A few diagnostic challenges in dermatology are as consequential as determining whether a medication is responsible for skin reaction. However, the answer is often less straightforward than it appears. Drug-induced skin reactions are among the most diagnostically challenging conditions encountered in dermatologic practice. At the European Academy of Dermatology and Venereology (EADV) Symposium 2026 in Athens, Greece, Deepak M.W. Balak, MD, PhD, of Leiden University Medical Center in Leiden, Netherlands, used a series of clinical cases to illustrate why medications are often suspected as the cause of dermatologic reactions but may not always be responsible.

Immune Checkpoint Inhibitor (ICI)-Associated Psoriasis

In the first case, Balak described a patient with metastatic endometrial carcinoma who developed a generalized pruritic eruption after three cycles of the PD-L1 inhibitor durvalumab. Clinically, the relatively sharply demarcated lesions and positive candle-wax phenomenon were consistent with psoriasis.

The case highlighted known immune-mediated cutaneous adverse effects of ICIs, which can both trigger de novo psoriasis and exacerbate preexisting disease. From a pathophysiologic perspective, T-cell hyperactivation is considered the primary mechanism.

Diagnostic Clues

Balak emphasized that drug-induced and idiopathic psoriasis are often difficult to distinguish clinically and histologically. Features that may suggest a medication-associated cause include a psoriasiform presentation that is not entirely classic, fewer Munro microabscesses, or atypical histopathologic patterns, such as spongiotic or lichenoid infiltrates. However, the absence of eosinophilic infiltrates did not preclude drug-induced psoriasis.

Treatment generally follows established psoriasis management principles but must consider the underlying oncologic condition. The topical betamethasone-calcipotriol combination may be sufficient in some cases. Among systemic therapies, options with little or no immunosuppressive effects, such as acitretin, may be particularly attractive. Apremilast and interleukin (IL)-23 inhibitors have also been discussed as potential treatment options.

Cutaneous Lupus

The second case involved a 34-year-old patient with chronic inflammatory demyelinating polyneuropathy who was receiving intravenous immunoglobulin therapy. Two months after treatment initiation, the patient developed pruritic lesions on the neck, upper back, and face. Histopathological findings and positive anti-SSA antibodies supported the diagnosis of subacute cutaneous lupus.

Balak noted that drug-induced forms of cutaneous lupus are not uncommon. They are most often present as subacute cutaneous lupus, whereas idiopathic disease commonly manifests as chronic discoid lupus.

Drug-induced cases may also be clinically more extensive, with the involvement of non-sun-exposed areas and, in some cases, bullous or erythema multiforme-like lesions. Potential triggers include antihypertensive agents, lipid-lowering drugs, proton pump inhibitors, and TNF-alpha inhibitors.

Balak also highlighted the paradox that intravenous immunoglobulins can both trigger cutaneous lupus and be used therapeutically to treat it. In the presented case, the skin lesions improved with topical therapy, allowing continuation of immunoglobulin treatment required for management of the patient's neurologic condition.

Paradoxical Eczema

In the third case, a 48-year-old patient with plaque psoriasis developed increasing pruritus and poorly demarcated erythematous lesions on the trunk, back, and lower legs despite successful treatment with an IL-23 inhibitor. Balak identified the eruption as paradoxical eczema.

The condition refers to eczematous skin changes that occur during biologic therapy for psoriasis. It has been reported primarily with TNF-alpha and IL-17 inhibitors and less frequently with IL-23 inhibitors. Prevalence is estimated at approximately 1%-3%, although underreporting is likely. Reported risk factors include older age, female sex, and preexisting atopy.

Balak noted that paradoxical eczema may differ pathophysiologically from classic atopic dermatitis. Rather than being driven primarily by a type 2 immune response, it appears to involve type 1 inflammatory pathways, including TNF-alpha, interferon‐alpha, and gamma. This has generated interest in Janus kinase inhibitors as potential therapeutic options.

Epidermal Growth Factor Receptor (EGFR) Inhibitors

In another case, a 59-year-old woman with non-small cell lung cancer developed a papulopustular eruption on the trunk during treatment with an EGFR inhibitor. Balak described the eruption as an acneiform rash, a well-recognized adverse effect of this class of drugs.

He emphasized this distinction from acne vulgaris. Acneiform eruptions are characterized by papules and pustules without comedones. The face and trunk are commonly affected, and the lesions may be pruritic or painful. The underlying mechanism is EGFR inhibition within hair follicles and the epidermis.

The patient was treated with topical clindamycin and retinoids, resulting in improvement in skin lesions and continuation of cancer treatment.

Causality Assessment

The fifth and final case highlighted the importance of careful diagnostic evaluation. Three weeks after starting metoprolol and rivaroxaban for atrial fibrillation, the patient developed generalized pruritus accompanied by a sensation of insects crawling on the skin. Drug-induced pruritus was initially suspected.

However, dermatoscopic examination revealed a pubic louse, confirming the diagnosis of pediculosis pubis.

Balak noted that even a convincing temporal relationship between medication exposure and symptom onset does not necessarily indicate a drug reaction. Although the Naranjo Scale can support a structured assessment of causality, it cannot replace a thorough clinical evaluation.

Conclusion

In summarizing the cases, Balak emphasized that ICIs can trigger psoriasis, that a possible drug-induced cause should always be considered in patients with subacute cutaneous lupus, and that paradoxical eczema associated with biologic therapy warrants greater recognition. He also highlighted the characteristic acneiform eruptions associated with EGFR inhibitors.

Overall, these cases highlighted the need for a careful and systematic diagnostic approach when evaluating suspected drug-related skin reactions.

This story was translated from Coliquio, part of the Medscape Professional Network.