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
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