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Case presentation Rheumatology . History. 39 yr old female pt, unemployed from Bloemfontein Routine follow up at rheumatology Background history of hypertension Diagnosis of ? Mixed connective tissue disease/ Overlap syndrome/ seronegative rheumatoid arthritis
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History • 39 yr old female pt, unemployed from Bloemfontein • Routine follow up at rheumatology • Background history of hypertension • Diagnosis of • ? Mixed connective tissue disease/ Overlap syndrome/ seronegative rheumatoid arthritis • Previous serology: ANF, AntiRNP, Scl 70, Anti Jo, elevated CK’s
History(cont..) • Severe generalised joint pains • No associated swelling reported • Morning stiffness • Constitutional symptoms • Dryness of the eyes • No other systemic complaints • Sober habits
History(cont..) • Medication list: • MTX 20 mg /week • Nivaquine 200mg daily • Prednisone 10mg daily • Folate 5mg daily • Ridaq 12.5mg daily • Pharmapress 20 mg daily po • Losec 20 mg daily po • Voltaren • Dolorol forte
Clinical examination • General examination: • In discomfort due to pain • No pallor/jaundice/adenopathy • No vasculitic or skin changes • Systemic exam: • CVS: haemodynamically stable • Resp: clear • GIT: no tenderness or organomegaly • M/S: bilateral symmetrical tenderness and warmth of joints in upper and lower extremities. No effusions.
Evaluation • Assessment • Flare of arthritis • Management • DepoMedrol 160 mg imi stat • Bloods for : • Inflammatory markers • AST/ALT/Alb • Methotrexate increased to 25 mg/week
Differential diagnosis • Drug induced hepatitis • Viral hepatitis • Autoimmune hepatitis(AIH)
Differential diagnosis(cont..) • Patient admitted for evaluation • Reports good response to steroids • Methotrexate stopped • Follow up blood results
Investigations • Virological studies • Hepatitis A, B and C studies were negative • HIV negative • Serology • ANA , ANCA negative • Anti smooth muscle Ab’s unfortunately not done • SPEP • Normal • Abdominal ultrasound • Normal
Hepatitis in autoimmune disease • Causes related to: • Underlying autoimmune disease • Concurrent infections • Chronic viral hepatitis • Opportunistic infections • Drug related toxicity • Methotrexate • Azathioprine • Other causes • Alcoholic liver disease • Metabolic disorders • Malignancy
Autoimmune hepatitis • Cell-mediated immunologic attack against genetically predisposed hepatocytes • Progressive necroinflammatory and fibrotic process. • Association with other autoimmune diseases • Rheumatologic conditions • Rheumatoid arthritis and Felty syndrome • Sjögren syndrome • Systemic sclerosis • Mixed connective-tissue disease
Autoimmune hepatitis • Presentation is heterogeneous, and clinical manifestations vary • Asymptomatic • Debilitating symptoms • Fulminant hepatic failure • Women are affected more often than men (70-80% of patients are women) • Response to steroid and/or immunosuppressive therapy
Drug induced hepatotoxicity • Risk factors associated with drug induced liver injury • Age: elderly at high risk • Sex: more common in females • Alcohol use • Underlying liver disease • Co- morbid disease • Pregnancy • Other drugs • Genetic factors
Methotrexatehepatotoxicity • Methotrexate can induce: • hepatocyte necrosis • Increased ALT • Hepatic fibrosis and cirrhosis • Common setting in pt treated for psoriasis
Methotrexate toxicity(cont..) Premethotrexate Evaluation Complete blood count with differential countPlatelet countSerum creatinineUrea UrinalysisLiver function tests Serum bilirubinSerum albuminHepatitis A, B, and C serologiesHIV risk assessment/testing, if appropriateChest radiograph Information from Roenigk HH, Auerbach R, Maibach H, Weinstein G, Lebwohl M. Methotrexate in psoriasis: consensus conference. J Am AcadDermatol 1998; 38:478-85.
Methotrexate toxicity(cont..) • Indications for liver biopsy in pt with RA • Persistently elevated liver enzymes • Abnormal results in five of nine determinations of AST levels within a 12-month period( done 4-8 weekly) • Decrease in serum albumin values below the normal range • Not cost-effective in the first 10 years in pt’s with normal enzymes • Presence of moderate fibrosis/cirrhosis warrants discontinuation
Our patient AIH MTH hepatotoxicity • Female gender • Underlying autoimmune disorder • Previous +ANA • ?Response of transaminases to steroids • Hepatocellular injury pattern in pt on MTX • ?Other possible precipitating factor • ?Did pt increase her treatment due to pain
Our patient • Decline in LFT’s to near normal • MTX stopped indefinately • Prednisone increased to 20 mg • For reevaluation in 2/52, ?liver biopsy