Antibody-based "biologic" therapies are widely used in dermatology for various indications, including psoriasis, atopic dermatitis, and other inflammatory conditions. During treatment with these agents, a variety of unique, paradoxical cutaneous reactions may occur. Worsening of a preexisting immune-mediated disorder (eg, psoriasis) has also been reported. Overlapping reactions may also occur. Onset may be shortly after initiation of treatment, or several months afterwards. Tumor necrosis factor alpha (TNF-α) inhibitors carry the highest risk of paradoxical reactions.

The following reactions have been reported:

TNF-α inhibitors

• Psoriasiform eruptions: Most common paradoxical eruption. Patients may present with new-onset psoriasis or changes in the preexisting morphology. Plaque type and palmoplantar psoriasis are the most common phenotypes. Inverse, guttate, generalized / pustular, and psoriatic alopecia-like reactions have also been reported. Infliximab is the most common culprit.
• Lupus-like reactions: This is a rare reaction. Patients may present with systemic lupus erythematosus with renal involvement, lupus-like syndromes, or isolated cutaneous lupus. Infliximab is the most common culprit, followed by adalimumab and etanercept.
• Sarcoidosis-like and other granulomatous reactions: This is a rare reaction with potential pulmonary and cardiac involvement. In addition, granuloma annulare and interstitial granulomatous drug reaction may also occur. Etanercept is the most common culprit.
• Other reactions: alopecia areata, vitiligo, hidradenitis suppurativa, lichenoid eruption, bullous pemphigoid, dermatomyositis, and pyoderma gangrenosum.

Interleukin (IL)-17A/17R inhibitors

• Eczematous reactions: The most common cutaneous eruption. It usually occurs within 4 months of initiating treatment. The phenotypes may include generalized atopic dermatitis-like eruptions, facial dermatitis, and/or dyshidrotic eczema. Ixekizumab appears to be the most common culprit, but it has also been reported in patients on secukinumab.
• Other reactions: psoriasiform eruption, sarcoidosis, alopecia areata, lichenoid eruption, pyoderma gangrenosum, Behçet syndrome, hidradenitis suppurativa, granuloma annulare, lupus-like reaction, vitiligo, erythema multiforme, bullous pemphigoid, and pemphigus.

IL-23 (p19) inhibitors

• Eczematous reactions: May occur 2.5-3 months after initiation of treatment. It is reported in patients on guselkumab only.

IL-12/23 (p40) inhibitor (ustekinumab)

• Psoriasiform eruptions: Usually occur within 3 months of treatment.
• Other reactions: vitiligo, alopecia areata, eczematous dermatitis, bullous pemphigoid, sarcoidosis-like reaction, lupus-like reaction, morphea, hidradenitis suppurativa, frontal fibrosing alopecia, Wells syndrome, erythema annulare centrifugum, and linear IgA bullous dermatoses.

IL-4Rα inhibitor (dupilumab)

• Psoriasiform reactions: This usually happens during the first year of therapy. Phenotypes may include plaque type and, less commonly, erythrodermic, guttate, palmoplantar, and scalp psoriasis.
• Eczematous dermatitis: This may present as localized dermatitis with a predilection for the face, periocular, and neck regions. It usually occurs within 6 months of therapy.
• Other reactions: alopecia areata, face / neck dermatitis, sarcoidosis-like reaction, and rosacea.