T-helper immune phenotype may underlie 'paradoxical' tumour necrosis factor-α inhibitor therapy-related psoriasiform dermatitis.

BACKGROUND: Therapeutics targeting tumour necrosis factor (TNF)-α are effective for psoriasis; however, in patients treated for other disorders, psoriasis may worsen and psoriasiform dermatitis (PsoD) may arise. T helper (Th) cytokines in psoriasis upregulate keratin (K)17, which modulates TNF-α transduction, leading to vascular adhesion molecule upregulation and lymphocytic extravasation. AIM: We investigated Th phenotype and expression of K17, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 in psoriasis and anti-TNF-α-related PsoD. METHODS: Skin biopsies from patients with psoriasis unresponsive to TNF-α inhibitor therapy (n = 11), PsoD-related to TNF-α inhibition (n = 9), untreated psoriasis (n = 9) or atopic dermatitis (AD; n = 9) were immunohistochemically analysed for Th1, Th2, Th17 and Th22. Expression of K17, ICAM-1 and VCAM-1 was also examined. RESULTS: Anti-TNF-α-unresponsive psoriasis and anti-TNF-α-related PsoD showed decreased Th1 : Th2 raio and increased Th17 : Th1 ratio compared with untreated psoriasis. Anti-TNF-α-unresponsive psoriasis had significantly fewer Th1 (4% vs. 12%) and more Th17 (51% vs. 20%) cells than untreated psoriasis. No difference in Th22 cells was identified. K17 was present in all cases of untreated psoriasis and anti-TNF-α-related PsoD, 91% of anti-TNF-α-unresponsive psoriasis, and only 22% of AD. VCAM-1 and ICAM-1 in anti-TNF-α-related PsoD was akin to untreated psoriasis, but decreased in anti-TNF-α-unresponsive psoriasis. CONCLUSIONS: These findings further the current understanding of the anti-TNF-α-related psoriasiform phenotype and support a rationale for therapeutic targeting of interleukin-17 and TNF-α in combination.

Delayed type IV hypersensitivity reaction to porcine acellular dermal matrix masquerading as infection resulting in multiple debridements.

INTRODUCTION: Delayed type IV hypersensitivity reactions are well established in the surgical setting with respect to external exposure via topical antibiotics and internal exposure via synthetic materials. In contrast, biologic matrix is derived from decellularized human or animal tissues and is consequently believed to elicit a minimal host inflammatory response. OBJECTIVE: We report a case of delayed type IV hypersensitivity reaction secondary to a biologic comprised of porcine-derived acellular dermal matrix, [Strattice™]. CONCLUSIONS: While biologic matrix is often preferred over synthetic mesh due to its decreased risk for infection, this case emphasizes that potential for hypersensitivity to the material persists. Type IV hypersensitivity reactions should be included in the differential diagnosis for suspected post-operative infections.

Genetic basis of TNF-α antagonist associated psoriasis in inflammatory bowel diseases: a genotype-phenotype analysis.

BACKGROUND: Anti-tumour necrosis factor (anti-TNF) biologic associated psoriasis has been reported in inflammatory bowel disease (IBD) patients. However, little is known regarding its pathogenesis. AIM: To identify potential genetic predispositions to anti-TNF associated psoriasis in IBD patients. METHODS: This retrospective chart review included IBD patients enrolled in a prospective registry. Cases of anti-TNF associated psoriasis and idiopathic psoriasis unrelated to anti-TNF exposure were confirmed by an expert dermatologist. All patients were genotyped on the Illumina Immunochip. A weighted genetic risk score ascertaining genetic pre-disposition towards psoriasis was calculated and overall genetic pre-disposition as well as differential distribution of individual polymorphisms was compared across the three groups. RESULTS: Our study included 724 IBD patients who initiated anti-TNF therapy and did not develop psoriasis, 35 patients with anti-TNF associated psoriasis, and 38 patients with idiopathic psoriasis. Anti-TNF users who developed psoriasis had a modest but statistically significantly greater psoriasis genetic risk score than anti-TNF controls (mean 0.64 vs. 0.61, P = 0.04), and had a similar genetic risk score as those with idiopathic psoriasis (0.64 vs. 0.62, P = 0.22). Two loci associated with NOS2 and ETS1 genes achieved P < 0.05 when comparing anti-TNF associated psoriasis to anti-TNF controls. Three loci were significantly different between anti-TNF associated psoriasis and idiopathic psoriasis including a polymorphism near NOS2 encoding for inducible nitric oxide synthase that is produced by dendritic cells in skin lesions in psoriasis. CONCLUSION: Patients with anti-TNF associated psoriasis had a modestly greater genetic pre-disposition towards psoriasis but no single causative polymorphism was identified.

Psoriasis associated with anti-tumour necrosis factor therapy in inflammatory bowel disease: a new series and a review of 120 cases from the literature.

BACKGROUND Anti-tumour necrosis factor (TNF) antibodies are used to treat both psoriasis and inflammatory bowel disease. The seemingly paradoxical occurrence of psoriasis in patients treated with anti-TNF antibodies is increasingly recognised, but the distinct features associated with inflammatory bowel disease have been incompletely characterised. AIM To identify inflammatory bowel disease patients who developed psoriasis while receiving an anti-TNF antibody at two academic medical centres between 2000 and 2009 and review all published cases of this phenomenon in inflammatory bowel disease. METHODS We identified retrospectively all cases of anti-TNF-induced psoriasis in inflammatory bowel disease patients attending two North American healthcare centres. We analysed these cases alongside the published reports of anti-TNF-induced psoriasis. RESULTS We identified 30 subjects who developed a psoriatic rash while receiving anti-TNF therapy for inflammatory bowel disease. Forty-seven per cent (14/30) responded to topical therapy and 23% (7/30) ultimately discontinued the anti-TNF. The new data were combined with those from 120 published cases of anti-TNF-induced psoriasis in inflammatory bowel disease. Anti-TNF-induced psoriasis in inflammatory bowel disease was more common in women (70%). The most common distributions were palmoplantar (43%) and scalp (42%). Complete follow-up in 148 cases showed that 41% responded to topical therapy but 43% required definitive withdrawal of anti-TNF therapy due to the rash. A second anti-TNF was tried in 27 cases with recurrence or persistence of the rash in 14 (52%). CONCLUSIONS In this analysis, psoriasiform lesions related to anti-TNF therapy in inflammatory bowel disease occurred most commonly in women. Approximately 41% of those who developed psoriasis while on anti-TNFs responded to topical therapy and were able to continue the drug, while 52% of those treated with an alternate anti-TNF had recurrence of the rash.