Psoriasis and Pustular Dermatitis Triggered by TNF-α Inhibitors in Patients With Rheumatologic Conditions

Abstract

Background: New onset or worsening of psoriasis has been reported in patients treated with tumor necrosis factor ␣ (TNF-␣) inhibitors for a variety of rheumatologic conditions. There is mounting evidence that a key innate immune pathway for triggering common human autoimmune disease, including psoriasis, involves plasmacytoid dendritic cell precursors (PDCs) and type 1 interferon (IFN) production. We present herein a case series with clinical and histopathologic evidence of psoriasis in patients with rheumatologic disease treated with TNF-␣ inhibitors. We propose that the cross regulation between TNF-␣ and IFN may have a role in the pathogenesis of this reaction. Observations:We observed new-onset psoriasis (n=13) or severe exacerbation of psoriasis (n = 2) in 15 patients with a variety of rheumatologic conditions-rheumatoid arthritis (n=13), psoriatic arthritis (n=1), and seronegative arthritis (n=1)-during treatment with etanercept (n=6), infliximab (n=5), and adalimumab (n=4). Immunohistochemical staining of skin biopsy specimens for myxovirus-resistance protein A (MxA, a surrogate marker for lesional type 1 IFN activity) showed increased staining in TNF-␣ inhibitor-induced psoriasis compared with psoriasis vulgaris.Conclusions: New onset or severe exacerbation of psoriasis is a rare complication of TNF-␣ inhibitor therapy. The finding of increased production of IFN-␣ in TNF-␣ inhibitor-induced psoriasis is a possible pathophysiologic explanation for this reaction.

Severe Skin Lesions Cause Patients With Inflammatory Bowel Disease to Discontinue Anti–Tumor Necrosis Factor Therapy

“…32 TNF inhibits PDC maturation from hematopoietic progenitors as well as IFN-α production. 33 Subsequently, inhibition of TNF may allow unlimited and unregulated production of IFN-α by PDCs. Increased IFN-α expression was found in the dermal vasculature and in perivascular lymphocytic infiltrate of lesional skin of patients with TNF antagonist therapy.…”

Lack of evidence for erythema multiforme in skin reaction to adalimumab: Comment on the article by Beuthien et al

“…The most common skin reaction associated with anti-TNF␣ treatment seems to be inflammatory skin conditions such as pustular psoriasis and eczema (45% of reactions) (5,6). New-onset psoriasis has been reported in patients treated with TNF␣ antagonists for a variety of rheumatologic conditions, with mounting evidence that the cross-reaction between TNF␣ and interferon may have a role in the pathogenesis of this reaction (6). We hypothesize that the case reported by Beuthien et al (1) could be pustular psoriasis of the palms and soles, triggered by TNF␣ inhibitor therapy.…”

Clinical experience of combination therapy of infliximab and total glucosides of paeony for severe psoriasis with liver disorder history

“…Interferon (IFN)-α produced by dermal plasmacytoid dendritic cells has been identified as a key element in psoriatic skin lesion formation. As TNF-α regulates IFN-α production and the inhibition of TNF-α has been shown to induce the overexpression of IFN-α-regulated genes, therefore it is proposed that TNF-α inhibition might induce locally sustained IFN-α production in patients developing psoriasis while undergoing anti-TNF therapy [26] . In another research, anti-TNF drug-induced psoriasiform skin lesions are attributed to the infiltrates of interleukin (IL)-17A/ IL-22-expressing Th17 cells and IFN-expressing Th1 cells, and the severity of skin disease were positively correlated with the number of IL-17A-expressing T cells [27] .…”