Generalized Pustular Psoriasis as a Systemic Inflammatory Disease: Experience With 38 Japanese Cases Over 15 Years at a Single Institution

Pustular psoriasis is a rare subtype of psoriasis, classified into two broad forms: generalized and localized. In the present study, we retrospectively analyzed 41 cases of pustular psoriasis over a 15-year period at a single institution. There were 38 cases of generalized and three cases of localized pustular psoriasis. Among the 38 patients with generalized pustular psoriasis (GPP), 15 (39.5%) had a prior history of psoriasis, while the remaining patients developed GPP de novo. Eighteen patients were former or current smokers, and arthritis was observed in 12 patients. Four patients, including one with Turner syndrome, developed GPP in childhood. Episodes of generalized pustulation occurred once in seven patients, once in three patients, twice in three patients, and three times in one patient. The triggers of pustulation were upper respiratory infection (n=2), pregnancy (n=2), withdrawal of methotrexate (n=1), and paradoxical induction by infliximab (n=2). The comorbidities were hypertension (n=10), diabetes mellitus (n=6), dyslipidemia (n=2), hyperuricemia (n=2), chronic kidney disease (n=2), ischemic heart disease (n=4), Crohn's disease (n=3), and acute respiratory distress syndrome (n=1). Nail involvement was observed in 21 patients. Treatment included etretinate in 20 patients, cyclosporine in nine, methotrexate in two, and apremilast in one. Biologics were used in 14 patients: infliximab in eight, secukinumab in six, adalimumab in three, brodalumab in two, and ixekizumab and golimumab in one each. Immunohistochemistry revealed high expression levels of S100A8 and S100A9, with less intense expression of S100A15. IL-36γ was detected in neutrophilic abscesses, as well as in the upper epidermis and cellular infiltrates below the epidermis. IL-36α and IL-36γ serum levels were elevated in the active phase of GPP compared to the inactive phase. In conclusion, this study highlights the systemic inflammatory nature of GPP, emphasizing its association with various comorbidities and organ involvement.