentation rate). Evidence of myositis can be identified in 98% of children with active JDM by elevated serum muscle enzymes, including aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase, aldolase, and lactate dehydrogenase. Electromyography and muscle biopsy can document the myositis. Magnetic resonance imaging is a noninvasive means of showing muscle inflammation.


Pediatrics_Nelson

Pediatrics_Nelson. Diagnosis of JDM is based on the presence of documented muscle inflammation in the setting of classic rash (Table 91-1).A small percentage of children have muscle disease without skin manifestations, but polymyositis is sufficiently rare in children that they should have a muscle biopsy to exclude other causes of muscle weakness, such as muscular dystrophy (particularly boys). The differential diagnosis also includes postinfectious myositis and other myopathies (see Chapter 182).


Pediatrics_Nelson

Pediatrics_Nelson. Methotrexate, supplemented by short-term use of systemic corticosteroids, is the cornerstone of therapy for JDM. Initial treatment with pulse intravenous methylprednisolone is followed by several months of tapering doses of oral prednisone. Early institution of methotrexate significantly decreases the duration of corticosteroid use and its associated toxicities. In severe or refractory cases, it may be necessary to use cyclosporine or cyclophosphamide. Intravenous immunoglobulin is useful as adjunctive therapy. Hydroxychloroquine or dapsone has been used for the skin manifestations. These drugs do not significantly affect the muscle disease. Exposure to the sun worsens the cutaneous manifestations and exacerbates the muscle disease; sunlight may lead to flare. Patients should be advised to wear sun block and refrain from prolonged sun exposure. Accordingly supplementation with calcium and active forms of vitamin D is also indicated.


Pediatrics_Nelson

Pediatrics_Nelson. The most serious complication of JDM is the development of calcinosis. Dystrophic calcification can occur in the skin and soft tissues in any area of the body; it ranges from mild to extensive (calcinosis universalis). Although it is difficult to predict who will develop calcinosis, it occurs more commonly in children with cutaneous vasculitis, prolonged disease activity, or delays in onset of therapy. Patients with JDM who develop vasculitis also are at risk for gastrointestinal perforation and gastrointestinal bleeding. JDM has been associated with lipoatrophy and insulin resistance, which can progress to type 2 diabetes. Control of insulin resistance frequently leads to improvement in muscle disease in these patients.


Pediatrics_Nelson

Pediatrics_Nelson. The outcome of JDM depends greatly on the extent of muscle disease and the time between disease onset and initiation of therapy. JDM follows one of three clinical courses: a monophasic course, in which patients are treated and improve without significant sequelae; a chronic recurrent course; and a chronic progressive course marked by poor response to therapy and resulting loss of function. Patients who ultimately develop calcinosis are at risk for chronic loss of mobility, depending on the extent of calcium deposition. The association of dermatomyositis with malignancy seen in adults does not occur in children. Growing pains, or benign musculoskeletal pain syndrome, occur in 10% to 20% of school-age children. The peak age range is 3 to 7 years; the syndrome seems to be more common in boys than girls. There is no known etiology, although there seems to be a familial predisposition.


Pediatrics_Nelson

Pediatrics_Nelson. Children with growing pains complain of deep, crampy pain in the calves and thighs. It most typically occurs in the evening or as nocturnal pain that occasionally can waken the child from sleep. Growing pains tend to be more common in children who are extremely active; bouts are exacerbated by increased physical activity. The physical examination is unremarkable, with no evidence of arthritis or muscular tenderness or weakness. Laboratory studies or x-rays, if performed, are normal. The diagnosis of growing pains is based on a typical history and a normal physical examination. Hypermobility excludes the diagnosis. It is important to consider leukemia as a cause of nocturnal leg pain in children of this age group, so it is prudent to document a normal complete blood count.


Pediatrics_Nelson

Pediatrics_Nelson. The treatment of growing pains consists of reassurance and a regular bedtime ritual of stretching and relaxation. The pain can be relieved by massage. Some patients may benefit from a nighttime dose of acetaminophen or an analgesic dose of a nonsteroidal anti-inflammatory drug (NSAID). Occasionally nocturnal awakening has been of long duration, leading to disruptive behavior patterns. In these cases, intervention must be aimed at decreasing the secondary gain associated with nighttime parental attention and should focus on sleep hygiene. Other than the negative behavioral patterns that can occur, there are no significant complications. Growing pains are not associated with other illnesses and resolve over time. Figure 92-1 Hyperextension of the knees, an example of hypermobility.


Pediatrics_Nelson

Pediatrics_Nelson. Figure 92-1 Hyperextension of the knees, an example of hypermobility. Hypermobility syndromes are disorders of unknown etiology that cause musculoskeletal pain secondary to excessive mobility of joints. These disorders most commonly present in children 3 to 10 years of age. Girls are more commonly affected than boys. There is a familial predisposition to hypermobility syndromes. Hypermobility can be isolated to a specific joint group or can present as a generalized disorder. Symptoms vary depending on the joints involved. The most consistent symptom is pain, which may occur during the day or night. The discomfort may increase after exertion but rarely interferes with regular physical activity. Children with hypermobility of the ankles or feet may complain of chronic leg or back pain.


Pediatrics_Nelson

Pediatrics_Nelson. Joint hypermobility may be quite marked. Range of motion may be exaggerated with excessive flexion or extension at the metacarpophalangeal joints, wrists, elbows, or knees (genu recurvatum) (Fig. 92-1). There may be excessive pronation of the ankles. Hypermobility of the foot (flat foot; pes planus) is shown by the presence of a longitudinal arch of the foot that disappears with weight bearing and may be associated with a shortened Achilles tendon (see Chapter 200). These findings Touch thumb to flexor aspect of the 1 point each for right and forearm Extend fifth metacarpophalangeal 1 point each for right and joint to 90 degrees left >10 degrees hyperextension of 1 point each for right and elbow left >10 degrees hyperextension of knee 1 point each for right and left Touch palms to floor with knees 1 point straight *>6 points defines hypermobility.


Pediatrics_Nelson

Pediatrics_Nelson. Touch palms to floor with knees 1 point straight *>6 points defines hypermobility. are rarely associated with tenderness on examination. No laboratory test abnormalities are apparent, and radiographs of affected joints are normal. The diagnosis of isolated hypermobility is made on the basis of physical examination with demonstration of exaggerated mobility of a joint. Generalized hypermobility is diagnosed by the presence of sufficient criteria (Table 92-1) and the absence of evidence of other underlying disorders. Excessive skin elasticity, easy bruisability, or mitral valve prolapse suggests Ehlers-Danlos syndrome or Marfan syndrome rather than benign hypermobility.


Pediatrics_Nelson

Pediatrics_Nelson. The treatment of hypermobility consists of reassurance and regular stretching, similar to treatment for other benign musculoskeletal disorders. NSAIDs can be administered as needed but do not need to be prescribed on a regular basis. Arch supports can be helpful in children with symptomatic pes planus but are not indicated in the absence of symptoms. Benign hypermobility tends to improve with increasing age and is not associated with long-term complications.


Pediatrics_Nelson

Pediatrics_Nelson. The myofascial pain syndromes are a group of noninflammatory disorders characterized by diffuse musculoskeletal pain, the presence of multiple tender points, fatigue, malaise, and poor sleep patterns. The etiology of these disorders is unknown, although there seems to be a familial predisposition. Although these disorders sometimes follow viral infection or trauma, no causal relationship has been shown. The myofascial pain syndromes are most common in adults but can occur in children (particularly >12 years of age). The syndromes are more common in girls than in boys. The prevalence of fibromyalgia in children has been reported to be 6%.


Pediatrics_Nelson

Pediatrics_Nelson. Patients with myofascial pain syndromes complain of long-standing diffuse pain in muscles and in the soft tissues around joints that can occur at any time of day, awaken the patient from sleep, and interfere with regular activities. There is frequently a high degree of school absenteeism, despite maintaining adequate school performance. A significant percentage of patients with myofascial pain syndromes exhibit symptoms consistent with depression. An increased incidence of sexual abuse has been reported in children presenting with fibromyalgia. Physical examination is typically unremarkable with the exception of the presence of specific points that are painful—not just tender—to digital palpation. These points often are located on the neck, back, lateral epicondyles, greater trochanter, and knees. There is no evidence of arthritis or muscular weakness.


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Pediatrics_Nelson. Patients with myofascial pain syndromes frequently undergo extensive medical testing because of the concern for underlying inflammatory disease. These tests are invariably normal. Children may have a false-positive antinuclear antibody, which is found in 20% of the normal pediatric population. The diagnosis of myofascial pain syndrome is based on the presence of multiple tender points in the absence of other illness. To fulfill strict criteria for a diagnosis of fibromyalgia, the patient must have a history of diffuse pain for at least 3 months and the presence of 11 of 18 specific tender points on examination. It is important to exclude underlying inflammatory diseases, such as systemic lupus erythematosus, or the post-infectious fatigue that characteristically follows Epstein-Barr virus and influenza virus infection. Mood and conversion disorders also should be considered.


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Pediatrics_Nelson. Treatment consists of pain control, usually using NSAIDs, physical therapy, relaxation techniques, and education regarding sleep hygiene. Patients may require low doses of medications, such as amitriptyline to regulate sleep or gabapentin to reduce pain sensitivity. Education and reassurance are crucial. Because of the disability associated with myofascial pain syndromes, patients and parents frequently believe that the child has a serious underlying condition and may be resistant to reassurance. It should be emphasized that there is no simple cure, and time and perseverance are required. The long-term outcomes in the myofascial pain syndromes vary. Patients and families who focus on therapy and are positive in their approach tend to have better outcomes. Patients who demand prolonged evaluations, especially from multiple health care providers, may do more poorly. Overall children with fibromyalgia and myofascial pain syndromes have better prognoses than their adult counterparts.


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Pediatrics_Nelson. Connelly M, Schanberg L: Latest developments in the assessment and management of chronic musculoskeletal pain syndromes in children, Curr Opin Rheumatol 18:496–502, 2006 Falcini F: Kawasaki disease, Curr Opin Rheumatol 18:33–38, 2006 Feldman BM, Rider LG, Reed AM, et al: Juvenile dermatomyosítis and other idiopathic inflammatory myopathies of childhood, Lancet 371:2201–2212, Gottlieb BS, Ilowite NT: Systemic lupus erythematosus in children and adolescents, Pediatr Rev 27:323–330, 2006 Ravelli A, Martini A: Juvenile idiopathic arthritis, Lancet 369:767–778, 2007 Tizard EJ, Hamilton-Ayres MJJ: Henoch Schonlein purpura, Arch Dis Child Ed Pract 93:1–8, 2008 Matthew P. Kronman and Sherilyn Smith 16


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Pediatrics_Nelson. Tizard EJ, Hamilton-Ayres MJJ: Henoch Schonlein purpura, Arch Dis Child Ed Pract 93:1–8, 2008 Matthew P. Kronman and Sherilyn Smith 16 Overlapping clinical symptoms caused by infectious and noninfectious illnesses make the diagnosis of some diseases difficult. Clinicians are concerned that an untreated minor infection may progress to a life-threatening illness, if appropriate treatment is not given. However unnecessary treatment with antimicrobial agents may lead to a serious problem—emergence of antimicrobial resistant organisms. Accurate diagnosis of infectious and noninfectious diseases and providing specific treatment only as indicated reduce the unnecessaryuse of antibiotics. A thorough assessment of the patient, including a detailed history, complete physical examination, and appropriate diagnostic testing is the cornerstone of optimal care.


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Pediatrics_Nelson. A thorough assessment of the patient, including a detailed history, complete physical examination, and appropriate diagnostic testing is the cornerstone of optimal care. The ability to diagnose specific infections accurately begins with an understanding of the epidemiology; risk factors, including exposures to sick contacts or environmental risks (e.g., zoonosis); and age-related susceptibility reflecting the maturity of the immune system. Obtaining a thorough history and physical examination identifies most of these elements (Tables 93-1 and 93-2) and guides appropriate use of other diagnostic tests.


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Pediatrics_Nelson. Unique questions that help identify whether an infectionis causing the patient’s symptoms include a detailed environmental history (including sick contacts, travel, and animal exposure) (see Table 93-1). Certain infections are more common in specific geographic areas. For instance parasitic infections are more common in tropical climates. Diarrhea maybe bacterial, viral, or parasitic in the tropics, but in temperateclimates parasitic causes of diarrhea, other than giardiasis,are much less likely. Certain fungal infections have specificgeographic distribution (coccidioidomycosis in the southwestern United States, blastomycosis in the upper Midwest,and histoplasmosis in central United States). In other areas,fungal pneumonias are rare except in immunocompromised persons.


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Pediatrics_Nelson. An immunization history is critical for determining susceptibility to vaccine preventable diseases. Family history, especially of unexpected deaths of male infants, may suggest familial immunodeficiency (see Chapters 73 through 76). Localization of symptoms to a specific site may narrow diagnostic possibilities (see Table 93-2). A complete physical examination is essential to identify signs of infection, which may be systemic, such as fever and shock, or focal, including swelling, erythema, tenderness, and limitation of function. Many infectious diseases are associated with characteristic cutaneous signs (see Table 97-1). Accurate otolaryngologic examination is critical for diagnosing upper respiratory tract infections and otitis media, the most common childhood infectious diseases in the United States. Available @ StudentConsult.com Fever and Rash Fever without a Source Fever of Unknown Origin


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Pediatrics_Nelson. Available @ StudentConsult.com Fever and Rash Fever without a Source Fever of Unknown Origin Fever does not always represent infection. Rheumatologic disease, inflammatory bowel disease, Kawasaki disease, poisoning, and malignancy also may present with fever. Particularly, children with overwhelming infection may be afebrile or hypothermic. Common symptoms, such as bone pain or lymphadenopathy that suggest infection, may also be due to leukemia, lymphoma, juvenile idiopathic arthritis, or Kawasaki disease (see Chapters 88, 89, and 153). Acute mental status changes or focal neurologic impairment could be manifestations of infections (encephalitis, meningitis, or brain abscess) or noninfectious causes (brain or spinal tumors, inflammatory conditions, postinfectious sequelae, or impairment from toxic ingestions or inhalants). Many manifestations of mucosal allergy (rhinitis, diarrhea) may mimic common infectious diseases (see Chapter 77).


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Pediatrics_Nelson. Some infections are prone to recurrence, especially if treatment is suboptimal (inadequate antimicrobial or shorter duration). Recurrent, severe, or unusual (opportunistic) infections suggest the possibility of immunodeficiency (see Chapters 72 and 125). Laboratory diagnosis of infection includes examination of bacterial morphology using Gram stain, various culture techniques,


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Pediatrics_Nelson. Season of year Age General health Weight change Fever—presence, duration, and pattern Previous similar symptoms Previous infections and other illnesses Previous surgeries, dental procedures Preceding trauma Presence of outbreaks or epidemics in the community Exposures to infected individuals Exposures to farm or feral animals and pets Exposures to ticks and mosquitoes Sexual history, including possibility of sexual abuse Illicit drug use Transfusion of blood or blood products Travel history Daycare or school attendance Sources of water and food (e.g., undercooked meat, unpasteurized dairy products) Home sanitary facilities and hygiene Pica Exposure to soil-borne and waterborne organisms (e.g., swimming in brackish water) Presence of foreign bodies (e.g., indwelling catheters, shunt, grafts) Immunization history Immunodeficiency (chemotherapy, acquired, congenital) Current medications molecular microbiologic methods such as polymerase chainreaction, and assessment of the immune


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Pediatrics_Nelson. grafts) Immunization history Immunodeficiency (chemotherapy, acquired, congenital) Current medications molecular microbiologic methods such as polymerase chainreaction, and assessment of the immune response with antibodytiters or skin testing. The acute phase response is a nonspecificmetabolic and inflammatory response to infection, trauma, autoimmune disease, and some malignancies. Acute phase reactantssuch as erythrocyte sedimentation rate and C-reactive proteinare commonly elevated during an infection but are not specificfor infection and do not identify any specific infection. Thesetests are often used to monitor response to therapy.


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Pediatrics_Nelson. A complete blood count is frequently obtained for evidence of infection. The initial response to infection, especially in children, is usually a leukocytosis (increased number of circulating leukocytes) with an initial neutrophilic response to both bacterial and viral infections. With most viral infections, this response is transient and is followed quickly by a characteristic mononuclear response. In general, bacterial infections are associated with greater neutrophil counts than viral infections (Table 93-3). A shift-to-the-left is an increase in the numbers of circulating immature cells of the neutrophil series, including band forms, metamyelocytes, and myelocytes and indicates the rapid release of cells from the bone marrow. It is characteristic of the early stages of infection and, if sustained, bacterial infections. Transient lymphopenia at the beginning of illness and lasting 24 to 48 hours has been described with many viral infections. Atypical lymphocytes are mature T


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Pediatrics_Nelson. and, if sustained, bacterial infections. Transient lymphopenia at the beginning of illness and lasting 24 to 48 hours has been described with many viral infections. Atypical lymphocytes are mature T lymphocytes with larger, eccentrically placed, and indented nuclei classically seen with infectious mononucleosis caused by Epstein-Barr virus. Other infections associated with atypical lymphocytosis include cytomegalovirus infection, toxoplasmosis, viral hepatitis, rubella, roseola, mumps, and some drug reactions. Eosinophilia is characteristic of allergic diseases but may be seen with tissue-invasive multicellular parasites, such as the migration of the larval stages of parasites through skin, connective tissue, and viscera. High-grade eosinophilia (>30% eosinophils, or a total eosinophil count >3000/μL) frequently occurs during the muscle invasion phase


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Pediatrics_Nelson. Table 93-2 Localizing Manifestations of Infection SITE LOCALIZING SYMPTOMS LOCALIZING SIGNS* Eye Eye pain, double vision, photophobia, conjunctival discharge Periorbital erythema, periorbital edema, drainage, chemosis, limitation of extraocular movements Ear pain, drainage Red bulging tympanic membrane, drainage from ear canal Upper respiratory Rhinorrhea, sore throat, cough, drooling, stridor, Nasal congestion, pharyngeal erythema, enlarged tonsils with exudate, tract trismus, sinus pain, tooth pain, hoarse voice swollen red epiglottis, regional lymphadenopathy Lower respiratory Cough, chest pain, dyspnea, sputum Tachypnea, crackles, wheezing, localized diminished breath sounds, tract production, cyanosis intercostal retractions Gastrointestinal Nausea, vomiting, diarrhea, abdominal pain Hypoactive or hyperactive bowel sounds, abdominal tenderness (focal tract (focal or diffuse), anorexia, weight loss or generalized), hematochezia


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Pediatrics_Nelson. Liver Anorexia, vomiting, dark urine, light stools Jaundice, hepatomegaly, hepatic tenderness, bleeding diatheses, coma Genitourinary tract Dysuria, frequency, urgency, flank or Costovertebral angle or suprapubic tenderness, cervical motion and suprapubic pain, vaginal discharge adnexal tenderness Central nervous Lethargy, irritability, headache, neck stiffness, Nuchal rigidity, Kernig sign, Brudzinski sign, bulging fontanelle, focal system seizures neurologic deficits, altered mental status, coma Musculoskeletal Limp, bone pain, limited function Local swelling, erythema, warmth, limited range of motion, point bone (pseudoparalysis) tenderness, joint line tenderness *Fever usually accompanies infection as a systemic manifestation. of trichinellosis, the pulmonary phases of ascariasis and hookworm infection (eosinophilic pneumonia), and the hepatic and central nervous system phases of visceral larva migrans.


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Pediatrics_Nelson. of trichinellosis, the pulmonary phases of ascariasis and hookworm infection (eosinophilic pneumonia), and the hepatic and central nervous system phases of visceral larva migrans. Other common screening tests include urinalysis for urinary tract infections, transaminases for liver function, and lumbar puncture for evaluation of the cerebrospinal fluid if there is concern for meningitis or encephalitis (see Chapters 100 and 101). Various tests may help distinguish viral versus bacterial infection, but definitive diagnosis requires identifying the agent by culture or another test, such as polymerase chain reaction.


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Pediatrics_Nelson. Cultures are the mainstay of diagnosis of many infections. Blood cultures are sensitive and specific for bacteremia, which may be primary or secondary to a focal infection (osteomyelitis, gastroenteritis, urinary tract, and endocarditis). Urine cultures are important to confirm urinary tract infection, which may be occult in young infants. Cultures should be obtained with every lumbar puncture, aspiration, or biopsy of other fluid collections or masses. Specific types of cultures (bacterial, fungal, viral, or mycobacterial) are guided by the clinical problem. Tissue culture techniques are used to identify viruses and intracellular bacterial pathogens.


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Pediatrics_Nelson. Antibiotics often are begun before a definitive diagnosis is established, complicating the ability to rely on subsequent cultures for microbiologic diagnosis (see Chapter 95). Although persistent or progressive symptoms, despite antibiotic treatment, may indicate the need to change the regimen, more frequently this indicates the need to stop all antibiotics to facilitate definitive diagnosis by obtaining appropriate cultures. Antibiotics should not be given before obtaining appropriate cultures unless there is a life-threatening situation (e.g., septic shock). Rapid tests, such as antigen tests, are useful for preliminary diagnosis and are included in numerous bacterial, viral, fungal, and parasitic antigen detection tests. Serologic tests, using enzyme-linked immunosorbent assay or Western CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; IL, interleukin; PAF, platelet-activating factor; TNF, tumor necrosis factor.


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Pediatrics_Nelson. CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; IL, interleukin; PAF, platelet-activating factor; TNF, tumor necrosis factor. *Adenovirus and herpes simplex may cause leukocytosis and increased ESR; Epstein-Barr virus may cause petechiae and increased ESR. †Early viral (enterovirus, arbovirus) meningitis initially may have a neutrophilic pleocytosis. ‡Nuchal rigidity, bulging fontanelle, Kernig sign, Brudzinski sign. blotting, showing an IgM response, high IgG titer, or seroconversion between acute and convalescent sera, can be used for diagnosis. Molecular tests, such as polymerase chain reaction for DNA or RNA, offer the specificity of culture, high sensitivity, and rapid results. When an unusual infection is suspected, a microbiologist should be consulted before samples are obtained.


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Pediatrics_Nelson. The choice of diagnostic imaging mode should be based on the location of the findings. In the absence of localizing signs and during an acute infection, imaging of the entire body is less productive. Plain x-rays are useful initial tests for respiratory tract infections. Ultrasonography is a noninvasive, nonirradiating technique well suited to infants and children for imaging solid organs. It also is useful to identify soft tissue abscesses with lymphadenitis and to diagnose suppurative arthritis of the hip. Computed tomography (CT) (with contrast enhancement) and magnetic resonance imaging (MRI) (with gadolinium enhancement) allow characterization of lesions and precise anatomic localization and are the modalities of choice for the brain. CT shows greater bone detail, and MRI shows greater tissue detail. MRI is especially useful for diagnosis of osteomyelitis, myositis, and necrotizing fasciitis. High-resolution CT is useful for complicated chest infections. Judicious use of CT scans


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Pediatrics_Nelson. tissue detail. MRI is especially useful for diagnosis of osteomyelitis, myositis, and necrotizing fasciitis. High-resolution CT is useful for complicated chest infections. Judicious use of CT scans is important because of the longterm effects of radiation on children’s health. Contrast studies (upper gastrointestinal series, barium enema) are used to identify mucosal lesions of the gastrointestinal tract, whereas CT or MRI is preferred for evaluation of appendicitis and intra-abdominal masses. A voiding cystourethrogram may be used to evaluate for vesicoureteral reflux, a predisposing factor for upper urinary tract infections. Radionuclide scans, such as technetium-99m for osteomyelitis and dimercaptosuccinic acid for acute pyelonephritis, are often informative.


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Pediatrics_Nelson. Childhood immunization has markedly reduced the impact of major infectious diseases. Active immunization induces immunity through the administration of a vaccine or toxoid (inactivated toxin). Passive immunization includes transplacental transfer of maternal antibodies and the administration of antibody, either as immunoglobulin or monoclonal antibody.


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Pediatrics_Nelson. Vaccinations may be with live attenuated viruses (measles, mumps, rubella [MMR], varicella, nasal influenza), inactivated or killed viruses (polio, hepatitis A, intramuscular influenza), recombinant products (hepatitis B, human papillomavirus), reassortants (rotavirus), or immunogenic components of bacteria (pertussis, Haemophilus influenzae type b, Neisseria meningitidis, and Streptococcus pneumoniae), including toxoids (diphtheria, tetanus). Many purified polysaccharides are T-independent antigens that initiate B-cell proliferation without involvement of CD4 T lymphocytes and are poor immunogens in children younger than 2 years of age. Conjugation of a polysaccharide to a protein carrier induces a T-dependent response in infants and creates immunogenic vaccines for H. influenzae type b, S. pneumoniae, and N. meningitidis.


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Pediatrics_Nelson. Childhood immunization standards and recommendations in the United States (Figs. 94-1 and 94-2) are formulated by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (ACIP), the American Academy of Pediatrics, and the American Academy of Family Physicians. In the United States, due to state laws requiring immunization for school entry, approximately 95% of children entering kindergarten are vaccinated for the common infectious diseases. The ACIP recommends that children in the United States routinely receive vaccines against 16 diseases (see Fig. 94-1). This schedule includes up to 21 injections in four to five visits by 18 months of age. Children and adolescents who are at increased risk for pneumococcal infections should receive the pneumococcal polysaccharide vaccine, as well. Children who are behind in immunization should receive catch-up immunizations as rapidly as feasible. Infants born prematurely, regardless of birth weight,


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Pediatrics_Nelson. polysaccharide vaccine, as well. Children who are behind in immunization should receive catch-up immunizations as rapidly as feasible. Infants born prematurely, regardless of birth weight, should be vaccinated at the same chronologic age and according to the same schedule as full-term infants and children (see Fig. 94-2). The single exception to this practice is providing hepatitis B vaccine for infants weighing less than 2000 g if the mother is hepatitis B virus surface antigen (HBsAg)-negative at 1 month instead of at birth. Vaccines for adolescents should be given at 11 to 12 years of age (see Fig. 94-1), with completion of any vaccine series at 13 to 18 years of age and a booster for N. meningitidis at 16 years of age.


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Pediatrics_Nelson. Vaccines should be administered after obtaining informed consent. The National Childhood Vaccine Injury Actrequires that all health care providers provide parents or patients with copies of Vaccine Information Statements prepared by the Centers for Disease Control and Prevention ( http://www.cdc.gov/vaccines/pubs/vis/default.htm ) before administering each vaccine dose. Most vaccines are administered by intramuscular or subcutaneous injection. The preferred sites for administration are the anterolateral aspect of the thigh in infants and the deltoid region in children and adults. Multiple vaccines can be administered simultaneously at anatomically separate sites (different limbs, or separated by >1 in.) without diminishing the immune response. MMR and varicella vaccines should be administered simultaneously or more than 30 days apart. Administration of blood products and immunoglobulin can diminish response to live virus vaccines if administered before the recommended interval.


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Pediatrics_Nelson. General contraindications to vaccination include serious allergic reaction (anaphylaxis) after a previous vaccine dose or to a vaccine component, immunocompromised states or pregnancy (live virus vaccines), and moderate or severe acute illness with or without fever. History of anaphylactic-like reactions to eggs is a contraindication to influenza and yellow fever vaccines, which are produced in embryonated chicken eggs. Current preparations of measles and mumps vaccines, which are produced in chick embryo fibroblast tissue culture, do not contain significant amounts of egg proteins and may be administered without testing children with history of egg allergy. Mild acute illness, with or without fever, convalescent phase of illness, recent exposure to infectious diseases, current antimicrobial therapy, breastfeeding, mild to moderate local reaction or low-grade to moderate fever after previous vaccination, and history of penicillin or other nonvaccine allergy or receiving allergen


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Pediatrics_Nelson. therapy, breastfeeding, mild to moderate local reaction or low-grade to moderate fever after previous vaccination, and history of penicillin or other nonvaccine allergy or receiving allergen extract immunotherapy are not contraindications to immunization.


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Pediatrics_Nelson. Severe immunosuppression resulting from congenital immunodeficiency, human immunodeficiency virus (HIV) infection, leukemia, lymphoma, cancer therapy, or a prolonged course of high-dose corticosteroids (>2 mg/kg/day for >2 weeks) predisposes to complications and is a contraindication for live virus vaccines. For HIV-infected children who do not have evidence of severe immunosuppression, MMR vaccination is recommended at 12 months of age with a second dose 1 month later rather than waiting until 4 to 6 years of age. Varicella vaccine is contraindicated for persons with cellular immunodeficiency but is recommended for persons with impaired humoral immunity (hypogammaglobulinemia or dysgammaglobulinemia) and at 12 months of age for HIV-infected children without evidence of severe immunosuppression, given as two doses 3 months apart.


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Pediatrics_Nelson. The National Childhood Vaccine Injury Act requires that clinically significant adverse events after vaccination be reported to the Vaccine Adverse Event Reporting System (VAERS) ( http://www.vaers.hhs.gov or (800) 822-7967). Suspected cases of vaccine-preventable diseases should be reported to state or local health departments. The act also established the National Vaccine Injury Compensation Program, a no-fault system in which persons thought to have suffered an injury or death as a result of administration of a covered vaccine can seek compensation. Prophylaxis may include antibiotics, immunoglobulin or monoclonal antibody, vaccine, alone or in combination; they may be used postexposure, for perinatal exposure, and preexposure for persons at increased risk for infection. Primary prophylaxis is used to prevent infection before a first occurrence. Secondary prophylaxis is used to prevent recurrence after a first episode.


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Pediatrics_Nelson. Primary prophylaxis to all contacts of index cases of N. meningitidis infection should be administered as soon as possible (see Chapter 100). Prophylaxis is recommended for all household contacts, especially young children; child care or nursery school contacts in the previous 7 days; for direct exposure to the index patient’s secretions through kissing or sharing of toothbrushes or eating utensils; and for mouth-to-mouth resuscitation or unprotected contact during endotracheal intubation within 7 days before onset of illness. Prophylaxis is also recommended for contacts who frequently sleep or eat in the same dwelling as the index patient or passengers seated directly next to the index case during airline flights lasting longer than 8 hours. Chemoprophylaxis is not recommended for casual contacts with no history of direct exposure to the patient’s oral secretions (school or work mate), indirect


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Pediatrics_Nelson. Recommended immunization schedule for persons aged 0 through 18 years – 2013. (FOR THOSE WHO FALL BEHIND OR START LATE, SEE THE CATCH-UP SCHEDULE [FIGURE 94-2]). These recommendations must be read with the footnotes that follow. For those who fall behind or start late, provide catch-up vaccination at the earliest opportunity as indicated by the green bars in Figure 94-1. To determine minimum intervals between doses, see the catch-up schedule (Fig. 94-2). School entry and adolescent vaccine age groups are in bold.