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Severe Skin Lesions Complicate Anti-TNF Therapy for IBD


 

Skin lesions led to discontinuation of anti–tumor necrosis factor-alpha therapy for inflammatory bowel disease in 34% of patients, reported Dr. Jean François Rahier and colleagues in the December issue of Clinical Gastroenterology and Hepatology.

Moreover, the occurrence of psoriasiform and eczematiform lesions associated with anti-TNF-alpha therapy was especially pronounced among patients with a previous history or family history of psoriasis or atopy.

Dr. Rahier of the Cliniques Universitaires de Mont-Godinne, Yvoir, Belgium, studied 85 patients with skin lesions and IBD who were seen at 35 gastroenterology centers in Belgium, France, Switzerland, and Austria.

A total of 69 patients had Crohn’s disease, 15 had ulcerative colitis, and 1 had indeterminate colitis. In all, 23 of the 85 patients were male. Data were collected using a standardized questionnaire. All cases were then reviewed simultaneously by a gastroenterologist and a dermatologist, wrote the authors (Clin. Gastroenterol. Hepatol. 2010 December [doi:10.1016/j.cgh.2010.07.022]).

Psoriasiform lesions (defined as well-delineated, scaly, erythematous plaques, as well as nail pitting, nail discoloration, and palmoplantar pustulosis) were observed in 62 patients. Their median age at the time of lesion development was 32 years, with a female: male ratio of 2:1.

"Fourteen patients (23%) had a previous history of psoriasis before treatment with any anti-TNF agent," wrote the authors. The remainder were diagnosed as having a "new onset of psoriasiform eruption," and among these, eight (17%) reported a history of familial psoriasis, two (4%) reported a history of familial atopy, and six (13%) reported a personal history of atopy.

Overall, 25 of these patients had a good response to topical treatment, whereas the remaining 37 patients had no response. In all, 16 of these nonresponders stopped anti-TNF treatment immediately because of their lesions.

The remaining 21 patients switched to another TNF antagonist; 7 of those patients discontinued this anti-TNF treatment as well. Two patients attempted a third anti-TNF agent, unsuccessfully.

That amounted to an overall discontinuation rate of 40% (25/62) because of psoriasiform skin lesions.

Eczematiform lesions (defined as xerosis and pruriginous, ill-limited plaques with erythematous or squamous macules or vesicles) were noted in 23 patients. The median age at the time of occurrence was 31 years, and the female:male ratio in this group was 6:7.

Of these patients, 10 (44%) had a history of atopy, and 13 were incident cases. Four of these incident cases (31%) had a familial history of atopy, one had a personal history of psoriasis, and one reported familial psoriasis.

A total of 16 patients (70%) had a good response to topical treatment of their lesions, and 7 (30%) had no response.

"Overall a definitive withdrawal of anti-TNF therapies due to uncontrolled [eczematiform] skin lesion was required in 4/23 (17%) patients," wrote the authors.

That equated to a total withdrawal among the entire population of 29 patients, or 34% of the study’s subjects.

The occurrence of lesions was not correlated with disease activity in the bowel. The authors noted that although the majority of lesions occurred in patients taking infliximab, compared with certolizumab or adalimumab, "this most probably reflects the earlier approval of this drug in Europe."

The authors also conceded that the true incidence of withdrawal may have been overstated in this population, since "this paper is a selected cohort of patients presenting with severe psoriasiform and eczematiform skin lesions seen in various centers."

Nevertheless, in light of the high rate of anti-TNF discontinuation shown in this study, they recommended that "all patients should be referred to a dermatologist for clinical evaluation and biopsy of skin lesions if indicated.

"Future research is needed to further explore epidemiological, clinical and fundamental aspects of this vexing paradoxical reaction," they added.

Dr. Rahier disclosed receiving lecture fees from Abbott Laboratories and Schering-Plough. Several other authors also disclosed financial relationships with pharmaceutical companies. They reported that they received no funding for the study.

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