Generalized pustular psoriasis (GPP) is a rare subset of psoriasis involving episodes of sterile pustules accompanied by inflammation and, often, systemic involvement. The inflammatory nature of GPP has potential for severe multisystem complications including high‐output cardiac failure, infections, digestive system issues, and disfiguring or lethal acute flare episodes. The disease tends to have higher prevalence in females and Asians. The IL‐1/IL‐36 inflammatory pathway is a critical facet of GPP's pathology. Genetic mutations that are associated with GPP include modifications of Interleukin 36 Receptor Antagonist (IL36RN), Caspase Recruitment Domain Family Member 14 (CARD14), Adaptor Related Protein Complex 1 Subunit Sigma 3 (AP1S3), Myeloperoxidase (MPO) and Serpin Peptidase Inhibitor Clade A Member 3 (SERPINA3) genes. Treatment guidelines for GPP are not well‐entrenched. Currently, only one GPP‐specific treatment, the interleukin‐36 receptor antagonist (IL‐36Ra) spesolimab, has been approved for use in the United States. Additional anti‐IL‐36 pathway therapies are currently being developed. Other treatment options include other biologic therapies such as IL‐17 inhibitors, IL‐23 inhibitors and TNFα inhibitors. Non‐biologic therapeutic options include retinoids, cyclosporine and methotrexate. Treatment options differ throughout the world; most countries utilize retinoids, cyclosporine and methotrexate as first‐line non‐biologic options. China and United Kingdom have no GPP‐specific biologic therapies approved for use, while several biologic therapies are approved for use in Japan. This review aims to serve as an update on the current global management of GPP while also including relevant aspects of disease pathogenesis, diagnosis, clinical presentation, histopathology, aetiology and epidemiology.
Acrophialophora is a saprotrophic genus of fungi found in both temperate and tropical regions. The genus is comprised of 16 species, with the subspecies A. fusispora and A. levis necessitating the most clinical concern. Acrophialophora is an opportunistic pathogen with a broad range of clinical manifestations; the fungus has been implicated in cases of fungal keratitis, lung infection, and brain abscess. Acrophialophora infection is particularly of concern for immunocompromised patients, who often present with a more severe disease course involving disseminated infection and may not exhibit typical symptoms. Early diagnosis and therapeutic intervention are critical to the successful clinical management of Acrophialophora infection. Guidelines for antifungal treatment have yet to be established, partially due to the lack of documented cases. Aggressive use of antifungal agents and long-term treatment is required, especially in immunocompromised patients and patients with systemic involvement, due to the potential for morbidity and mortality. In addition to outlining the rarity and epidemiology of the disease, this review provides an overview of the diagnosis and clinical management of Acrophialophora infection to facilitate an early diagnosis and appropriate interventions.
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