Retrospective analysis of autoimmune bullous diseases in Middle Franconia.

Introduction: Autoimmune bullous diseases (AIBDs) are a group of rare cutaneous disorders affecting cornified skin and mucous membranes. They are characterized by tense or flaccid blistering and erosions due to autoantibodies against desmosomal and hemidesmosomal structural proteins of the skin. This group of disorders can be divided into those of pemphigoid and those of pemphigus diseases. If left untreated, these autoimmune diseases can cause serious or even life-threatening complications such as loss of fluid, superinfections or impaired food intake. Due to modern standardized serological assays, the diagnosis of AIBDs can usually be confirmed in combination with their clinical appearance. Whereas for a long time corticosteroids were the major players in the treatment of these diseases, with the approval of rituximab and other immunosuppressive agents, the therapy has increasingly improved. Methods: In this study, we aimed to investigate epidemiologic and clinical features as well as diagnostics and therapy of bullous autoimmune diseases in Middle Franconia, a governorate within the German federal state of Bavaria. Patients diagnosed or treated because of a AIBDs between 01.04.2013 and 31.03.2019 at the dermatological department of the university hospital Erlangen were included in this retrospective study (n = 242). Patients were either diagnosed for the first time (n=176) or the diagnosis has been confirmed (n=66) at the department. The respective incidence was calculated among the 176 subjects who had been diagnosed at the center in this period. Data was taken from patient records and analyzed with Microsoft® Excel. The evaluation included the diagnoses of pemphigus vulgaris (PV), pemphigus foliaceus (PF), bullous pemphigoid (BP), mucous membrane pemphigoid (MMP), linear IgA dermatosis (LAD), epidermolysis bullosa acquisita (EBA), and dermatitis herpetiformis (DH). Results: This study shows that the incidence of each AIBDs in Middle Franconia is low and comparable (PV, PF, LAD, EBA) or lower (BP, MMP, DH) than in other studies and regions. BP is the most common newly diagnosed AIBD in Middle Franconia. Discussion: Due to the chronic and sometimes severe course of AIBDs, repeated in-house treatments are often necessary. To date, mainly topically and systemically applied corticosteroids in combination with immunomodulators are used as first-line therapy.

Pruritus Is Associated with an Increased Risk for the Diagnosis of Autoimmune Skin Blistering Diseases: A Propensity-Matched Global Study.

Autoimmune bullous skin diseases (AIBDs), such as bullous pemphigoid (BP) and pemphigus, are characterized and caused by autoantibodies targeting structural proteins. In BP, clinical experience and recent systematic evaluation identified pruritus to be common and an important cause of impaired quality of life. Furthermore, chronic pruritus may be the sole clinical symptom of BP. In pemphigus, a retrospective study recently documented a high prevalence of pruritus. The temporal relation between pruritus and BP/pemphigus are, however, unknown. Likewise, the presence of pruritus in AIBDs other than BP and pemphigus is unknown. To address this, we performed propensity-matched retrospective cohort studies using TriNetX, providing real-world patient data to (i) assess the risk to develop AIBDs following the diagnosis of pruritus and (ii) vice versa. We assessed this in eight AIBDs: BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita, dermatitis herpetiformis, lichen planus pemphigoides (LPP), pemphigus vulgaris, pemphigus foliaceous, and paraneoplastic pemphigus (PNP). For all AIBDs, pruritus was associated with an increased risk for the subsequent diagnosis of each of the eight investigated AIBDs in 1,717,744 cases (pruritus) compared with 1,717,744 controls. The observed hazard ratios ranged from 4.2 (CI 3.2-5.5; p < 0.0001) in MMP to 28.7 (CI 3.9-211.3; p < 0.0001) in LPP. Results were confirmed in two subgroup analyses. When restricting the observation time to 6 months after pruritus onset, most HRs noticeably increased, e.g., from 6.9 (CI 6.2-7.9; p < 0.0001) to 23.3 (CI 17.0-31.8; p < 0.0001) in BP. Moreover, pruritus frequently developed following the diagnosis of any of the eight AIBDs, except for PNP. Thus, all AIBDs should be considered as differential diagnosis in patients with chronic pruritus.

Economic Burden of Palmoplantar Pustulosis in Sweden: A Population-based Register Study.

The aim of this study was to estimate the economic burden of palmoplantar pustulosis, a chronic relapsing skin condition commonly occurring in combination with psoriasis vulgaris. Using data from the Swedish National Patient Register and Swedish Prescribed Drug Register for 2015, the study estimated all-cause and palmoplantar pustulosis-specific healthcare resource use (inpatient stays, physician visits and drug use) for 14,715 patients with palmoplantar pustulosis, and compared these both with matched controls from the general population and with patients with psoriasis vulgaris (without palmoplantar pustulosis). Mean annual direct costs for a patient with palmoplantar pustulosis was higher compared with costs for the general population (3,000 vs 1,700 Euro, p < 0.001). Compared with psoriasis vulgaris, more patients with palmoplantar pustulosis had inpatient stays, but fewer had physician visits and psoriasis-related drugs; the overall costs were similar. Only a small fraction of the costs of physician visits and inpatient stays for patients with palmoplantar pustulosis were attributable to specific palmoplantar pustulosis problems, indicating a clear comorbidity burden in palmoplantar pustulosis.

Pediatric autoimmune blistering disorders - a five-year demographic profile and therapy experience.

BACKGROUND: There is a paucity of literature on pediatric autoimmune bullous disorders (AIBD) in the Indian population. We aimed to retrospectively evaluate the clinico-demographic profile of pediatric AIBDs in our patients and their response to various therapeutic modalities. MATERIALS AND METHODS: This was a retrospective chart review of patients enrolled in our immunobullous disease clinic from November 2013 to August 2019. The clinical records of all the patients aged less than 18 years old with a definitive diagnosis of AIBD were reviewed based on clinical, histopathological, and immunological features. RESULTS: Forty out of 1209 patients with AIBD (3.3%) belonged to the pediatric age group. Pemphigus vulgaris (PV) was the most common AIBD (24, 60%) followed by chronic bullous disease of childhood (CBDC) at 15% (6) and pemphigus foliaceus (PV) at 12.5% (5). Subepidermal blistering disorders had a significantly younger age of onset (P = 0.04) compared to intraepidermal blistering disorders but higher frequency of achieving complete remission off therapy (P = 0.02). The mean time to achieve remission was significantly shorter in PV patients treated with a combination of rituximab and corticosteroids compared to those treated with oral prednisolone and oral immunosuppressive adjuvants (P = 0.001). Rituximab was tolerated well in all 12 pemphigus patients. Oral lesions in PV patients took significantly longer time to achieve remission compared to the cutaneous lesions (P = 0.001). CONCLUSION AND RELEVANCE: PV was the most common pediatric AIBD in Indian patients. Rituximab was a safe and effective modality of treatment in moderate to severe pediatric pemphigus.

The Prevalence and Disease Characteristics of Generalized Pustular Psoriasis.

Generalized pustular psoriasis (GPP) is a rare disease that has only recently benefited from a consistent definition and clinical coding standard. A lack of disease awareness combined with clinical similarities to other types of psoriasis have historically complicated the diagnosis of GPP. It is now clear that GPP requires a differential diagnosis from psoriasis vulgaris (plaque psoriasis), and better understanding of the genetic characteristics underlying GPP may improve the accuracy of diagnoses in the future. GPP can present at any age but is most common in the fifth decade of life. There appears to be a female preponderance in GPP, although there is notable variability in prevalence by geographical region and between ethnicities. GPP is potentially life-threatening, associated with several serious complications, and may require emergency treatment, particularly for complications arising from systemic inflammation. As with many rare diseases, there are inherent challenges to understanding the epidemiology of GPP. In addition to small patient numbers, estimating the prevalence of rare diseases is further complicated by studies that use non-standardized methodologies and that are conducted in different populations. These complications in data gathering have led to marked variability in GPP case estimates by geographical region and between ethnicities. There is ongoing research into disease characteristics, and insights into regional measures of prevalence are essential to increasing our understanding of GPP.

Management strategies of autoimmune bullous diseases during the outbreak of 2019 Novel Coronavirus disease (COVID-19).

Since late December 2019, an outbreak of the novel coronavirus disease, which is mainly characterized by pulmonary lesions, has spread quickly worldwide. With the spread of the novel coronavirus, the outpatient lines of hospitals have mostly shut down, which means that routine clinical diagnosis and treatment for autoimmune bullous diseases patients have been disturbed. Due to the serious condition of autoimmune bullous diseases patients, they are prone to immune suppression and circulatory failure, and are more susceptible to infection than healthy individuals. These patients should thus be a priority group for novel coronavirus disease prevention. In this context, the protection and control measures for autoimmune bullous diseases patients against the novel coronavirus are of serious concern. Clinicians should strengthen their communication with patients, pay attention to changes in patients' conditions, and carefully adjust the treatment strategy, while protecting against the novel coronavirus infection, to ensure the continuity, safety, and effectiveness of autoimmune bullous diseases treatment.

Vitamin D status in patients with autoimmune bullous dermatoses: a meta-analysis.

BACKGROUND: The association between autoimmune bullous dermatoses (AIBD) and serum vitamin D levels has been revealed by some studies, however, inconsistent. OBJECTIVES: We aimed to evaluate the difference in vitamin D status between AIBD patients and controls. METHODS: We searched the studies about the vitamin D status of AIBD patients in electronic databases published before January 2020. Mean difference (MD) and 95% confidence intervals (CI) of eligible studies were calculated in meta-analyses of 25(OH)D levels. Pooled odds ratio (OR) and 95%CI were used in analyses of the prevalence of hypovitaminosis D. Different subgroup analyses, sensitivity analyses and publication bias assessment were conducted. RESULTS: We included nine case-control studies in the meta-analysis. Vitamin D level was significantly lower in both pemphigus (MD: -7.02, 95%CI: -10.30 to -3.74) and bullous pemphigoid (BP) (MD: -6.37, 95%CI: -12.15 to -0.58) patients than that in controls. Active pemphigus patients were at higher risk of presenting hypovitaminosis D (OR: 6.95, 95%CI: 1.37-35.25). CONCLUSIONS: Abnormal vitamin D status are more common in AIBD patients than that in general population. Therefore, regular monitoring of vitamin D levels and vitamin D supplementation should be considered as part of the management strategy for AIBD.

Evaluation of a Case Series of Patients With Palmoplantar Pustulosis in the United States.

IMPORTANCE: Palmoplantar pustulosis (PPP) is a is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and health care utilization in adults with PPP across the US. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal case series from 20 academic dermatology practices in the US included a consecutive sample of 197 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for PPP between January 1, 2007, and December 31, 2018. Data analysis was performed June 2020 to December 2020. MAIN OUTCOMES AND MEASURES: The primary outcome was to describe the patient characteristics, associated medical comorbidities, treatment patterns, complications, and PPP-specific health care utilization. RESULTS: Of 197 patients, 145 (73.6%) were female, and the mean (SD) age at presentation was 53.0 (12.6) years, with a mean (SD) follow-up time of 22.1 (28.0) months. On initial presentation, 95 (48.2%) patients reported skin pain, and 39 (19.8%) reported difficulty using hands and/or feet. Seventy patients (35.5%) were treated with systemic treatments, and use of more than 20 different systemic therapies was reported. In patients with at least 6 months of follow-up (n = 128), a median (IQR) of 3.7 (4-10) dermatology visits per year were reported; 24 (18.8%) patients had 5 or more visits during the study period. CONCLUSIONS AND RELEVANCE: In this case series, PPP was associated with persistent symptoms, continued health care utilization, and a lack of consensus regarding effective treatments, emphasizing the unmet medical need in this population. Additional research is necessary to understand treatment response in these patients.

Bullous Dermatoses and Depression: A Systematic Review.

IMPORTANCE: There is a lack of evidence synthesis on the association between bullous skin disease and depression. OBJECTIVE: To synthesize and interpret the current evidence on the association between bullous skin disease and depression. EVIDENCE REVIEW: This review was conducted according to PRISMA guidelines and reviewed literature related to bullous skin disease and depression in the PubMed, Embase, PsycInfo, and Cochrane databases published between 1945 and February 2021. The quality of each included article was assessed via the Newcastle-Ottawa Scale. This review was registered with PROSPERO (CRD42021230750). FINDINGS: A total of 17 articles were identified that analyzed a total of 83 910 patients (55.2% female; specifically, 6951 patients with bullous pemphigoid, 1669 patients with pemphigus, and 79 patients with epidermolysis bullosa were analyzed). The prevalence of depressive symptoms among patients with bullous dermatoses ranged from 40% to 80%. The prevalence of depression diagnosis among patients with bullous dermatoses ranged from 11.4% to 28%. CONCLUSIONS AND RELEVANCE: In this systematic review, high rates of depression and depressive symptoms existed among patients with bullous skin disease. Adequate treatment of bullous dermatoses may be associated with a decrease in mental health burden on patients.

Autoimmune bullous diseases in pregnancy: clinical and epidemiological characteristics and therapeutic approach

Abstract Autoimmune bullous dermatoses are a heterogeneous group of diseases with autoantibodies against structural skin proteins. Although the occurrence of autoimmune bullous dermatoses during pregnancy is low, this topic deserves attention, since the immunological and hormonal alterations that occur during this period can produce alterations during the expected course of these dermatoses. The authors review the several aspects of autoimmune bullous dermatoses that affect pregnant women, including the therapeutic approach during pregnancy and breastfeeding. Gestational pemphigoid, a pregnancy-specific bullous disease, was not studied in this review.

Impact of COVID-19 on autoimmune blistering diseases.

Since the beginning of the COVID-19 outbreak, attention has gradually moved from the respiratory manifestations of the disease toward its dermatologic aspects. The need for wearing personal protective measures and their cutaneous side effects, detection of related or specific COVID-19 skin eruptions, and the evaluation of certain risk groups of immunosuppressed dermatologic patients have initiated significant discussions about various therapeutic interventions and, in particular, about biologic therapy for psoriasis and for autoinflammatory, orphan, or malignant cutaneous disorders. Autoimmune bullous dermatoses have been of concern due to their chronic course, at times life-threatening prognosis, and the need for prolonged and often aggressive immunomodulatory therapy. We have summarized the current knowledge regarding the impact of COVID-19 infection on autoimmune bullous dermatoses, including recommendations for the main treatment strategies, available patient information, and the registries organized for documentation during the COVID-19 pandemic.

Bullous Autoimmune Dermatoses­Clinical Features, Diagnostic Evaluation, and Treatment Options.

BACKGROUND: Bullous autoimmune dermatoses are a clinically and immunopatho - logically heterogeneous group of diseases, characterized clinically by blisters or erosions of the skin and/or mucous membranes. In Germany, their prevalence is approximately 40 000 cases nationwide, and their incidence approximately 20 new cases per million people per year. METHODS: This review is based on publications that were retrieved by a selective search of the literature focusing on the current German and European guidelines. RESULTS: Recent years have seen the publication of guidelines, controlled prospective clinical trials, and multicenter diagnostic studies improving both diagnosis and therapy. Specific monovalent and multivariate serological test systems and pattern analysis of tissue-bound autoantibodies allow identification of the target antigens in 80-90% of patients. This enables the precise classification of disease entities, with implications for treatment selection and disease outcome. In 2019, the anti-CD20 antibody rituximab was approved by the European Medicines Agency for the treatment of moderate and severe pemphigus vulgaris, with an ensuing marked improvement in the care of the affected patients. To treat mild and moderate bullous pemphigoid, topical clobetasol proprionate is recommended, in severe disease, combined with systemic treatment, i.e. usually (a) prednisolone p.o. at an initial dose of 0.5mg/kg/d , (b) an immunomodulant, e.g. dapsone or doxycycline, or (c) prednisolone plus an immunomodulant. CONCLUSION: The early recognition and precise diagnostic evaluation of bullous autoimmune dermatoses now enables improved, often interdisciplinary treatment, in accordance with the available guidelines. Current research projects are focused on new treatment approaches, an improved understanding of the underlying pathophysiology, and further refinements of diagnostic techniques.

Autoimmune bullous diseases in pregnancy: clinical and epidemiological characteristics and therapeutic approach.

Autoimmune bullous dermatoses are a heterogeneous group of diseases with autoantibodies against structural skin proteins. Although the occurrence of autoimmune bullous dermatoses during pregnancy is low, this topic deserves attention, since the immunological and hormonal alterations that occur during this period can produce alterations during the expected course of these dermatoses. The authors review the several aspects of autoimmune bullous dermatoses that affect pregnant women, including the therapeutic approach during pregnancy and breastfeeding. Gestational pemphigoid, a pregnancy-specific bullous disease, was not studied in this review.

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.

Subepithelial autoimmune blistering dermatoses: Clinical features and diagnosis.

Subepithelial autoimmune blistering dermatoses are a group of rare skin disorders that are characterized by the disruption of the dermal-epidermal junction through the action of autoantibodies. The third article in this continuing medical education series explores the background, epidemiology, clinical features, and diagnostic criteria of each of the major subepithelial autoimmune blistering dermatoses, including bullous pemphigoid, pemphigoid gestationis, lichen planus pemphigoides, mucous membrane pemphigoid, linear IgA bullous dermatosis, and dermatitis herpetiformis.