eneralized pustular psoriasis (GPP) is an orphan disease characterized by the rapid appearance of sterile pustules and generalized erythema. Patients are often systemically ill and may experience severe organ dysfunction and rarely death. The genetic risk factors for pustular psoriasis are different from other types of psoriasis. To date, variations have been identified in the following genes: IL36RN (interleukin-36 receptor antagonist), CARD14 (caspase recruitment domain family member 14), AP1S3 (adapter related protein complex 1 subunit sigma 3), SERPINA3 (serpin family A member 3), and MPO (myeloperoxidase); however, the majority of patients do not have a known genetic variant. 1 Owing to the rarity of GPP, there is limited information about the natural disease course. The only epidemiological data from the United States is a report of 63 patients seen over 29 years at a single institution. 2 The objective of this study is to describe the clinical characteristics, natural disease course, treatments, and health care utilization of patients with GPP across the United States. Methods Study Design and PopulationThis is a retrospective, longitudinal case series of adults (≥18 years) with a diagnosis of GPP confirmed by a dermatologist (January 1, 2007-December 31, 2018) (Table 1). Up to 5 potential cases were identified from each of 20 participating sites' electronic health records or site-specific databases, starting with cases seen most recently. All diagnoses were confirmed by the principal investigator at each site at the time of data entry. Only patients who met the European Rare and Severe Psoriasis Expert Network (ERASPEN) consensus definition of GPP with documentation of "primary, sterile, macroscopically visible pustules on nonacral skin, excluding cases where pustulation is restricted to psoriatic plaques" 3 and had had a dermatology encounter with active pustular disease during the study period were included.IMPORTANCE Generalized pustular psoriasis (GPP) is a chronic, orphan disease with limited epidemiological data.OBJECTIVE To describe the clinical characteristics, treatments, longitudinal disease course, and disease-specific health care utilization among patients with GPP across the United States. DESIGN, SETTING, AND PARTICIPANTSA retrospective longitudinal case series involving 95 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for GPP and were treated at 20 US academic dermatology practices between January 1, 2007, and December 31, 2018. MAIN OUTCOMES AND MEASURESThe primary outcome is to describe the patient characteristics, associated medical comorbidities, treatment patterns complications, and GPP-specific health care utilization.RESULTS Sixty-seven of 95 patients (70.5%) were women (mean age, 50.3 years [SD, 16.1 years]). In the initial encounter, 35 patients (36.8%) were hospitalized and 64 (67.4%) were treated with systemic therapies. In total, more than 20 different systemic therapies were tried. During the follow-up period, 19 patients (35.8%) rep...

IMPORTANCEAcute generalized exanthematous pustulosis (AGEP) is a rare, severe cutaneous adverse reaction associated with systemic complications. Currently available data are largely limited to small retrospective case series.OBJECTIVE To describe the clinical characteristics, disease course, and outcomes of a heterogeneous group of patients with AGEP across the US. DESIGN, SETTING, AND PARTICIPANTSA retrospective review of a case series of patients was conducted from January 1, 2000, through July 31, 2020. All 340 included cases throughout 10 academic health systems in the US were scored retrospectively using the EuroSCAR scoring system, and patients with a score corresponding to probable or definite AGEP and aged 18 years or older were included. MAIN OUTCOMES AND MEASURESPatient demographic characteristics, clinical course, suspected causative agent, treatment, and short-and long-term outcomes.RESULTS Most of the 340 included patients were women (214 [62.9%]), White (206 [60.6%]), and non-Hispanic (239 [70.3%]); mean (SD) age was 57.8 (17.4) years. A total of 154 of 310 patients (49.7%) had a temperature greater than or equal to 38.0 °C that lasted for a median of 2 (IQR, 1-4) days. Of 309 patients, 263 (85.1%) developed absolute neutrophilia and 161 patients (52.1%) developed either absolute or relative eosinophilia. Suspected causes of AGEP were medications (291 [85.6%]), intravenous contrast agents (7 [2.1%]), infection (3 [0.9%]), or unknown (39 [11.5%]). In 151 cases in which a single medication was identified, 63 (41.7%) were β-lactam antimicrobials, 51 (33.8%) were non-β-lactam antimicrobials, 9 (6.0%) were anticonvulsants, and 5 (3.3%) were calcium channel blockers. The median time from medication initiation to AGEP start date was 3 (IQR, 1-9) days. Twenty-five of 298 patients (8.4%) had an acute elevation of aspartate aminotransferase and alanine aminotransferase levels, with a peak at 6 (IQR, 3-9) days. Twenty-five of 319 patients (7.8%) experienced acute kidney insufficiency, with the median time to peak creatinine level being 4 (IQR, 2-5) days after the AGEP start date. Treatments included topical corticosteroids (277 [81.5%], either alone or in combination), systemic corticosteroids (109 [32.1%]), cyclosporine (10 [2.9%]), or supportive care only (36 [10.6%]). All-cause mortality within 30 days was 3.5% (n = 12), none of which was suspected to be due to AGEP.CONCLUSIONS AND RELEVANCE This retrospective case series evaluation of 340 patients, the largest known study cohort to date, suggests that AGEP onset is acute, is usually triggered by recent exposure to an antimicrobial, may be associated with liver or kidney complications in a minority of patients, and that discontinuation of the triggering treatment may lead to improvement or resolution.

almoplantar pustulosis (PPP) is a limited form of pustular psoriasis characterized by persistent, sterile macroscopic pustules on the palms and/or soles and presents both in isolation and in patients with a history of plaque psoriasis. Previous research suggests there is a genetic overlap between PPP and plaque psoriasis, 1-4 but despite any similarities, there are also key differences. Palmoplantar pustulosis predominantly presents in women, while psoriasis occurs in men and women equally. Despite the limited body surface area associated with PPP compared with psoriasis, patients with palmoplantar psoriasis have been shown to experience greater health-related quality-of-life impairment than those with moderate to severe plaque psoriasis. 5,6 Finally, treatments for PPP and palmoplantar psoriasis are similar, but much less is known about the response to treatment in patients with PPP. The objective of this study is to describe the clinical characteristics, longitudinal disease course, treatments, and health care utilization in patients with PPP across the US. Methods Study Design and PopulationThis is a retrospective case series of adults (age ≥18 years) with a diagnosis of PPP made by a dermatologist between January 1, 2007, and December 31, 2018. Up to 10 potential cases were identified from each of 20 sites using electronic health records and/or site-specific databases, starting with cases seen most recently. All diagnoses were confirmed by the principal investigator at each site at the time of data entry, and only patients who met the European Rare and Severe Psoriasis Expert Network consensus definition for PPP-documentation of primary, persistent (<3 months), sterile, macroscopic pustules on the palms and/or soles, not occurring within psoriatic plaques 7 -and had a dermatology encounter with active pustular disease during the study period were included. This study was granted exempt status by the University of Penn-IMPORTANCE Palmoplantar pustulosis (PPP) is a is a chronic, orphan disease with limited epidemiological data. OBJECTIVE To describe the clinical characteristics, treatments, longitudinal disease course, and health care utilization in adults with PPP across the US.

Cutaneous T-cell lymphomas (CTCLs) represent a heterogeneous group of non-Hodgkin's lymphoma characterized by an accumulation of malignant CD4 T cells in the skin. The group IIIa metal salt, gallium nitrate, is known to have antineoplastic activity against B-cell lymphoma in humans, but its activity in CTCLs has not been elaborated in detail. Herein, we examined the antineoplastic efficacy of a gallium compound, gallium maltolate (GaM), in vitro and in vivo with murine models of CTCLs. GaM inhibited cell growth and induced apoptosis of cultured CTCL cells. In human CTCL xenograft models, peritumoral injection of GaM limited the growth of CTCL cells, shown by fewer tumor formations, smaller tumor sizes, and decreased neovascularization in tumor microenvironment. To identify key signaling pathways that have a role in GaM-mediated reduction of tumor growth, we analyzed inflammatory cytokines, as well as signal transduction pathways in CTCL cells treated by GaM. IFN-γ-induced chemokines and IL-13 were found to be notably increased in GaM-treated CTCL cells. However, immunosuppressive cytokines, such as IL-10, were decreased with GaM treatment. Interestingly, both oxidative stress and p53 pathways were involved in GaM-induced cytotoxicity. These results warrant further investigation of GaM as a therapeutic agent for CTCLs.

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