Adult onset still's disease (AOSD) Presented by Dr.Md.Saddam Hossain IMO ( dept of medicine) Government employee hospital

Presented by
DR.MD.SADDAM HOSSAIN
MBBS, BCS, CCD( Diabetes - Birdem)
FCPS part 2 ( Medicine), PGT( Gastro)
IMO( Dept of medicine)
Government Employee Hospital, Furbaria, Dhaka

1. Adult-Onset Still’s Disease Dr. Md. Saddam Hossain MBBS, FCPS-II Trainee (Medicine) Medical officer Department of Medicine Sarkari Karmachari Hospital Fulbaria , Dhaka.

2. Definition Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder of unknown aetiology, characterized by- Daily spiking of high fever A ccompanied by a fleeting rash Arthritis Systemic manifestations.

3. Epidemiology : Men and women are equally affected with bimodal peaks at ages 15–25 years and 36–46 years . Association with pregnancy and in the post partum period.

4. Pathogenesis: There may be a genetic predisposition. Possible link with HLA-B17, B18, B35 and DR2 Genetic polymorphisms of the IL-18 gene may also be linked to AOSD susceptibility and/or severity. Continue…

5. Various infectious triggers have been postulated, suggesting AOSD may be a reactive syndrome. These include- Virus: EBV, Echovirus , CMV, Parvovirus B19, Coxsackie virus, Influenza. B acteria including Mycoplasma, Pneumonia , Chlamydia, Pneumonia , Brucella abortus , and Borrelia burgdorferi . T helper1 (Th1) cytokines present in blood and tissues are thought to play a role in the pathogenesis of AOSD in addition to IL-1, IL-6 , IL-18, TNF α, and IFN- γ.

6. Clinical features Fever: Acute onset of daily spiking high fever exceeding 40°C is often the first symptom. 2. Typically peaks once daily in late afternoon or early evening (quotidian) 3 . Lasting < 4 hours , and normalizing in 80% without antipyretics. 4.There may be a double quotidian pattern , with highest spikes occurring in late afternoon.

7. Rash: Evanescent salmon-pink , macular or macular papular eruption, predominantly involving proximal limbs and trunk. Continue…

8. The overall incidence of the rash in AOSD is ~70%. The rash usually appears in conjunction with fever, and may exhibit Koebner phenomenon . There may be pruritus and appearances confused with drug allergy.

9. Musculo-cutaneous Disease: Arthritis may initially be mild, oligoarticular , and transient, and may evolve gradually into a more severe, destructive, and symmetrical polyarthropathy affecting mainly knees, wrists, and ankles. Elbows, shoulders, hips interphalangeal joints, and temporo -mandibular joints may also be involved. Generalized myalgia with fever spikes are seen in the majority of patients , but inflammatory myopathy is rare.

10. Pharyngitis: Estimated to occur in ~70% of AOSD cases. Others: Liver : Hepatomegaly occurs in 50–70%, Lymph node: Tender cervical lymphadenopathy and splenomegaly occur in 50%. (Lymph node biopsy may resemble lymphoma on light microscopy, but immunohistochemistry demonstrates benign polyclonal B-cell hyperplasia . ) Cardiopulmonary disease : S erositis occurs in30–40% ( pleuritis , pericarditis ).

11. Laboratory and radiographic findings There is no specific diagnostic test in AOSD, and no association with RF or positive ANA. ESR is raised in virtually all cases, CRP may be elevated. Marked elevations in serum ferritin occur in ~70%, (>10000 is suggestive). Continue…

12. Leucocytosis : (>10 ×109/L), with a granulocyte predominance. Normocytic normochromic anaemia Elevated liver transaminases , lactate dehydrogenase , and bilirubin level Liver biopsy : changes are non-specific. Very high levels of IL-18 have been demonstrated in a number of studies of AOSD. There are no specific radiographic findings

13. Differential diagnosis: 1. Epstein barr virus 2. Cytomegalovirus 3. HIV 4. Hepatitis B 5. Lyme disease 6. Brucellosis 7. Acute rheumatic fever 8. SLE 9. Reactive arthritis 10. Lymphoma 11. Miliary Tuberculosis

14. Complications Secondary haemophagocytic syndrome (HS ) Diffuse intravascular coagulation (DIC) Pancytopenia

15. Treatment : Treatment strategies are based on Organ involvement Disease severity Aiming to control fever Arthritis and Systemic disease

16. Treatment options 1. NSAID’s can be used first line 2. Glucocorticoids remain first-line treatment, regardless of presentation. Dose : The usual dose is 0.5–1 mg/kg/day of prednisolone. Pulsed methyl prednisolone is helpful. Severe disease is refractory to oral glucocorticoids.

17. 3. MTX For refractory AOSD, MTX is a commonly used GC-sparing agent Dose : 7.5-20mg/dl Indications : Disease refractory to glucocorticoid Chronic a rticular involvement Can facilitate tapering of Glucocorticoid

18. 4. Immunoglobulin ( IVIg ) Dose : 2g/kg over 2–5 days. Indications : Macrophage activation syndrome AOSD flare during pregnancy .

19. 5. Biologic DMARDs Anakinra (IL-1 antagonist), Tocilizumab (IL-6 inhibitor) Indications : 1. Systemic disease 2. Articular features

20. Anti TNF α Indication : Chronic polyarticular disease. Adalimumab and Etanercept Indications : Macrophage activation syndrome Paradoxical disease flares.

21. Course of disease and prognosis : There are three main patterns of disease, with 1/3 rd of patients falling into each category. Self-limiting or monophasic pattern : C haracterized by a single disease episode. Most achieve complete remission within 1 year . Continue…

22. Intermittent or polycyclic systemic pattern : C onsisting of recurrent attacks, with remission between flares . Chronic articular pattern : Associated with poor prognosis. Disease is persistent with predominant articular symptoms resulting in severe destructive arthritis and arthroplasty frequent within 2 years.