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.

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.

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.

暂无摘要。

BACKGROUND: Limited information exists on the epidemiology, treatment, and burden of palmoplantar pustulosis (PPP) and defining the optimal course of treatment remains challenging without approved targeted treatments in most countries. Here, we describe the clinical and demographic characteristics, treatments received, and negative health outcomes experienced among patients with PPP in the United States (US) and Germany.
METHODS: Retrospective cohort study between 2016 and 2021 using data from the US Merative™ MarketScan® Research Database and IQVIA™ German Disease Analyzer. Adult patients with PPP (ICD-10-CM L40.3) were followed from the date of their first qualifying PPP diagnosis and continued until the earlier of disenrollment or end date of database, during which treatment patterns and incidence rates of negative health outcomes were assessed. Treatment patterns included adherence, non-persistence, discontinuation, re-initiation, switching, and combination therapy.
RESULTS: The prevalence of PPP was 0.005% and 0.065% in the MarketScan database and German Disease Analyzer, respectively, with 1629 and 3866 patients meeting the inclusion criteria. Most patients were female (71.3%, 67.8%), with mean (SD) age of 54.1 (11.7) and 56.9 (14.3) years, respectively. One year post index, most patients received topical treatment (77.4%, 65.3%), but non-persistence and discontinuation were high. Oral and biologic treatments displayed higher levels of adherence, particularly apremilast and tofacitinib among oral treatments and TNF inhibitors and IL-23 inhibitors among biologics. Rates of negative health outcomes were higher among patients not receiving treatment post-index compared with those receiving treatment post-index across both databases, regardless of prior treatment history.
CONCLUSIONS: Establishing treatment guidelines remains an unmet need for patients with PPP and could improve quality of life by reducing the occurrence of negative health outcomes. The findings from this study may provide insight into the effectiveness of current treatment options for patients with PPP and can be leveraged to support the development of treatment guidelines.

Over 1.1 billion people smoke worldwide. The alkaloid nicotine is a prominent and addictive component of tobacco. In addition to tumors and cardiovascular disorders, tobacco consumption is associated with a variety of chronic-inflammatory diseases. Although neutrophilic granulocytes (neutrophils) play a role in the pathogenesis of many of these diseases, the impact of nicotine on neutrophils has not been systematically reviewed so far.
The aim of this systematic review was to evaluate the direct influence of nicotine on human neutrophil functions, specifically on cell death/damage, apoptosis, chemotaxis, general motility, adhesion molecule expression, eicosanoid synthesis, cytokine/chemokine expression, formation of neutrophil extracellular traps (NETs), phagocytosis, generation of reactive oxygen species (ROS), net antimicrobial activity, and enzyme release.
This review was conducted according to the PRISMA guidelines. A literature search was performed in the databases NCBI Pubmed® and Web of Science™ in February 2023. Inclusion criteria comprised English written research articles, showing in vitro studies on the direct impact of nicotine on specified human neutrophil functions.
Of the 532 originally identified articles, data from 34 articles were finally compiled after several evaluation steps. The considered studies highly varied in methodological aspects. While at high concentrations (>3 mmol/l) nicotine started to be cytotoxic to neutrophils, concentrations typically achieved in blood of smokers (in the nmol/l range) applied for long exposure times (24-72h) supported the survival of neutrophils. Smoking-relevant nicotine concentrations also increased the chemotaxis of neutrophils towards several chemoattractants, elevated their production of elastase, lipocalin-2, CXCL8, leukotriene B4 and prostaglandin E2, and reduced their integrin expression. Moreover, while nicotine impaired the neutrophil phagocytotic and anti-microbial activity, a range of studies demonstrated increased NET formation. However, conflicting effects were found on ROS generation, selectin expression and release of β-glucuronidase and myeloperoxidase.
Nicotine seems to support the presence in the tissue and the inflammatory and selected tissue-damaging activity of neutrophils and reduces their antimicrobial functions, suggesting a direct contribution of nicotine to the pathogenesis of chronic-inflammatory diseases via influencing the neutrophil biology.

Palmoplantar pustulosis (PPP) is a stubborn skin disease involving repeated aseptic small pustules on the palms and soles of the feet, which is triggered and exacerbated by metals and dental focal infections. There are few reports of an exacerbation of PPP symptoms after orthognathic surgery. The patient is a 40-year-old female who consulted an orthodontist at our hospital, complaining of a protruding maxilla and malocclusion. Under the diagnosis of skeletal prognathism, she underwent surgery for jaw deformity. Although no allergic symptoms were observed during the orthodontic treatment prior to surgery, postoperative scaling on the palms and soles of her feet worsened, and itching was observed on the skin, especially on the titanium plate used to secure the bone fragments. Under the diagnosis of metal allergy, treatment with steroids and vitamin D ointment failed to improve the condition, so surgery was performed to replace the metal plate with a non-metallic absorbable plate in the third postoperative month. Afterwards, the pruritus resolved, and erythema and scale on the palms and soles nearly disappeared. In the present case, though, oral bacterial infection, a past history of smoking, and stress from surgery were also considered to be possible causes of PPP exacerbation, and we concluded that one of the causes of PPP exacerbation was metal allergy from the plates or screws used to fix the bone fragments.

Secukinumab, a monoclonal antibody targeting interleukin-17 (IL-17), has exhibited encouraging results in the therapeutic management of palmoplantar pustulosis (PPP). The development of alopecia areata (AA) is closely related to IL-17, and IL-17A inhibitors were considered as a potential treatment modality. Therefore, the development of AA during secukinumab treatment for PPP is a rare adverse event that has been rarely reported worldwide. Here we report a 35-year-old female patient with PPP who developed AA after completing the induction period of secukinumab treatment. Discontinuing secukinumab and initiating treatment with tofacitinib resulted in a significant improvement in both PPP and AA. The emergence of AA in this patient can be attributed to paradoxical skin reactions associated with IL-17 inhibitors. Tofacitinib appears to alleviate biologic-induced AA during PPP syndrome treatment.

Palmoplantar pustulosis (PPP) is a chronic inflammatory condition characterized by sterile pustules on the palms and soles. This study evaluated the epidemiology of PPP using claims and electronic health record (EHR) databases.
Patients coded for PPP in the United States (US) and Japan from 2016 to 2020 were identified. Several PPP definitions were evaluated; the specific definition (≥ 2 visits coded for PPP, the second 31-730 days after diagnosis) was chosen for characterizing PPP epidemiology. Baseline characteristics and pre- and post-diagnosis treatments were summarized. Prevalence and incidence rates were analyzed by calendar year, sex, age, and database.
Prevalence and incidence of PPP were higher in Japan than the US. PPP prevalence increased over time. PPP occurred predominantly in adulthood and was more common among women. Features of metabolic syndromes, anxiety, and depression were more common among US PPP patients. Consistently high baseline use of anti-bacterial, anti-inflammatory/anti-rheumatic, and obstructive airway disease treatments was observed among PPP patients. Potential miscoding or misclassification of PPP limited this analysis. Prevalence estimates from databases may differ from field- and population-based approaches.
The burden of PPP was greater in Japan than in the US. Additional studies are needed to further elucidate PPP epidemiology worldwide.