MEK inhibitors (MEKis) – including trametinib, selumetinib, and binimetinib – are targeted therapies that inhibit the MAPK signaling pathway, frequently used in cancers with RAS or BRAF mutations. By disrupting downstream signaling, MEK inhibition suppresses tumor proliferation. However, these agents also impair epidermal homeostasis, leading to frequent cutaneous adverse effects.

Dermatologic toxicities are among the most common side effects of MEKi therapy. These typically emerge within the first 1-4 weeks of treatment but can develop as early as a few days after initiation or arise later in the treatment course. Lesions may persist, recur, or evolve over time, especially with continuous exposure. Common presentations include acneiform eruptions, paronychia, xerosis, eczematous dermatitis, and photosensitivity. While most reactions are mild to moderate (grade 1-2), they can cause significant discomfort and psychosocial distress and can necessitate dose reduction or interruption.

Serious or life-threatening dermatologic reactions are rare. However, MEKis have been associated with severe cutaneous adverse reactions (SCARs), including drug-induced hypersensitivity syndrome (DIHS), which require immediate discontinuation of the drug and urgent intervention.

In pediatric populations, MEKis are increasingly used to treat low-grade gliomas and neurofibromatosis type 1-associated plexiform neurofibromas. Children exhibit a somewhat distinct reaction profile, with xerosis, dermatitis, paronychia, and hair pigmentary changes among the most frequent manifestations. Acneiform eruptions are more common in adolescents, likely due to increased sebaceous gland activity, and may be underrecognized in terms of psychosocial impact.

Patients receiving combination therapy with BRAF inhibitors and MEKis may experience a modified toxicity profile. While combination regimens may lower the risk of some proliferative lesions (eg, keratoacanthomas), inflammatory and irritant reactions remain common. MEKi-induced dusky erythema is an erythema multiforme-like eruption that occurs more frequently in patients on combination therapy than in those on MEKi therapy alone. Onset is within a few weeks to months.

Immunocompromised patients may present with atypical or more severe manifestations.