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Adult Onset Still's Disease - 12/17/2012

posted Dec 17, 2012, 7:36 AM by Rohit Das   [ updated Dec 27, 2012, 6:37 AM by Purnema Madahar ]

I feel like talking about a “zebra” today – Adult Onset Still’s Disease (AOSD). The platform for this was a patient at Weiler who carries this diagnosis, leading me to read more about it, so I figured I’d write about it. Soooo…

·         What is AOSD – who gets it…and why?

·         What are the clinical manifestations, and when should one suspect it? How is it diagnosed?

·         What is the prognosis of AOSD, and how is it treated?

What is Still’s Disease – who gets it, and why?

·         AOSD was first coined in 1971 by Bywaters in the Annals of Rheumatologic Disease, but characterized by an English knight in in the early 1900s, whose last name was….Still! Bywaters initially described a syndrome of symptoms that did not fulfill criteria for rheumatoid arthritis, but had very similar features to a childhood illness – systemic juvenile idiopathic arthritis. And thus, a new label was born…

·         The latter aspect of the above question is tricky – no one really knows. There are some studies and reports associating AOSD with several HLA antigens, and others hypothesizing that it is triggered by various infectious etiologies. More recent data suggest that alterations in Th1 helper cell cytokine production play a very important role.

·         AOSD seems to occur worldwide, effects women slightly more than women, and mainly prevalent in the younger population – 16 to 35 years old based on larger retrospective reviews. Overall, it is a very rare illness, with an estimated incidence of 0.16 cases per 100,000 persons/year.

What are the clinical manifestations, and when should one suspect it? How is it diagnosed?

·         The classic presentation of AOSD is a characteristically febrile illness (with one to two fever spikes per day typically) with associated musculoskeletal symptoms (arthritis/arthralgias) and a “salmon-colored,” usually truncal rash that tends to occur with fever spikes (and thus termed evanescent). Patients generally present after 1-2 weeks of symptoms. The fever is characteristic, occurring in 96% of patients. In this context, AOSD may present as a FUO. Musculoskeletal symptoms are also characteristic, with an incidence of 70-100%. The presentation is generally polyarthritic and symmetric, and the joints that are typically involved are the knees, wrists and ankles. Symptoms typically are at their worst during fever spikes. The rash has an estimated average incidence of 70%, and is often confused with a drug allergy.

·      Table 1 of the attached review article gives a good overview of the clinical manifestations, based around previous case series. Other less prevalent manifestations include splenomegaly (30-60%), serosal disease (20-50%) and lymphadenopathy (30-70%).  Regarding specific organ systems, AOSD can involve the heart (pericarditis, myocarditis), the lungs (pleural effusions, fibrosis) and the kidneys (interstitial or glomerular disease). All of these are exceedingly rare, however.

·         Interestingly, our patient had an associated diagnosis of pulmonary arterial hypertension (PAH). For the life of me, I was able to find only one case report on this…I felt relieved though, as the authors themselves only found 5 case reports of AOSD-associated PAH from 1990 to 2011 - so this complication is exceedingly rare. They reported a case of a 27 year old woman of Middle-Eastern descent who had refractory AOSD for 7 years, who presented with symptoms of right sided heart failure. Interestingly, both her AOSD and PAH responded remarkably well to Anakinra, an IL-1 receptor antagonist, that our patient was also sent home on! Hopefully she does just as well…

·         As far as other diagnostic tools…there aren’t many unfortunately. Autoimmune serologies are usually negative. Inflammatory markers, like ESR, C-reactive protein and Ferritin are elevated, and 70-80% of patients will also have liver test abnormalities. Regarding ferritin, it is usually above 3,000, and levels correlate with disease activity; at a 5-fold elevation, it is 80% sensitive, only 40% specific. Glycosylated ferritin is a more specific marker of AOSD; in healthy patients, glycosylated ferritin approaches 50-80%, but drops to 20-50% in most inflammatory diseases. In AOSD, the drop is even more precipitous, getting as low as <20%. Combined with a five-fold elevation in serum ferritin, a <20% glycosylated ferritin fraction is 95% specific for AOSD.

·         Overall, AOSD is a clinical diagnosis that can be substantiated with the above laboratory date. Additionally, it is a diagnosis of exclusion – AOSD has a wide differential, including hematologic malignancies, autoimmune diseases, and various infectious etiologies. Several diagnostic schema have been reported, the most prominent of which is probably the Yamaguchi’s criteria, which has a sensitivity of around 93%. More recently, Fautrel et. al. published a schema utilizing ferritin and it’s glycosylated fraction, which decreased sensitivity to 80%, but led to a much higher specificity (98%). The various diagnostic criteria are reviewed in Table 3 of the attached review article.

What is the prognosis of AOSD, and how is it treated?

·         Rule of thirds is always most convenient by default; one-third of patients have a monocyclic, isolated episode and an excellent prognosis. Another third have a polycyclic course with intermittent flares and complete remission between flares. The last, unfortunate third have a chronic pattern dominated by debilitating articular disease and joint destruction. Predictors of this last prognostic pattern include a polyarticular presentation, shoulder/hip involvement, and need for ≥2 years of systemic glucocorticoid therapy.

·         There have been no controlled trials on treatment, and current recommendations are based on case reports and retrospective series. NSAIDs, prednisone and anti-rheumatic drugs are the main options. NSAIDs only control symptoms in 10-15% of patients, and thus most ultimately require steroids, with around 50% requiring maintenance steroids. The use of anti-rheumatics in AOSD is very problematic, as the lack of controlled trials places their efficacy, as compared to their risks, in a nebulous cloud of ambiguity. Generally, they are reserved for patients in whom NSAIDs and steroids don't control disease activity and for those who cannot tolerate the adverse effects of steroids and need to be tapered…it’s all voodoo from there…

Interesting disease, but unfortunately too rare to get a real handle of the efficacy of the various therapeutics. The attached review article gives a nice synopsis…till next time…

Diagnosis and Management of Adult Onset Still's Disease
Efthimiou et. al., Ann Rheum Dis 2006, Volume 65: 564-572

Campos et. al., Case Reports Rheum 2012, E-published August 2012