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Refractory Generalized Pustular Psoriasis in Pregnancy Successfully Treated with Spesolimab

Case Studies 3 min 587

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Created On: 12/03/2026

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Poster abstract

Generalized pustular psoriasis (GPP) of pregnancy is a rare, life-threatening inflammatory dermatosis associated with significant maternal and fetal morbidity. A pregnant patient in the second trimester developed rapidly progressive, severe pustular dermatosis refractory to systemic corticosteroids, cyclosporine, and tumor necrosis factor-alpha (TNF-α) inhibition, with worsening systemic complications.

Intravenous spesolimab was initiated, resulting in rapid clinical improvement within one week and sustained remission on maintenance therapy. Maternal status stabilized after steroid taper, and serial fetal surveillance remained reassuring. She delivered a healthy term neonate without complications. This case highlights rapid and durable disease control with spesolimab in refractory antepartum GPP and underscores its potential as a steroid-sparing therapeutic option when conventional immunomodulators fail.

Complaints

The patient was a 39-year-old African American woman who had been pregnant eight times in total (gravida 8). She has delivered six pregnancies at a viable gestational age (para 6) and had experienced one pregnancy loss before viability (abortus one). She presented with:

Progressively worsening generalized scaling rash involving the trunk and extremities
Rapid development of painful blistering and widespread skin sloughing over several days
Abdominal discomfort limiting mobility
Generalized malaise and fatigue
Subjective decrease in perceived fetal movement

Anamnesis

Introduction

GPP of pregnancy (formerly known as impetigo herpetiformis) is an uncommon, severe inflammatory skin disorder characterized by sterile pustule formation, systemic inflammation, and metabolic disturbances. It most often appears in the third trimester and usually resolves following childbirth.

It has been associated with stress, pregnancy-related changes, hypocalcemia, withdrawal of corticosteroids, and beta-blocker use. Also, dysregulation of innate immune pathways, particularly interleukin (IL)-36 signaling, plays a central role in disease pathogenesis. Patients commonly experience fatigue, malaise, leukocytosis, and sterile pustules that begin in intertriginous regions and spread centrifugally with subsequent desquamation. Maternal mortality has been reported to reach 16%, largely due to septic shock or cardiopulmonary failure. Fetal complications include placental insufficiency and stillbirth.

This case is presented to highlight the successful use of spesolimab, a first-in-class IL-36 receptor antagonist, as rescue therapy for severe, treatment-refractory GPP during pregnancy.

Medical History

Chronic conditions: Chronic hypertension, obesity with body mass index of 33, history of preeclampsia.
Obstetric history: Grand multiparity, history of spontaneous preterm birth at 29 weeks gestational age, two previous cesarean deliveries, including one classical incision.
Medications before admission: Antihypertensive therapy (labetalol 100 mg twice daily) was initiated early in pregnancy.

Within 1 week, she developed a diffuse pruritic erythematous rash that progressively worsened despite treatment with oral methylprednisolone and antihistamines. Repeated emergency evaluations failed to control the condition, and the eruption advanced to widespread blistering and desquamation, necessitating inpatient maternal–fetal assessment for suspected severe inflammatory dermatosis of pregnancy.

Examination

The vital signs were a blood pressure of 106/90 mmHg, a heart rate of 109 beats/min, and a temperature of 36.6°C.
Dermatologic examination revealed diffuse erythematous, desquamative plaques with sheets of sterile pustules involving the scalp, trunk, abdomen, flanks, and bilateral upper and lower extremities.
There was extensive superficial blistering and active skin sloughing, with sparing of the mucous membranes.
Laboratory evaluation revealed pronounced leukocytosis (23.7 × 10³/µL), accompanied by electrolyte abnormalities, and an elevated serum lactate (3.2 mmol/L) level.
Urine and blood cultures were negative for microbial growth. Her routine antenatal infection screening was negative, including investigations for syphilis and human immunodeficiency virus.
Histopathologic assessment of a punch skin biopsy showed intraepidermal neutrophilic pustules, and direct immunofluorescence testing did not reveal immune complex deposition.
The overall clinical, laboratory, and histopathologic findings indicated GPP pregnancy diagnosis.

Treatment

The patient was initially treated with intravenous methylprednisolone (0.5 mg/kg twice daily), topical corticosteroids, and empiric antibiotic (cephalexin) therapy.
Owing to rapid clinical deterioration with extensive skin involvement, she was transferred to the burn intensive care unit for specialized wound care, fluid management, and close maternal–fetal monitoring.
She received a 10-day course of intravenous cefazolin, 25 days of intravenous cyclosporine therapy, and two doses of infliximab; however, the dermatologic response remained suboptimal.
Prolonged systemic corticosteroid therapy led to severe hyperglycemia requiring high-dose insulin and contributed to difficult-to-control chronic hypertension necessitating multidrug antihypertensive therapy.
After multidisciplinary counseling, intravenous spesolimab was administered as targeted rescue therapy for refractory GPP.
Remarkable clinical improvement was observed within one week of the first infusion, with marked reduction in pustules and skin inflammation.
She was transitioned to subcutaneous spesolimab 300 mg administered every four weeks as maintenance therapy, which effectively sustained remission until delivery.
Corticosteroids were gradually tapered, allowing discontinuation of insulin therapy while maintaining stable dermatologic and fetal status until term delivery.

Results

Discussion

This case demonstrates an early, severe presentation of GPP of pregnancy that was refractory to systemic corticosteroids, cyclosporine, and TNF-α inhibition, with progressive maternal complications related to prolonged immunosuppression. These findings highlight the limitations and risks of conventional therapies in the pregnant population.

Treatment with spesolimab led to rapid and sustained resolution of cutaneous disease, stabilization of maternal comorbidities, and avoidance of further therapeutic escalation. Disease control was maintained throughout gestation with reassuring fetal surveillance and an uncomplicated term delivery.

Despite limited pregnancy-specific data, this case supports the consideration of spesolimab as rescue therapy for severe, treatment-refractory GPP when the risks of uncontrolled disease outweigh the potential risks of targeted biologic treatment.

Key Learnings

GPP of pregnancy is a rare, high-risk inflammatory dermatosis requiring prompt recognition and aggressive management.
Standard treatments such as systemic corticosteroids, cyclosporine, and TNF-α inhibitors may fail in severe or refractory GPP cases.
Prolonged high-dose corticosteroid use during pregnancy increases the risk of steroid-induced hyperglycemia, uncontrolled hypertension, infection, and metabolic instability.
Spesolimab, an IL-36 receptor antagonist, may provide rapid and sustained disease control in severe, refractory cases of GPP of pregnancy.
Careful maternal–fetal surveillance is critical when using novel biologic agents during pregnancy.