The burden of neurological comorbidities in six autoimmune bullous diseases: a population-based study.

BACKGROUND: Apart from bullous pemphigoid (BP), the association of other autoimmune bullous diseases (AIBDs) with neurological conditions is poorly understood. OBJECTIVE: To estimate the association between a wide array of AIBDs and neurological conditions. METHODS: A retrospective cross-sectional study recruited patients with BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita (EBA), pemphigoid gestationis (PG), pemphigus vulgaris (PV) and pemphigus foliaceus (PF). These patients were compared with their age- and sex-matched control subjects with regard to the lifetime prevalence of Parkinson's disease (PD), Alzheimer's disease (AD), stroke, epilepsy and multiple sclerosis (MS). Logistic regression was used to calculate OR for specified neurological disorders. RESULTS: The current study included 1743, 251, 106, 126, 860 and 103 patients diagnosed with BP, MMP, EBA, PG, PV and PF, respectively. These patients were compared with 10 141, 1386, 606, 933, 5142 and 588 matched controls, respectively. Out of the investigated neurological conditions, PD associated with BP (OR, 2.71; 95% CI, 2.19-3.35); AD with BP (OR, 2.11; 95% CI, 1.73-2.57), MMP (OR, 2.37; 95% CI, 1.03-5.47), EBA (OR, 6.00; 95% CI, 1.90-18.97) and PV (OR, 2.24; 95% CI, 1.40-3.60); stroke with BP (OR, 1.84; 95% CI, 1.55-2.19) and EBA (OR, 2.79; 95% CI, 1.11-7.01); and epilepsy with BP (OR, 2.18; 95% CI, 1.72-2.77) and PV (OR, 1.80; 95% CI, 1.19-2.73). MS did not significantly cluster with any of the six AIBDs. CONCLUSION: In addition to BP, EBA and PV were found to cluster with neurological comorbidities. Patients with these AIBDs with compatible symptoms may be carefully assessed for comorbid neurological disorders.

[Paediatric vulval clinic]. / Pädiatrische Vulvasprechstunde.

In 2008 a vulval clinic was established at the University Clinic of Schleswig Holstein, Campus Luebeck, Department of Dermatology. A total of 1227 patients were referred to the clinic between 2008 and October 2020, including 91 children (age range 1-13 years) and 17 adolescents (age range 14-17 years). The most common paediatric vulval conditions encountered were lichen sclerosus (33%), vulvitis (23%) and vulval psoriasis (7%). Quality of life was measured in 81 children using the paediatric version of the Dermatology Life Quality Index (DLQI). Of a maximum 30 points, the mean score was 7.2, confirming the association between vulval diseases and impaired quality of life in children and adolescents.

A sensitive and specific assay for the serological diagnosis of antilaminin 332 mucous membrane pemphigoid.

BACKGROUND: Antilaminin 332 mucous membrane pemphigoid (MMP) is an autoimmune subepidermal blistering disease with predominant mucosal involvement and autoantibodies against laminin 332. Malignancies have been associated with this disease; however, no standardized detection system for antilaminin 332 serum antibodies is widely available. OBJECTIVES: Development of a sensitive and specific assay for the detection of antilaminin 332 antibodies. METHODS: An indirect immunofluorescence (IF) assay using recombinant laminin 332 was developed and probed with a large number of antilaminin 332 MMP patient sera (n = 93), as well as sera from patients with antilaminin 332-negative MMP (n = 153), bullous pemphigoid (n = 20), pemphigus vulgaris (n = 20) and noninflammatory dermatoses (n = 22), and healthy blood donors (n = 100). RESULTS: In the novel IF assay, sensitivities with the laminin 332 heterotrimer and the individual α3, ß3 and γ2 chains were 77%, 43%, 41% and 13%, respectively, with specificities of 100% for each substrate. The sensitivity for the heterotrimer increased when an anti-IgG4 enriched antitotal IgG conjugate was applied. Antilaminin 332 reactivity paralleled disease activity and was associated with malignancies in 25% of patients with antilaminin 332 MMP. CONCLUSIONS: The novel IF-based assay will facilitate the serological diagnosis of antilaminin 332 MMP and may help to identify patients at risk of a malignancy.

Low incidence of heparin-induced skin lesions in orthopedic surgery patients with low-molecular-weight heparins.

BACKGROUND: Heparins are widely prescribed for prevention and therapy of arterial and venous thromboembolic diseases. Heparin-induced skin lesions are the most frequent adverse effect of subcutaneous heparin treatment in non-surgical patients (7.5%-39.8%); no data exist on surgical patients. Commonly, they are due to a delayed-type hypersensitivity reaction (DTH), but may also be a manifestation of life-threatening heparin-induced thrombocytopenia (HIT). Lesions of both entities resemble initially. The risk of HIT is highest among heparin-anticoagulated orthopedic surgery patients. OBJECTIVE: To determine incidence and causes of heparin-induced skin lesions in major orthopedic surgery patients. METHODS: In a prospective cohort study, consecutive patients with subcutaneous low-molecular-weight heparin (LMWH) treatment were examined for cutaneous adverse effects. Further diagnostics (skin biopsy, clinical/laboratory assessment for thrombosis, bleeding, HIT, cross-allergies) were performed. RESULTS: Six of 316 enrolled patients (1.9%; 95% CI: 0.4%-3.4%) developed heparin-induced skin lesions. All were caused by a DTH reaction, and none was due to HIT or other rare heparin-associated skin diseases. Therapeutic use (dosage) of LMWH was identified as only risk factor (odds ratio: 3.1, 95% CI: 1.4-4.9; P = .00141). In addition to DTH, 5 thromboembolic, 4 major bleeding complications but no cases of HIT or cross-allergies were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Orthopedic surgery patients have-unlike non-surgical patients-a low risk for heparin-induced skin lesions during LMWH treatment; all lesions were due to a DTH reaction. The risk for DTH differs considerably between individual patient cohorts. No association with HIT was observed. These data help to tailor anticoagulatory treatment individually and to increase patient safety.

Influence of cigarette smoking on pemphigus - a systematic review and pooled analysis of the literature.

Epidemiological evidence suggests that smoking cigarettes may be beneficial in pemphigus, but no systematic evaluation exists to corroborate this assumption. Therefore, a systematic literature review with pooled data analysis of the smoking status in patients with pemphigus was conducted. Electronic searches using PubMed from inception to November 2017 identified 13 reports meeting predetermined inclusion and exclusion criteria. Most were case-control studies partly reporting that pemphigus vulgaris and foliaceus occurred less frequently in current and former smokers. Studies also indicated that duration of smoking and number of cigarettes smoked were lower in patients with pemphigus than controls and that remission may be achieved sooner in those who smoke. However, although a generally low prevalence of smoking was demonstrated in patients with pemphigus, which was lower than in controls by pooled analysis, some investigations found no difference regarding the smoking status compared with non-pemphigus subjects. One study demonstrated more severe mucosal involvement in non-smoking patients with pemphigus, whereas another observed no difference in the rate of cutaneous or mucosal lesions between smokers and non-smokers with pemphigus. This review indicates that smoking may be a possible protective factor in pemphigus, although some compromised study methodologies yet hinder any firm conclusion. Further investigations with a refined quality design are required to resolve the so far partly conflicting results in this area.

Are Sonographically Measured Vascular Haemodynamic Parameters Reproducible Using Magnetic Resonance Imaging?

OBJECTIVE/BACKGROUND: Hemodynamic measurements of blood flow in the common femoral vein and artery can be performed readily using duplex sonography. The ratio of venous to arterial volume flow in these vessels, the venous arterial flow index (VAFI), is increased in patients with varicose veins and/or chronic venous disease. The objective was to determine the reproducibility of sonographically measured hemodynamic flow parameters using phase contrast magnetic resonance imaging (MRI). METHODS: Based on hemodynamic volume flow measurements from the common femoral vein and artery the VAFI was calculated in seven patients with varicose veins (C2, Ep, As, Pr) and 32 healthy controls using standard duplex sonography and MRI. RESULTS: Based on duplex sonography, the average VAFI (VAFI_d) was 1.05 ± 0.17. The same ratio, using MRI (VAFI_mri) was 1.05 ± 0.19. There was a significant correlation between the VAFI_d and the VAFI_MRI (p = .0021). In patients with venous disease, the average VAFI_d and VAFI_mri were 1.36 ± 0.21 and 1.36 ± 0.20, respectively. In contrast, in the healthy cohort the VAFI_d was 1.00 ± 0.12 and the VAFI_mri measured 1.01 ± 0.15. As expected, there was a significant difference between the VAFI measured in those with venous disease when compared with that of healthy controls (p < .0001). CONCLUSION: There is a significant correlation between the VAFI measured using sonography and MRI. The study confirmed the elevation of VAFI in patients with chronic venous disease.

TNFAIP3 and IL12B gene polymorphisms associated with psoriasis vulgaris in an Egyptian cohort.

BACKGROUND: Psoriasis vulgaris is a common chronic inflammatory skin disease. Development of early onset psoriasis is, to some extent, genetically determined and a strong association with the major histocompatibility complex HLA-Cw6 has been demonstrated. The use of genome-wide association studies has highlighted novel genes associated with the development of psoriasis as IL12B, IL23R, TNFAIP3 and IL13 for instance. The majority of these studies were performed on cohorts of European descent. OBJECTIVE: To determine whether inter-ethnic differences exist in the genetic susceptibility to psoriasis, we genotyped single-nucleotide polymorphism variations in the vicinity of candidate genes in 132 Egyptian patients and 175 healthy controls. METHODS: Blood samples of patients and controls were screened for nucleotide polymorphisms in four candidate genes by TaqMan single-nucleotide polymorphisms Genotyping Assays. RESULTS: We found a significant association between psoriasis and the single-nucleotide polymorphism rs610604, within the TNFAIP3 gene. The TNFAIP3 gene is involved in the TNF-α signalling cascade (P-value: 0.004952), a key step in the pathogenesis of psoriasis. Although there was no significant association found between rs610604 (IL12B) and rs11209026 (IL23R) in this population, the interaction of these two genes showed a significant association with psoriasis (P-value: 0.025). Moreover, when selecting the patients with early disease onset (less than 30 years), we also found that the association of IL12B and psoriasis was highly significant (P-value 1.14 × 10(-12)). No association between rs20541 (IL13) and psoriasis was observed in our Egyptian cohort. CONCLUSION: Replicating the association of single-nucleotide polymorphisms in the TNFAIP3, IL12B and IL23R genes with psoriasis vulgaris, in subjects from different ethnic backgrounds, underlines their importance in the pathogenesis of the disease. In contrast, the lack of any association between rs20541 (IL13) and psoriasis in our Egyptian cohort suggests the existence of important inter-ethnic genetic differences in psoriasis susceptibility.

Serum autoantibodies against the dermal-epidermal junction in patients with chronic pruritic disorders, elderly individuals and blood donors prospectively recruited.

BACKGROUND: Bullous pemphigoid (BP) is a subepidermal blistering autoimmune disease characterized by autoantibodies against two structural proteins of the epidermal basal membrane zone (BMZ), BP180 (type XVII collagen) and BP230. Patients are usually old and suffer from severe pruritus. Advanced age and severe pruritus have been hypothesized as potential risk factors for the development of autoantibodies in BP. OBJECTIVES: To prospectively determine anti-BMZ antibodies in sera from patients with advanced age and/or pruritus compared with regular blood donors. METHODS: Sera from (i) patients with chronic pruritic skin disorders (PSD, n = 78; mean age 62 years), (ii) patients with noninflammatory skin disease aged ≥ 70 years (n = 93; mean age 78 years), and (iii) blood donors (n = 50; mean age 41 years) were included. A large panel of validated test systems used for routine diagnosis were employed comprising indirect immunofluorescence (IF) microscopy on monkey oesophagus and human salt-split skin, BP180 NC16A- and BP230-specific enzyme-linked immunosorbent assay (ELISA) systems, and immunoblotting with various substrates, including LAD-1 (the soluble ectodomain of BP180), BP180, BP230, laminin 332, p200 antigen, laminin γ1 and type VII collagen. RESULTS: No statistically significant difference was seen between the three study groups. The same result was obtained when data for IF microscopy, ELISA and immunoblotting were analysed separately. CONCLUSIONS: Neither advanced age nor chronic pruritus have been verified as risk factors for autoantibodies against the epidermal BMZ.

Catheter-directed foam sclerotherapy of great saphenous veins in combination with pre-treatment reduction of the diameter employing the principals of perivenous tumescent local anesthesia.

OBJECTIVES: The aim of this study was to evaluate occlusion rates of great saphenous veins (GSV) with a diameter between 5-10 mm that received a pre-treatment size reduction via perivenous tumescent application (TA) followed by catheter-directed foam sclerotherapy (CDFS). METHODS: A prospective blinded randomized clinical trial comparing the occlusion rates of GSV at 1-, 6-, and 12-month follow-up. Fifty patients were included and randomized into two groups. CDFS was performed accessing the GSV at knee level and applying 8 mL of 2% polidocanol-foam (EasyFoam) while the catheter was withdrawn. Strictly perivenous TA was performed in group 1 before applying the sclerosant agent. Occlusion rates and clinical scores were assessed by blinded examiners. RESULTS: After 12 months in group 1 full occlusion was achieved in 73.9%, partial occlusion in 8.7%, and 17.4% were classified as treatment failure. In group 2, 75% of the targeted GSV were fully occluded, 20% were partially occluded, and 5% were diagnosed as treatment failure. Both groups showed a significant reduction of the vein diameter. Patient's tolerance and satisfaction with the treatment was high in both groups. CONCLUSION: No benefit could be found using additional TA to reduce the vein diameter before the treatment.

A comparison of new bone formation in patients with ankylosing spondylitis and patients with diffuse idiopathic skeletal hyperostosis: a retrospective cohort study over six years.

OBJECTIVE: Ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) are both characterized by new bone formation in the spine but presumably have a different pathogenesis. This study was undertaken to compare the natural course of new bone formation in AS and DISH. METHODS: Lateral radiographs of the cervical and lumbar spine from AS and DISH patients obtained at ≥2 time points within 6 years were analyzed to quantify osteophyte development. Radiographs were scored in a blinded manner by 2 readers using the modified Stoke AS Spine Score (mSASSS). Bone spurs were categorized as having an angle of <45° or >45°. RESULTS: AS patients (n = 146) were younger than DISH patients (n = 141) (mean ± SD 54.2 ± 12.3 years versus 60.3 ± 7.7 years). Symptom duration (mean ± SD) was 23.6 ± 11.2 years in AS patients and 21.6 ± 12.4 years in DISH patients. The mSASSS at baseline was lower in DISH patients (mean ± SD 14.3 ± 6.7) than in AS patients (20.5 ± 14.5) but had increased by a similar amount at followup (3.3 ± 4.2 versus 4.1 ± 9.5). The mean mSASSS progression rate per year (1.3 units) was also comparable. The mean ± SD number of syndesmophytes per patient was higher in AS (5.7 ± 5.5) than DISH (2.7 ± 2.8) patients (P < 0.001), while degenerative bone spurs (mean ± SD) were more frequent in DISH (1.4 ± 1.8) than AS (1.0 ± 1.4) patients. AS patients developed more new bone spurs with an angle of <45° than >45° per patient (mean ± SD 2.1 ± 2.7 versus 0.6 ± 0.9) (P < 0.001), while similar amounts of both types of bone formation were seen in DISH patients. CONCLUSION: Our findings indicate that the rates of new bone formation in AS and DISH are largely similar. Both groups show osteophyte development, but as expected, syndesmophytes are more frequent in AS patients while DISH patients have more degenerative bone spurs. The nature of the different mechanisms of bone formation needs further study.