Gastrointestinal: Improvement of granuloma annulare with anti‐tumour necrosis factor alpha therapy for Crohn's disease

Abstract

A 61 year old Greek woman attended our Inflammatory Bowel Disease clinic with a 24 year history of ileocolonic Crohn's disease. She had disseminated granuloma annulare (GA) involving her hands, forearms, and lower limbs. Past medical history also included type 2 diabetes mellitus, rheumatic fever, thalassemia minor, and depression. Her ileocolonic Crohn's disease was diagnosed in 1985 and required recurrent hospitalization, parenteral corticosteroids, and culminated in a terminal ileal resection in 1995. Despite surgery, the patient continued to have multiple symptomatic flares. Intolerance or lack of efficacy has been documented with methotrexate, azathioprine, 6-mercaptopurine, and cyclosporine. Infliximab was commenced in 2007, with a total of 5 infusions (5 mg/kg) over a 2-year period. Interestingly, during treatment with infliximab her GA also improved dramatically, to the point of being barely noticeable. Unfortunately following improvement in the skin rash there was secondary loss of response to infliximab and the GA recurred. Adalimumab was commenced in 2008 and induced durable remission of the Crohn's disease. Once again there was significant improvement in her GA after 6 months of treatment. [1A and 1B, 2A and 2B (before commencement of Adalimumab), 1A and 1B, 2A and 2B (after maintenance treatment with Adalimumab)]. GA is a benign, asymptomatic, papular eruption that can occur at all ages. The primary skin lesion usually is grouped papules in an enlarging annular shape, with colour ranging from flesh-coloured to erythematous. It may be localized or disseminated in distribution. Although GA tends to be idiopathic, several case reports have shown an association with diabetes mellitus and solar radiation. There are also weaker associations with bacillus Calmette-Guerin vaccination, drugs (allopurinol, zalcitabine), viral infections [Epstein-Barr virus, human immunodeficiency virus, hepatitis C, parvovirus B19 and herpes simplex virus], autoimmune thyroiditis and malignant conditions (Hodgkin disease, pulmonary adenocarcinoma, breast carcinoma, prostate, and ovarian cancer). GA is not a recognized extra-intestinal manifestation of IBD. GA has been documented to respond to treatment with dapsone, retinoids, antimalarials, psoralen plus ultraviolet A therapy,fumaric acid esters, tacrolimus, and pimecrolimus. Case reports of both improvements and deteriorations in GA following treatment with anti-TNF therapy have been published. As far as we are aware, this is the first reported case of improvement of GA related to treatment of IBD using both infliximab and adalimumab and may support the role of tumour necrosis factor-alpha in the pathophysiology of GA.