Paradoxical Cutaneous Reaction: Secukinumab–Associated PLEVA in Palmoplantar Pustulosis

Introduction

Palmoplantar pustulosis (PPP) is a chronic, inflammatory dermatosis primarily affecting the palms and soles, characterized by recurrent sterile pustules that often cause significant pain and impair quality of life.¹ Although the pathogenesis of PPP has not been fully elucidated, it shares several immunopathological features with psoriasis, including upregulation of interleukin-17 (IL-17) in lesional skin, leading some to consider it as a localized variant of pustular psoriasis.² Based on these shared immune pathways, monoclonal antibodies targeting IL-17A, such as secukinumab, have been used off-label in refractory PPP with encouraging clinical outcomes.³

With the growing use of IL-17A inhibitors, a series of paradoxical cutaneous adverse reactions has been increasingly recognized. Previous reports have described Behçet-like lesions, alopecia areata, eczematous eruptions, and other paradoxical manifestations occurring during IL-17A blockade.^4–6 These reactions are thought to result from immune imbalance and compensatory activation of alternative cytokine pathways following inhibition of a dominant inflammatory axis. However, to the best of our knowledge, the development of acute pityriasis lichenoides et varioliformis acuta (PLEVA) as a paradoxical reaction specifically to secukinumab has not been previously reported.

Here, we report a rare case of acute PLEVA emerging during secukinumab therapy for PPP. This case highlights a potential but uncommon adverse effect of IL-17A inhibition and provides additional insight into the complex immune consequences associated with this therapeutic class.

Case Presentation

A 25-year-old woman presented with a 4-year history of PPP. She had previously been treated with oral acitretin and topical corticosteroids, with inadequate response. Secukinumab therapy was initiated at a dose of 300 mg weekly for 5 consecutive weeks, resulting in marked improvement of PPP symptoms.

However, at week 6 of treatment, the patient developed erythematous papules, papulovesicles, small erosions, and crusts on the face, back, and lower extremities (Figure 1). Skin biopsy revealed parakeratosis and hyperkeratosis of the epidermis, focal vacuolar degeneration of basal cells, and dense perivascular lymphocytic infiltration with scattered plasma cells in the dermis (Figure 2). Based on the clinical manifestations and histopathological findings, a diagnosis of PLEVA was established.

Figure 1 Clinical presentation of acute PLEVA eruption six weeks after initiating secukinumab therapy for palmoplantar pustulosis. The widespread eruption consisted of erythematous papules, vesicles, and small crusted ulcers, involving the (A) face, (B) back, and (C) lower extremities.

Figure 2 Histopathological findings of a skin biopsy from a PLEVA eruption (Hematoxylin and eosin stain). The image demonstrates characteristic features of acute pityriasis lichenoides et varioliformis acuta, including parakeratosis, basal cell vacuolization, and a dense perivascular lymphocytic infiltrate in the superficial dermis.

Given the temporal association between the onset of PLEVA and the administration of secukinumab, the biologic agent was considered the likely trigger. Secukinumab was discontinued, and the patient was switched to tofacitinib 5 mg twice daily, leading to gradual resolution of the papules and papulovesicles. After 12 weeks of treatment, her skin lesions had markedly improved, with only residual post-inflammatory hyperpigmentation (Figure 3).

Figure 3 Clinical resolution following discontinuation of secukinumab and initiation of tofacitinib therapy. Photographs taken at the 12-week follow-up show near-complete resolution of the acute PLEVA eruption with residual post-inflammatory hyperpigmentation on the (A) face, (B) back, and (C) lower extremities.

Discussion

Paradoxical reactions can occur during biologic therapy for inflammatory dermatoses, manifesting as exacerbation of the primary disease, phenotype shifts, or the emergence of new lesions.⁷ These reactions encompass a wide spectrum of clinical presentations, including psoriasis, eczematous eruptions, and alopecia areata.^8,9 Although current evidence suggests that cytokine imbalance and altered T-cell polarization may contribute to their pathogenesis, the precise mechanisms remain unclear. Here, we report a case of PLEVA that developed in a patient with PPP during treatment with secukinumab. As a single case report, a definitive causal relationship cannot be established; however, the clear temporal sequence following drug initiation and the subsequent resolution upon its discontinuation support a probable paradoxical reaction. This extends the known spectrum of adverse events associated with IL-17 blockade.

The immunopathogenesis of such reactions is multifactorial, often attributed to cytokine network imbalance. Inhibition of a dominant pathway like IL-17A may precipitate compensatory shifts in the immune milieu.¹⁰ For instance, cross-regulation between the IL-17 and TNF-α pathways is well-documented; inhibition of one may lead to upregulation of the other.¹¹ Given the implicated role of TNF-α in PLEVA,¹² this compensatory mechanism represents a plausible hypothesis for our observation. The occurrence of PLEVA with other targeted therapies (eg, checkpoint inhibitors, TNF-α antagonists) further underscores immune disequilibrium as a shared cornerstone of paradoxical reactions across drug classes.^9,10 In the context of this report, serial cytokine or immunophenotyping data before and after treatment were not available; such profiling in future cases would be invaluable for directly testing this hypothesis and elucidating the precise pathways involved.

A key clinical insight from this case is the observed response to the JAK inhibitor tofacitinib. The JAK-STAT pathway is a convergence point for multiple cytokines potentially involved in both PPP (eg, IL-23) and PLEVA (eg, type I interferons).¹³ Therefore, its inhibition may simultaneously modulate the disparate inflammatory drivers of the primary disease and the paradoxical eruption. Clinical evidence has accumulated supporting the effectiveness of JAK inhibitors in the treatment of PPP.^14,15 Similarly, several case reports have suggested that upadacitinib, a selective JAK1 inhibitor, may also be beneficial for PLEVA.^16,17 While this single case provides preliminary, hypothesis-generating evidence for JAK inhibition as a potential therapeutic alternative in this specific scenario, it is not yet a broadly established strategy. Its efficacy and safety in managing biologic-induced paradoxical reactions require validation in larger studies.

Conclusion

In summary, we report a case in which secukinumab, an IL-17A inhibitor used for PPP, was associated with the development of PLEVA. While based on a single observation, the simultaneous improvement of both conditions with a JAK inhibitor suggests this drug class may be a potential therapeutic alternative supported by emerging case-level evidence. Clinicians should remain vigilant for these uncommon adverse reactions to ensure timely recognition and appropriate management.