Long‐term remission and normal pregnancy with successful delivery in a patient with generalized pustular psoriasis after spesolimab

Dear Editors, Generalized pustular psoriasis (GPP) is a rare yet severe variant of psoriasis that is characterized by the sudden eruption of superficial, sterile pustules with a wide distribution. Several studies have indicated that the interleukin (IL)-36 pathway has an important role in the occurrence and development of GPP.1, 2 Herein we report a female with GPP who was treated with spesolimab, an IL-36R inhibitor. She conceived 3 months later and delivered a healthy baby at 40 weeks' gestation with no complications. A 25-year-old female had pustules covering her body for one year and psoriasis vulgaris for 10 years. The medical history was otherwise benign. The obstetric history was significant with three spontaneous abortions (no embryonic cardiac activity and fetal demise). She had had a severe psoriasis attack with each pregnancy loss. Eight months before seeking evaluation at our hospital, oral methotrexate (10 mg weekly) was administered for pustules for nearly 2 months. Despite this treatment, the lesions recurred sporadically. Five days before admission to our hospital the patient reported worsening symptoms, which included erythema and an increase in pustules covering the entire body. Furthermore, she reported recurring fevers and a loss of appetite. At the time of admission, the physical examination was significant for erythema, desquamation, pustule formation, pus lakes, and scattered scaly plaques studded with non-follicular-based pustules across the entire body (Figure 1a,b). She had a generalized pustular psoriasis physician global assessment (GPPGA) score > 3 and the generalized pustular psoriasis area and severity index (GPPASI) was 56.4 at the time of admission. Based on the above findings, this patient was diagnosed with GPP. After screening for the appropriate biological treatment, the IL-36R inhibitor spesolimab was administered. A pregnancy test was negative before administering spesolimab. Remarkable efficacy was noted 24 h after a single dose of spesolimab. Two days later most of the pustules had dried up and desquamated from head to toe (Figure 1c,d). Persistent fevers (peak, 39.3°C) were treated with oral tripterygium glycosides tablets (20 mg 3 times daily), which is a traditional Chinese herb with anti-inflammatory properties that has been widely used in the treatment of psoriasis, rheumatoid arthritis, and other immunologic diseases.3 Seven days after administration of spesolimab, all the pustules had dried up and signs of re-epithelialization were evident. There was a 90% improvement in the GPPASI and the GPPGA score was reduced to 1 (Figure 1e,f). By the 4th week of follow-up evaluations, she had discontinued all medications, and the skin lesions were completely clear. The GPPASI and GPPGA score were reduced to 0 (Figure 1g,h). At the 87-day follow-up evaluation she had a confirmed pregnancy. Because she had a history of recurrent spontaneous abortions, she chose to continue the pregnancy. All pregnancy related tests were normal. She had an uneventful pregnancy and delivered a healthy girl. In addition, psoriasis and GPP were in long-term remission without any adverse events, even 2 months postpartum. Generalized pustular psoriasis remains a complex disease due to its rarity and unpredictable disease course. Studies have established that IL-36R signaling triggers the activation of NFκB and mitogen-activated protein kinases in GPP.4 The spesolimab metabolic pathway involves degradation to small peptides and amino acids by catabolic pathways in the same manner as endogenous IgG, which can traverse the placental barrier. The terminal half-life of spesolimab is 25.5 days.1 The patient described herein was in the residual effect period of spesolimab according to a published clinical trial from 2021.2 The patient had long-term remission and had no adverse events for 15 months and delivered a healthy baby. According to a previous study,5 we hypothesize that spesolimab may have altered the placental IL-36 axis and regulated the maternal immune responses. Generalized pustular psoriasis is sometimes induced and exacerbated by pregnancy. Impetigo herpetiformis (IH) is a type of GPP associated with pregnancy that may result in poor or fatal neonatal outcomes. In addition, maternal death may occur if the clinical course is severe and of long duration. Although our patient did not have IH, this is the first report of a patient who used spesolimab and had a pregnancy when still in the spesolimab residual-effect period. Fortunately, she had a normal pregnancy and successfully delivered a healthy female baby vaginally, weighing 2,600 g. Yang et al.6 recently reported a patient with IH at the 17th week of gestation with a lack of response to prednisone. Spesolimab was administered, satisfactory results were achieved, and a healthy baby was delivered. Our patient and the above report6 confirm the safety and efficacy of spesolimab. This work was funded by a grant award by Na Wang from the National Natural Science Foundation of China (81903230) and Shandong Provincial Medical and Health Science and Technology Development Plan (202004120262). None.