1. ADULT ONSET STILL DISEASE
Dr. Müge Bıçakçıgil Kalaycı

2. 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

3. 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.
No etiopathogenesis has been acceptably proposed or proven. An infectious etiology or trigger has been inferred based upon the prodromal sore throat that heralds the onset or flare of disease.
Although no etiologic factor has been identified, some have advocated that an infectious, and possibly viral, agent initiates a cascade of the immunological events resulting in the characteristic clinical syndrome of AOSD
Reactivity to these microbes may be dependent upon genetic, immunologic and other unidentified host factors.
* Nearly, half of the patient demonstrated microbiologic evidence of coexistent viral infections. Nonetheless, it is unknown whether such identification constitutes causal proof. In many instances these findings are either coincidental or may reflect a nonspecific response to heightened immunologic activity.

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

5. Clinical Features

6. 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

7. * 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

8. FEVER
Quotidian 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

9. 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

11. RASH 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)

12. 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.

16. 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

17. 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

19. 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

20. 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

21. 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.

22. 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

23. Laboratory Investigations

24. 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

25. 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.

26. 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.

27. Diagnosis

28. 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

29. 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%)

30. Treatment

31. Treatment Mild disease with no life- threatening visceral involvement
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.

32. 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

33. 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