TNFα and IL‐17A are differentially expressed in psoriasis‐like vs eczema‐like drug reactions to TNFα antagonists

Abstract

Background Tumor necrosis factor α (TNFα) blocking drugs are in use for a wide range of autoimmune disorders. In up to 5% of patients, this class of drugs produces puzzling cutaneous side effects that are the subject of this investigation, namely psoriasiform and eczema‐like skin inflammation. These side effects can occur after any time of treatment and regardless of the underlying disorders. The exact pathophysiology is as yet unknown. Methods A total of 33 patients (19 female, average age 52 years) who had a cutaneous reaction to infliximab, adalimumab or etanercept were included. The type of inflammatory reaction was determined, and the corresponding cytokine expression was evaluated by immunohistochemistry for TNFα, IL‐1β, IL‐22, IL‐6, IL‐17A, IL33, IL‐8 and IL‐36α (semi‐quantitative grading system from − to ++++). In addition, RNA expression levels of IL‐17A and TNFα were confirmed by quantitative real‐time PCR. Results IL‐17A (P < .039) and TNFα (P < .008) were expressed at significantly higher levels in psoriasis or pustular‐like reactions (PPR) compared to eczematous‐like reactions (ELR). There was no significant difference in the expression of IL‐1β, IL‐22, IL‐6, IL‐33, IL‐8 and IL‐36α between PPR and ELR. Conclusion TNFα and IL‐17A are both cytokines known to be involved in psoriasis but less so in non‐psoriasiform dermatitis or eczema. Therefore, their overexpression in PPR is plausible and suggests that the pathogenesis of PPR mirrors at least in part those of psoriasis. Further investigations will define the exact role of these cytokines in rare cutaneous side effects of anti‐TNFα therapy. Our results suggest that IL‐17A inhibition could be a therapeutic option in patients with anti‐TNF induced psoriasis.

Skin Manifestations in Pediatric Patients Treated With a TNF-Alpha Inhibitor for Inflammatory Bowel Disease: A Retrospective Study

“…Interleukin 17 (IL-17) and 22 (IL-22), derived from Th17, are involved in the pathogenesis of anti-TNF-induced psoriasiform reactions, and higher expression of Th17 cells has been observed in more severely affected patients, who respond well to the anti-IL-12/23 ustekinumab. 30,31 However, exacerbation of the previous psoriasiform reactions during ustekinumab therapy have been described. 32 Vedolizumab, a gut-specific α4β7 integrin inhibitor, approved for both Crohn's disease and ulcerative colitis, has shown promising results in a few cases of anti-TNF-induced psoriasis.…”

HIV infection confers distinct mechanisms in severe drug eruption: Endogenous virus activation with aberrant Th2/Th1 and CD8+ T cells function

“…Cytokines, such as IL‐4, IL‐6, IL‐13, IFN‐γ, TNF‐α, CCL17 and CXCL9 that are released by T lymphocytes and mononuclear macrophages may participate in the occurrence and development of ADRs . TNF‐α and IFN‐γ are the key cytokines in SJS/TEN .…”

Pathogenesis of psoriasis in the “omic” era. Part III. Metabolic disorders, metabolomics, nutrigenomics in psoriasis in psoriasis

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