Dr. Müge Bıçakçıgil Kalaycı

ADULT ONSET STILL DISEASE Multi-system inflammatory disease begins with a sore throat may develop days to weeks before the typical quotidian fever Rash Joint pains

ETIOLOGY no etiologic factor has been identified Infectious?? prodromal sore throat fever Possible mechanism; - viral agent initiates a cascade of the immunological events resulting in the characteristic clinical syndrome of AOSD.

Implicated organisms in AOSD -Rubella -Ebstein Barr -Staphylococcus -Parvovirus -Yersinia enterocolitica Brucela abortus -Mycoplasma -Borelia burgdoferi -Cytomegalovirus -Mumps -Parainfluenza

Clinical Features

Common Clinical Features *Fever of at least 39ºC lasting one week or longer *Arthralgias or arthritis lasting two weeks or longer *Characteristic rash which is a macular or maculopapular, nonpruritic, salmon-pink eruption usually apparent over the trunk or extremities during febrile episodes * Leukocytosis (10,000/µL or greater) with 80 percent or more granulocytes

* Sore throat * Recent development of significant lymph node swelling * Hepatomegaly or splenomegaly *Abnormal liver function studies, particularly aminotransferases and lactate dehydrogenase *Negative tests for antinuclear antibody and rheumatoid factor

FEVER Quotidian or "double-quotidian" with a brief peak in the late afternoon or early evening. Temperature swings can be dramatic, with changes of 4 º C occurring in four hours. Approximately 20 percent of cases, fever persists between spikes. Over 99 % of patients manifest with fever > 39 0 C

FEVER The febrile paroxysms are cyclic and tend to recur every 24 or sometimes every 12 hours. Characteristically very high in the evening, returning to normal by morning. Paroxysms are heralded by shaking chills, followed by 2-4 hours of high fever (> 104°F), and ending with defervescence and drenching sweats

Still's rash is seen in 86% of patients Periodic appearance and location Appears during febrile attacks and may last for several hours It is typically salmon-colored (infrequently erythematous), maculopapular and may be confluent or show areas of central clearing. Trunk, neck, extremity( extensor surface) RASH

Usually the face, palms, and soles are spared. Dermatographism: is an exaggerated cutaneous urticarial response to cutaneous stimuli (ie, the scratch test). Rash is typically nonpruritic.

Articular Manifestations Arthralgias dominate the early clinical picture During the first 6 mos. the onset of polyarthritis is expected in > 90% of patients and may involve large and small articulations Myalgias

Affected joints: the knees, wrists, ankle, elbow, shoulder, PlPs, DlPs, TMJ and cervical spine. Bony ankylosis of carpal, carpometacarpal. Intertarsal joints Erosive and destructive polyarthritis, especially in those with a chronic polyarticular course

Reticuloendothelial Disease Splenomegaly Very common early in the disease and reflects tissue infiltration with inflammatory cells and heightened immunologic activity within the reticuloendothelial system (RES). Palpable or radiographic demonstration of splenomegaly is seen in 42% of individuals Hepatomegly 40% of patients are found to have hepatomegaly 70% demonstrate abnormalities of hepatic enzymes at some time during their illness

Lymphadenopathy 65% of AOSD patients. Generalized mild to moderate nodal enlargement of nontender lymph nodes located in the cervical, axillary, epitrochlear, or inguinal regions. Mesenteric, para-aortic and hilar nodes may be discovered during diagnostic imaging

SEROSITIS Pleuritis (40%) Pleural effusions are usually bilateral, seldom large enough to be symptomatic, and rarely produce pleural thickening. Thoracentesis often yields bloody, exudative effusions with white blood cell counts ranging from 3-20 x 103/mm3 with a polymorphonuclear predominance.

Pneumonitis Pneumonitis is found in over 20% of patients These individuals often appear septic with complaints of fever, dry cough, dyspnea and are found to have pulmonary infiltrates that are unresponsive to anti-infective therapy Infiltrates tend to be bilateral more commonly than unilateral, alveolar or interstitial in pattern and responds well to anti-inflammatory therapy with steroids

Laboratory Investigations

Absence of antinuclear antibodies Absence of rheumatoid factor, Elevated ESR and C-reactive protein Neutrophilic leukocytosis Elevated serum amyloid A Thrombocytosis Elevated serum ferritin and glycosylated ferritin Elevations the hepatic enzymes Hypoalbuminemia

Leukocytosis Leukocytes counts generally range between 12,500-40,000 cells/mm3, with the highest recorded to be 69,000 ESR 90% of AOSD patients have an ESR > 50 mm/hr and 50% have and ESR > 90 mm/hr.

Hyperferritinemia It has been suggested that extreme elevations of the acute phase reactant, ferritin, may be of diagnostic value in assessing patients with AOSD Hyperferritinemia with values between 4000­ ­ 30,000 mg/ml have often been reported in association with the onset and/or flare of disease activity Levels as high as 250,000 mg/ml have been reported AOSD.

Diagnosis

Diagnosis Diagnosis Still disease lacks serologic test or histopathology and thus, remains a clinical diagnosis of exclusion. AOSD is now being considered earlier in the course of evaluation of patients with fever, dermatitis and arthritis. Diagnostic steps should include a comprehensive, noninvasive workup, documentation of fever pattern

Yamaguchi et al 1992 AOSD ­ Total of > 5 criteria (including 2 major) Major Criteria Minor Criteria Fever > 39°C Sore throat Arthralgia > 2 wks. LN or splenomegaly Still's rash Liver dysfunction Neutrophilic leukocytosis Negative RF & ANA specificities greater than 92%, the sensitivity of Yamaguchi (96%)

Treatment

NSAIDS or Aspirin Mild disease with no life- threatening visceral involvement % respond (good prognosis group with mild disease activity) Aspirin or an NSAID should be continued for one to three months following disease remission.

GLUCOCORTICOSTEROIDS Patients with very high fever, Joint involvement that is disabling Potentially life-threatening visceral involvement (myocarditis) Starting dose of 0.5 to 1.0 mg/kg per day PO

Immunomodulating drugs There are no controlled trials assessing the efficacy of any of the immunomodulating drugs in ASD * Intramuscular gold salts * Hydroxychloroquine, * Azathioprine, * Cyclophosphamide, * Cyclosporine, * Sulfasalazine, * Methotraxate * Intravenous immune globulin, * Anti-TNF-alpha agents