Epidemiological, Genetic, Clinical, and Treatment Differences of Generalized Pustular Psoriasis and Acrodermatitis Continua of Hallopeau Across Ethnicities: A Systematic Review.

Background: Ethnic differences of the clinicopathological characteristics in many immune-mediated skin diseases have been reported, including psoriasis vulgaris (PV). However, the ethnic differences of pustular psoriasis have been less studied.

Objective: The aim of this study was to compare the differences in epidemiology, genetic background, clinical manifestations, treatment patterns and responses among Asian and non-Asian patients with pustular psoriasis, including generalized pustular psoriasis (GPP) and acrodermatitis continua of Hallopeau (ACH).

Methods: This systematic review was based on a comprehensive search of Cochrane, PubMed, and Embase databases from earliest available date to 31 December 2024, and all studies reporting on patients with either GPP or ACH irrespective of study design. Studies with study size below five patients or those focusing on quality of life or economic aspects were excluded. In each publication, the ethnic composition, demographics information, disease course and manifestation, as well as genetic mutations, treatment type and response were collected if available.

Results: Of 2187 screened studies, 141 studies were included, with the majority being cohort studies. Compared with other ethnicities, East Asians with GPP carried more null IL36RN mutations, while AP1S3 mutations seemed absent in Asians. Phenotypically, Asians had younger onset age, bimodal age distribution, less family history of PV, and more scalp/nail involvement. In Asians, absence of coexisting PV was associated with severe disease. GPP with PV had shorter pre-pustular duration among Asians than non-Asians. Use of acitretin appeared higher and more effective among East Asians compared with other populations. In ACH, Asians mostly carried homozygous null IL36RN mutations and had younger onset age, more multi-digit involvement, persistent treatment course, and more coexisting GPP than Europeans. Biologics use was less common in Asia in both GPP and ACH than in Europe and the US.

Conclusions: This systematic review underscores notable ethnic differences in genetic profiles, clinical features, and therapeutic responses in GPP and ACH. The diagnosis of GPP and ACH may differ across studies and the true impacts of ethnicities on these differences remain to be confirmed. Nonetheless, the results from this study enhance our understanding of the heterogeneous characteristics of GPP and ACH, highlighting the necessity of incorporating ethnic differences into the diagnosis, genetic testing, and management strategies for patients with GPP and ACH.