Hepatitis and Lupus-Like Syndrome during Infliximab Therapy for Psoriasis
A 23-year-old female presented with generalized plaque psoriasis of 10 years duration. She was married and using an intrauterine device for contraception. Her quality of life was severely affected (dermatology life quality index = 16), body surface area involvement was 17%, and her body mass index was 28 (overweight). Scalp, nails and flexures were involved, while the palms, soles and joints were spared at that time. The patient had received different systemic and topical conventional therapeutic modalities including methotrexate (cumulative dose of 430 mg) with variable responses. She had no history of alcohol consumption or smoking and no history of other drugs that may exacerbate or induce hepatitis or lupus erythematosus. Infliximab was initiated in February 2010 at a dose of 5 mg/kg per infusion session on 0, 2 and 6 weeks and then every 8 weeks. The patient responded nicely to therapy, but after the fifth injection session in July 2010, she noticed dark urine and lethargy. Liver function tests showed a marked elevation in liver enzymes and total bilirubin. The level of immunoglobulin G was 2,100 mg/dl, i.e. about 130% of the upper limit (normal 700–1,600 mg/dl); other immunoglobulins (IgM and IgA) showed normal findings, while anti-nuclear antibodies (ANAs) turned positive with a titer of 1:320 (speckled). The laboratory results are displayed in table . Screening for viral hepatitis (A, B, C and E) showed negative result. Anti-microsomal antibodies, anti-mitochondrial antibodies, anti-soluble liver antigen, anti-smooth-muscle antibody, anti-liver-kidney microsomal antibodies, prothrombin time and international normalized ratio were all within normal ranges or negative. Anti-soluble liver antigen/liver-pancreas antibodies and pANCA were not done. Liver ultrasound was normal, showing normal hepatic size and echogenicity as well as normal gallbladder and bile ducts.\nThe patient did not give consent for liver biopsy. She was diagnosed as suffering from AIH and given corticosteroids; the following dose of infliximab was suspended. Her liver function test improved dramatically within the first 4 weeks. She was given etanercept 50 mg bi-weekly for 12 weeks, which unfortunately showed primary lack of response and injection site hypersensitivity. Her liver function test returned to baseline after 2 months. Under care by a hepatologist and with consent of the patient, infliximab therapy was resumed with great caution due to flare-up of the skin condition.\nThe patient received three re-initiation doses with good response and no changes in liver function tests. This was followed by five doses over a year. In January 2012 she was admitted to hospital with fever (39°C), severe arthralgia, myalgia, lethargy and depression. Erythrocyte sedimentation rate and C-reactive protein were highly elevated. On examination there were severe symmetrical peripheral arthritis lesions with swelling, effusion and mobility problems involving the knees, elbows and proximal small joints of both hands and feet. There was no axial joint involvement. There was an ANA titer of 1:1,280 (homogenous), positive anti-Sm, positive anti-histone antibodies, negative anti-double-stranded DNA (anti-dsDNA) antibodies, negative rheumatoid factor and normal serum complement. No malar rash, photosensitivity, mouth ulceration, visceral organ involvement, serositis, renal involvement, proteinuria, cytopenia or any other manifestations of lupus erythematosus were observed. The patient was diagnosed as having lupus-like syndrome due to infliximab therapy. Infliximab was eventually discontinued. The condition was controlled by corticosteroids, leflunomide and azathioprine. Her general condition and arthritis improved within 2 months, liver function tests remained within normal limits, and anti-Sm and anti-histone antibodies returned to normal values. Her ANA titer went down to 1:160 (homogenous); 24 months later the condition remained stable with no relapse or recurrence of drug-related symptoms (table ). Corticosteroids were stopped 7 months later; she is maintained on sulfasalazine, hydroxychloroquine and ustekinumab injections. The main complaint of the patient during the latest period was worsening of the joint condition, especially in the small joints of the hands that started to show erosive arthritis and minor deformities.