Treatment Of Adult-onset Still's Disease Research Articles

Index of Suspicion

An 18-year-old girl presents with nighttime fevers to 39°C for 8 days. She complains also of headache, myalgia, and rash during the fevers. Eighteen days ago, she removed a tick from her neck after attending a festival in the northeastern United States. One week ago, she presented to her pediatrician with a sore throat and rash. She was hyponatremic (sodium, 129 mEq/dL) and was started on doxycycline for presumed Rocky Mountain spotted fever (RMSF). Her condition has not improved. She admits to multiple unprotected sexual encounters and cocaine abuse. The girl appears weak. Her vital signs include temperature of 38.7°C; heart rate, 84 beats per minute; respiratory rate, 20 breaths per minute; and blood pressure, 113/73 mm Hg. A salmon-colored macular rash is present on her trunk and proximal extremities. She also exhibits dermatographia. There are no mucosal lesions. The liver is enlarged to 2.5 cm beyond the rib margin, and she has right upper quadrant tenderness. Her muscles are tender to deep palpation in all four extremities. She is able to bear weight but refuses to ambulate due to bilateral lower extremity myalgia and arthralgia. A CBC demonstrates a normochromic, normocytic anemia, and leukocytosis with a left shift. ESR and CRP are elevated at 109 mm/hour and 19.8 mg/dL, respectively. A mild transaminitis is present. Ultrasonography reveals a mildly enlarged and echogenic liver. Small pleural and pelvic effusions are present on CT scan. A bone marrow biopsy and a glycosylated ferritin fraction are obtained. A clinical diagnosis is made. An 11-year old Hispanic boy who had poststreptococcal reactive arthritis (PSRA) and rheumatic fever (RF) diagnosed at age 6 years has been symptom-free while taking oral penicillin (PCN). Two months ago, he developed lemon-sized, reddish, painful subcutaneous nodules that were warm to touch on both lower extremities and revealed acute …

Etanercept-refractory adult-onset Still’s disease with thrombotic thrombocytopenic purpura successfully treated with tocilizumab

We report the case of a 69-year-old Japanese woman who presented with thrombotic thrombocytopenic purpura (TTP) which had manifested soon after the onset of adult-onset Still's disease (AOSD). Her disease was multi-drug resistant. She had undergone treatment with high-dose glucocorticoids, two courses of steroid pulse therapy, and cyclosporine A. The patient initially had a favorable response to the administration of etanercept (an anti-tumor necrosis factor agent) and glucocorticoids. However, her disease became refractory to etanercept after 6 months. Therefore, we administered tocilizumab (a humanized monoclonal anti-IL-6 receptor antibody) which dramatically improved the patient's refractory AOSD with TTP. This is the first report of an effective treatment for AOSD with TTP using the biological agents. Our report strongly suggests that biological agents, especially a humanized monoclonal anti-IL-6 receptor antibody, may be a new option for a safe and effective treatment of multi-drug-resistant AOSD and TTP associated with AOSD.

Clarithromycin in adult-onset Still’s disease: a study of 6 cases

Adult-onset Still's disease (AOSD) is a rare rheumatological condition characterized by an acute systemic involvement. There are no treatment guidelines. Glucocorticoids (GC), methotrexate (MTX), cyclosporin A and biologic agents have been successfully used, often in association. We treated six cases of AOSD with clarithromycin (CM) in combination with low-mild dose of GC and MTX. Four of them were not responsive to high-dose GC added to DMARDs, while two of them were treated with low-mild dose of GC added to CM from the beginning. CM, 500 mg b.i.d., was added to a mild-low dose of GC and to MTX. The dose of the drugs was reduced (and stopped where possible) following clinical and laboratory parameters. ACR criteria were used to assess clinical improvement. At 6 months 5 patients reached ACR 70% and could stop any therapy in 6-18 months; 1 continued chronic therapy with low-dose GC added to CM and MTX to maintain ACR 50%. CM can be a useful drug for the treatment of AOSD, even in patients not responsive to high-dose GC and DMARDs. No definitive conclusion can be drawn based on the present study.

Pathogenesis and Management of Adult-Onset Still’s Disease

To review recent literature regarding the pathogenesis and treatment of adult-onset Still's disease (AOSD). We searched MEDLINE and PUBMED from 1971 to present using the following terms: adult-onset Still's disease, AOSD, or adult Still's disease. In addition we manually retrieved relevant abstracts from recent American College of Rheumatology and European League Against Rheumatism meetings. The etiology of AOSD, a rare, immune-mediated, multisystem inflammatory disorder characterized by quotidian spiking fevers, evanescent rash, and arthritis, remains unknown. An infectious etiology has been postulated, although a definitive agent has yet to be identified. Cytokines, such as interleukin (IL)-1, IL-6, interferon (IFN)-gamma, and tumor necrosis factor-alpha, are elevated in patients with AOSD. IL-18 and macrophage-colony stimulating factor also seem to play a role. Treatment historically consisted of nonsteroidal antiinflammatory drugs, often in combination with low-dose corticosteroids. Immunosuppressants (mainly methotrexate, but also intramuscular gold, azathioprine, cyclosporine A, leflunomide, and cyclophosphamide) and intravenous gamma-globulin are efficacious and have been used as steroid-sparing drugs. The recently reported use of anticytokine (anti-TNF-alpha, anti-IL-1, and anti-IL-6) agents in refractory cases has opened new horizons in the treatment of AOSD and provided important clues for its pathophysiology. Advances in immunology have enhanced our understanding of the role of cytokines in AOSD pathogenesis. Early, promising studies of anticytokine agents in AOSD may provide further insight into the pathogenetic mechanisms of this complex disease.

Leflunomide and Azathioprine Combination in Refractory Adult-Onset Still's Disease

To present a case of Adult-onset Still's disease (ASD) in a patient who was successfully treated with leflunomide and azathioprine. A 24-year-old woman with ASD was initially treated with indomethacin, corticosteroids, and hydroxychloroquine; there was no clinical improvement. Methotrexate was added to the regimen, followed by azathioprine. The patient still experienced disease flares with this treatment, and cyclophosphamide was started. However, because of persisting disease activity, leflunomide combined with azathioprine was given. Only on this regimen was complete disease control achieved, with a normal erythrocyte sedimentation rate as well as normal C-reactive protein and ferritin levels. No recurrences or adverse effects attributable to leflunomide or azathioprine were observed at the one-year follow-up. Clinical experience concerning leflunomide and azathioprine combination in ASD is limited. This combination may be modifying the clinical expression of ASD through its effects on T lymphocyte clonal expansion and production of proinflammatory cytokines. Leflunomide combined with azathioprine appears to be an effective and safe treatment of ASD.