Chapter 12. Rheumatology

Clinical Summary

Kawasaki disease (KD; also known as mucocutaneous lymph node syndrome) is an immune-mediated disorder of unknown etiology that occurs in genetically predisposed children leading to endothelial cell injury and vasculitis of mainly medium-sized arteries (predilection for coronary arteries). Small arterioles, larger arteries, capillaries, and veins are affected to a lesser extent. KD occurs in all ethnic groups; however, incidence is highest in East Asia and in children of Asian descent. Clinical and epidemiologic features strongly support an infectious etiology. About 80% of patients are <5 years of age (peak: between 18 and 24 months); about 90% of patients are <8 years. There is no specific test for KD; diagnosis is based on clinical criteria summarized in Table 12.1. Other findings include extreme irritability, aseptic meningitis (50%), urethritis (sterile pyuria, 70%), hepatic dysfunction (40%), hydrops of gallbladder, diarrhea, vomiting, abdominal pain, arthritis, or arthralgia (knees, ankles, hips), uveitis, pneumonitis, testicular swelling, peripheral gangrene, erythema, or induration at bacille Calmette-Guérin inoculation site.

Incomplete Kawasaki disease refers to KD with incomplete clinical manifestations and occurs more commonly in young infants than in older children. Incomplete KD is the preferred term over atypical KD as these patients do not have any atypical features, but they lack sufficient signs to fulfill the diagnosis of KD. Laboratory findings are similar in both classic and incomplete KD.

Emergency Department Treatment and Disposition

Obtain CBC (normal to elevated WBC count with a predominance of polymorphonuclear leukocytes and normocytic anemia), ESR and C-reactive protein (usually elevated), liver enzymes (elevated with hypoalbuminemia), and urinalysis (sterile pyuria and proteinuria). If clinically indicated, perform a lumbar puncture; cerebrospinal fluid will show mild pleocytosis with normal glucose and usually normal protein. Obtain chest radiograph to look for cardiomegaly and an ECG for evidence of myocarditis, pericarditis, or arrhythmias. Admit patients with clinical diagnosis of KD or incomplete KD for continuous cardiac monitoring and treatment that includes intravenous immune globulin (IVIG; given as a single dose over 8–12 hours) and anti-inflammatory dose aspirin (given until patient is afebrile for at least 3–4 days) followed by antithrombotic dose (given until platelet count, ESR and ECHO are normal). Low-dose aspirin therapy is continued indefinitely if a coronary artery abnormality is detected. Consult cardiology on admission. Patients need a 2-dimensional ECHO at baseline and during subsequent follow-ups.

Pearls

1. KD is a leading cause of acquired heart disease in children.

2. Administration of IVIG in the acute phase (within 10 days of onset of fever) significantly reduces the prevalence of coronary artery dilation and aneurysms.

3. Perineal desquamation seen within the first week of illness in a highly febrile infant or child is an important early diagnostic clue.

4. Significant thrombocytosis (platelet count up to 1 million) occurs in the second week of illness.

5. Diagnosis is often delayed in young infants (incomplete KD) and in older children leading to higher prevalence of cardiovascular complications.

6. Consider incomplete KD in any infant with prolonged and unexplained fever lasting for >5 days even in the absence of other clinical criteria. Prolonged fever may be the sole manifestation of KD in infants.

7. Leukopenia and a normal ESR in an infant or child with fever, rash, and red eyes does not suggest a laboratory profile compatible with KD (suggests a viral infection).

8. Acute adenoviral infection shares many features of KD. Purulent conjunctivitis and exudative pharyngitis suggests adenoviral infection, whereas perineal desquamation, extremity changes, and sterile pyuria suggest KD.

9. Exudative conjunctivitis, Koplik spots, cough, and rash starting on face behind the ears, becoming confluent, and fading with a brownish hue suggest measles. KD rash is most prominent on the trunk and extremities and fades abruptly without residua. Perineal desquamation is also not seen in measles.

Clinical Summary

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of unknown etiology, characterized by production of autoantibodies and protean clinical manifestations. There is genetic predisposition making the disease more common and severe in African Americans, Latinos, and Asian Americans. Environmental (sunlight exposure) and hormonal factors also play a role. There is female predominance (9:1 female-male) and onset is usually after puberty, with peak incidence between 11 and 13 years of age. Exposure to exogenous estrogens (eg, oral contraceptive pills or hormone replacement therapy) increases the risk of developing lupus. Certain drugs can lead to drug-induced SLE (eg, isoniazid, hydralazine). Morbidity is related to nephritis, antiphospholipid antibody syndrome, infections, and therapeutic complications.

Emergency Department Treatment and Disposition

Obtain CBC with differential, platelet count, ESR, comprehensive metabolic panel, serum complements C3 and C4 (commonly reduced, especially with renal lupus), and urinalysis. If clinically indicated, obtain ECG (pericarditis) and a chest radiograph to look for cardiomegaly due to pericardial effusion or pleural effusion. Immunologic tests include ANA, anti-double-stranded DNA (anti-dsDNA), antibodies to Sm nuclear antigen (anti-Sm), and antiphospholipid antibodies.

Admit all patients with nephritis, pericarditis, central nervous system (CNS)-lupus, and those with complications of therapy such as infection with neutropenia. Consult rheumatology and nephrology as appropriate. Refer stable patients to a pediatric rheumatologist for long-term management. Treatment options include nonsteroidal anti-inflammatory drugs, antimalarial drugs (eg, hydroxychloroquine), and immunosuppressive agents (eg, cyclophosphamide or azathioprine) and systemic corticosteroids.

Pearls

1. The most common clinical presentations of SLE are cutaneous, renal, and joint. Consider SLE in the differential diagnosis of many signs and symptoms ranging from fevers of unknown origin to arthralgia, anemia, and nephritis.

2. Psychosis and seizures are the most common CNS manifestations.

3. Pericarditis is the most common cardiac manifestation.

Clinical Summary

Neonatal lupus (NL) is caused by transplacental passage of maternal autoantibodies to the fetus and is characterized by skin lesions and/or congenital heart block (CHB) (prolongation of PR interval to complete heart block). The majority of antibodies are maternal IgG anti-Ro (also known as SSA) and/or anti-La (also known as SSB). About 50% of mothers with babies with NL have clinical features of either Sjögren syndrome or SLE, whereas 50% of women are asymptomatic. Skin lesions occur in about 50% of affected infants and are either present at birth or appear within 4 months of age and may be precipitated by sun exposure. Erythematous annular or elliptical macules with slight central atrophy and raised active margins are seen in the periorbital region (most common distribution), scalp, trunk, extremities, neck, and intertriginous areas. Lesions disappear in 6 to 8 months (with disappearance of autoantibodies) usually without scarring or atrophy. Complete heart block may be diagnosed in utero or at birth and infant may be asymptomatic, may require pacemaker, or develop signs of congestive heart failure. Neonatal carditis and late-onset dilated cardiomyopathy may also develop in these infants. Other findings of NL include anemia, leukopenia, thrombocytopenia, hepatomegaly, and cholestatic hepatitis. Infants with NL are at risk of developing other autoimmune diseases during childhood or adolescence.

Emergency Department Treatment and Disposition

Obtain CBC with differential and platelet count, chest radiograph, and ECG. Additional tests include anti-Ro/SSA (seen in about 95% of NL), anti-La/SSB (seen in 70% of NL), and antinuclear antibody (may be positive). Admit all symptomatic infants (eg, those with CHB or signs of CHF) for further management. Refer asymptomatic patients to cardiology for follow-up and to dermatology, if the diagnosis is unclear. For cutaneous lesions, sunscreen, protective clothing, and mild topical corticosteroids may be used. Refer the mother to a rheumatologist for the workup for SLE or other connective tissue disease.

Pearls

1. The skin lesions of NL are benign and self-resolve. The most serious manifestation is CHB, which is permanent. Both skin lesions and CHB are seen together in ˜10% of patients.

2. Periorbital “owl-eye” appearance of the facial rash is an important clue for the diagnosis.

3. The NL rash is often misdiagnosed as seborrheic or atopic dermatitis, psoriasis, or tinea (faciei or corporis).

4. The presence of anti-Ro/SSA antibodies in the infant and mother confirms the diagnosis of NL.

Clinical Summary

Raynaud phenomenon (RP; also known as Raynaud syndrome) is an exaggerated vasospastic response most commonly affecting the arterioles of the hands. RP is classified as primary when there is no underlying cause or secondary when it is associated with systemic disease (eg, SLE, scleroderma, polymyositis/dermatomyositis, rheumatoid arthritis, mixed connective tissue disease, Sjögren syndrome). Primary RP is more common and seen in girls more often than boys. Physical examination is normal between attacks. Secondary RP may be associated with typical findings of underlying disease. Diagnosis is made by a history of well-demarcated digital discoloration induced by cold exposure. Differential diagnosis of RP includes acrocyanosis (usually painless, persistent cyanosis of distal extremities due to exaggerated vasomotor response that can occur at any age), chilblains (spasm-induced vessel and tissue damage, episodic color changes after exposure to cold, presence of nodules), and frostbite (see Figures 8.5, 8.6, 8.7, and 8.8).

Emergency Department Treatment and Disposition

Obtain CBC, electrolytes, blood urea nitrogen, creatinine, ESR, and urinalysis. Refer patient to rheumatology for further diagnostic workup if secondary RP is suspected. Educate patients to avoid triggers including cold exposure, cessation of smoking, and behavioral therapy for stress management. Admit patient with severe signs and symptoms requiring emergent intervention. Therapeutic options include calcium channel blockers (eg, nifedipine), α1-adrenergic blockers (eg, prazosin), pentoxifylline, captopril, and topical nitroglycerin.

Pearls

1. Patients with RP classically describe triphasic color changes in the digits; however, not every patient has all three phases.

2. Ulcerations and small areas of digital gangrene can be seen in severe cases.

Clinical Summary

Lyme disease (Borreliosis or Lyme borreliosis) is a spirochetal infection transmitted by ticks infected with Borrelia species (B burgdorferi in the United States; B burgdorferi, B afzelii, and B garinii in Europe and Asia). There is a biphasic peak of incidence in children 2 to 15 years old and adults 30 to 55 years old. The most characteristic manifestation is erythema migrans (˜90% of children). Multiple lesions are cutaneous markers of disseminated disease resulting from hematogenous spread of spirochete. Acute peripheral facial palsy is the most frequent manifestation of neuroborreliosis in childhood and bilateral facial palsy is pathognomonic. Varying degrees of AV block (first-, second-, or third-degree) are the most frequent manifestation of Lyme carditis. Diagnosis is made clinically (see Table 12.5).

Emergency Department Treatment and Disposition

Remove any still attached ticks promptly; Transmission of B burgdorferi requires attachment for >48 hours). Do not squeeze the body of the tick during removal. Grasp the tick with a pair of fine tweezers as close to the skin as possible and remove the tick by gently pulling straight out, and not with a twisting motion. Protect the fingers with gloves or tissue and wash thoroughly after tick removal.

Routine laboratory tests are rarely useful in making the diagnosis. Obtain CBC (normal or elevated WBC), ESR (usually elevated), and ECG, if clinically indicated. In patients with meningitis, cerebrospinal fluid examination shows mild pleocytosis with predominance of lymphocytes (aseptic meningitis). An enzyme-linked immunosorbent assay (ELISA) is the most common initial serologic test used to support the diagnosis (false-positive ELISA testing occurs with other Borrelial or spirochetal diseases). Positive Western blot tests in patients with positive or equivocal ELISA tests confirm the diagnosis.

Admit patients with meningitis, encephalitis, carditis, or arthritis after consultations with rheumatology, cardiology, neurology, as clinically indicated. Refer to the guidelines published by the American Academy of Neurology and the Infectious Diseases Society of America for the treatment of Lyme disease in the United States and refer to primary care physician for follow-up.

Pearls

1. Lyme disease is the most common vector-borne disease in the United States and Europe.

2. Prophylactic antibiotics are not indicated after tick bite.