A Review of the Use of Intravenous Immunoglobulin Therapy in Dermatology.

Intravenous immune globulin (IVIG) is a manufactured blood product commonly used to treat immunodeficiency syndromes, inflammatory disorders, and autoimmune diseases of the skin. The use of IVIG in dermatology has evolved and expanded over time, serving as a useful therapeutic intervention for several inflammatory skin disorders. In addition to demonstrating efficacy in treating several cutaneous pathologies, IVIG also mitigates the need for steroids or other immunosuppressant medications in many dermatologic diseases. This review highlights the evidence for IVIG use across several dermatologic conditions, emphasizing the dosing regimens and safety considerations.

Drug-Induced Pseudoporphyria: A Case Report.

Pseudoporphyria is an uncommon dermatosis resembling porphyria cutanea tarda (PCT). The exclusion of true porphyria, especially PCT, is critically essential for diagnosing pseudoporphyria. It has an unknown underlying pathophysiology with a normal or near-normal porphyrin profile. Pseudoporphyria has been associated with chronic renal failure and hemodialysis, medications, and tanning beds. In drug-induced pseudoporphyria cases, eliminating the suspected photosensitizing drug improves the disease typically within weeks to months (on average eight weeks). In genetically predisposed individuals, phototoxic metabolites may trigger the development of skin fragility, bullae, milia, and scarring on the dorsum of the hands and other sun-exposed areas. Wearing a broad-spectrum sunscreen and maintaining strict ultraviolet protection is essential in cases of pseudoporphyria. We report the case of a 20-year-old male who presented to us with complaints of photosensitivity and multiple erosions with irregular scars over photo-exposed areas involving the dorsum of the hands and face predominantly. The patient was evaluated further to determine the underlying cause. A wood's lamp examination of the urine was done, which did not show fluorescence. Based on clinical and laboratory findings, the diagnosis of pseudoporphyria was made, and the patient was started on the oral antimalarial agent hydroxychloroquine sulfate with strict sun protection.

The Prevalence of Clinically Undiagnosed Depression in Patients With Autoimmune Bullous Diseases Seen at Inkosi Albert Luthuli Central Hospital, Durban, South Africa.

Background Chronic autoimmune bullous diseases have been associated with major depression in previous studies. This has been attributed to inflammatory cytokines, chronic pain, and the chronicity and debilitating nature of the disease. As no similar studies have been conducted in our setting, we aimed to determine the prevalence and severity of clinically undiagnosed depression in patients with autoimmune bullous diseases. Methodology We performed a cross-sectional study among outpatients managed in a bullous disease clinic at Inkosi Albert Luthuli Central Hospital, a quaternary provincial hospital in Durban, South Africa. Results A total of 44 participants were recruited and included in this study. The majority of the participants were females (29, 65.9%). The most common autoimmune bullous diseases were pemphigus vulgaris (19, 43.2%), bullous pemphigoid (18, 40.9%), and pemphigus foliaceus (5, 11.4%). The overall prevalence of at least mild and at least moderate depression in patients with autoimmune bullous diseases in our clinic was 52.3% and 20.5%, respectively. Pemphigus vulgaris showed the highest median Patient Health Questionnaire-9 score compared to other bullous dermatoses. Statistically significant differences were observed between females and males for the duration with the bullous disease (p = 0.014) and between intraepidermal and subepidermal disease for both the mean age (p = 0.038) and age at onset (p = 0.015). Conclusions Clinically undiagnosed depression is common in patients with autoimmune bullous disease. Its frequency and severity may differ depending on the underlying autoimmune bullous disease and possibly other factors. Dermatologists should always be alert to this fact and prompt psychiatric consultation as required to comprehensively manage these patients.

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.

Bullous Pemphigoid in a Centenarian Male Simulating Toxic Epidermal Necrolysis.

Bullous pemphigoid (BP) is one of the most common autoimmune blistering diseases and classically presents as large, tense bullae. We report a case of BP with toxic epidermal necrolysis (TEN)-like manifestations in a 103-year-old male, the oldest known patient to present with an acute onset of BP. Our patient presented with extensive erosive lesions comprising 12% of the total body surface area, raising suspicion of TEN and Staphylococcal scalded skin syndrome. Detailed clinical, histological, and immunofluorescence analyses were performed, confirming a diagnosis of BP. Atypical presentations of blistering disorders can be a diagnostic challenge and require the use of histologic and direct immunofluorescence testing to distinguish between clinically similar cutaneous diseases. Proper diagnosis is essential to ensure appropriate management and patient care.

Direct Immunofluorescence of IgG on Formalin-Fixed Paraffin-Embedded Tissue by Heat-Induced Antigen Retrieval as a Sensitive Method for the Diagnosis of Pemphigus.

Purpose: Direct immunofluorescence (DIF) on frozen sections (DIF-F) plays a key role in the identification and differential diagnosis of bullous dermatoses, which are a group of critical autoimmune diseases that include pemphigus, bullous pemphigoid (BP), and epidermolysis bullosa acquisita (EBA). However, this technique requires specialized laboratory equipment conditions, sample acquisition and sample preservation. In this study, the application value of DIF on paraffin-embedded tissue sections (DIF-P) detecting IgG using heat-induced antigen retrieval (HIAR) in the diagnosis of bullous dermatosis was explored. Patients and Methods: Samples from 12 patients with pemphigus vulgaris (PV), 10 patients with pemphigus foliaceus (PF), 17 patients with BP, and 4 patients with EBA were retrospectively studied for DIF-P IgG detection. Formalin-fixed, paraffin-embedded tissue (FFPE) was used, and the antigen retrieval method used in the experiment was HIAR. All patients were diagnosed with the autoimmune bullous disease (AIBD) based on clinical presentation, histopathology, DIF-F, and enzyme-linked immunosorbent assay (ELISA). Results: Intercellular staining for IgG in the epidermis was successful in paraffin-embedded tissue sections in 11 of 12 PV samples and in all 10 PF samples. IgG at the basement membrane zone (BMZ) was not detected by immunofluorescent staining in 17 BP samples and 4 EBA samples. Conclusion: The detection of IgG by DIF-P using HIAR can be used for the diagnosis of pemphigus as an alternative method to DIF-F.

Management Options for Linear Immunoglobulin A (IgA) Bullous Dermatosis: A Literature Review.

Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is an autoimmune condition with various triggers. Because of the lack of randomized controlled trials on LABD treatment, management options are mostly anecdotal. This paper provides a comprehensive review of treatment options from a literature review of reported treatments to arm clinicians with a guideline for the management of LABD in both pediatric and adult patients as well as those recalcitrant to first-line therapy (dapsone and steroids). We additionally illustrate an algorithm to use for the management of LABD to aid clinicians when faced with unique patient circumstances.

Paraneoplastic Pemphigus Mimicking Pemphigus Vulgaris Associated With Castleman Disease.

Paraneoplastic pemphigus (PNP) is a rare bullous disease with a polymorphic presentation. Diagnosis can be difficult because it can mimic other bullous diseases, while the underlying neoplasm may be completely asymptomatic. We present the case of a 19-year-old female with a four-year history of exclusively oral bullous lesions, mimicking pemphigus vulgaris, before the diagnosis of a retroperitoneal Castleman disease. While PNP is a severe and sometimes deadly condition, our patient had a mild and long evolution on minimal treatment, with complete resolution after tumor excision. Practitioners should be aware of PNP in young patients presenting with bullous disease and should conduct prompt systemic investigations in refractory or long-evolving cases, even when PNP diagnostic criteria are not fully met.

Concordance of Clinical, Histologic and Direct Immunofluorescence Findings in Patients with Autoimmune Bullous Dermatoses in Vietnam.

Introduction: Autoimmune bullous dermatoses (ABD) represent a heterogeneous group of blistering disorders that may be debilitating with high morbidity. Clinical, histological, and direct immunofluorescence (DIF) studies are essential in establishing an accurate diagnosis of ABD, which is essential for its clinical management. Our study objective was to perform a systematic evaluation of ABD cases in a patient population at an academic medical center in Ho Chi Minh City, Vietnam, and determine the degree of concordance of clinical, histological, and DIF findings in ABD. Methodology: A systematic retrospective cross-sectional study was performed on 92 patients diagnosed with ABD by clinical, histological, and DIF studies at the University of Medicine and Pharmacy in Ho Chi Minh City, Vietnam, between September 2019 and September 2021. The clinical histories, H and E stained tissue sections, and DIF stains were evaluated by pathologists at the University of Medicine and Pharmacy. Results: ABD was evaluated as a whole and subdivided into an intraepidermal blister subgroup and a subepidermal blister subgroup. The analysis of paired diagnostic methods (clinical, histological, and DIF) for concordance with the final diagnosis was performed and showed that there were no statistically significant differences between the paired methods (McNemar's test, p > 0.05). There was moderate concordance between the clinical, histological, and DIF diagnoses among all ABD cases (Brennan-Prediger coefficient Kappa test, κBP = 0.522, CI = 0.95). In the intraepidermal blister subgroup, the diagnostic accuracies of the histology and DIF stains were comparable to each other, and both were more accurate than a clinical diagnosis alone. In the subepidermal blister subgroup, there was no statistically significant difference in each pair of the three diagnostic methods (clinical, histological, and DIF) (McNemar's test, p > 0.05). The concordance between the clinical, histological, and DIF diagnoses was high for the intraepidermal blister subgroup (Kappa test, κBP = 0.758, CI = 0.95). However, the concordance between the clinical, histological, and DIF diagnoses was slight for the subepidermal blister subgroup (Kappa test, κBP = 0.171, CI = 0.95). Conclusion: Histological evaluation is highly accurate in the diagnosis of the intraepidermal blister subgroup, but it is not as accurate in the diagnosis of the subepidermal blister subgroup in the Vietnamese patient cohort in which clinical, histological, and DIF studies were performed. DIF stains are a crucial diagnostic tool for ABD in this patient population.

The Role of VD/VDR Signaling Pathway in Autoimmune Skin Diseases.

BACKGROUND: Immune-related cutaneous diseases are a series of disorders, such as alopecia areata, psoriasis, atopic dermatitis, systemic lupus erythematosus and autoimmune bullous dermatoses. Vitamin D is a fat-soluble vitamin, which is known for its classical pleiotropic effect. Recent studies have found that vitamin D, after catalyzed into its biologically active form [1,25(OH) 2D], correlated with its receptor, vitamin D receptor, plays a vital role in multiple pathophysiological processes, including immune-related dermatoses. This review mainly summarizes evidence on the role of vitamin D/vitamin D receptor in immune-related cutaneous diseases and the potential therapeutic targets for skin disorders. METHODS: We have carried out a comprehensive literature search in PubMed and Google Scholar databases using keywords like "vitamin D", "vitamin D receptor", "immune", "psoriasis", "atopic dermatitis", "skin", "systemic lupus erythematosus", "alopecia areata" and "autoimmune bullous dermatoses". Only articles related to the topic were included in this review. Conference, patent, graduation thesis and articles without available full text were excluded. RESULTS: Vitamin D/vitamin D receptor is critical for skin in regulating the proliferation and differentiation of keratinocytes, keeping the integrity of the skin barrier as well as maintaining the homeostasis of the "skin's immune system". Vitamin D deficiency/vitamin D receptor mutations are potential risk factors for some immune-related cutaneous diseases. CONCLUSION: Vitamin D is a pleiotropic hormone, which is important in the homeostasis of human body. Many studies have revealed vitamin D deficiency in several skin diseases. Thus, vitamin D supplementation may be a useful therapeutic option for immune-related skin diseases.

Epidemiological Study of Autoimmune Bullous Dermatoses in Northeastern Romania.

BACKGROUND: Autoimmune bullous diseases (ABDs) are a rare but significant group of dermatoses that pose great challenges to the treating dermatologist. ABDs are characterized by the presence of tissue-bound and circulating autoantibodies directed against disease-specific target antigens of the skin. Most epidemiological studies have focused on a single ABD. More than that, there are few data about the incidence and prevalence of autoimmune blistering diseases in Romania. METHODS: In this study, between 2015 and 2019, we retrospectively investigated a total of 225 patients with autoimmune bullous diseases from the northeastern region of Romania. The diagnosis was based on the clinical and histo- and immunohistological findings. RESULTS: Pemphigus was the most frequently encountered ABD, with an incidence of 8.16/1,000,000 inhabitants, representing 58.7% (132 cases), followed by 24% cases of bullous pemphigoid (54 cases), 15.4% of patients were diagnosed with dermatitis herpetiformis (37 cases), and 0.9% other subepidermal autoimmune bullous dermatoses. The average age of onset of pemphigus vulgaris was 59.4 years, the majority of patients being male, while the average age of patients diagnosed with bullous pemphigoid was 73.8 years, the majority being female. CONCLUSIONS: Pemphigus vulgaris is the most frequently encountered ABDs in the northeast of Romania, with a higher incidence than in Western European countries, and this may be due to specific peculiarities of the geographical area, as well as to a genetic susceptibility of the population in this region.

Blisters and Milia around the Peritoneal Dialysis Catheter: A Case of Localized Bullous Pemphigoid.

We report on the appearance of multiple tense blisters surrounding the exit site of a Tenckhoff catheter in a 79-year-old woman with end-stage renal disease in peritoneal dialysis. The differential diagnoses included a contact allergic or irritative dermatitis to peritoneal dialysis catheter material and antiseptic agents, bacterial infection, and herpes virus infection, but milia were a clue for a subepidermal blistering disease and lead to appropriate investigations. The laboratory findings, the histopathological examination and the direct immunofluorescence assay confirmed the diagnosis of localized bullous pemphigoid. The disorder typically occurs in elderly people and may be related to drugs, hematological malignancies or neurological conditions but it can also be a complication of hemodialysis or peritoneal dialysis.

Exacerbation of Autoimmune Bullous Diseases After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination: Is There Any Association?

Background and Aim: There have been concerns regarding the potential exacerbation of autoimmune bullous diseases (AIBDs) following vaccination against COVID-19 during the pandemic. In the current study, vaccine safety was evaluated in patients with AIBDs. Methods: In this study, patients with AIBDs were contacted via face-to-face visits or phone calls. Patient demographics, vaccine-related information, pre- and post-vaccine disease status, and complications were recorded. The exacerbation was considered either relapse in the remission/controlled phase of the disease or disease worsening in the active phase. The univariate and multivariate logistic regression tests were employed to determine the potential risk factors of disease exacerbation. Results: Of the patients contacted, 446 (74.3%) reported receiving at least one dose of vaccine injection (54.7% female). Post-vaccine exacerbation occurred in 66 (14.8%) patients. Besides, there were 5 (1.1%) patients with AIBD diagnosis after vaccination. According to the analysis, for every three patients who received vaccines during the active phase of the disease one experienced disease exacerbation. The rate of disease exacerbation increased by three percent with every passing month from the last rituximab infusion. Active disease in the past year was another risk factor with a number needed to harm of 10. Conclusion: Risk of AIBD exacerbation after the COVID-19 vaccine is not high enough to prevent vaccination. This unwanted side effect, can be reduced if the disease is controlled at the time of vaccination.

A global, cross-sectional survey of patient-reported outcomes, disease burden, and quality of life in epidermolysis bullosa simplex.

BACKGROUND: Epidermolysis bullosa simplex (EBS) comprises a group of rare, blistering genodermatoses. Prior work has been limited by small sample sizes, and much remains unexplored about the disease burden and health-related quality of life (QOL) of patients with EBS. The aim of this study was to characterize the most common patient-reported clinical manifestations and the health-related impact of QOL in EBS, and to examine differences in disease burden by age. METHODS: Patients with a diagnosis of epidermolysis bullosa (EB) or their caregivers completed a one-time online survey administered by EBCare, an international online EB registry. Survey data from respondents self-reporting a diagnosis of EBS were analyzed for clinical and wound manifestations, medication use, and QOL (using Quality of Life in Epidermolysis Bullosa [QOLEB] scores). Differences across age groups were assessed using Kruskal-Wallis and Fisher's exact tests. RESULTS: There were 214 survey respondents with EBS. The mean age was 32.8 years (standard deviation = 19.2). Many respondents reported blisters (93%), recurrent wounds (89%), pain (74%), chronic wounds (59%), itch (55%), and difficulty walking (44%). Mean QOLEB score was 14.7 (standard deviation = 7.5) indicating a "moderate" impact on QOL, and 12% of respondents required regular use of opiates. Findings were consistent in subgroup analyses restricted to respondents with diagnostic confirmation via genetic testing or skin biopsy (n = 63 of 214). Age-stratified analyses revealed differences in disease burden: younger respondents were more likely to self-report severe disease (24% vs. 19% vs. 5% for respondents aged 0-9 vs. 10-17 vs. 18 + , p = 0.001), failure to thrive (9% vs. 15% vs. 3%, p = 0.02), and use of gastrostomy tubes (15% vs. 12% vs. 1%, p < 0.001) and topical antibiotics (67% vs. 69% vs. 34%, p < 0.001), while older respondents were more likely to be overweight or obese (6% vs. 0% vs. 51%, p < 0.001) and have difficulty walking (24% vs. 46% vs. 48%, p = 0.04). CONCLUSIONS: In the largest international cross-sectional survey of EBS patients conducted, respondents reported extensive disease burden including significant wounding, pain, itch, difficulty walking, and impact on QOL. Age stratified disease manifestations. These findings suggest significant unmet need, and treatment and counseling for EBS patients should consider age-specific differences.

Bullous Pemphigoid: A Spontaneous Presentation in a Patient With Chronic Kidney Disease.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering pathology characterized by the development of pruritic, tense bullae and blisters on the lower extremities, axilla, and trunk. Its dermatopathology entails autoantibodies that target hemidesmosomes located in the basement membrane. The disease typically manifests in individuals over 50 years old with a higher prevalence in patients with concurrent neurological or dermatological autoimmune diseases. In this report, we discuss a case of a 67-year-old male who presented with a one-month history of itchy blisters occurring bilaterally in the lower extremities. The manifestation of BP, its pathophysiology, and treatment modalities are explored, We also engage in a review of the relevant literature.

Current and Innovated Managements for Autoimmune Bullous Skin Disorders: An Overview.

Autoimmune bullous skin disorders are a group of disorders characterized by the formation of numerous blisters and erosions on the skin and/or the mucosal membrane, arising from autoantibodies against the intercellular adhesion molecules and the structural proteins. They can be classified into intraepithelial or subepithelial autoimmune bullous dermatoses based on the location of the targeted antigens. These dermatoses are extremely debilitating and fatal in certain cases, depending on the degree of cutaneous and mucosal involvement. Effective treatments should be implemented promptly. Glucocorticoids serve as the first-line approach due to their rapid onset of therapeutic effects and remission of the acute phase. Nonetheless, long-term applications may lead to major adverse effects that outweigh the benefits. Hence, other adjuvant therapies are mandatory to minimize the potential harm and ameliorate the quality of life. Herein, we summarize the current therapeutic strategies and introduce promising therapies for intractable autoimmune bullous diseases.