Another paradox in Crohnʼs disease: New onset of psoriasis in a patient receiving tumor necrosis factor-α antagonist

This is the authors' abstract. We don't add key points for this paper.

To the Editor: Tumor necrosis factor-α (TNF-α) is a pivotal molecule in the pathogenesis of psoriatic skin lesions.1 Although TNF-α antagonists seem to be effective in the treatment of refractory psoriasis,2 in the last 2 years unexpected onset of psoriasis or psoriasiform skin lesions has been reported in patients receiving treatment with TNF-α inhibitors for rheumatological or gastroenterological conditions. A 28-year-old male with extended Crohn's disease (CD) involving 40 cm of terminal ileum, colon, stomach, and duodenum was referred to our Gastroenterology Unit in July 2004 for the development of perianal lesions. CD had been diagnosed in 2001 according to standard endoscopic, radiologic, and histologic criteria. Over the next 3 years CD showed a chronic relapsing course under maintenance treatment with oral mesalazine (2.4 g/day) requiring episodic courses of steroids. In July 2004 for the development of superficial perianal fistulas not communicating with the anal canal and refractory to antibiotic therapy, treatment with azathioprine (2.5 mg/kg/day) was started. From July 2004 to October 2006 the patient received infliximab infusions (5 mg/kg) at weeks 0, 2, and 6 and then a maintenance treatment with a total of 13 infliximab infusions at 5 mg/kg every 8 weeks. Each infusion was preceded by premedication with hydrocortisone 100 mg intravenously. Three days after the 13th infusion of Infliximab the patient developed red pustular skin lesions (Fig. 1A,B). Lesions started in the wrists, scalp, feet (both plantar and dorsal surface), and legs but in a few days spread to the back and arms, involving about 75% of the body surface. The onset of widespread pustulosis was also accompanied by itching and mild serotinous fever. The biopsy of skin lesions had histopathological features of psoriasis. (A,B) Onset of widespread pustulosis on the back and on the legs 3 days after the 13th infusion of infliximab. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.] The patient had no personal or familial history of psoriasis but he revealed that he had discontinued azathioprine treatment almost 3 months before the appearance of skin lesions. Infliximab was therefore stopped and topical treatment was started. Venous blood assessment revealed a mild rise in the erythrocyte sedimentation rate (35 mm/h) and C-reactive protein (1.8 mg/dL). The skin lesions did not respond favourably to topical agents. No clinical and serological evidence of infection was found. After 30 days from the appearance of the lesions, treatment with steroids (prednisone 0.7 mg/kg/day) and azathioprine (2 mg/kg/day) was started. Pustular lesions and itching disappeared after 3 days of systemic treatment and diffuse erythematous lesions and cutaneous desquamation improved but did not disappear after 2 months of systemic therapy (Fig. 2A,B). A second biopsy of skin lesions confirmed histopathological features of psoriasis. (A,B) Improvement of cutaneous lesions on the back and on the legs 1 month after the beginning of steroid therapy. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.] To date, more than 30 cases of psoriasis were reported in patients receiving TNF-α inhibitors for rheumatological conditions but only 2 cases have been described in patients receiving them for inflammatory bowel diseases (1 case in CD and 1 case in ulcerative colitis).3,–5 Similar to former reports, our patient had no personal or familial history of psoriasis and the onset of psoriasis occurred more than 12 weeks after the TNF-α inhibitor was started. The recent discontinuation of azathioprine could have a role as a trigger factor. While the vast majority of former reports described psoriasis vulgaris with resolution after discontinuation of an anti-TNF-α agent and the use of topical treatment, in this case the pustular lesions required systemic treatment with steroids and immunosuppressive agents. How psoriatic skin lesions could appear in patients receiving TNF-α inhibitors remains difficult to explain. A possible explanation may be found in the complexity and variability of the human immune response, in which the blockade of a single molecule may result in unexpected effects on different immunological pathways.