Paradoxical lichenoid drug eruption following dupilumab use for atopic dermatitis: A case report

Abstract

Dupilumab is a monoclonal antibody targeting interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling, approved for moderate-to-severe atopic dermatitis. Although generally well tolerated, paradoxical cutaneous reactions have been reported. We present a case of a 30-year-old male with longstanding atopic dermatitis who developed a lichenoid eruption several weeks after initiating dupilumab therapy. Biopsy confirmed a lichenoid drug eruption, prompting treatment modification. This case contributes to the growing recognition of paradoxical immune-mediated skin reactions associated with biologics and outlines a management approach balancing drug efficacy with adverse effect mitigation.

Introduction

Dupilumab has emerged as a key systemic treatment for patients with moderate-to-severe atopic dermatitis, offering durable control by modulating type 2 inflammation through inhibition of IL-4 and IL-13 signaling. ¹ While its safety profile is favorable, paradoxical reactions such as psoriasiform, eczematous, and lichenoid eruptions can occur.^1,2 These reactions challenge clinicians to distinguish between drug-induced effects and new primary dermatoses. Here, we report a case of a biopsy-confirmed lichenoid drug eruption occurring 7 weeks after initiating dupilumab.

Case report

A 30-year-old Caucasian man with a history of severe eczema since infancy presented in March 2025 with new-onset papular lesions after initiating dupilumab therapy in January 2025. His background included asthma, anxiety, environmental allergies, and multiple food allergies. He had a documented Dermatology Life Quality Index (DLQI) DLQI score of 23, indicating a significant impact on quality of life.

Over the years, his eczema had been recalcitrant to topical corticosteroids, with involvement of the back, axillae, arms, and lower extremities. He trialed multiple topicals, including Bryhali (halobetasol 0.01%), Protopic (tacrolimus 0.1%), and Zoryve (roflumilast) cream, which were applied inconsistently due to application burden. He had also trialed mirtazapine 15 mg as needed for itch with some benefit. His background treatments included antihistamines and topical emollients, though he struggled with adherence due to occupational demands (working underground) and skin sensitivity to various moisturizers.

On January 29, 2025, he was started on a 600 mg subcutaneous loading dose of dupilumab, followed by 300 mg dose every 2 weeks. Within a few weeks, he reported dramatic improvement in his eczema with a reduction in itch and clearance of lesions on his arms and legs. However, in mid-to-late February, he began to notice a new eruption: pink-to-violaceous flat-topped papules on the bilateral upper arms, back, and abdomen. The rash was non-pruritic, non-vesicular, and described as irritating rather than itchy. Some lesions appeared linear, raising suspicion for lichenoid reaction or Koebnerization. There were no systemic symptoms, recent travel, new medications, or infections. The patient denied ocular symptoms (e.g., conjunctivitis) and consumed alcohol 3–4 days per week on days off. A 4 mm punch biopsy of the right upper arm was performed. Clinical photographs were taken (Figure 1).

Figure 1.

Clinical presentation of paradoxical lichenoid drug eruption following dupilumab therapy. (a) and (b) Clustered flat-topped and violaceous papules on the right elbow and right forearm. (c)–(e) Scattered flat-topped lesions on the lower back, right lateral bicep, and right abdominal flank.

Histopathology of the punch biopsy showed epidermal acanthosis and hypergranulosis with a lymphocyte-predominant infiltrate within superficial dermis and at the epidermal junction (Figures 2–5). The findings from the biopsy and clinical presentation suggest a diagnosis of lichenoid interface dermatitis, favoring a lichenoid drug eruption with lichen planus and lichenoid keratosis as less favored possibilities. Consent was obtained for this case report. The patient’s paradoxical reaction was resolved when the dupilumab was stopped for 6 weeks; however, the eczema re-emerged 3 weeks after that. As a result, his treatment regimen was changed to dupilumab every 4 weeks and the addition of opzelura every 4 weeks.

Figure 2.

H&E 2×: Lichenoid inflammation with lymphohistiocytic perivascular infiltrate.

Figure 3.

H&E 5×: Lymphocyte-predominant superficial dermal infiltrate. There are admixed histiocytes. There is at least a focal vacuolar change at the dermo-epidermal junction.

Figure 4.

H&E 10×: Lichenoid infiltrate with perivascular inflammation. Epidermis is acanthotic with hypergranulosis and orthokeratosis. The basement membrane appears at least focally obscured.

Figure 5.

H&E ×20: Perivascular infiltrate consisting predominantly of lymphocytes.

Discussion

Paradoxical cutaneous eruptions are increasingly described in association with biologic therapies. ³ Although dupilumab primarily modulates type 2 inflammation, its effect on broader immune signaling may permit the emergence of Th1/Th17-mediated conditions such as lichen planus. ¹ In this case, the development of a new eruption within weeks of dupilumab initiation, combined with clinical morphology and biopsy findings, supports the diagnosis of a lichenoid drug eruption secondary to dupilumab.

Distinguishing lichenoid drug eruption from idiopathic lichen planus is clinically and histologically nuanced. ⁴ The lack of pruritus, absence of mucosal involvement, and presence of linear papules suggest a medication-related cause. Histopathology favored drug eruption, particularly based on clinical context, although there is histologic overlap between lichenoid drug eruption and lichen planus as well as other entities exhibiting lichenoid inflammation. Specifically, features such as basal vacuolar degeneration, hypergranulosis, and a lymphocyte-predominant lichenoid infiltrate may be seen. The temporal association with dupilumab and the absence of alternative triggers further support causality.

Management in this case focused on maintaining disease control while mitigating adverse effects. Rather than discontinuing dupilumab, the frequency was reduced. Potent topical steroids were reintroduced, and topical Janus kinase (JAK) inhibition was prepared as a secondary option. This stepwise approach is supported in literature for paradoxical eruptions when the biologic offers substantial benefit. ⁵