Adult Still's Disease

Author: Dr. Subrahmanyam Karuturi, MD

Introduction
Adult-onset Still's disease (ASD or AOSD) is a rare multisystem inflammatory disorder characterized by acute arthritis, characteristic rash, and quotidian or double-quotidian fevers. Adult Still's disease is used to describe an adult patient who do not fulfill the classic criteria of Rheumatoid arthritis but who has features similar to Juvenile idopathic arthirits.

Etiopathogenesis
Unknown Most plausible hypothesis is an infectious agent which triggers this inflammation in a genetically susceptible host Complex interpaly between genetic, infectious and environmental factors HLAB17, B18, B35 and DR2 were associated with AOSD

Epidemiology
1.5 cases per 100,000-1000,000 people Adult-onset Still's disease cases were reported in India Affects young people and has a bimodal age distribution with two peaks - at 15-25 and 36-46 years of age More in females

Clinical Features
Fever - quotidian or double-quotidian (two fever spikes per day) - Can present as fever of unknown origin (FUO) Arthralgia Arthritis - mild, transient, and oligoarticular - may evolve into severe, destructive polyarthritis - Most commonly involved joints are knees, wrists, ankles, elbows, proximal interphalangeal joints, and shoulders Myalgias - serum creatinine kinase elevated - no muscle weakness Sore Throat - nonsuppurative pharyngitis - may be associated with odynophagia Rash - evanescent, salmon-pink, maculopapular eruption, which frequently appears during febrile attacks and is predominantly found on the proximal limbs and trunk with rare involvement of the face and distal limbs. Dermatographism Lympadenpathy Splenomegaly Pericarditis Pleural Effusions Liver disease - AST, ALT, ALP are elevated Reactive hemophagocytic syndrome or macrophage activation syndrome - numerous, welldifferentiated macrophages (histiocytes) that are engaged actively in the phagocytosis of hematopoietic elements on bone marrow examination

The clinical course of ASD can be divided into three main patterns: monophasic, intermittent, and chronic. Monophasic - 1/3rd of Patients - Disease course lasts less than a year with complete resolution of symptoms Intemittent - 1/3rd of Patients - One or more disease flares with complete remissions between episodes Chronic - 1/3rd of Patients - Persistently active disease, usually associated with a destructive arthritis Predictors of chronic disease - development of a polyarthritis early in the course of ASD, involvement of the shoulders or hips, need for more than two years of systemic glucocorticoid therapy

Investigations
Elevated ESR, CRP Leukocytosis Normocytic Normochromic Anemia Reactive Thrombocytosis Elevated AST, ALT Elevated Serum Ferritin - Serum ferritin values above 3000 ng/mL in a patient with compatible symptoms should lead to suspicion of ASD in the absence of a bacterial or viral infection. Antinuclear antibodies and rheumatoid factor - ABSENT Radiographic findings - nonerosive narrowing of the carpometacarpal and intercarpal joint spaces of the wrist

Diagnosis
o o o There is no specific test or combination of tests that can be used to establish the diagnosis of ASD. A variety of classification criteria has been proposed, and the Yamaguchi criteria are most widely used. The Yamaguchi criteria require the presence of five features, with at least two being major diagnostic criteria Yamaguchi criteria Major Yamaguchi criteria Fever of at least 39C (102.2F) lasting at least one week Arthralgias or arthritis lasting two weeks or longer A nonpruritic macular or maculopapular skin rash that is salmon-colored in appearance and that is usually found over the trunk or extremities during febrile episodes Leukocytosis (10,000/microL or greater), with at least 80 percent granulocytes Minor Yamaguchi criteria Sore throat Lymphadenopathy Hepatomegaly or splenomegaly

o o o o

Abnormal liver function studies, particularly elevations in aspartate and alanine aminotransferase and lactate dehydrogenase concentrations Negative tests for antinuclear antibody and rheumatoid factor

Differential Diagnosis
Brucellosis Tuberculosis Bacterial endocarditic infections Malignant diseases, especially lymphoma Autoimmune disorders like systemic lupus erythematosus and systemic vasculitides

Treatment
NSAIDs - Ibuprofen 800mg TID or Naproxen 500mg BID Glucocorticoids - Majority of patients require steroids - Prednisolone 1mg/kg/day - Pulse methylprednisolone (eg, 1000 mg/day times three) can be used for life-threatening disease like severe hepatic involvement, cardiac tamponade, DIC Biologic Agents - TNF inhibitors (etanercept, infliximab, and adalimumab), IL-1 receptor antagonist (Anakinra), Anti CD-20 antibody (Rituximab) DMARDs - Used only when no response to NSAIDs, glucocorticoids, or biologic agents, or have developed side effects from these medications - Methotrexate, Cyclosporine

Prognosis
The functional status of patients with ASD is generally good, even in the setting of a chronic disease pattern Joint arthroplasty has significantly improved the functional status of many ASD patients with chronic destructive arthritis Chronic active inflammation can lead to secondary (AA) amyloidosis Poor prognostic factors - development of a polyarthritis early in the course of ASD, involvement of the shoulders or hips, need for more than two years of systemic glucocorticoid therapy

References
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