Atopic dermatitis is associated with an increased risk of cardiovascular diseases: A large-scale, propensity-matched US-based retrospective study.

BACKGROUND: Atopic dermatitis is a chronic relapsing inflammatory skin disease characterized by intense itch impacting heavily on patients' and caregivers' quality of life. Its clinical presentation is accompanied by a variety of type 2 comorbidities, e.g. asthma, hay fever, food allergies. However, current data on cardiovascular comorbidities are inconsistent. OBJECTIVES: To identify risk of cardiovascular diseases in patients with atopic dermatitis. METHODS: Data from Electronic Health Records (EHRs) of 1,070,965 atopic dermatitis patients and equally propensity score matched controls were retrieved from the US Collaborative Network part of the federated TriNetX network. Hazard ratios for risk of onset of cardiovascular diseases with a prevalence of ≥1% in both cohorts within 20 years after diagnosis were determined. RESULTS: A total of 55 cardiovascular diseases belonging to 8 major cardiovascular groups were identified. Of those, 53 diagnoses displayed a significantly increased risk in atopic dermatitis patients. Different diagnoses of heart failure and heart disease were found most often, followed by valve insufficiencies, arrhythmia, tachycardia, atrial fibrillation, flutter, but also MACE and venous thromboembolism. The individual diagnoses venous insufficiency, atherosclerosis of native arteries of the extremities, and unspecified diastolic (congestive) heart failure displayed highest hazard ratios. CONCLUSION: Atopic dermatitis is associated with an increased risk for multiple cardiovascular diseases.

Risk of cardiovascular disorders in hidradenitis suppurativa patients: a large-scale, propensity-matched global retrospective cohort study.

BACKGROUND: Patients with hidradenitis suppurativa (HS) often suffer from comorbid diabetes, metabolic syndrome, and hyperlipidemia and, therefore, are susceptible to the development of cardiovascular diseases (CVDs). Moreover, systemic inflammation plays a vital role in the development of atherosclerosis. The creation of atherosclerotic plaque is characterized by endothelial dysfunction driven by elevated concentrations of interleukin (IL)-1, IL-6, and IL-18 among others, as well as tumor necrosis factor (TNF) alpha. METHODS: This study aimed to assess the risk of HS patients developing CVDs. We performed a large-scale, propensity-matched global retrospective cohort study analyzing the risk of development of CVDs in patients suffering from HS. The analysis included 144,100 HS patients with 144,100 healthy controls (HC). The cohorts were matched regarding demographics and history of diseases relevant to CVDs, e.g., diabetes, obesity, and nicotine dependence. A total of 90 cardiovascular disorders were identified. The identification of cardiovascular disorders was based on ≥1% appearance of the event, based on absolute numbers, in both cohorts. RESULTS: Before the matching, HS patients displayed a higher frequency in excess weight or obesity (25 vs. 14.4%, respectively), nicotine dependence, and diabetes mellitus, but lower odds of primary hypertension in comparison to healthy controls. A total of 47 CVDs are associated with an increased risk of onset in HS patients. Although the highest hazard ratio (HR; 2.1; 95% CI: 1.95-2.269) was found for unspecified heart failure, the HS cohort was exceptionally predisposed to developing myocardial infarction (HR: 2.06; 95% CI: 1.88-2.27) and an acute embolism and deep vein thrombosis of the lower extremity (HR: 1.93; 95% CI: 1.74-2.14). CONCLUSIONS: This is the most extensive study on the association of HS with CVDs. We demonstrated that HS patients are at significantly greater risk of developing various CVDs compared to matched controls, with heart failure being the most common one.

Case report: Clinical features of COVID-19 vaccine-induced exacerbation of psoriasis-A case series and mini review.

Recently, COVID-19 vaccination-induced exacerbation or new-onset of psoriasis have been reported. Underlying immune pathogenesis is unclear and different mechanisms are assumed. Further, clinical- and vaccine-related features and characteristics are partly inconsistent and remain to be elucidated. To add to the understanding of COVID-19 vaccination-triggered psoriasis, we report five cases with exacerbation or new-onset of psoriasis. In our cohort, one patient experienced the new onset of psoriasis, while four had an exacerbation following COVID-19 vaccination. In most patients, exacerbation or new onset occurred after the 2nd or 3rd vaccination. The mean latency from the day of vaccination was 7.2 (1.8) days (SD). The clinical impact with a mean PASI increase following COVID-19 vaccination of 7.2 (5.6) was considered relevant. In most cases, psoriatic lesions almost cleared after applying topical steroids in addition to current treatment, while one patient with psoriatic arthritis required systemic treatment. New onset and exacerbation of psoriasis have also been noted following COVID-19 infections. Hence, the underlying inflammatory response is most likely the culprit agent triggering psoriasis. This underscores that the benefits of COVID-19 vaccination far outweigh the risks, as also in patients with psoriasis.

DNA-Chip-basierte Diagnose der Onychomykose und Tinea pedis.

HINTERGRUND UND ZIELE: Onychomykose (OM) und Tinea pedis (TP) sind häufige Pilzinfektionen der Haut. Aktuell basiert die Diagnose vornehmlich auf mikroskopischem Direktnachweis und/oder Kultur. Beide Methoden haben jedoch eine geringe bis mäßige Sensitivität und benötigen teilweise mehrere Wochen, bis endgültige Laborergebnisse vorliegen. Um die Diagnose kutaner Pilzinfektionen zu verbessern, wurden PCR-basierte Methoden entwickelt. Hier haben wir hier die Sensitivität und Spezifität einer Chip-basierten Multiplex-PCR mit mikroskopischen Direktnachweis und verglichen. PATIENTEN UND METHODIK: In einer monozentrischen, prospektiven Studie wurden bei Patienten mit Verdacht auf OM (n  =  67) oder TP (n  =  73) Schuppenpräparate entnommen und mittels mikroskopischem Direktnachweis, Kultur und DNA-Chip-Technologie der Erregernachweis durchgeführt. In einem weiteren Ansatz wurde überprüft, ob Abstriche als Alternative zur Entnahme eines Schuppenpräparates verwendet werden können. Hierfür wurden 24 weitere OM/TP-Patienten rekrutiert und die Ergebnisse der DNA-Chip-Technologie aus Abstrichen mit denen aus den Schuppenpräparaten verglichen. ERGEBNISSE: Im Vergleich aller Methoden hatte die DNA-Chip-Technologie die höchste Sensitivität, eine Kombination von DNA-Chip-Technologie mit mikroskopischem Direktnachweis erhöhte dies weiter. Ergebnisse dieser kombinierten Labordiagnostik sind innerhalb von 24 Stunden verfügbar. Der Vergleich der Probenentnahmetechniken (Abstrich beziehungsweise Schuppenpräparat) zeigte vergleichbare Ergebnisse. SCHLUSSFOLGERUNGEN: Die molekulare Diagnostik (mittels DNA-Chip-Technologie) hat eine hohe Sensitivität für die OM- und TP-Diagnostik, insbesondere in Kombination mit dem mikroskopischen Direktnachweis.

DNA chip-based diagnosis of onychomycosis and tinea pedis.

BACKGROUND AND OBJECTIVES: Onychomycosis (OM) and tinea pedis (TP) are common fungal infections. Currently, diagnosis is based on direct microscopy and culture that have a low to moderate sensitivity and/or require up to 3-4 weeks until results are obtained. PCR techniques have emerged for the diagnosis of fungal infections, but little is known about their sensitivity and specificity in diagnosing. Here, we compared the diagnostic value of a DNA-chip technology, that detects 56 fungal pathogens, in a single-center prospective diagnostic study with microscopy and culture in suspected OM/TP. PATIENTS AND METHODS: Microscopy, culture and DNA microarray assays were performed on scraping material from patients with suspected OM (n = 67) or TP (n = 73). To test whether swabs can be used as an alternative for scraping, PCR yields were compared in a further 13 patients with OM and 11 patients with TP. RESULTS: DNA microarrays had the highest sensitivity. Combination of DNA-chip technology with microscopy further increased the sensitivity, and results from this combined laboratory diagnosis can be obtained within 24 hours. Comparison of sampling techniques (scraping, dry or wet swab) for DNA-chip assays showed similar results in suspected OM or TP. CONCLUSIONS: DNA-chip technology shows high sensitivity for OM and TP diagnosis, especially when combined with microscopy.

Biodiversity of mycobial communities in health and onychomycosis.

Onychomycosis (OM) is a common fungal nail infection. Based on the rich mycobial diversity in healthy toenails, we speculated that this is lost in OM due to the predominance of a single pathogen. We used next generation sequencing to obtain insights into the biodiversity of fungal communities in both healthy individuals and OM patients. By sequencing, a total of 338 operational-taxonomic units were found in OM patients and healthy controls. Interestingly, a classifier distinguished three distinct subsets: healthy controls and two groups within OM patients with either a low or high abundance of Trichophyton. Diversity per sample was decreased in controls compared to cases with low Trichophyton abundance (LTA), while cases with a high Trichophyton abundance (HTA) showed a lower diversity. Variation of mycobial communities between the samples showed shifts in the community structure between cases and controls-mainly driven by HTA cases. Indeed, LTA cases had a fungal ß-diversity undistinguishable from that of healthy controls. Collectively, our data provides an in-depth characterization of fungal diversity in health and OM. Our findings also suggest that onychomycosis develops either through pathogen-driven mechanisms, i.e., in HTA cases, or through host and/or environmental factors, i.e., in cases with a low Trichophyton abundance.

Drug survival of secukinumab, ustekinumab, and certolizumab pegol in psoriasis: a 2-year, monocentric, retrospective study.

OBJECTIVE: To investigate the drug survival of secukinumab (SEC), ustekinumab (UST), and certolizumab pegol (CZP) in real-world conditions and to identify the predictors and reasons for treatment discontinuation. METHODS: We performed a 2-year retrospective single-center analysis of 110 treatment courses in 98 patients with moderate to severe plaque-type psoriasis and/or psoriatic arthritis (SEC n = 68; UST n = 29; and CZP n = 13). Drug survival was examined using the Kaplan-Meier analysis and the influence of demographic factors on drug survival with Cox regression analysis. RESULTS: Drug survival rates at 12 and 18 months were respectively 68.5% and 59% for the entire study population, 85% and 69% for UST, 68% and 59% for SEC, and 34% for CZP. Both UST and SEC showed a significantly longer survival rate compared to CZP (p<.05), but not between each other. A total of 30 treatment discontinuations were observed, predominantly due to loss of efficacy and adverse events. Treatment selection predicted the survival rate. Other predictors could not be identified. CONCLUSIONS: Drug survival is the resultant of many factors such as long-term effectiveness, safety, compliance, and convenience of use. UST and SEC had higher retention rates in comparison with CZP.

Evaluation of Site- and Autoantigen-Specific Characteristics of Mucous Membrane Pemphigoid.

IMPORTANCE: Mucous membrane pemphigoid (MMP) is a rare, heterogeneous subepithelial autoimmune bullous disease. The association between its clinical and immunological features is yet to be fully evaluated. OBJECTIVES: To characterize the clinical, immunoserological, and immunopathological characteristics of patients with MMP and to identify site- and autoantigen-specific characteristics. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study encompassing all consecutive patients diagnosed with MMP from January 2007 through February 2020 in 2 tertiary referral centers in Germany. MAIN OUTCOMES AND MEASURES: The clinical, immunoserological, and immunopathological features of eligible patients were evaluated. Associations of different anatomical sites and autoantigens were assessed using a multivariable logistic regression model. RESULTS: The study encompassed 154 patients (96 [62.3%] women and 58 [37.7%] men; mean [SD] age at diagnosis, 66.2 [13.8] years) with MMP, of whom 125 (81.2%), 61 (39.6%), 34 (22.1%), and 16 (10.4%) presented with lesions involving the oral, ocular, nasal, and genital mucosae, respectively, and 35 (22.7%) presented with cutaneous involvement. Among the 154 patients, the most frequently targeted antigen was BP180 (90 patients [58.4%]), followed by laminin 332 (13 patients [8.4%]) and BP230 (3 patients [1.9%]). Ocular disease was inversely associated with oral (adjusted odds ratio [aOR], 0.02; 95% CI, 0.01-0.13) and nasal (aOR, 0.20; 95% CI, 0.04-0.91) involvement and was associated with a 13-fold increased risk of malignant neoplasm (aOR, 13.07; 95% CI, 1.56-109.36). Anti-laminin 332 reactivity was associated with malignant neoplasm (aOR, 23.27; 95% CI, 1.83-296.68), whereas anti-BP180 NC16A immunoglobulin G seropositivity was associated with absence of ocular lesions (aOR, 0.09; 95% CI, 0.01-0.99). CONCLUSIONS AND RELEVANCE: In this cohort study of patients with MMP, malignant neoplasms were associated with ocular disease and anti-laminin 332 reactivity, suggesting potential benefit of malignant neoplasm screening in these patients.

Immunological features and factors associated with mucocutaneous bullous pemphigoid - a retrospective cohort study.

BACKGROUND AND OBJECTIVES: The features of bullous pemphigoid (BP) patients presenting with mucosal lesions are not established. We aimed to elucidate the clinical and immunological features of BP patients with mucosal involvement, and to identify factors associated with mucosal lesions. PATIENTS AND METHODS: A retrospective study encompassing all consecutive patients diagnosed with BP throughout the years 2009-2019 in a tertiary referral center. RESULTS: The study encompassed 273 patients with BP, of whom 31 (11.4 %) presented with mucosal lesions. The oral mucosa was the most frequently affected mucosal surface (71.0 %), followed by the genital (25.8 %) and the nasal (22.6 %) mucosae. Relative to other patients with BP, patients with mucosal involvement had a more prominent palmoplantar involvement (67.7 % vs. 37.2 %; P = 0.001); lower seropositivity rate (18.2 % vs. 54.2 %; P = 0.027) and lower levels (29.3 ± 64.5 vs. 129.5 ± 304.4 U/ml; P = 0.016) of anti-BP230 autoantibodies; and decreased peripheral eosinophil counts (760.0 ± 638.6 vs. 1296.3 ± 1013.7; P < 0.001). Absence of anti-BP230 autoantibodies (OR, 5.32; 95 % CI, 1.07-26.32; P = 0.026) and lack of peripheral eosinophilia (OR, 4.31; 95 % CI, 1.14-16.39; P = 0.021) were associated with the presence of mucosal involvement in BP. CONCLUSIONS: Mucosal involvement is present in a notable subgroup of patients with BP and is associated with the absence of both anti-BP230 antibodies and peripheral eosinophilia.

Prevalence and presumptive triggers of localized bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune skin disease, caused by autoantibodies to BP180 and/or BP230. While both these autoantigens are expressed in the entire skin, only some parts of the body become affected. Rare clinical observations indicate that BP may also manifest locally, usually following exposure to triggers. Here, we evaluated the occurrence and potential triggers of localized BP (LBP) in a cohort of 285 BP patients. Medical records of all BP patients hospitalized between 2009 and 2019 were reviewed. In 7/285 BP patients, a localized variant was identified. In 5/7 LBP patients, the disease remained local, while in 2/7 patients, an initial LBP subsequently spread. All cases were preceded by presumptive triggers, including previously described triggers and bacterial infections. Overall, LBP is rare. LBP, however, might be underdiagnosed and should thus be considered in the differential diagnosis, particularly when trigger factors preceded.

Itch in Scabies-What Do We Know?

Scabies is a common parasitic skin infestation characterized by severe itch and a heterogenous clinical presentation. Itch, as the cardinal symptom of scabies, is imposing a high burden on affected patients and is often difficult to manage. Decreased life quality and secondary complications, caused by an itch-related disruption of the epidermal barrier and subsequent superinfections, illustrate the need to treat scabies and to understand the underlying mechanisms of itch in respective patients. This review summarizes available data on itch in scabies with a special focus on the clinical aspects and its underlying pathomechanisms.

More Severe Erosive Phenotype Despite Lower Circulating Autoantibody Levels in Dipeptidyl Peptidase-4 Inhibitor (DPP4i)-Associated Bullous Pemphigoid: A Retrospective Cohort Study.

BACKGROUND: The clinical and immunological profile of patients with dipeptidyl peptidase-4 inhibitor (DPP4i)-associated bullous pemphigoid (BP) is inconsistent in the current literature. OBJECTIVES: The aims were to investigate the clinical and immunological features of patients with DPP4i-associated BP and to examine whether there are intraclass differences between different DPP4i agents. METHODS: A retrospective cohort study was conducted, including all consecutive patients diagnosed with BP throughout the years 2009-2019 in a tertiary referral center. RESULTS: The study encompassed 273 patients with BP (mean age at diagnosis 79.1 ± 9.9 years), of whom 24 (8.8%) were associated with DPP4i. Sitagliptin was the prescribed agent for 17 patients (70.8%), and vildagliptin was prescribed in seven patients (29.2%). Relative to other patients with BP, patients with DPP4i-associated BP had more prominent truncal involvement (95.8% vs. 73.9%; P = 0.017), greater erosion/blister Bullous Pemphigoid Disease Area Index (BPDAI) subscore (29.8 ± 17.4 vs. 20.6 ± 14.4; P = 0.018), and lower levels of anti-BP180 NC16A (279.2 ± 346.1 vs. 572.2 ± 1352.0 U/ml; P = 0.009) and anti-BP230 (25.5 ± 47.8 vs. 128.6 ± 302.9 U/ml; P = 0.009) antibodies. Relative to patients with sitagliptin-associated BP, those with vildagliptin-associated BP had a lower seropositivity rate (57.1% vs. 94.1%, P = 0.031) and lower levels (96.7 ± 139.0 vs. 354.5 ± 376.5; P = 0.023) of anti-BP180 NC16A antibodies, and tended to present with higher erosion/blister BPDAI subscore (36.3 ± 9.6 vs. 25.8 ± 19.7; P = 0.095). CONCLUSIONS: DPP4i-associated BP is characterized by a more severe blistering and erosive presentation despite lower levels of typically pathogenic antibodies.

Presence of Cutaneous Complement Deposition Distinguishes between Immunological and Histological Features of Bullous Pemphigoid-Insights from a Retrospective Cohort Study.

The practical implications of complement deposition in direct immunofluorescence (DIF) microscopy and its influence on the disease phenotype are poorly understood. We aimed to investigate whether the presence of complement deposition in DIF microscopy gives rise to differences in the morphological, immunological, and histological characteristics of patients with BP (bullous pemphigoid). We performed a retrospective study encompassing patients with BP in a specialized tertiary referral center. Logistic regression model was utilized to identify variables independently associated with complement deposition. The study included 233 patients with BP, of whom 196 (84.1%) demonstrated linear C3 deposition along the dermal-epidermal junction (DEJ) in DIF analysis. BP patients with C3 deposition had higher mean (SD) levels (645.2 (1418.5) vs. 172.5 (243.9) U/mL; p < 0.001) and seropositivity rate (86.3% vs.64.9%; p = 0.002) of anti-BP180 NC16A and less prevalent neutrophilic infiltrate in lesional skin specimens (29.8% vs. 52.4%; p = 0.041). C3 deposition was found positively associated with the detection of anti-BP180 NC16A autoantibodies (OR, 4.25; 95% CI, 1.38-13.05) and inversely associated with the presence of neutrophils in lesional skin (OR, 3.03; 95% CI, 1.09-8.33). To conclude, complement deposition influences the immunological and histological features of BP. These findings are in line with experimental data describing the pathogenic role of complement in BP.

Successful Treatment of Refractory Palmoplantar Pustular Psoriasis With Apremilast: A Case Series.

Introduction: Palmoplantar pustular psoriasis (PPPP) is a debilitating inflammatory skin disorder of the palms and soles that poses a high burden on affected patients. Satisfactory treatment response is rarely achieved using current treatment options, little is known about the potential benefit of the PDE4 inhibitor apremilast in the treatment of refractory PPPP patients. We aimed to evaluate the use of apremilast in PPPP patients. Patients and Methods: Six patients, four with severe physician global assessment (PGA) = 3 on a scale of 0-4 and two with very severe (PGA = 4) treatment-refractory PPPP [mean age (years ± SD): 56.2 ± 15.6], were included in this study. Five patients had concomitant psoriatic arthritis (PsA). Prior to apremilast administration, topical corticosteroids, psoralen-UVA and multiple systemic oral and biologic anti-inflammatory treatments were insufficient to improve their skin condition or had to be discontinued due to adverse events. Apremilast (titrated to a maintenance dose of 30 mg 2x/d) was commenced in all patients with clinical follow-up over 18 months. Results: Within the first 4 weeks of treatment, each patient's symptoms improved as assessed by PGA score. At 3 months, four patients had a mild PGA score and two were cleared from PPPP. After 18 months of follow-up, three patients improved from PGA = 3 to PGA = 1 and one patient from PGA = 4 to PGA = 1. Two patients discontinued treatment, one due to a lack of efficacy against PsA and the other to a desire to have a child. However, both patients recorded improvements before discontinuing treatment. Conclusion: Apremilast may be a promising treatment option for refractory and severely affected PPPP patients. Our observation, however, requires further validation.

Evaluation of lymphocyte transformation tests as compared with patch tests in nickel allergy diagnosis.

BACKGROUND: The patch test is considered to be the gold standard for diagnosing nickel (Ni) allergy. The lymphocyte transformation test (LTT) can also be used to detect Ni sensitization. However, little is known about the correlation between patch test and LTT reactions to Ni. OBJECTIVE: To establish and validate an LTT for Ni sensitization by comparison with patch test reaction and history. METHODS: Fifty individuals without self-reported 'Ni allergy' (controls) and 50 patients with self-reported suspicion of Ni allergy were included. A questionnaire-aided history was taken, and patch tests with at least the baseline series and LTTs with various NiSO4 dilutions were performed. RESULTS: In the patch tests, 2 of 50 controls and 18 of 50 patients with self-reported suspicion of Ni allergy showed positive reactions to Ni. In the LTTs, 2 of 50 controls and 26 of 50 patients with self-reported suspicion of Ni allergy showed positive reactions to NiSO4 2.5 × 10-5 m, and 2 of 50 controls and 17 of 50 patients with self-reported suspicion of Ni allergy showed positive reactions to NiSO4 1 × 10-5 m. Sixteen of the 18 history-positive and patch test-positive patients (i.e. 88% sensitivity) were also LTT-positive, in contrast to only 2 positive LTT reactors within the 48 PT and history negative individuals (i.e. 96% specificity). [Correction added on 16 February 2017, after first online publication: The preceding sentence has been edited for language and this has been amended in this version.] CONCLUSION: Performing the LTT with optimized stimulating conditions might be a useful additional tool for the diagnosis of Ni allergy if non-sensitized controls are included.