Case presentationRheumatology

39 yr old female pt, unemployed from Bloemfontein

Routine follow up at rheumatologyBackground history of hypertensionDiagnosis of

? Mixed connective tissue disease/ Overlap syndrome/ seronegative rheumatoid arthritis

Previous serology: ANF, AntiRNP, Scl 70, Anti Jo, elevated CK’s

History

Severe generalised joint painsNo associated swelling reported Morning stiffness Constitutional symptomsDryness of the eyesNo other systemic complaintsSober habits

History(cont..)

Medication list:MTX 20 mg /weekNivaquine 200mg daily Prednisone 10mg dailyFolate 5mg daily Ridaq 12.5mg dailyPharmapress 20 mg daily poLosec 20 mg daily poVoltarenDolorol forte

History(cont..)

General examination: In discomfort due to painNo pallor/jaundice/adenopathyNo vasculitic or skin changes

Systemic exam:CVS: haemodynamically stableResp: clearGIT: no tenderness or organomegalyM/S: bilateral symmetrical tenderness and

warmth of joints in upper and lower extremities. No effusions.

Clinical examination

AssessmentFlare of arthritis

ManagementDepo Medrol 160 mg imi statBloods for :

Inflammatory markers AST/ALT/Alb

Methotrexate increased to 25 mg/week

Evaluation

Evaluation(cont..)

06/11/2009 16/04/2010

Total Bili 9

AST 86 669

ALT 73 760

Albumin 40 36

Drug induced hepatitisViral hepatitisAutoimmune hepatitis(AIH)

Differential diagnosis

Patient admitted for evaluationReports good response to steroidsMethotrexate stoppedFollow up blood results

Differential diagnosis(cont..)

16/04/2010 26/04/2010Total Bili 9 9AST 669 295ALT 760 500Albumin 36 40

Virological studiesHepatitis A, B and C studies were negativeHIV negative

SerologyANA , ANCA negativeAnti smooth muscle Ab’s unfortunately not done

SPEP Normal

Abdominal ultrasoundNormal

Investigations

Diagnostic challenge ?

Causes related to:Underlying autoimmune diseaseConcurrent infections

Chronic viral hepatitisOpportunistic infections

Drug related toxicityMethotrexateAzathioprine

Other causesAlcoholic liver diseaseMetabolic disordersMalignancy

Hepatitis in autoimmune disease

Cell-mediated immunologic attack against genetically predisposed hepatocytes

Progressive necroinflammatory and fibrotic process.

Association with other autoimmune diseasesRheumatologic conditions

Rheumatoid arthritis and Felty syndromeSjögren syndromeSystemic sclerosisMixed connective-tissue disease

Autoimmune hepatitis

Presentation is heterogeneous, and clinical manifestations varyAsymptomaticDebilitating symptomsFulminant hepatic failure

Women are affected more often than men (70-80% of patients are women)

Response to steroid and/or immunosuppressive therapy

Autoimmune hepatitis

Autoimmune hepatitis

Risk factors associated with drug induced liver injuryAge: elderly at high riskSex: more common in femalesAlcohol useUnderlying liver diseaseCo- morbid diseasePregnancy Other drugsGenetic factors

Drug induced hepatotoxicity

Methotrexate can induce: hepatocyte necrosis

Increased ALTHepatic fibrosis and cirrhosis

Common setting in pt treated for psoriasis

Methotrexate hepatotoxicity

Premethotrexate Evaluation Complete blood count with differential countPlatelet countSerum creatinineUrea UrinalysisLiver function testsSerum 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 Acad Dermatol 1998; 38:478-85.

Methotrexate toxicity(cont..)

Indications for liver biopsy in pt with RAPersistently 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

Methotrexate toxicity(cont..)

AIHFemale genderUnderlying

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 patientMTH hepatotoxicity

Decline in LFT’s to near normalMTX stopped indefinatelyPrednisone increased to 20 mgFor reevaluation in 2/52, ?liver biopsy

Our patient