UNASSIGNED: Real-world data on health-related quality of life (HRQoL) in palmoplantar pustulosis (PPP) are scarce and few studies have analysed the generic HRQoL.
UNASSIGNED: To assess HRQoL using the generic EQ-5D instrument and the Dermatology Life Quality Index (DLQI) instrument in PPP compared to plaque psoriasis.
UNASSIGNED: Cross-sectional data from PsoReg, the Swedish National Registry for Systemic Treatment of Psoriasis (2006-2021), were examined. The study included 306 patients with PPP, out of which 22% had concomitant plaque psoriasis (n = 68), and 7041 patients with plaque psoriasis only. EQ-5D and DLQI were compared between patients with PPP and patients with plaque psoriasis, overall and stratified by sex. A subgroup analysis compared outcomes for patients with PPP vs. patients with severe plaque psoriasis (Psoriasis Area and Severity Index ≥10). Multiple regression analyses were performed to control for potential confounders (age, sex, comorbidities, lifestyle factors).
UNASSIGNED: Patients with PPP were to a larger extent female (79% vs. 37%, p < .01) and older (mean [SD] age 59.9 [11.9] vs. 50.7 [16.0] years, p < .01) than patients with plaque psoriasis. EQ-5D values were significantly lower (worse) in patients with PPP (mean [SD] 0.622 [0.309]) compared to patients with plaque psoriasis (mean [SD] 0.715 [0.274]). No significant difference was observed compared to patients with severe plaque psoriasis (p = .237). DLQI was comparable in PPP and plaque psoriasis patients (p = .117). In the regression analyses, PPP only and PPP with plaque psoriasis were associated with lower EQ-5D values of 0.065 (p < .01) and 0.061 points (p < .10) compared to plaque psoriasis patients.
UNASSIGNED: PPP had a substantial negative impact on patients\' generic and dermatology-specific HRQoL. Patients with PPP were worse off in terms of generic HRQoL compared with patients with plaque psoriasis when controlling for the impact of potential confounders.
Real-world data on health-related quality of life in palmoplantar pustulosis (PPP) are scarce and previous studies have been predominantly restricted to the Dermatology Life Quality Index.This study also shows a significant impairment of the generic HRQoL (assessed by the generic EQ-5D instrument) in patients with PPP.Patients with PPP rated their generic HRQoL worse than patients with plaque psoriasis.

BACKGROUND: Palmoplantar pustulosis (PPP) is an inflammatory disease characterized by relapsing eruptions of neutrophil-filled, sterile pustules on the palms and soles that can be clinically difficult to differentiate from non-pustular palmoplantar psoriasis (palmPP) and dyshidrotic palmoplantar eczema (DPE).
OBJECTIVE: To identify overlapping and unique PPP, palmPP, and DPE drivers to provide molecular insight into their pathogenesis.
METHODS: We performed bulk RNA sequencing of lesional PPP (n=33), palmPP (n=5), and DPE (n=28) samples, as well as 5 healthy non-acral and 10 healthy acral skin samples.
RESULTS: Acral skin shows a unique immune environment, likely contributing to a unique niche for palmoplantar inflammatory diseases. Compared with healthy acral skin, PPP, palmPP, and DPE displayed a broad overlapping transcriptomic signature characterized by shared upregulation of pro-inflammatory cytokines (TNF, IL36), chemokines, and T cell-associated genes, along with unique disease features of each disease state, including enriched neutrophil processes in PPP and to a lesser extent in palmPP, and lipid antigen processing in DPE. Strikingly, unsupervised clustering and trajectory analyses demonstrated divergent inflammatory profiles within the three disease states. These identified putative key upstream immunological switches, including eicosanoids, interferon responses, and neutrophil degranulation, contributing to disease heterogeneity.
CONCLUSIONS: We demonstrate the molecular overlap between different inflammatory palmoplantar diseases that supersedes clinical and histologic assessment, yet highlighting the heterogeneity within each condition, suggesting limitations of current disease classification and the need to move toward a molecular classification of inflammatory acral diseases.

Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a rare autoinflammatory disease characterized by bone inflammation and skin manifestations including acne, palmoplantar pustulosis, psoriasis, or hidradenitis suppurativa. SAPHO syndrome is considered on the same spectrum as chronic nonbacterial osteomyelitis/chronic recurrent multifocal osteomyelitis (CNO/CRMO), the former often being the nomenclature in adults and the latter in children. The diagnosis is made on patterns of clinical manifestations and is a diagnosis of exclusion. While skin and bone manifestations are commonly described with SAPHO syndrome, pleural involvement is rare, and few cases have been described in the literature, especially in pediatric patients. Herein we present a 14-year-old female with a past medical history of hidradenitis supprtiva, eczema, psoriasis, and a prior episode of culture-negative osteomyelitis who presented to the emergency room with chief complaints of right sided pain with inspiration and back pain. Exam revealed palmoplantar pustulosis, hidradenitis supprativa, psoriasis, and tenderness of vertebrae. Imaging showed a right sided pleural effusion and multiple sites of osteitis. Laboratory evaluation revealed elevated inflammatory markers, an exudative pleural effusion with neutrophilic predominance, and no evidence of malignancy, infection, or immunodeficiency. The patient was diagnosed with SAPHO syndrome and treated with naproxen, methotrexate, and golimumab with significant improvement including resolution of the pleural effusion. Pediatric SAPHO syndrome is a rare disease that classically causes osteitis and skin manifestations. This case highlights that pleural effusion can be a rare manifestation of pediatric SAPHO syndrome. Patients with suspected SAPHO syndrome with respiratory symptoms should be evaluated for pleural effusion.

Palmoplantar pustulosis (PPP) is a chronic inflammatory recurrent disease characterized by sterile pustules involving palms and/or feet. Presently, there are no standard recommended treatment regimens. Tofacitinib is an oral Janus kinase (JAK) inhibitor, mainly acts on JAK 1 and 3 and has been approved for the treatment of rheumatoid arthritis in adults. Herein, we present a case of a patient with PPP who did not respond to IL-17A inhibitor secukinumab but was successfully treated by the JAK inhibitor tofacitinib.

UNASSIGNED: Palmoplantar pustulosis (PPP) is a complex inflammatory skin disease. Currently, no standardized treatments exist, and traditional systemic therapies often display limited effectiveness and substantial adverse effects. Biologics, however, have shown potential for enhanced clinical outcomes in psoriasis patients, thereby prompting this investigation into their applicability in PPP treatment.
UNASSIGNED: This study constitutes the first comprehensive review to assess the effectiveness and underlying mechanisms of biologics for PPP.
UNASSIGNED: We conducted a PubMed search to identify studies on biologics for PPP from 1992 onward. The review focused on assessing the efficacy of biologics targeting cytokines like IL-1, IL-8, IL-17, IL-12/23, IL-36, and TNF-α.
UNASSIGNED: Biologics for PPP are generally less effective than for psoriasis. Secukinumab and guselkumab, IL-17 and IL-23 inhibitors respectively, have shown better results compared to other biologics in trials. However, the effectiveness of other biologics remains uncertain due to limited data.
UNASSIGNED: More research is needed to find effective treatments for PPP, and selecting the right biologic for each patient is challenging.

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BACKGROUND: Palmoplantar pustulosis (PPP) is a pruritic, painful, chronic dermatitis that greatly impacts functioning and quality of life and can be difficult to treat. Approved treatment options for PPP are limited, and many patients do not fully respond to current treatments.
METHODS: This was a randomized, double-blind, placebo-controlled, phase 2 study in Japanese patients with moderate to severe PPP and inadequate response to topical treatment. Patients were randomized 1:1 to receive apremilast 30 mg twice daily or placebo for 16 weeks followed by an extension phase where all patients received apremilast through week 32. PPP Area and Severity Index (PPPASI), modified PPPASI (which evaluates pustules and vesicles separately), and Palmoplantar Severity Index (PPSI) total scores and subscores (erythema, pustules/vesicles, and desquamation/scales) were evaluated over 32 weeks of apremilast treatment. Achievement of ≥ 50% improvement in PPPASI (PPPASI-50) was evaluated at week 16 among baseline demographic and clinical characteristic subgroups.
RESULTS: At week 16, improvements in total score and subscores for PPPASI, modified PPASI, and PPSI, as well as rates of PPPASI-50 were at least moderately greater with apremilast than placebo. Mean PPPASI total score decreased by - 68.3% from baseline to week 32 with continued apremilast treatment. At week 32, mean change from baseline in PPPASI/modified PPPASI subscores ranged from - 58.5% to - 77.0% with apremilast. At week 32, PPSI total score for physician and patient assessments decreased by - 51.3% and - 40.0%, respectively, with continued apremilast treatment. PPPASI-50 response at week 16 was greater with apremilast versus placebo in most demographic and baseline characteristic subgroups.
CONCLUSIONS: Improvements in all PPPASI and PPSI total scores and subscores observed with apremilast over 16 weeks were maintained through 32 weeks in patients with moderate to severe PPP and inadequate response to topical treatment. Rates of PPPASI-50 response at week 16 were mostly consistent across patient subgroups.
RESULTS: GOV: NCT04057937.

UNASSIGNED: Variations in circulatory cytokine levels have been observed during the onset and course of palmoplantar pustulosis (PPP); however, whether these changes are due to etiological or secondary factors is unclear. To clarify the causal relationship, we conducted a summarized-level bidirectional Mendelian randomization (MR) analysis in this study.
UNASSIGNED: A FinnGen biobank genome-wide association study (GWAS) of 212,766 individuals (524 PPP patients and 212,242 controls) provided summary data for PPP, whereas genetic instrumental variables (IVs) linked to circulation cytokine levels were gathered from a GWAS of 14,824 European individuals. The inverse-variance weighted (IVW), weighted median (WME), simple mode, and MR-Egger methods were used to ascertain the changes in PPP pathogenic cytokine taxa. Sensitivity analysis, which included horizontal pleiotropy analysis, was then conducted. The reliability of the results was assessed using the leave-one-out approach and the MR Steiger test, which evaluated the strength of a causal relationship. To evaluate the reverse causality between PPP and circulating cytokine levels, a reverse MR analysis was carried out.
UNASSIGNED: Our study demonstrated positive associations between C-X-C motif chemokine 6 (CXCL6) and PPP (odds ratio, OR 1.257, 95%CI: 1.001-1.570, p = 0.043). C-C motif chemokine 19 (CCL19) and interleukin-6 (IL-6) were suggested to be protectively associated with the development of PPP (OR: 0.698,95% CI: 0.516-0.944, p = 0.020; OR: 0.656, 95%CI:0.437-0.985, p = 0.042). The results were steady after sensitivity and heterogeneity analyses.
UNASSIGNED: At the genetic prediction level, we identified causally connected inflammation-related variables that contributed to the onset and development of PPP. The therapeutic options for some refractory PPP have expanded due to tailored cytokine therapy, generating fresh concepts for PPP diagnostics and mechanism investigation.

BACKGROUND: Palmoplantar pustulosis (PPP) is an inflammatory skin disorder that mostly affects smokers and manifests with painful pustular eruptions on the palms and soles. Although the disease can present with concurrent plaque psoriasis, TNF and IL-17/IL-23 inhibitors show limited efficacy. There is therefore a pressing need to uncover PPP disease drivers and therapeutic targets.
OBJECTIVE: We sought to identify genetic determinants of PPP and investigate whether cigarette smoking contributes to disease pathogenesis.
METHODS: We performed a genome-wide association meta-analysis of 3 North-European cohorts (n = 1,456 PPP cases and 402,050 controls). We then used the scGWAS program to investigate the cell-type specificity of the association signals. We also undertook genetic correlation analyses to examine the similarities between PPP and other immune-mediated diseases. Finally, we applied Mendelian randomization to analyze the causal relationship between cigarette smoking and PPP.
RESULTS: We found that PPP is not associated with the main genetic determinants of plaque psoriasis. Conversely, we identified genome-wide significant associations with the FCGR3A/FCGR3B and CCHCR1 loci. We also observed 13 suggestive (P < 5 × 10-6) susceptibility regions, including the IL4/IL13 interval. Accordingly, we demonstrated a significant genetic correlation between PPP and TH2-mediated diseases such as atopic dermatitis and ulcerative colitis. We also found that genes mapping to PPP-associated intervals were preferentially expressed in dendritic cells and often implicated in T-cell activation pathways. Finally, we undertook a Mendelian randomization analysis, which supported a causal role of cigarette smoking in PPP.
CONCLUSIONS: The first genome-wide association study of PPP points to a pathogenic role for deregulated TH2 responses and cigarette smoking.