Dr. Müge Bıçakçıgil Kalaycı

ADULT ONSET STILL DISEASEMulti-system inflammatory disease

begins with a sore throat may develop days to weeks before

the typical quotidian feverRashJoint pains

ETIOLOGY

no etiologic factor has been identifiedInfectious??

prodromal sore throatfever

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

FEVERQuotidian or "double-quotidian" with a brief

peak in the late afternoon or early evening.

Temperature swings can be dramatic, with changes of 4ºC 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

RASHUsually 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.

DiagnosisDiagnosis

DiagnosisDiagnosis

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

Treatment

NSAIDS or Aspirin

Mild disease with no life- threatening visceral involvement

20-25 % 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