Herpes simplex risk during biologic treatment for erythrodermic psoriasis

Abstract

Disseminated herpes simplex virus infection in erythrodermic psoriasis remains exceedingly uncommon, yet it poses substantial diagnostic and therapeutic challenges in patients receiving biologic therapy. The recent case by Berjawi et al illustrates an atypical presentation of widespread herpes simplex virus-1 in a patient undergoing treatment with ixekizumab and topical corticosteroids, highlighting diagnostic uncertainty, cumulative immunosuppression, and therapeutic decision-making in severe psoriasis. This correspondence aims to emphasize the challenges of early herpes simplex virus recognition, discuss the potential but associative role of interleukin-17 inhibition in antiviral defence, and underscore the lack of clinical guidance regarding interruption and safe reintroduction of biologic therapy following viral clearance.

Key Words: Erythroderma; Psoriasis; Herpes simplex virus; Biologic therapy; Immunomodulation; Cutaneous infection

Core Tip: Disseminated herpes simplex virus-1 is a rare but potentially life-threatening complication in erythrodermic psoriasis treated with biologics. This case highlights diagnostic ambiguity in inflamed skin, the impact of cumulative immunosuppression, and the absence of standardized guidance on when and how to safely reintroduce biologic therapy after viral resolution.

TO THE EDITOR

We read with great interest the case report by Berjawi et al[1], describing disseminated herpes simplex virus type-1 in a patient with erythrodermic psoriasis treated with ixekizumab and topical corticosteroids. This case is highly instructive, as disseminated herpes simplex virus-1 (HSV-1) remains rare even among individuals receiving biologic therapy, and its manifestation in the setting of erythrodermic psoriasis is exceptionally unusual.

The report draws attention to the unique predisposition of erythrodermic skin to infectious complications. Widespread barrier disruption, increased transepidermal water loss, and impaired cutaneous immunity create a permissive environment for viral proliferation[2,3]. This vulnerability may be further amplified by systemic immunomodulation, particularly therapies targeting cytokines involved in mucocutaneous immune surveillance[4-6]. The patient described had multiple converging risk factors-including recent infliximab exposure, initiation of ixekizumab, potent topical corticosteroids, and underlying hepatic disease-illustrating the cumulative nature of immunosuppressive risk rather than a single causative factor.

Moreover, the authors emphasize an important diagnostic challenge: Differentiating disseminated HSV-1 from eczema herpeticum in the context of inflamed or desquamating skin. Because clinical morphology may be misleading, early virologic confirmation is essential. Polymerase chain reaction testing from skin lesions remains the preferred diagnostic modality due to its high sensitivity and rapid turnaround, allowing prompt initiation of antiviral therapy and avoidance of unnecessary immunosuppression[7-9].

This case also raises broader questions regarding the optimal timing of biologic reinitiation following viral clearance. The cautious reintroduction of ixekizumab after clinical improvement of HSV lesions reflects a pragmatic, individualized strategy; however, formal guidance on biologic interruption, timing of reinitiation, and the role of antiviral prophylaxis is currently lacking[10,11].

CURRENT SITUATION AND CHALLENGES

Erythrodermic psoriasis continues to represent one of the most severe and medically unstable variants of psoriasis. Mortality is influenced by sepsis, thermoregulatory failure, and electrolyte imbalance[2]. Although biologic agents are increasingly used to control severe inflammation, their use during active infection presents a therapeutic dilemma, requiring clinicians to balance disease control against infectious risk.

Evidence linking biologic therapy; particularly interleukin-17 (IL-17) inhibition to disseminated HSV infection is limited predominantly to isolated case reports and observational data. While IL-17 plays a role in mucocutaneous host defence, the association between IL-17 blockade and HSV reactivation remains associative rather than causative, and should be interpreted cautiously.

KEY ASPECTS OF DISSEMINATED HSV-1 IN ERYTHRODERMA

This case highlights several practical considerations for clinicians managing erythrodermic psoriasis: New vesicular or erosive eruptions in biologic-treated erythroderma warrant immediate evaluation for HSV using polymerase chain reaction based diagnostics. Temporary interruption of biologic therapy during active HSV infection remains a prudent approach until lesions resolve and systemic stability is achieved. Decisions regarding biologic reintroduction should be individualized, guided by clinical recovery, virologic resolution, and multidisciplinary assessment, in the absence of standardized protocols. Antiviral prophylaxis may be considered in select high-risk patients requiring ongoing biologic therapy, although evidence remains limited.

CLINICAL AND THERAPEUTIC IMPLICATIONS

This case highlights several practical lessons for clinicians managing erythrodermic psoriasis:

Early detection is critical

Any new vesicular eruption in erythrodermic or biologic-treated patients should prompt an immediate workup for HSV-1, HSV-2, and varicella-zoster virus.

Treatment should balance infection control and inflammation control

Temporary interruption of biologic therapy during active HSV infection remains a prudent approach until lesions improve and systemic symptoms stabilize.

Reinitiation of biologics requires careful timing

There is insufficient evidence on the optimal timing for restarting biologic agents after viral clearance. Until consensus statements are developed, individualized decisions guided by clinical improvement and virologic resolution are essential.

Long-term prophylaxis may be warranted

For patients requiring ongoing biologic therapy after a disseminated HSV episode, antiviral prophylaxis; as used successfully in the case by Berjawi et al[1] is a reasonable consideration.

CONCLUSION

Beyond supporting the original case, this correspondence emphasizes an unmet clinical need: Clearer guidance on diagnostic strategies, biologic interruption, and safe reintroduction following serious viral infections in erythrodermic psoriasis. As biologic use expands, systematic data are required to inform monitoring strategies and optimize patient safety in complex, high-risk settings.