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...

Parasites interact intimately with their hosts, and the interactions shape both parties. The common human parasite Toxoplasma gondii replicates exclusively in a vacuole in a host cell and alters its host cell’s environment through secreted proteins. One of these secreted proteins, MAF1b, acts to concentrate mitochondria around the parasite’s vacuole, and this relocalization alters the host immune response. Many other intracellular pathogens also recruit host mitochondria, but the identities of the partners that mediate this interaction have not previously been described in any infection. Here, we show that Toxoplasma MAF1b binds to the multifunctional MIB protein complex on the host mitochondria. Reducing the levels of the proteins in this mitochondrial complex reduces the close association of host cell mitochondria and the parasite’s vacuole. This work provides new insight into a key host-pathogen interaction and identifies possible targets for future therapeutic intervention as well as a more molecular understanding of important biology.

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.