Disseminated herpes simplex virus type 1 treated with ixekizumab in a patient with erythrodermic psoriasis: A case report

Abstract

BACKGROUND

Erythrodermic psoriasis (EP) is a rare and life-threatening form of psoriasis associated with significant morbidity and mortality. Systemic immunosuppressive therapies are often required but may predispose to opportunistic infections. Disseminated herpes simplex virus type-1 (HSV-1) is an unusual complication in otherwise immunocompetent patients and has not been reported in association with ixekizumab therapy for EP.

CASE SUMMARY

We describe a 49-year-old man with longstanding severe plaque psoriasis, liver cirrhosis, and bipolar disorder who developed EP involving > 90% of body surface area [Psoriasis Area and Severity Index (PASI) 45]. Following initial stabilization, he was admitted to the intensive care unit (ICU) with hemodynamic instability, leukocytosis with eosinophilia, and diffuse desquamation. Ixekizumab was initiated with high-dose topical clobetasol. During his ICU stay, he developed recurrent bacteremias and neurologic decline (Glasgow Coma Scale 7/15), followed by the appearance of widespread vesicles and hemorrhagic crusts. HSV-1 infection was confirmed by polymerase chain reaction (PCR). Immunosuppressive therapy was withheld, and intravenous acyclovir was started, leading to progressive improvement. After ten days, ixekizumab was reintroduced with careful monitoring, resulting in marked clinical improvement (PASI 9.7 at six weeks). The patient remained stable on long-term follow-up with oral acyclovir prophylaxis.

CONCLUSION

This case highlights the diagnostic and therapeutic challenges of managing EP in the setting of biologic therapy. Disseminated cutaneous HSV-1 should be considered in immunosuppressed patients presenting with new vesicular eruptions, and prompt PCR testing with early antiviral therapy is essential. A multidisciplinary approach is critical to balance immunosuppression for disease control with infection risk.

Key Words: Erythroderma; Psoriasis; Disseminated herpes; Ixekizumab; Topical steroids; Case report

Core Tip: Erythrodermic psoriasis (EP) is a rare, severe form of psoriasis associated with high morbidity and mortality. Management frequently requires systemic immunosuppression, which increases susceptibility to opportunistic infections. We describe a patient with EP who developed disseminated herpes simplex virus type 1 while receiving biologic and corticosteroid therapy. This case emphasizes the importance of early recognition of vesicular eruptions, timely diagnostic testing, and prompt antiviral therapy. Clinicians must balance disease control with infection risk, highlighting the need for vigilant monitoring and multidisciplinary management in EP.

INTRODUCTION

Erythrodermic psoriasis (EP) is an uncommon and severe manifestation of psoriasis vulgaris, with an estimated prevalence of 1%-2.25% among patients with psoriasis[1]. It is the leading cause of erythroderma, accounting for approximately one-quarter of cases, and carries high morbidity and mortality due to complications such as fluid loss, electrolyte imbalance, infection, and cardiovascular instability[1].

Management of EP is complex and often requires systemic immunosuppressive agents, including cyclosporine, methotrexate, and biologics such as infliximab and ixekizumab[2]. While these therapies can achieve disease control, they may increase susceptibility to opportunistic or disseminated infections. Disseminated herpes simplex virus type-1 (HSV-1) infection is rarely reported in otherwise immunocompetent individuals, and its occurrence during treatment of EP has not been described previously.

In the present case, HSV-1 involvement was confined to the skin without evidence of visceral disease. Such a presentation overlaps with eczema herpeticum, also known as Kaposi varicelliform eruption, which represents disseminated HSV-1 infection superimposed on diseased skin[3,4]. The distinction between disseminated cutaneous HSV-1 and eczema herpeticum can be challenging, particularly in patients with underlying inflammatory dermatoses.

This case report was prepared in accordance with the CARE (CAse REport) guidelines, which provide a structured framework for transparent and comprehensive case reporting[5]. We present the case of a 49-year-old man with EP complicated by cutaneous disseminated HSV-1 infection following biologic and corticosteroid therapy, highlighting the diagnostic and therapeutic challenges encountered in balancing immunosuppression with infection control.

CASE PRESENTATION

Chief complaints

A 49-year-old man presented with rapidly progressive generalized erythema, scaling, and edema involving more than 90% of his body surface area (BSA), accompanied by fever, chills, and altered consciousness.

History of present illness

Two weeks before admission, the patient developed worsening erythema and scaling that began on the upper extremities and rapidly progressed to involve over 75% of his BSA (Figure 1). He self-initiated oral prednisone, which was subsequently discontinued at dermatology follow-up and replaced with topical corticosteroids and emollients. Three days later, due to continued deterioration, he received an infusion of infliximab (5 mg/kg) without clinical improvement. He was admitted with diffuse erythema and fever, treated with antibiotics, and discharged after transient stabilization. Ten days later, he was re-admitted to the intensive care unit (ICU) with severe erythroderma (> 90% BSA), generalized edema, recurrent fevers, hemodynamic instability, and neurologic decline.

Figure 1  Early erythrodermic psoriasis with approximately 75% body surface area involvement during the first hospitalization, prior to intensive care admission.

History of past illness

The patient had a 10-year history of severe plaque psoriasis refractory to multiple systemic agents, including methotrexate, cyclosporine, secukinumab, and topical corticosteroids. Ixekizumab had previously achieved partial control but was discontinued one year earlier due to unavailability. Additional comorbidities included liver cirrhosis secondary to non-alcoholic fatty liver disease with portal hypertension and esophageal varices (on propranolol), and bipolar disorder managed with paroxetine, mirtazapine, and chlorpromazine. He had undergone prior esophageal variceal band ligation.

Personal and family history

The patient was married and lived with his family. He reported no history of alcohol use, smoking, or illicit drug use. There was no family history of psoriasis, autoimmune disease, or dermatologic disorders.

Physical examination

At ICU admission, vital signs were blood pressure 85/55 mmHg, heart rate 125 beats/minutes, temperature 39.0 °C, respiratory rate 28/minutes, and oxygen saturation 91% on 2 L/minutes oxygen. Examination revealed diffuse confluent erythema with scaling involving > 90% of BSA, generalized edema, and desquamation. No ulcerations were noted initially. During his ICU stay, the patient developed widespread vesicles, erosions, and hemorrhagic crusts. Neurologic assessment showed a Glasgow Coma Scale score of 7/15, necessitating intubation.

Laboratory examinations

Initial laboratory studies demonstrated leukocytosis (17.2 × 10⁹/L), eosinophilia (1.2 × 10⁹/L), elevated C-reactive protein (120 mg/L), hypoalbuminemia (2.6 g/dL), and mild hyponatremia (Na 131 mmol/L). Renal function was preserved (creatinine 0.9 mg/dL). HSV-1 polymerase chain reaction (PCR) from vesicular swabs was positive.

Imaging examinations

No radiologic imaging was required for diagnosis.

MULTIDISCIPLINARY EXPERT CONSULTATION

Given the patient’s critical condition and overlapping dermatologic and infectious complications, a multidisciplinary team was assembled. The consultation included dermatology, infectious diseases, critical care, and gastroenterology specialists.

The dermatology team guided the diagnosis of erythrodermic psoriasis and recommended initiation of biologic therapy with ixekizumab after failure of infliximab. The infectious diseases team managed recurrent bacteremias and directed antiviral therapy once disseminated HSV-1 was confirmed. The critical care team stabilized the patient’s hemodynamic status, managed airway protection during neurologic decline, and coordinated supportive care. The gastroenterology team provided input on the management of underlying liver cirrhosis, portal hypertension, and medication safety in the context of hepatic dysfunction.

Consensus was reached to temporarily withhold immunosuppressive therapy during active HSV-1 infection, initiate intravenous acyclovir, and later reintroduce ixekizumab cautiously once the viral lesions had resolved.

FINAL DIAGNOSIS

Erythrodermic psoriasis complicated by disseminated cutaneous herpes simplex virus type-1 infection in the context of biologic (ixekizumab) and corticosteroid therapy.

TREATMENT

Upon ICU admission, the patient was stabilized with intravenous fluids and empiric broad-spectrum antibiotics, later de-escalated based on culture results. Ixekizumab was initiated along with high-potency topical corticosteroids (clobetasol propionate 0.05%, approximately 30 g/day). During the ICU course, the patient developed recurrent bacteremias and a widespread vesicular eruption. HSV-1 PCR confirmed disseminated infection. Ixekizumab and corticosteroids were withheld, and intravenous acyclovir (5 mg/kg every 8 hours) was started with renal function monitoring. Following ten days of antiviral therapy and resolution of cutaneous lesions, ixekizumab was reintroduced with cautious tapering of topical corticosteroids (Table 1, Figures 2 and 3).

Figure 2  Disseminated cutaneous herpes simplex virus type-1 eruption arising during the second intensive care unit admission, approximately one week after initiation of ixekizumab.

Figure 3  Marked clinical improvement at six-week follow-up, with resolution of widespread erythema and palmoplantar scaling after antiviral therapy and reintroduction of ixekizumab.

Table 1 Timeline of clinical course, investigations, and interventions.

Date/interval	Clinical events	Investigations/labs/vitals	Interventions	Outcomes
2 weeks before first hospital admission	Severe itching and erythema of upper extremities progressing rapidly	-	Self-initiated oral prednisone (unprescribed) → discontinued at dermatology visit; switched to topical corticosteroids and moisturizers	Erythema progressed to > 75% BSA
3 days later	Worsening erythema with fever	Vitals: BP 115/70 mmHg, HR 110 bpm, Temp 38.2 °C, RR 22/min, SpO2 96% RA. Labs: WBC 13.5 × 109/L, eosinophils 0.8 × 109/L, CRP 45 mg/L, other labs normal	Infliximab infusion (5 mg/kg)	No improvement; admitted for first hospitalization
First hospital admission	Diffuse erythema (> 75% BSA) with fever	As above	Broad-spectrum antibiotics → de-escalated to MSSA coverage; discharged on oral Augmentin	Temporary stabilization
10 days later (second admission, ICU)	Increasing chills, diffuse edema, worsening erythema (> 90% BSA). PASI 45 calculated	Vitals: BP 85/55 mmHg, HR 125 bpm, Temp 39.0 °C, RR 28/minutes, SpO2 91% on 2 L O2. Labs: WBC 17.2 × 109/L, eosinophils 1.2 × 109/L, CRP 120 mg/L, albumin 2.6 g/dL, Na 131 mmol/L, creatinine 09 mg/dL	ICU admission; fluid resuscitation	Hemodynamically unstable
Early ICU course (second admission)	Confluent erythroderma and desquamation	Punch biopsy performed: Hypogranulosis, ectatic dermal vessels, neutrophils in stratum corneum, scattered dermal eosinophils	Ixekizumab initiated; topical clobetasol approximately 30 g/day	Recurrent bacteremias; progressive decline in consciousness (GCS 7/15); intubated
1 week after ixekizumab	Disseminated vesicles, erosions, hemorrhagic crusts (Figure 2)	HSV-1 PCR positive	IV acyclovir 5 mg/kg q8h; clobetasol stopped; ixekizumab withheld	Gradual clinical improvement
10 days later	Improvement in HSV lesions	-	Topical corticosteroids reintroduced; ixekizumab restarted	Steady recovery (Figure 3)
6-week follow-up	Resolution of widespread erythema and palmoplantar scaling (PASI 9.7)	-	Continued ixekizumab; oral acyclovir prophylaxis	Stable improvement; no relapses (Figure 3)

BSA: Body surface area; BP: Blood pressure; HR: Heart rate; Temp: Temperature; RR: Respiratory rate; SpO₂: Peripheral capillary oxygen saturation; RA: Room air; WBC: White blood cell count; CRP: C-reactive protein; MSSA: Methicillin-sensitive staphylococcus aureus; ICU: Intensive care unit; PASI: Psoriasis Area and Severity Index; Na: Sodium; HSV-1: Herpes simplex virus type 1; IV: Intravenous; q8h: Every 8 hours (dosing interval); GCS: Glasgow Coma Scale.

OUTCOME AND FOLLOW-UP

The patient demonstrated steady improvement after antiviral therapy and reinitiation of ixekizumab. By six weeks, his Psoriasis Area and Severity Index (PASI) had improved from 45 to 9.7, with resolution of widespread erythema and palmoplantar scaling. He was discharged on oral acyclovir prophylaxis, which was continued for six months. At follow-up visits, the patient remained clinically stable with no relapses or new adverse events.

DISCUSSION

To our knowledge, no published articles have reported disseminated HSV-1 infection in the setting of erythrodermic psoriasis treated with ixekizumab in combination with topical corticosteroids. This case underscores the complexity of managing severe psoriasis while balancing the risks of immunosuppression and opportunistic infection.

EP is frequently precipitated by abrupt withdrawal of systemic therapy, including corticosteroids, cyclosporine, or methotrexate. Its pathogenesis is not fully understood, although an increased T helper 2 immune response has been proposed as a mechanism that may predispose to disseminated viral infections such as eczema herpeticum or Kaposi varicelliform eruption[3]. In line with recommendations from the National Psoriasis Foundation, first-line therapy for severe EP includes infliximab or cyclosporine[2]. In our case, infliximab was attempted after prior cyclosporine failure. Despite this, the patient deteriorated, and the presence of eosinophils on skin biopsy suggested a possible paradoxical drug reaction. Given the patient’s history of partial response to ixekizumab, this biologic was reintroduced with topical clobetasol as primary therapy. The subsequent emergence of disseminated HSV-1 infection highlights a rare but important complication of combining biologic and corticosteroid therapy in a patient with extensive barrier disruption.

Disseminated HSV-1 infection is exceptionally rare in immunocompetent individuals and has been described only in isolated case reports[6-9]. In our patient, multiple factors likely contributed to susceptibility, including recent infliximab exposure, initiation of ixekizumab, and concurrent use of high-dose topical corticosteroids. Disseminated herpes zoster is more frequently reported than disseminated HSV-1, particularly in immunosuppressed populations such as patients with AIDS or those receiving mycophenolate and tacrolimus[7]. It has also been observed during the coronavirus disease 2019 pandemic in patients receiving immunomodulatory therapy, including high-dose corticosteroids[8]. Isolated reports document systemic HSV-1 infection following oral corticosteroid therapy alone[9], or in the context of infliximab therapy for rheumatoid arthritis[10]. These observations support the conclusion that both biologics and corticosteroids may serve as predisposing factors for disseminated herpes infections.

Our patient’s diagnosis was established by PCR confirmation of HSV-1, emphasizing the importance of maintaining a high index of suspicion in immunosuppressed patients presenting with new vesicular or erosive lesions. The differential diagnosis is broad and includes Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms, bullous pemphigoid, and vasculitic eruptions. Early virologic testing is therefore critical to distinguish disseminated HSV-1 from these mimics, as timely antiviral therapy can be lifesaving.

Ixekizumab is a monoclonal antibody targeting interleukin-17A, with demonstrated efficacy and an acceptable safety profile in psoriasis, psoriatic arthritis, and ankylosing spondylitis[11-15]. However, infections remain a theoretical and increasingly recognized risk. A 2020 case report documented herpes zoster following ixekizumab in a patient with erythrodermic psoriasis[16], and our case extends these observations by describing disseminated HSV-1 under similar conditions. This raises the possibility that patients with severe EP and extensive skin barrier compromise may be particularly vulnerable to viral reactivation or dissemination when treated with biologics.

In summary, this case illustrates the therapeutic challenges of managing erythrodermic psoriasis in the presence of multiple comorbidities. Disseminated HSV-1 should be considered in the differential diagnosis of new vesicular eruptions in immunosuppressed patients with EP. Prompt recognition, PCR confirmation, and initiation of antiviral therapy were essential for the favorable outcome observed. A multidisciplinary approach remains indispensable in balancing disease control with infection risk in this fragile patient population.

CONCLUSION

This case illustrates the therapeutic challenges of managing erythrodermic psoriasis in a patient with multiple comorbidities. Disseminated HSV-1 should be considered in the differential diagnosis of new vesicular eruptions in immunosuppressed patients with psoriasis. Timely PCR confirmation, prompt antiviral therapy, and cautious reintroduction of biologics were critical to achieving a favorable outcome. Clinicians should remain vigilant for severe opportunistic infections when treating erythrodermic psoriasis with ixekizumab or other biologics.

ACKNOWLEDGEMENTS

The authors thank the intensive care, dermatology, infectious diseases, and gastroenterology teams involved in the management of this patient.