Pregnancy outcome in patients with adult onset Still's disease

Pregnancy outcome of patients with adult onset Still's disease (AOSD) has not been addressed. We report the maternal and fetal morbidity of 5 pregnancies from 3 Chinese patients with AOSD and review another 17 pregnancies from 14 patients reported in the English literature. Nine patients had their first manifestation in the 5th to 6th gestational month. Disease relapse in patients with known AOSDoccurred most commonly in the post-partum period. Most did not respond satisfactorily to nonsteroidal antiinflammatory agents alone, but responded to administration of corticosteroids, especially in high doses.     

Bone marrow findings in patients with adult Still's disease

OBJECTIVE: Peripheral neutrophilia is one of characteristic laboratory findings in patients with adult Still's disease (ASD). We performed this study to identify the bone marrow findings in patients ASD. METHODS: We examined 12 bone marrow biopsy specimens from patients with ASD. RESULTS: The most frequent finding was granulocyte hyperplasia (12/12, 100%) and hypercellularity was observed in 75.0% (8/12) of patients. Plasmacytosis was present in 8.3% (1/12) of specimens. Histiocytosis and reactive hemophagocytosis were found in 25.0% (4/12) and in 16.7% (2/12) respectively. CONCLUSION: Our results show that bone marrow granulocyte hyperplasia is the main possible mechanism for peripheral neutrophilia and that histiocytic activation is a not infrequent bone marrow findings in patients with ASD.     

Serum cytokine profiles in patients with adult onset Still's disease

OBJECTIVE: Adult onset Still's disease (AOSD) is a systemic inflammatory disorder characterized by fever, arthritis, and rash. Although the pathogenesis is not known, immunologically mediated inflammation occurs in active AOSD. To evaluate the pathogenesis and disease activity of AOSD, we measured serial serum concentrations of several cytokines in patients with active and inactive disease. METHODS: Seventeen patients diagnosed as having AOSD were enrolled. We analyzed clinical and laboratory findings retrospectively. Serial serum samples were obtained from 14 patients with active and inactive AOSD. Interleukin 18 (IL-18), soluble IL-2 receptor (sIL-2R), IL-6, interferon-g (IFN-g), and IL-8 were determined by ELISA. RESULTS: Serum levels of IL-18, IFN-g, and IL-8 were significantly higher in patients with AOSD than in healthy controls (p < 0.01), but there were no significant differences between patients with active and inactive AOSD. Serum sIL-2R levels tended to be higher in the active state than in healthy controls, but there was no statistically significant difference between the 2 groups. Serum sIL-2R levels decreased significantly with antiinflammatory therapy (p < 0.05). Serum IL-18 and sIL-2R levels correlated significantly with serum ferritin levels in the active AOSD group (p < 0.05). CONCLUSION: Overproduction of IL-18 may contribute to the pathogenic mechanism of AOSD, and serum sIL-2R levels may be used as a marker for monitoring disease activity in AOSD.     

Leucopenia in adult Still's disease during treatment with azathioprine and sulphasalazine

Summary The experience is reported concerning treatment of adult Still's disease with a combination of azathioprine and sulphasalazine. In three patients a favourable effect on the symptoms was noted. In one of these patients a year-long prednisone treatment was withdrawn and replaced by sulphasalazine. In all these cases, however, a decrease was seen in leucocyte counts to subnormal levels after the addition of sulphasalazine to a basis therapy with azathioprine 150–200 mg/d (2.1–3.3 mg/kg). The effect was only transitory in two patients, while it lasted several months in the third. In a fourth patient agranulocytosis developed after four days following the combined treatment with azathioprine 150 mg/d (2.3 mg/kg) and 250–1000 mg/d (4–15 mg/kg) of sulphasalazine, lasting four days before recovery. A later resumption of the combination therapy with these same drugs, but in a lower dosage, did not induce any acute changes in leucocyte counts. The skin rash provoked by sulphasalazine in two of the patients did not recur after desensitization. It is concluded, that this combination therapy is valuable in adult Still's disease, but that caution should be exerted during the initiation of sulphasalazine therapy. This should be monitored by daily measurements of leucocyte counts in the first weeks and preferably started by the use of a desensitising kit.     

Liver failure in adult Still's disease during corticosteroid treatment

Adult Still's disease is a well-characterized rheumatic disorder of unknown origin, which may affect multiple organs and may have a fatal course. However, liver failure has rarely been described in adult Still's disease. We present the case of a 25-year-old woman who was admitted with acute liver failure 2 years after the start of symptoms (arthritis, fever, sore throat) of a yet undefined rheumatic disease. She had been treated with prednisolone for 2 months before admission. The diagnosis of adult Still's disease was made in accordance with well-established criteria. Other causes of liver failure were excluded. Withdrawal of prednisolone did not affect the course of liver disease. Ursodeoxycholic acid therapy was started when the patient slowly began to recover. To the best of our knowledge, this is the first case of adult Still's disease reported in which hepatic failure developed when other symptoms were well controlled by corticosteroid treatment.     

Low dose methotrexate treatment in adult Still's disease.

Six patients with adult Still's disease who had either failed to respond to or had adverse effects from previous therapy were given weekly low dose methotrexate (MTX) therapy. They were followed for 4-28 months (mean 14 +/- 9 months). At 12 months of therapy 3 patients were evaluated as having a complete response. One patient had a partial response to MTX after 7 months. Therapy was discontinued in 1 patient at 4 months due to flares of rash and arthralgias after each MTX administration. One patient failed to respond to therapy despite maximum dosage, but was able to reduce his corticosteroid dose. MTX may be a useful therapy to consider in patients with adult Still's disease who are resistant to conventional therapy and may allow a reduction in the concomitant dose of corticosteroids.     

Myocarditis in adult Still's disease

An original case study of a myocardial involvement in a patient with adult Still's disease is presented. The fibrinoid necrosis appearance of a myocardial vessel is an unusual finding at histology.     

Infliximab (anti-TNF-alpha) treatment in patients with adult Still's disease. Experience in 2 cases

Adult Still's disease is a systemic inflammatory disorder of unknown etiology. First-line treatment for Still's disease includes nonsteroidal anti-inflammatory drugs and corticosteroids. In refractory cases o when the dose of corticosteroid is unacceptably high, other disease modifying antirheumatic drugs have been used. But recent study showed the efficacy anti-TNF therapy in adult Sill's disease refractory to conventional therapy. We report a favourable response to infliximab in two patients who has proved resistant to conventional therapy.     

Nationwide epidemiological survey of 169 patients with adult Still's disease in Japan

Abstract

Objectives. A nationwide survey was conducted to assess the number of patients, clinical aspects, treatment, and prognosis of adult Still's disease (ASD) in Japan.

Methods. A primary questionnaire was sent to randomly selected medical institutions in order to estimate the number of patients. We sent a secondary questionnaire to the same institutions to characterize the clinical manifestations and treatment of ASD.

Results. The estimated prevalence of ASD was 3.9 per 100,000. Analysis of 169 patients showed a mean age at onset of 46 years. The main clinical symptoms were fever, arthritis, and typical rash in agreement with previous surveys. Oral glucocorticoids were used to treat 96% of the patients, while methotrexate was used in 41% and biological agents were used in 16%. Lymphadenopathy and macrophage activation syndrome were significantly associated with increased risk of relapse (P < 0.05, each). Patients who achieved remission after tocilizumab therapy had significantly longer disease duration (6.2 years) than patients who did not (1.9 years) (p < 0.05).

Conclusions. The 2010–2011 nationwide survey of ASD identified important changes in treatment and improvement of prognosis compared with previous surveys.     

Successful treatment of a patient with refractory adult Still's disease by tacrolimus

Adult Still's disease (ASD) is a systemic rheumatic disease characterized by high spiking fever, erythema, polyarthritis, and increased levels of C-reactive protein, ferritin, and interleukin (IL)-18. Recently, biological agents targeting proinflammatory cytokines such as tumor necrosis factor (TNF) α, IL-1, and IL-6 have been described as effective treatments for refractory ASD. Herein, we present a patient with ASD, who was successfully treated by tacrolimus concomitant with corticosteroid, while infliximab and etanercept were not effective. Tacrolimus may be one of the drugs for the ASD patients refractory to the conventional treatments including TNF inhibitors.     

Thrombotic microangiopathy in adult Still's disease

Adult Still's disease (ASD) is a rare systemic disorder characterized by fever, arthralgia, cutaneous rash, and lymphadenopathy, with high polymorphonuclear leucocytosis and low glycosylated ferritinaemia. Kidney involvement has been reported rarely. We present a patient with ASD who developed haemolytic uraemic syndrome (HUS). The 42-year-old patient was admitted for unexplained fever related to ASD according to Yamaguchi's classification criteria. As Still's disease was resistant to prednisone, high-dose intravenous immunoglobulins (IV Ig) were administered. During the follow-up the patient developed acute renal failure and non-immune haemolytic anaemia with high levels of antiphospholipid antibodies (IgG anticardiolipin antibodies and anti-beta2 glycoprotein 1 antibodies). Renal biopsy disclosed thrombotic microangiopathy (TMA) with arteriolar and glomerular involvement. Treatment with steroids and intravenous IV Ig was reinitiated but renal function worsened towards end-stage renal failure. In this case, we suggest that antiphospholipid antibodies could have promoted arteriolar and glomerular TMA. HUS may be the cause of acute renal failure in Still's disease.