Anti-tumor necrosis factor (TNF)-alpha therapies (etanercept, adalimumab, infliximab, certolizumab pegol [may be safe for use during pregnancy], golimumab, and their biosimilars) are used to treat various inflammatory conditions, including psoriasis, psoriatic arthritis, rheumatoid arthritis, juvenile idiopathic arthritis, inflammatory bowel disease, and ankylosing spondylitis.

Several paradoxical cutaneous eruptions have been described with anti-TNF-alpha use, including:

• Injection site reactions
• Infusion reactions (with infliximab) – Both an acute hypersensitivity reaction within the first 2 hours and a delayed-type hypersensitivity reaction 1-14 days after the infusion.
• Cutaneous infections – Various types of viral, bacterial, and fungal infections have been reported. Patients who are immunosuppressed, have other comorbidities, and/or are on higher doses of anti-TNF-alpha therapies may be at higher risk for infections.
• Psoriasis – New-onset or exacerbated psoriasis has been reported. Palmoplantar pustular psoriasis is a common presentation, but plaque psoriasis is also reported.
• Nonmelanoma skin cancer (NMSC) – The risk of NMSC may be increased, especially in those who are immunosuppressed.
• Lupus-like syndrome – More common in patients who receive etanercept or infliximab. It typically resolves after anti-TNF-alpha therapy is stopped.
• Lichen planus-like eruptions
• Granulomatous reactions, including granuloma annulare and cutaneous and systemic sarcoidosis
• Cutaneous vasculitis – The risk appears to be higher in patients with rheumatoid arthritis.

Rare reports of anti-TNF-alpha-induced alopecia, urticaria, atopic dermatitis, rosacea, folliculitis, oral swelling, oral ulcers, gingivitis, pityriasis rosea, erythema nodosum, neutrophilic eccrine hidradenitis, Sweet syndrome, granuloma annulare, vitiligo, and tongue discoloration have also been described. Erythema multiforme (EM) and Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) have very rarely been described. The risk appears to be higher in female patients on TNF-alpha blockade for treatment of rheumatoid arthritis.

Related topics: cutaneous adverse effects of anti-PD-1 and anti-PD-L1 therapy, immune-related adverse effects