A 19-year-old previously healthy male adolescent presents to our hospital with polyarthralgia, fatigue, and a 4.4-lb (2-kg) weight loss during the previous month, as well as 2 weeks of night sweats and quotidian fevers (up to 101.9 °F 38.8 °C).Symptoms first began a month earlier with sore throat, a palpable cervical lymph node, fatigue, bilateral lower extremity myalgias, and a diffuse erythematous, blanching maculopapular rash involving the trunk, extremities, and palms but sparing the soles of his feet. On presentation to an outside hospital within a few days of initial symptoms, a complete blood cell count, comprehensive metabolic profile, creatine kinase (CK) level, and urinalysis were normal. A heterophile antibody screen and influenza rapid test were negative. He received intravenous fluids and dexamethasone for presumed viral syndrome, with improved throat pain before discharge. During the following 2 weeks, his lymphadenopathy resolved, but he began having migratory joint pain, night sweats, and quotidian fevers. He returned to the emergency department 10 days later, where he was found to be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive via polymerase chain reaction (PCR) testing, and symptoms were attributed to an acute viral illness. Chest radiography did not show any pulmonary infiltrates or other cardiopulmonary abnormalities, and CK level was again within normal limits. Symptoms continued to worsen during the following 2 weeks to include difficulty ambulating, bilateral knee pain and swelling, pleuritic sternal chest pain, shortness of breath, and intermittent left jaw and bilateral forehead tingling, at which point he presented to our hospital. There was no recent travel or animal exposure in the months preceding presentation.On examination, he is tired but well-appearing. He is tachycardic (heart rate, 107 beats/min), with otherwise normal vital signs, including a temperature of 99.1 °F (37.3 °C). Cardiopulmonary and abdominal examination findings are normal. Musculoskeletal examination is significant for nonreproducible chest pain, mild tenderness to palpation of bilateral elbows and left knee, significant pain to palpation of the medial aspect of his right knee joint with mild effusion, and pain with active and passive range of motion of bilateral elbows and knees. Neurologic examination elicits normal mentation, deep tendon reflexes, and sensation; 5/5 strength in all extremities; and an antalgic gait. He has mild bilateral submandibular lymphadenopathy. There are no rashes.The patient is admitted to the hospital medicine service. Laboratory evaluation initiated in the emergency department reveals the following values: an elevated white blood cell count of 32 000/μL (32 × 109/L) (reference range RR, 3910–8,770/μL 3.91–8.77 × 109/L) with 80% neutrophil predominance; platelet count, 798 × 103/μL (798 × 109/L) (RR, 151–304 × 103/μL 151–304 × 109/L); alanine aminotransferase, 72 U/L (1.20 μkat/L) (RR, 19–49 U/L 0.32–0.82 μkat/L); aspartate aminotransferase, 24 U/L (0.40 μkat/L) (RR, 10–26 U/L 0.17–0.43 μkat/L); albumin, 2.5 g/dL (25 g/L) (RR, 3.8–5.6 g/dL 38–56 g/L); C-reactive protein, 12.11 mg/dL (121.1 mg/L) (RR, 80% polymorphonuclear neutrophils).5 Fever classically occurs once or twice daily, spiking to greater than 102.2 °F (>39 °C). Arthralgia or arthritis often begins as transient pain in the ankles, wrists, and feet, gradually becoming more persistent.5,6 More than half of patients experience macular or maculopapular salmon-pink rash and elevated ferritin levels.2,4 Less common symptoms and laboratory features include myalgias, weight loss, sore throat, abdominal pain, splenomegaly, lymphadenopathy, pericarditis, pleurisy, mildly to moderately elevated transaminase levels, and anemia.5,7 Levels of IL-18, a proinflammatory cytokine, are overproduced in AOSD.8As a diagnosis of exclusion,7 evaluation is directed at eliminating other etiologies. Serologies, PCR tests, and blood cultures can be used to eliminate viruses (EBV, CMV, human immunodeficiency virus), bacteria (Borrelia, mycoplasma, syphilis, gonorrhea, chlamydia), and infectious endocarditis.4 CT, positron emission tomography, or lymph node or bone marrow biopsy may be used to evaluate for suspected oncologic processes.5,7 Rheumatoid factor and ANAs are 2 widely accessible, although nonspecific, markers of lupus and rheumatoid arthritis.5,7Control of systemic inflammation is the mainstay of treatment, with different approaches tailored to illness severity. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as naproxen or ibuprofen, can be trialed for symptomatic relief while undergoing diagnostic evaluation, although 80% of patients with AOSD do not respond to these agents.9 First-line treatment for AOSD includes glucocorticoids and disease-modifying antirheumatic drugs.6 Although glucocorticoids result in remission for 65% of patients, the adverse effects are undesirable when used long-term and can mask oncologic processes if the diagnosis remains unclear.6 In patients for whom first-line treatments do not improve symptoms or cause intolerable adverse effects, IL-1 inhibitors such as anakinra or canakinumab are used.6,10In consultation with pediatric rheumatology, infectious disease, and oncology, a trial of scheduled naproxen was unsuccessful, yielding minimal improvement in fevers, night sweats, and pain. Antibiotics and corticosteroids were held while an evaluation was completed and laboratory markers for inflammation and macrophage activation syndrome, a known complication of AOSD, were monitored daily. Because symptoms were refractory to initial management with NSAIDs and the ferritin level was rapidly rising (peaking at 4008 ng/mL 4008 μg/L; RR, 10–244 ng/mL 10–244 μg/L) (Figure 1), the decision was made to initiate daily anakinra treatment. Symptoms improved dramatically over 1 week, and he was discharged on canakinumab, a once-monthly injection, to allow for ease of administration while in college. One week after discharge, his IL-18 level returned at greater than 23 000 pg/mL (RR, 89–540 pg/mL), further supporting his diagnosis. He was able to return to competitive collegiate basketball 2 months after symptoms began, 2 weeks after initiating anakinra, with minimal musculoskeletal pain, managed with NSAIDs as needed. Since diagnosis 15 months ago, he has had no relapses and sees rheumatology every 6 months.Adult-onset Still disease is a rare rheumatologic condition thought to exist along the same clinical continuum as systemic juvenile idiopathic arthritis and has a bimodal distribution of age at presentation (16–25 years and 36–46 years).Adult-onset Still disease is a clinical diagnosis of exclusion after infectious, oncologic, and other rheumatologic causes are ruled out. Although no specific diagnostic criteria exist, the classic symptom triad includes fever, arthralgia or arthritis, and rash.Disease management focuses on control of systemic inflammation. Mild to moderate disease can be treated with glucocorticoids or traditional disease-modifying antirheumatic drugs, such as methotrexate. Severe disease often requires interleukin-1 inhibitors, such as anakinra or canakinumab.
Gelin et al. (Wed,) studied this question.