Core outcome domains for lichen sclerosus: a CORALS initiative consensus statement.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory condition mainly affecting genital skin. It causes distressing symptoms that impact daily quality of life (QoL). It causes progressive anatomical changes and a potential risk of cancer. Published randomized controlled trials are of varying methodological quality and difficult to combine in meta-analyses. This is partly due to lack of agreed outcome measures to assess treatment response. Identification of core outcome sets (COSs), which standardize key outcomes to be measured in all future trials, is a solution to this problem. OBJECTIVES: To obtain international agreement on which outcome domains should be measured in interventional trials of genital LS. METHODS: Recommended best practice for COS domain development was followed: (i) identification of potential outcome domains: a long list was generated through an up-to-date LS literature search, including information collected during the LS priority-setting partnership; (ii) provisional agreement of outcome domains: a three-stage multi-stakeholder international electronic-Delphi (e-Delphi) consensus study; (iii) final agreement of outcome domains: online consensus meeting with international stakeholders including anonymized voting. RESULTS: In total, 123 participants (77 patients, 44 health professionals, 2 researchers) from 20 countries completed three rounds of the e-Delphi study. Eleven outcome domains were rated as 'critical' and were discussed at the online consensus meetings. The first set of consensus meetings involved 42 participants from 12 countries. Consensus was met for 'symptoms' (100% agreed) and 'QoL - LS-specific' (92% agreed). After the second set of meetings, involving 29 participants from 12 countries, 'clinical (visible) signs' also met consensus (97% agreed). CONCLUSIONS: The international community has agreed on three key outcome domains to measure in all future LS clinical trials. We recommend that trialists and systematic reviewers incorporate these domains into study protocols with immediate effect. CORALS will now work with stakeholders to select an outcome measurement instrument per prioritized core domain.

Comorbidity, life-style factors and healthcare utilization in incident chronic kidney disease: sex-specific analyses of claims data.

BACKGROUND: Chronic kidney disease (CKD) is common in aging men and women. In contrast to other European countries, Germany lacks CKD registries. The aim of this study was to determine the incidence of CKD stages 2-5 in men and women in Germany. Furthermore, differences between the sexes in terms of comorbidities, potentially inappropriate medications (PIM), and healthcare utilization were examined. METHODS: In this retrospective observational study, claims data from members of a statutory health insurance fund aged 18 years or older with incident CKD between 2011 and 2018 were analyzed. Incident CKD was defined as having two confirmed diagnoses of CKD stages 2-5 from outpatient care or one primary or secondary diagnosis from inpatient care. RESULTS: The age- and sex-standardized incidence of all CKD stages was 945/100 000 persons between 2011 and 2018. Incident CKD, especially stages 3 and 4, occurred more frequently in women, while the incidence of stages 2 and 5 was higher in men. While women visited their GP more frequently and were prescribed PIMs more often, men were more likely to visit a nephrologist and were more often hospitalized after the incident CKD diagnosis. CONCLUSION: More awareness needs to be raised towards the early detection of CKD and the use of PIMs, especially in women. Improved care coordination is needed to avoid an overprovision of patients with uncomplicated incident stages and ensure that patients with advanced CKD stages get timely access to specialist care.

Interventions for bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first published in 2002, because several new treatments have since been tried. OBJECTIVES: To assess the effects of treatments for bullous pemphigoid. SEARCH METHODS: We updated searches of the following databases to November 2021: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched five trial databases to January 2022, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: RCTs of treatments for immunofluorescence-confirmed bullous pemphigoid. DATA COLLECTION AND ANALYSIS: At least two review authors, working independently, evaluated the studies against the review's inclusion criteria and extracted data from included studies. Using GRADE methodology, we assessed the certainty of the evidence for each outcome in each comparison. Our primary outcomes were healing of skin lesions and mortality. MAIN RESULTS: We identified 14 RCTs (1442 participants). The main treatment modalities assessed were oral steroids, topical steroids, and the oral anti-inflammatory antibiotic doxycycline. Most studies reported mortality but adverse events and quality of life were not well reported. We decided to look at the primary outcomes 'disease control' and 'mortality'. Almost all studies investigated different comparisons; two studies were placebo-controlled. The results are therefore based on a single study for each comparison except azathioprine. Most studies involved only small numbers of participants. We assessed the risk of bias for all key outcomes as having 'some concerns' or high risk, due to missing data, inappropriate analysis, or insufficient information. Clobetasol propionate cream versus oral prednisone Compared to oral prednisone, clobetasol propionate cream applied over the whole body probably increases skin healing at day 21 (risk ratio (RR 1.08, 95% confidence interval (CI) 1.03 to 1.13; 1 study, 341 participants; moderate-certainty evidence). Skin healing at 21 days was seen in 99.8% of participants assigned to clobetasol and 92.4% of participants assigned to prednisone. Clobetasol propionate cream applied over the whole body compared to oral prednisone may reduce mortality at one year (RR 0.73, 95% CI 0.53 to 1.01; 1 study, 341 participants; low-certainty evidence). Death occurred in 26.5% (45/170) of participants assigned to clobetasol and 36.3% (62/171) of participants assigned to oral prednisone. This study did not measure quality of life. Clobetasol propionate cream may reduce risk of severe complications by day 21 compared with oral prednisone (RR 0.65, 95% CI 0.50 to 0.86; 1 study, 341 participants; low-certainty evidence). Mild clobetasol propionate cream regimen (10 to 30 g/day) versus standard clobetasol propionate cream regimen (40 g/day) A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen probably does not change skin healing at day 21 (RR 1.00, 95% CI 0.97 to 1.03; 1 study, 312 participants; moderate-certainty evidence). Both groups showed complete healing of lesions at day 21 in 98% participants. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change mortality at one year (RR 1.00, 95% CI 0.75 to 1.32; 1 study, 312 participants; low-certainty evidence), which occurred in 118/312 (37.9%) participants. This study did not measure quality of life. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change adverse events at one year (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 309 participants; low-certainty evidence). Doxycycline versus prednisolone Compared to prednisolone (0.5 mg/kg/day), doxycycline (200 mg/day) induces less skin healing at six weeks (RR 0.81, 95% CI 0.72 to 0.92; 1 study, 213 participants; high-certainty evidence). Complete skin healing was reported in 73.8% of participants assigned to doxycycline and 91.1% assigned to prednisolone. Doxycycline compared to prednisolone probably decreases mortality at one year (RR 0.25, 95% CI 0.07 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) = 14; 1 study, 234 participants; moderate-certainty evidence). Mortality occurred in 2.4% (3/132) of participants with doxycycline and 9.7% (11/121) with prednisolone. Compared to prednisolone, doxycycline improved quality of life at one year (mean difference 1.8 points lower, which is more favourable on the Dermatology Life Quality Index, 95% CI 1.02 to 2.58 lower; 1 study, 234 participants; high-certainty evidence). Doxycycline compared to prednisolone probably reduces severe or life-threatening treatment-related adverse events at one year (RR 0.59, 95% CI 0.35 to 0.99; 1 study, 234 participants; moderate-certainty evidence). Prednisone plus azathioprine versus prednisone It is unclear whether azathioprine plus prednisone compared to prednisone alone affects skin healing or mortality because there was only very low-certainty evidence from two trials (98 participants). These studies did not measure quality of life. Adverse events were reported in a total of 20/48 (42%) participants assigned to azathioprine plus prednisone and 15/44 (34%) participants assigned to prednisone. Nicotinamide plus tetracycline versus prednisone It is unclear whether nicotinamide plus tetracycline compared to prednisone affects skin healing or mortality because there was only very low-certainty evidence from one trial (18 participants). This study did not measure quality of life. Fewer adverse events were reported in the nicotinamide group. Methylprednisolone plus azathioprine versus methylprednisolone plus dapsone It is unclear whether azathioprine plus methylprednisolone compared to dapsone plus methylprednisolone affects skin healing or mortality because there was only very low-certainty evidence from one trial (54 participants). This study did not measure quality of life. A total of 18 adverse events were reported in the azathioprine group and 13 in the dapsone group. AUTHORS' CONCLUSIONS: Clobetasol propionate cream applied over the whole body is probably similarly effective as, and may cause less mortality than, oral prednisone for treating bullous pemphigoid. Lower-dose clobetasol propionate cream applied over the whole body is probably similarly effective as standard-dose clobetasol propionate cream and has similar mortality. Doxycycline is less effective but causes less mortality than prednisolone for treating bullous pemphigoid. Other treatments need further investigation.

Long-term effects of preeclampsia on maternal cardiovascular health and postpartum utilization of primary care: an observational claims data study.

PURPOSE: Preeclampsia occurs in up to 15% of pregnancies and constitutes a major risk factor for cardiovascular disease. This observational cohort study aimed to examine the association between preeclamptic pregnancies and cardiovascular outcomes as well as primary and specialized care utilization after delivery. METHODS: Using statutory claims data we identified women with singleton live births between 2010 and 2017. Main outcomes included the occurrence of either hypertension or cardiovascular disease after one or more preeclamptic pregnancies, number of contacts to a general practitioner or cardiologist after delivery and prescribed antihypertensive medication. Data were analyzed using Cox proportional hazard regression models adjusted for maternal age, diabetes, dyslipidemia, and obesity. RESULTS: The study cohort consisted of 181,574 women with 240,698 births. Women who experienced preeclampsia once had an increased risk for cardiovascular (hazard ratio, HR = 1.29) or hypertensive (HR = 4.13) events. In women affected by recurrent preeclampsia, risks were even higher to develop cardiovascular disease (HR = 1.53) or hypertension (HR = 6.01). In the following years after delivery, general practitioners were seen frequently, whereas cardiologists were consulted rarely (0.3 and 2.4%). CONCLUSION: Women affected by preeclampsia experience an increased risk of developing chronic hypertension and cardiovascular disease, especially those with recurrent preeclampsia. Future medical guidelines should take this potential risk into account.

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial.

BACKGROUND: Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. METHODS: We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3-9, 10-30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority. The primary safety outcome was the proportion with severe, life-threatening, or fatal (grade 3-5) treatment-related adverse events by 52 weeks. Analysis (modified intention to treat [mITT] for the superiority safety analysis and mITT and per protocol for non-inferiority effectiveness analysis) used a regression model adjusting for baseline disease severity, age, and Karnofsky score, with missing data imputed. The trial is registered at ISRCTN, number ISRCTN13704604. FINDINGS: Between March 1, 2009, and Oct 31, 2013, 132 patients were randomly assigned to doxycycline and 121 to prednisolone from 54 UK and seven German dermatology centres. Mean age was 77·7 years (SD 9·7) and 173 (68%) of 253 patients had moderate-to-severe baseline disease. For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1-26·1) favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening, and fatal events at 52 weeks were 18% (22 of 121) for those starting doxycycline and 36% (41 of 113) for prednisolone (mITT), an adjusted difference of 19·0% (95% CI 7·9-30·1), p=0·001. INTERPRETATION: Starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term. FUNDING: NIHR Health Technology Assessment Programme.

Twelve-week treatment of lentigo maligna with imiquimod results in a high and sustained clearance rate.

Topical imiquimod cream is increasingly applied in the treatment of lentigo maligna (LM), in particular for large lesions where surgery may lead to disfiguring scars. Published studies suggest that more frequent and prolonged treatment with topical imiquimod is associated with higher efficacy. In this study we prospectively treated 27 patients suffering from LM on the face with imiquimod 5% cream using an intensive treatment regimen consisting of daily applications for 12 weeks inducing skin inflammation for at least 10 weeks. Twenty-four patients completed the treatment as recommended, 23 were available for follow-up (mean 39 months). Clinical and histo-pathological clearance was observed in 20 patients after a mean of 14 weeks of treatment. Notably, histopathological examination of a skin biopsy showed clearance of the LM in all 24 patients, including those who still showed some hyperpigmentation at 4 weeks off treatment. A clinical recurrence occurred in only 1 of the 23 patients available at follow-up. These findings suggest that the efficacy of imiquimod can be improved by implementing a more intensive treatment regimen. Randomized controlled trials are needed to confirm our results and establish the role of topical imiquimod in the treatment of LM.

Safety of topical corticosteroids in pregnancy.

BACKGROUND: Topical corticosteroids are the most frequently prescribed dermatological treatment and are often used by pregnant women with skin conditions. However, little is known about their safety in pregnancy. OBJECTIVES: To assess the effects of topical corticosteroids on pregnancy outcomes in pregnant women. SEARCH METHODS: This is an update of a review previously published in 2009. We updated our searches of the following databases to July 2015: the Cochrane Skin Group Specialised Register, the Cochrane Pregnancy and Childbirth Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 6), MEDLINE, EMBASE, and LILACS. We also searched five trials registers and checked the reference lists of included studies, published reviews, articles that had cited the included studies, and one author's literature collection, for further references to relevant RCTs. SELECTION CRITERIA: Randomised controlled trials and cohort studies of topical corticosteroids in pregnant women, as well as case-control studies comparing maternal exposure to topical corticosteroids between cases and controls when studies reported pre-specified outcomes. The primary outcomes included mode of delivery, major congenital abnormality, birth weight, and preterm delivery (delivery before 37 completed weeks gestation); the secondary outcomes included foetal death, minor congenital abnormality, and low Apgar score (less than seven at 5 min). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two authors independently applied selection criteria, extracted data, and assessed the quality of the included studies. A third author was available for resolving differences of opinion. A further author independently extracted data from included studies that were conducted by authors of this systematic review. MAIN RESULTS: We included 7 new observational studies in this update, bringing the total number to 14, including 5 cohort and 9 case-control studies, with 1,601,515 study subjects.Most studies found no causal associations between maternal exposure to topical corticosteroids of any potency and pregnancy outcomes when compared with no exposure. These outcomes included: mode of delivery (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.15, 1 cohort study, n = 9904, low quality evidence); congenital abnormalities, including orofacial cleft or cleft palate and hypospadias (where the urethral opening is on the underside of the penis) (RR 0.82, 95% CI 0.34 to 1.96, 2 cohort studies, n = 9512, low quality evidence; and odds ratio (OR) 1.07, 95% CI 0.71 to 1.60, 1 case-control study, n = 56,557); low birth weight (RR 1.08, 95% CI 0.86 to 1.36; n = 59,419, 4 cohort studies; very low quality evidence); preterm delivery (RR 0.93, 95% CI 0.81 to 1.08, 4 cohort studies, n = 59,419, low quality evidence); foetal death (RR 1.02, 95% CI 0.60 to 1.73, 4 cohort studies, n = 63,885, very low quality evidence); and low Apgar score (RR 0.84, 95% CI 0.54 to 1.31, 1 cohort study, n = 9220, low quality evidence).We conducted stratified analyses of mild or moderate potency, and potent or very potent topical corticosteroids, but we found no causal associations between maternal exposure to topical corticosteroid of any potency and congenital abnormality, orofacial clefts, preterm delivery, or low Apgar score. For low birth weight, although the meta-analysis based on study-level data was not significant for either mild to moderate corticosteroids (pooled RR 0.90, 95% CI 0.74 to 1.09, 3 cohort studies, n > 55,713) or potent to very potent corticosteroids (pooled RR 1.58, 95% CI 0.96 to 2.58, 4 cohort studies, n > 47,651), there were significant differences between the two subgroups (P = 0.04). The results from three of the individual studies in the meta-analysis indicated an increased risk of low birth weight in women who received potent to very potent topical corticosteroids. Maternal use of mild to moderate potency topical steroids was associated with a decreased risk of foetal death (pooled RR 0.70, 95% CI 0.64 to 0.77, 2 studies, n = 48,749; low quality evidence), but we did not observe this effect when potent to very potent topical corticosteroids were given during pregnancy (pooled RR 1.14, 95% CI 0.69 to 1.88, 3 studies, n = 37,086, low quality evidence).We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group approach to rate the overall quality of the evidence. Data from observational studies started at low quality. We further downgraded the evidence because of imprecision in low birth weight and inconsistency in foetal death. Lower quality evidence resulted in lower confidence in the estimate of effect for those outcomes. AUTHORS' CONCLUSIONS: This update adds more evidence showing no causal associations between maternal exposure to topical corticosteroids of all potencies and pregnancy outcomes including mode of delivery, congenital abnormalities, preterm delivery, foetal death, and low Apgar score, which is consistent with the previous version of this review. This update provides stratified analyses based on steroid potency; we found no association between maternal use of topical corticosteroids of any potency and an increase in adverse pregnancy outcomes, including mode of delivery, congenital abnormality, preterm delivery, foetal death, and low Apgar score. Similar to the previous version of the review, this update identified a probable association between low birth weight and maternal use of potent to very potent topical corticosteroids, especially when the cumulative dosage of topical corticosteroids throughout the pregnancy is very large, which warrants further investigation. The finding of a possible protective effect of mild to moderate topical corticosteroids on foetal death could also be examined.

Blocking Fcα receptor I on granulocytes prevents tissue damage induced by IgA autoantibodies.

IgA represents the most prominent Ab class at mucosal surfaces and the second most prevalent Ab in human blood after IgG. We recently demonstrated that cross-linking of the granulocyte IgA FcR (FcαRI) by IgA induces a chemotactic-driven positive-feedback migration loop, hereby amplifying recruitment of granulocytes to IgA deposits. Therefore, we postulated that aberrant IgA-Ag complexes, which can be found in tissues in IgA-mediated diseases, are responsible for tissue damage by inducing continuous granulocyte migration and activation. Using an IgA-dependent skin-blistering disease as a model system, we demonstrated colocalization of FcαRI-positive granulocyte infiltrates with IgA in cryosections of lesional skin of patients suffering from this disease. Furthermore, we showed granulocyte migration to IgA deposits injected in human skin explants and in murine skin of FcαRI transgenic mice in vivo. Importantly, ex vivo migration and tissue damage were inhibited by blocking FcαRI, indicating that these events are dependent on the interaction of IgA autoantibodies with FcαRI. Thus, interrupting the granulocyte migration loop by blocking FcαRI reduces tissue damage in diseases with aberrant IgA-immune complexes. As such, our results may lead to development of new therapies for IgA-mediated chronic inflammatory diseases, hereby decreasing severe morbidity and improving quality of life for these patients.

[Genital lichen sclerosus and lichen planus]. / Genitaler Lichen sclerosus und Lichen planus.

Lichen sclerosus (LS) and lichen planus (LP) are chronic inflammatory dermatoses of unknown aetiology. They pose the most important differential diagnoses of inflammatory dermatoses in the genital area. There is often a delay in diagnosing LS and LP and subsequently treatment is initiated late in the course of the disease, which will lead to scarring and a decreased quality of life. There is an increased risk of the development of malignancies in the genital area in both diseases; however, early and continuous treatment with potent topical steroids will decrease this risk.

Systematic review and meta-analysis of randomized controlled trials on topical interventions for genital lichen sclerosus.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory dermatosis that occurs mainly in the anogenital area and causes itching and soreness. Progressive destructive scarring may result in burying of the clitoris in females and phimosis in males. Affected people have an increased risk of genital cancers. OBJECTIVE: We sought to assess the effects of topical interventions for genital LS. METHODS: We undertook a systematic review and meta-analysis using the methodology of the Cochrane Collaboration. RESULTS: We included 7 randomized controlled trials with a total of 249 participants covering 6 treatments. Clobetasol propionate 0.05% was better than placebo in treating genital LS (participant-rated improvement/remission of symptoms: risk ratio 2.85 [95% confidence interval {CI} 1.45-5.61]; investigator-rated global degree of improvement: standardized mean difference [SMD] 5.74 [95% CI 4.26-7.23]) as was mometasone furoate 0.05% (change in clinical grade of phimosis: SMD -1.04 [95% CI -1.77 to -0.31]). We found no evidence supporting the efficacy of topical androgens and progesterone. There were no differences between pimecrolimus and clobetasol propionate in relieving symptoms through change in pruritus (SMD -0.33 [95% CI -0.99 to 0.33]) and burning/pain (SMD 0.03 [95% CI -0.62 to 0.69]). However, pimecrolimus was less effective than clobetasol propionate in improving gross appearance (investigator-rated global degree of improvement: SMD -1.64 [95% CI -2.40 to -0.87]). LIMITATIONS: Most of the included studies were small. CONCLUSIONS: The current limited evidence supports the efficacy of clobetasol propionate, mometasone furoate, and pimecrolimus in treating genital LS. Further randomized controlled trials are needed.

Interventions for erosive lichen planus affecting mucosal sites.

BACKGROUND: Erosive lichen planus (ELP) affecting mucosal surfaces is a chronic autoimmune disease of unknown aetiology. It is often more painful and debilitating than the non-erosive types of lichen planus. Treatment is difficult and aimed at palliation rather than cure. Several topical and systemic agents have been used with varying results. OBJECTIVES: To assess the effects of interventions in the treatment of erosive lichen planus affecting the oral, anogenital, and oesophageal regions. SEARCH METHODS: We searched the following databases up to September 2009: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), and LILACS (from 1982). We also searched reference lists of articles and online trials registries for ongoing trials. SELECTION CRITERIA: We considered all randomised controlled trials (RCTs) that evaluated the effectiveness of any topical or systemic interventions for ELP affecting either the mouth, genital region, or both areas, in participants of any age, gender, or race. DATA COLLECTION AND ANALYSIS: The primary outcome measures were as follows:(a) Pain reduction using a visual analogue scale rated by participants; (b) Physician Global Assessment; and (c) Participant global self-assessment.Changes in scores at the end of therapy compared with baseline were analysed. MAIN RESULTS: A total of 15 RCTs were identified, giving a total of 473 participants with ELP. All studies involved oral ELP only. Six of the 15 studies included participants with non-erosive lichen planus. In these studies, only the erosive subgroup was included for intended subgroup analysis. We were unable to pool data from any of the nine studies with only ELP participants or any of the six studies with the ELP subgroup, due to small numbers and the heterogeneity of the interventions, design methods, and outcome variables between studies. One small study involving 50 participants found that 0.025% clobetasol propionate administered as liquid microspheres significantly reduced pain compared to ointment (Mean difference (MD) -18.30, 95% confidence interval (CI) -28.57 to -8.03), but outcome data was only available in 45 participants. However, in another study, a significant difference in pain was seen in the small subgroup of 11 ELP participants, favouring ciclosporin solution over 0.1% triamcinolone acetonide in orabase (MD -1.40, 95% CI -1.86 to -0.94). Aloe vera gel was 6 times more likely to result in at least a 50% improvement in pain symptoms compared to placebo in a study involving 45 ELP participants (Risk ratio (RR) 6.16, 95% CI 2.35 to 16.13). In a study involving 20 ELP participants, 1% pimecrolimus cream was 7 times more likely to result in a strong improvement as rated by the Physician Global Assessment when compared to vehicle cream (RR 7.00, 95% CI 1.04 to 46.95).There is no overwhelming evidence for the efficacy of a single treatment, including topical steroids, which are the widely accepted first-line therapy for ELP. Several side-effects were reported, but none were serious. With topical corticosteroids, the main side-effects were oral candidiasis and dyspepsia. AUTHORS' CONCLUSIONS: This review suggests that there is only weak evidence for the effectiveness of any of the treatments for oral ELP, whilst no evidence was found for genital ELP. More RCTs on a larger scale are needed in the oral and genital ELP populations. We suggest that future studies should have standardised outcome variables that are clinically important to affected individuals. We recommend the measurement of a clinical severity score and a participant-rated symptom score using agreed and validated severity scoring tools. We also recommend the development of a validated combined severity scoring tool for both oral and genital populations.

Polymyalgia Rheumatica.

BACKGROUND: Polymyalgia rheumatica (PMR) is among the most common inflammatory rheumatic diseases in older adults. Presumed risk factors include female sex, previous infections, and genetic factors. No epidemiological data on PMR in Germany have been available until now. METHODS: This review is based on publications retrieved by a selective literature search in PubMed. Moreover, the administrative incidence and prevalence of PMR in the years 2011-2019 was determined from data of the AOK Baden-Württemberg statutory health insurance carrier for insurees aged 40 and older. In addition, we quantified the number of consultations with physicians involved in the diagnosis. RESULTS: The annual age- and sex-standardized incidence and prevalence of PMR from 2011 to 2019 were 18.6/100 000 persons and 138.8/100 000 persons, respectively. The incidence was higher in women than in men (21.8/100 000 vs. 12.8/100 000 persons per year). 60% of the cases were diagnosed in primary care practices. The treatment of PMR with orally administered glucocorticoids usually results in a treatment response within a few days to weeks. Approximately 43% of patients experience recurrent symptoms within a year, requiring adjustment of the glucocorticoid dose. For older patients with impaired physical ability, additional non-pharmacological treatment with exercise programs plays an important role. CONCLUSION: PMR usually takes an uncomplicated course under treatment and can be managed in primary care, but these patients are often multimorbid and require frequent follow-up. Along with research on the etiology of the disease, further studies are needed to identify the risk factors for a chronic course and to evaluate the potential effects of non-pharmacological measures.

Topical interventions for genital lichen sclerosus.

BACKGROUND: Lichen sclerosus is a chronic, inflammatory skin condition that most commonly occurs in adult women, although it may also be seen in men and children. It primarily affects the genital area and around the anus, where it causes persistent itching and soreness. Scarring after inflammation may lead to severe damage by fusion of the vulval lips (labia); narrowing of the vaginal opening; and burying of the clitoris in women and girls, as well as tightening of the foreskin in men and boys, if treatments are not started early. Affected people have an increased risk of genital cancers. OBJECTIVES: To assess the effects of topical interventions for genital lichen sclerosus and adverse effects reported in included trials. SEARCH METHODS: We searched the following databases up to 16 September 2011: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), LILACS (from 1982), CINAHL (from 1981), British Nursing Index and Archive (from 1985), Science Citation Index Expanded (from 1945), BIOSIS Previews (from 1926), Conference Papers Index (from 1982), and Conference Proceedings Citation Index - Science (from 1990). We also searched ongoing trial registries and scanned the bibliographies of included studies, published reviews, and papers that had cited the included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of topical interventions in genital lichen sclerosus. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted data, and assessed the risk of bias. A third author was available for resolving differences of opinion. MAIN RESULTS: We included 7 RCTs, with a total of 249 participants, covering 6 treatments. Six of these RCTs tested the efficacy of one active intervention against placebo or another active intervention, while the other trial tested three active interventions against placebo.When compared to placebo in one trial, clobetasol propionate 0.05% was effective in treating genital lichen sclerosus in relation to the following outcomes: 'participant-rated improvement or remission of symptoms' (risk ratio (RR) 2.85, 95% confidence interval (CI) 1.45 to 5.61) and 'investigator-rated global degree of improvement' (standardised mean difference (SMD) 5.74, 95% CI 4.26 to 7.23).When mometasone furoate 0.05% was compared to placebo in another trial, there was a significant improvement in the 'investigator-rated change in clinical grade of phimosis' (SMD -1.04, 95% CI -1.77 to -0.31).Both trials found no significant differences in reported adverse drug reactions between the corticosteroid and placebo groups. The data from four trials found no significant benefit for topical testosterone, dihydrotestosterone, and progesterone. When used as maintenance therapy after an initial treatment with topical clobetasol propionate in another trial, topical testosterone worsened the symptoms (P < 0.05), but the placebo did not.One trial found no differences between pimecrolimus and clobetasol propionate in relieving symptoms through change in pruritus (itching) (SMD -0.33, 95% CI -0.99 to 0.33) and burning/pain (SMD 0.03, 95% CI -0.62 to 0.69). However, pimecrolimus was less effective than clobetasol propionate with regard to the 'investigator-rated global degree of improvement' (SMD -1.64, 95% CI -2.40 to -0.87). This trial found no significant differences in reported adverse drug reactions between the pimecrolimus and placebo groups. AUTHORS' CONCLUSIONS: The current limited evidence demonstrates the efficacy of clobetasol propionate, mometasone furoate, and pimecrolimus in treating genital lichen sclerosus. Further RCTs are needed to determine the optimal potency and regimen of topical corticosteroids, examine other topical interventions, assess the duration of remission or prevention of flares, evaluate the reduction in the risk of genital squamous cell carcinoma or genital intraepithelial neoplasia, and examine the efficacy in improving the quality of the sex lives of people with this condition.

An observational claims data analysis on the risk of maternal chronic kidney disease after preterm delivery and preeclampsia.

Women with complications of pregnancy such as preeclampsia and preterm birth are at risk for adverse long-term outcomes, including an increased future risk of chronic kidney disease (CKD) and end-stage kidney disease (ESKD). This observational cohort study aimed to examine the risk of CKD after preterm delivery and preeclampsia in a large obstetric cohort in Germany, taking into account preexisting comorbidities, potential confounders, and the severity of CKD. Statutory claims data of the AOK Baden-Wuerttemberg were used to identify women with singleton live births between 2010 and 2017. Women with preexisting conditions including CKD, ESKD, and kidney replacement therapy (KRT) were excluded. Preterm delivery (< 37 gestational weeks) was the main exposure of interest; preeclampsia was investigated as secondary exposure. The main outcome was a newly recorded diagnosis of CKD in the claims database. Data were analyzed using Cox proportional hazard regression models. The time-dependent occurrence of CKD was analyzed for four strata, i.e., births with (i) neither an exposure of preterm delivery nor an exposure of preeclampsia, (ii) no exposure of preterm delivery but exposure of at least one preeclampsia, (iii) an exposure of at least one preterm delivery but no exposure of preeclampsia, or (iv) joint exposure of preterm delivery and preeclampsia. Risk stratification also included different CKD stages. Adjustments were made for confounding factors, such as maternal age, diabetes, obesity, and dyslipidemia. The cohort consisted of 193,152 women with 257,481 singleton live births. Mean observation time was 5.44 years. In total, there were 16,948 preterm deliveries (6.58%) and 14,448 births with at least one prior diagnosis of preeclampsia (5.61%). With a mean age of 30.51 years, 1,821 women developed any form of CKD. Compared to women with no risk exposure, women with a history of at least one preterm delivery (HR = 1.789) and women with a history of at least one preeclampsia (HR = 1.784) had an increased risk for any subsequent CKD. The highest risk for CKD was found for women with a joint exposure of preterm delivery and preeclampsia (HR = 5.227). These effects were the same in magnitude only for the outcome of mild to moderate CKD, but strongly increased for the outcome of severe CKD (HR = 11.90). Preterm delivery and preeclampsia were identified as independent risk factors for all CKD stages. A joint exposure or preterm birth and preeclampsia was associated with an excessive maternal risk burden for CKD in the first decade after pregnancy. Since consequent follow-up policies have not been defined yet, these results will help guide long-term surveillance for early detection and prevention of kidney disease, especially for women affected by both conditions.

Systematic review of the safety of topical corticosteroids in pregnancy.

BACKGROUND: Pregnant women may have skin conditions that require topical corticosteroids. However, little is known about their safety in pregnancy. OBJECTIVE: We sought to evaluate the available evidence concerning the safety of topical corticosteroids in pregnancy. METHODS: We systematically searched 17 databases and trial registers, and contacted pharmaceutical companies. Randomized controlled trials and cohort studies of topical corticosteroids in pregnant women, and case-control studies comparing maternal exposure to topical corticosteroids between patients and control subjects were included. The Newcastle-Ottawa Scale was used for quality assessment of included studies. RESULTS: Seven studies, including two cohort and five case-control studies, were included. Most studies did not find significant associations of topical corticosteroids with congenital abnormality, preterm delivery stillbirth, and mode of delivery. One study found a significant association between first-trimester use of topical corticosteroids and orofacial cleft, and another study found a significant association between very potent topical corticosteroids and low birthweight. LIMITATIONS: The available data were limited and mainly on orofacial cleft. The quality of evidence was generally low. CONCLUSIONS: Currently limited and inconclusive data are unable to detect an association between topical corticosteroids and congenital abnormality, preterm delivery, or stillbirth. The current evidence shows no statistically significant difference between pregnant women who use and those who do not use topical corticosteroids. However, there does appear to be an association of very potent topical corticosteroids with low birthweight. Further cohort studies with comprehensive outcome measures, consideration of corticosteroid potency, dosage and indications, and a large sample size are needed.

Interventions for bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the West. Oral steroids are the standard treatment.This is an update of the review published in 2005. OBJECTIVES: To assess treatments for bullous pemphigoid. SEARCH STRATEGY: In August 2010 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials), MEDLINE, EMBASE, and the Ongoing Trials registers. SELECTION CRITERIA: Randomised controlled trials of treatments for participants with immunofluorescence-confirmed bullous pemphigoid. DATA COLLECTION AND ANALYSIS: At least two authors evaluated the studies for the inclusion criteria, and extracted data independently. MAIN RESULTS: We included 10 randomised controlled trials (with a total of 1049 participants) of moderate to high risk of bias. All studies involved different comparisons, none had a placebo group. In 1 trial plasma exchange plus prednisone gave significantly better disease control at 1 month (0.3 mg/kg: RR 18.78, 95% CI 1.20 to 293.70) than prednisone alone (1.0 mg/kg: RR 1.79, 95% CI 1.11 to 2.90), while another trial showed no difference in disease control at 6 months.No differences in disease control were seen for different doses or formulations of prednisolone (one trial each), for azathioprine plus prednisone compared with prednisone alone (one trial), for prednisolone plus azathioprine compared with prednisolone plus plasma exchange (one trial), for prednisolone plus mycophenolate mofetil or plus azathioprine (one trial), for tetracycline plus nicotinamide compared with prednisolone (one trial). Chinese traditional medicine plus prednisone was not effective in one trial.There were no significant differences in healing in a comparison of a standard regimen of topical steroids (clobetasol) with a milder regimen (RR 1.00, 95% 0.97 to 1.03) in one trial. In another trial, clobetasol showed significantly more disease control than oral prednisolone in people with extensive and moderate disease (RR 1.09, 95% CI 1.02 to 1.17), with significantly reduced mortality and adverse events (RR 1.06, 95% CI 1.00 to 1.12). AUTHORS' CONCLUSIONS: Very potent topical steroids are effective and safe treatments for BP, but their use in extensive disease may be limited by side-effects and practical factors. Milder regimens (using lower doses of steroids) are safe and effective in moderate BP. Starting doses of prednisolone greater than 0.75 mg/kg/day do not give additional benefit, lower doses may be adequate to control disease and reduce the incidence and severity of adverse reactions. The effectiveness of adding plasma exchange, azathioprine or mycophenolate mofetil to corticosteroids, and combination treatment with tetracycline and nicotinamide needs further investigation.