Systemic Onset Juvenile Idiopathic Arthritis

AUTHORS: Shahnawaz Amdani, MD; Sonali Malhotra, MD; Aditya Badheka, MD; Vivekananda Dasari, MD; Yuly Carreras, MD; Magda Mendez, MD; Yekaterina Sitnitskaya, MD; and Elita Gose-Balakrishnan, MD Lincoln Medical and Mental Health Center, Bronx, New York CITATION: Amdani S, Malhotra S, Badheka A, et al. Systemic onset juvenile idiopathic arthritis. Consultant for Pediatricians. 2013;12(6):281-282.   A 12-month-old girl presented to the emergency department with 10-day history of fever and a waxing and waning polymorphous rash (A). On arrival, her temperature was 37.9°C (100.3°F), heart rate was 175 beats per minute, respiratory rate was 32 breaths per minute, and oxygen saturation was 99% on room air. Physical examination revealed a generalized, macular, blanching, erythematous rash. The girl did not appear toxic, and no evidence of organomegaly or serositis was present. Results of a complete blood count showed leukocytosis, with neutrophilia and thrombocytosis. The C-reactive protein (CRP) level was elevated at 75 mg/L, and the erythrocyte sedimentation rate was elevated at 90 mm/hour. Results of electrocardiography and chest radiography were normal. During her hospital stay, the patient remained febrile, experiencing 2 to 3 fever spikes per day with a maximum temperature of 39.3°C (102.8°F). She was given cefuroxime and azithromycin for 48 hours pending urine and blood culture results, which eventually returned negative. Because of the girl’s prolonged fever without obvious focus, the waxing and waning rash, and the swelling of her hands and feet, echocardiography was done to rule out Kawasaki disease (KD); the results were normal. To rule out a viral or bacterial exanthem, serology tests were performed, including for Epstein-Barr virus, cytomegalovirus, parvovirus, and Mycoplasma pneumoniae; all results were negative. Results of lactate dehydrogenase and uric acid tests, done to rule out malignancy, also were normal. A rheumatology workup, including antistreptolysin O antibodies, antinuclear antibodies, and rheumatoid factor, yielded negative results. On hospital day 6 (fever day 17), her CRP level still was elevated at 90 mg/L. Dermatology was consulted. A skin punch biopsy was done, which showed perivascular and interstitial dermatitis with lymphocytes and neutrophils (B and C), findings suggestive of systemic-onset juvenile idiopathic arthritis (SJIA). The patient was then transferred to a medical center at which rheumatology services were available. After transfer, the girl’s fever continued to spike; intravenous immunoglobulin (IVIG) was administered, to which the patient responded very minimally, with low-grade fever spikes continuing. After IVIG therapy failure, the girl was started on anakinra (an interleukin-1 receptor blocker) and aspirin, after which the fever started to abate. SJIA (Still disease) is an important cause of morbidity and mortality among children with rheumatic diseases. Although it accounts for only 10% to 20% of cases of juvenile idiopathic arthritis (JIA), it contributes to more than two-thirds of the mortality seen with JIA.1 SJIA in children younger than 16 years of age is associated with a quotidian fever spiking to 39°C (102.2°F) or higher, with rapid return to normal or subnormal temperature, that persists for more than 2 weeks, along with at least one of the following clinical features of systemic inflammatory origin: an evanescent rash, lymphadenopathy, hepatosplenomegaly, or serositis (eg, pleuritis, pericarditis). Many children with SJIA have frequent relapses or persisting systemic disease activity, along with the risk of significant chronic morbidity, including joint destruction, chronic pain with motion, immobilization, significant growth retardation, and severe infections. Secondary macrophage activation syndrome (MAS) is a well-known complication of SJIA.2 SJIA often cannot be easily distinguished from incomplete KD in infants. Neither KD nor SJIA has diagnostic laboratory tests. Both conditions have similar laboratory findings of elevated CRP levels, leukocytosis, thrombocytosis, and anemia. Moreover, the initial presentation of SJIA appears consistent with the diagnosis of incomplete KD—prolonged fever and erythematous rash are common findings in both conditions. Incomplete KD is more common than SJIA in infants; hyperferritinemia is more common in patients with SJIA than with KD. A history of inflammatory joint pain is an important clinical sign for establishing a diagnosis of SJIA.3 In cases of prolonged fever and rash in children, SJIA should be on the list of differential diagnoses.4  REFERENCES: Ramanan AV, Schneider R, Batthish M, et al. Developing a disease activity tool for systemic-onset juvenile idiopathic arthritis by international consensus using the Delphi approach. Rheumatology (Oxford). 2005;44(12):1574-1578. Avcin T, Tse SM, Schneider R, Ngan B, Silverman ED. Macrophage activation syndrome as the presenting manifestation of rheumatic diseases in childhood. J Pediatr. 2006;148(5):683-686. Rigante D, Valentini P, Onesimo R, et al. Incomplete Kawasaki syndrome followed by systemic onset-juvenile idiopathic arthritis mimicking Kawasaki syndrome. Rheumatol Int. 2010;30(4):535-539. Yeh TL, Huang FY, Shyur SD, Chen TL, Lee CS, Huang DT. Juvenile idiopathic arthritis presenting with prolonged fever. J Microbiol Immunol Infect. 2010;43(3):169-174.