Autoimmune Blistering Skin Disease Research Articles

Role of auto-antibodies in the mechanisms of dengue pathogenesis and its progression: a comprehensive review.

A complex interaction among virulence factors, host-genes and host immune system is considered to be responsible for dengue virus (DENV) infection and disease progression. Generation of auto-antibodies during DENV infection is a major phenomenon that plays a role in the pathophysiology of dengue hemorrhagic fever and dengue shock syndrome. Hemostasis, thrombocytopenia, hepatic endothelial dysfunction, and autoimmune blistering skin disease (pemphigus) are different clinical manifestations of dengue pathogenesis; produced due to the molecular mimicry of DENV proteins with self-antigens like coagulation factors, platelets and endothelial cell proteins. This review elaborately describes the current advancements in auto-antibody-mediated immunopathogenesis which inhibits coagulation cascade and promotes hyperfibrinolysis. Auto-antibodies like anti-endothelial cell antibodies-mediated hepatic inflammation during severe DENV infection have also been discussed. Overall, this comprehensive review provides insight to target auto-antibodies that may act as potential biomarkers for disease severity, and a ground for the development of therapeutic strategy against DENV.

Is It Time to Reconsider Rituximab Dosing Regimens for Pemphigus Vulgaris?

Rituximab is currently approved for patients affected by moderate-to-severe pemphigus vulgaris, a severe autoimmune blistering skin disease that can be life-threatening. The standard rituximab dosing regimens, originally established for B-cell non-Hodgkin's lymphomas, have been recognized to exceed the effective dose required for inducing B-cell depletion, considering that the B-cell burden in pemphigus vulgaris is considerably lower than in lymphoproliferative disorders. We herein report our experience with very ultra-low-dose rituximab in two patients affected by pemphigus vulgaris.

Monocyte populations are involved in the pathogenesis of experimental epidermolysis bullosa acquisita.

Monocytes play a significant role in the pathogenesis of most inflammatory diseases, including autoimmune diseases. Herein, different subpopulations of monocytes often play differential, partially antagonistic roles, in the regulation of tissue populations. Pemphigoid diseases constitute a group of autoimmune blistering skin diseases featuring a marked infiltration of the dermis with immune cells, including monocytes. The monocyte subsets infiltrating the skin, however, have largely remained elusive. Monocyte adhesion and recruitment into the inflamed tissues are regulated by chemokine receptors, most prominently by CCR2 and CX3CR1. To delineate the involvement of monocyte populations in autoimmune blistering skin diseases, we spatiotemporally monitored the dynamic spectrum of monocyte populations that infiltrate the inflamed skin using multiphoton intravital imaging and reporter mice for chemokine receptors. Experimental epidermolysis bullosa acquisita (EBA) was induced by injection of anti-murine type VII collagen (amCOLVII) IgG into the Csf1rEGFP-reporter mice, where circulating myeloid cells, such as monocytes and neutrophils, express an EGFP. EGFP+ cells, including neutrophils and monocytes, were present in the skin, immediately after the deposition of the amCOLVII antibody at the dermal-epidermal junction. To investigate the recruitment and involvement of different monocyte-derived cell populations in the disease course further, EBA was induced in CCR2RFP/+-reporter and CX3CR1GFP/+-reporter mice. A comparable distribution of red fluorescent protein (RFP)+ or green fluorescent protein (GFP)+ was found in both diseased mice and their respective controls over time, indicating the similar recruitment of monocytes into the skin following the binding of autoantibodies. Experiments were extended to the CCR2RFP/RFP-deficient and CX3CR1GFP/GFP-deficient mice to determine whether monocyte recruitment and disease severity are compromised in the absence of the receptor. A comparable pattern was seen in the recruitment of monocytes into the skin in both reporter and deficient mice. However, in contrast to similar disease severity between CX3CR1-deficient and reporter mice, CCR2-deficient mice developed significantly less disease than CCR2-reporter mice, as indicated by the percentage of affected area of ears. Collectively, our observations indicate that while CCR2 and CX3CR1 receptors are not involved in the recruitment of monocytes into the skin, CCR2 deficiency is associated with improved disease outcomes in experimental EBA in mice.

The landscape of the immunoglobulin repertoire in endemic pemphigus foliaceus.

Primarily driven by autoreactive B cells, pemphigus foliaceus (PF) is an uncommon autoimmune blistering skin disease of sporadic occurrence worldwide. However, PF reaches a prevalence of 3% in the endemic areas of Brazil, the highest ever registered for any autoimmune disease, which indicates environmental factors influencing the immune response in susceptible individuals. We aimed to provide insights into the immune repertoire of patients with PF living in the endemic region of the disease, compared to healthy individuals from the endemic region and a non-endemic area. We characterized the B-cell repertoire in i) nontreated patients (n=5); ii) patients under immunosuppressive treatment (n=5); iii) patients in remission without treatment (n=6); and two control groups iv) from the endemic (n=6) and v) non-endemic areas in Brazil (n=4). We used total RNA extracted from peripheral blood mononuclear cells and performed a comprehensive characterization of the variable region of immunoglobulin heavy chain (IGH) in IgG and IgM using next-generation sequencing. Compared to individuals from a different area, we observed remarkably lower clonotype diversity in the B-cell immune repertoire of patients and controls from the endemic area (p < 0.02), suggesting that the immune repertoire in the endemic area is under geographically specific and intense environmental pressure. Moreover, we observed longer CDR3 sequences in patients, and we identified differential disease-specific usage of IGHV segments, including increased IGHV3-30 and decreased IGHV3-23 in patients with active disease (p < 0.04). Finally, our robust network analysis discovered clusters of CDR3 sequences uniquely observed in patients with PF. Our results indicate that environmental factors, in addition to disease state, impact the characteristics of the repertoire. Our findings can be applied to further investigation of the environmental factors that trigger pemphigus and expand the knowledge for identifying new targeted and more effective therapies.

Pemphigus Foliaceus in A Potato Donut Seller: A Case Report

Background: Pemphigus foliaceus is a condition of a rare and potentially life-threatening autoimmune blistering skin disease, thought to be caused by circulating autoantibodies against desmoglein-1 (Dsg-1), a glycoprotein with an integral role in maintaining intercellular adhesion between keratinocytes. Pemphigus foliaceus primary lesions generally manifest as erythematous papules, plaques, and erosions with the addition of scaly crusts as secondary lesions. Immunosuppressant is the mainstay therapy for pemphigus foliaceus. This case report describes the case of a female patient who worked as a potato donut seller with pemphigus foliaceus and analyzes the relationship between her disease and work.Case Presentation: A 31-year-old woman presented with a history of itchiness, redness, and burning sensation on her face, followed by the appearance of vesicles on her face, spreading to the back, arms, and legs. The patient worked as a potato donut seller and encountered numerous potential hazards. Upon further examination, the patient was diagnosed with pemphigus foliaceus. Discussion: Establishing an occupational disease requires a seven-step method, taking into account the clinical diagnosis, occupational, individual, and other exposures outside of work. In this case, neither occupational, individual, nor other environmental risk factors of pemphigus foliaceus was found. Conclusion: There are no substantial evidence that occupational exposures as a potato donut seller cause or exacerbate the patient’s diagnosis of pemphigus foliaceus. The patient’s innate genetic susceptibility remains the main factor contributing to her diagnosis.

Anti-NC16A IgA from Patients with Linear IgA Bullous Dermatosis Induce Neutrophil-Dependent Subepidermal Blistering in Mice

Linear IgA bullous dermatosis (LABD) is an acquired autoimmune subepidermal blistering skin disease characterized by circulating and tissue-bound IgA autoantibodies that recognize epitopes within the hemidesmosomal protein BP180, including its NC16A domain. Histologically, LABD has long been defined by neutrophil infiltration and dermal-epidermal separation. However, the pathogenic roles of anti-NC16A IgA and neutrophils in LABD, as well as their interactions, have not been thoroughly studied. We show that passive transfer of patient-derived anti-NC16A IgA induce clinical and histologic LABD pathology in humanized NC16A mice that are reconstituted locally or systemically with human neutrophils. The lesional skin of mice exhibits significantly elevated levels of the neutrophil chemoattractants CXCL-1 and CXCL-2. Furthermore, we show significantly increased levels of the neutrophil chemoattractant IL-8 in blister fluids of patients with LABD. This study provides direct evidence that anti-NC16A IgA in patients with LABD are pathogenic and interact with neutrophils to mediate tissue injury and subepidermal blister formation. This study further corroborates the importance of neutrophil-mediated tissue injury in LABD disease physiology and establishes a clinically relevant invivo model system that can be used to systematically dissect the immunopathogenesis of LABD.

005 Association between prescription drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a UK population-based study

Abstract Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease, manifested by painful itching of the skin and mucous membranes. Despite high mortality, poor quality of life and increasing incidence in older people, BP can be overlooked due to its rarity in the general population. The cause of BP is unknown, but there are reports of drug-induced BP and remission after the withdrawal of suspected drugs. Systematic reviews have found prescription drugs such as gliptins and loop diuretics to be associated with BP. However, previous studies did consider multiple drug exposures and had selected populations. Our UK population-based study aimed to determine whether drugs/vaccines prescribed between 1998 and 2021 for common conditions in older people are associated with BP. We conducted a population-based nested case–control study using the UK Clinical Practice Research Datalink (representing 8% of the UK population). Each person with BP (case) was matched by age, sex and general practice to up to five controls at the diagnosis time of their case. Multivariable conditional logistic regression was used to determine adjusted odds ratios (aOR) of developing BP within 1 year of taking at least one prescription for the following therapeutic groups: antibiotics, antidiabetics and insulin, antihypertensives, antithrombotics, lipid modifiers, analgesics, dementia drugs, antiepileptics, antipsychotics, antidepressants and influenza vaccine. Where possible, we report results for classes of drugs or subclasses. The results were adjusted for multiple exposures and corrected for multiple testing. We also explored potential confounders: ethnicity, deprivation, stroke, Parkinson disease and dementia. Six months of antibiotics prescriptions before the BP diagnosis was excluded to account for treating undiagnosed BP symptoms. We identified 16 844 patients with BP and 79 493 controls (mean age 76 years; 44% male). The drugs associated with an increased risk of BP were penicillinase-resistant penicillins [aOR 2.6, 95% confidence interval (CI) 2.4–2.8]; macrolides (aOR 1.5, 95% CI 1.4–1.7); gliptins (aOR 2.8, 95% CI 2.4–3.3); centrally acting anticholinesterases (aOR 2.3, 95% CI 2.0–2.7); N-methyl-D-aspartate receptor antagonists (aOR 2.2, 95% CI 1.7–2.9); antiepileptics (aOR 2.4, 95% CI 2.3–2.6); influenza vaccine (aOR 1.4, 95% CI 1.4–1.5) and loop diuretics (aOR 1.3, 95% CI 1.2–1.4). Reduced BP risk was associated with nonsteroidal anti-inflammatory drugs (aOR 0.8, 95% CI 0.8–0.9) and opioids (aOR 0.8, 95% CI 0.8–0.9). Potential confounders did not affect odds ratio estimates. All P values were &amp;lt; 0.001. No association was found for broad-spectrum penicillins, lipid-modifying drugs, anticoagulants, beta blockers, calcium channel blockers and potassium-sparing diuretics with another diuretic. Clinicians need to be aware of BP risk in older people following administration of penicillinase-resistant penicillins, gliptins, dementia and epilepsy drugs, in order to recognize BP early and consider withdrawal of the suspect drug.

P19 Diagnostic conundrums in paraneoplastic pemphigus

Abstract Paraneoplastic pemphigus (PNP) is a subset of pemphigus, a group of autoimmune blistering skin disorders. A 51-year-old man presented with paraneoplastic pemphigus associated with a hepatic neoplasm. He described an epigastric mass and associated mucositis affecting the orogenital mucosae, as well as the sclerae. Both computed tomography and magnetic resonance imaging demonstrated a 14-cm mass arising from the left lobe of the liver. A liver biopsy showed features of an atypical spindle-cell neoplasm, but a definite diagnosis was not possible. A diagnostic skin biopsy was taken from his outer lip mucosae. Histology showed surface ulceration with an acute inflammatory infiltrate, lichenoid lymphoplasmacytic infiltrate with focal basal vacuolar change, degenerate keratinocytes and adjacent suprabasal acantholysis and spongiosis. Perilesional direct immunofluorescence (DIF) was negative; however, indirect immunofluorescence (IIF) showed intercellular IgG antibodies on transitional epithelium with a high titre of 1 : 800 to rat bladder. These finding were consistent with the suspected clinical diagnosis of paraneoplastic pemphigus. The patient was commenced on oral prednisolone 1 mg kg−1 daily. Topical therapy included budesonide mixed with sweetener applied to the oral mucosae. Following this, a trial of 3 days of intravenous methylprednisolone along with 2% cocaine mouthwash, triple mouthwash (betamethasone, doxycycline and nystatin) and Dermovate® ointment was commenced, with improvement noted in pain, haemorrhage and ulceration. Intravenous immunoglobulin was administered preoperatively. The patient was subsequently transferred to a specialist centre for hepatobiliary surgery and listed for debulking of the liver mass. Postoperatively, he had plasmapheresis, with a noted reduction in mucosal ulceration and significant improvement in pain. Chemotherapy with doxorubicin and ifosfamide was initiated thereafter. PNP is a severe autoimmune blistering disorder characterized clinically by flaccid blisters and erosions. Although much is yet to be understood regarding the pathophysiology of PNP, studies show that the development of autoantibodies to the plakin family and desmogleins 1 and 3 play a particular role in its pathogenesis. In addition to autoantibodies, CD8+ T cells have also been shown to contribute to the development of PNP. In adults, the majority of cases are associated with an underlying haematological malignancy and, rarely, a solid-organ tumour. DIF findings include IgG and C3 deposition along the intercellular and basement membrane zones, while IIF detects autoantibodies to proteins found in transitional or stratified squamous epithelium. As in our case, reports have shown that the DIF can be negative, with one study showing a positive DIF in only 41% of cases. This case highlights the complex diagnostic and treatment challenges practitioners face when dealing with PNP and the patients it affects.

Eosinophils, Basophils, and Neutrophils in Bullous Pemphigoid.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease, of which the incidence has increased in recent years. BP is characterized by circulating IgG and IgE autoantibodies against the hemidesmosomal proteins BP180 and BP230. Although autoantibodies trigger inflammatory cascades that lead to blister formation, effector cells and cell-mediated autoimmunity must also be considered as important factors in the pathogenesis of BP. The aim of this review is to outline the current knowledge on the role of eosinophils, basophils, and neutrophils in BP.

Divergent in situ expression of IL-31 and IL-31RA between bullous pemphigoid and pemphigus vulgaris.

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two major autoimmune blistering skin diseases. Unlike PV, BP is accompanied by intense pruritus, suggesting possible involvement of the pruritogenic cytokine IL-31. However, the underlying mechanisms of the clinical difference between BP and PV in terms of pruritus are not fully understood. To compare the expression levels of IL-31 and its receptor IL-31RA in the lesional skin, including peripheral nerves in BP and PV patients, immunohistochemical staining for IL-31 and IL-31RA was performed in skin samples of BP and PV patients and healthy controls (HC). The IL-31RA-expressing area in epidermis and peripheral nerves was analysed using ImageJ and the percentage of positive cells for IL-31/IL-31RA in dermal infiltrating cells was manually quantified. Quantitative analyses revealed that IL-31/IL-31RA expressions in the epidermis and dermal infiltrate were significantly increased in BP compared to PV and HC. The difference between BP and PV became more obvious when advanced bullous lesions were compared. Peripheral nerves in BP lesions presented significantly higher IL-31RA expression compared to PV lesions. In conclusion, we found significantly augmented expressions of IL-31/IL-31RA in BP lesions, including peripheral nerves, in comparison to PV. These results suggest a possible contribution of IL-31/IL-31RA signalling to the difference between BP and PV in the facilitation of pruritus and local skin inflammation, raising the possibility of therapeutic targeting of the IL-31/IL-31RA pathway in BP patients.

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

Retrospective analysis of the long-term therapeutic effectiveness and safety profile of rituximab in the treatment of mucous membrane pemphigoid in a German university center between 2008 and 2019.

The B-cell-depleting anti-CD20 antibody rituximab (RTX) is often used as an adjuvant drug for the treatment of refractory cases of mucous membrane pemphigoid (MMP). This study aims to determine the therapeutic effectiveness and the safety profile of RTX in MMP. The medical records of all cases of MMP treated with RTX between 2008 and 2019 in our university medical center located in northern Germany, which specialized in autoimmune blistering skin diseases, were retrieved and systemically analyzed for treatment responses and potential adverse events over a median period of 27 months. We identified 18 MMP patients who received at least one cycle of RTX to treat MMP. RTX was always used as an adjuvant treatment, and its application did not change concomitant treatments. Under treatment with RTX, 67% of the patients achieved an improvement in their disease activity within 6 months. This was also reflected in a statistically significant reduction in the Mucous Membrane Pemphigoid Disease Index (MMPDAI) activity score. The frequency of infections under RTX treatment increased only slightly. The use of RTX is associated with an attenuation of MMP in a large proportion of MMP patients in our study. At the same time, its application was not found to further increase the susceptibility of the most strongly immunocompromised population of MMP patients to opportunistic infections. Collectively, our results suggest that the potential benefits of RTX outweigh its risks in patients with refractory MMP.

The Role of Non-Neuronal Acetylcholine in the Autoimmune Blistering Disease Pemphigus Vulgaris

The importance of acetylcholine (ACh) in keratinocyte adhesion and acantholysis has been investigated over the last three decades, particularly in the pathophysiology of autoimmune blistering dermatoses. Pemphigus vulgaris (PV) is an autoimmune blistering skin disease where autoantibody-mediated suprabasilar intraepidermal splitting causes flaccid blisters and non-healing erosions of the oral mucosa and sometimes also of the skin. Historically, acantholysis in PV was thought to be driven by anti-desmoglein (Dsg) antibodies. Herein, we describe the role of autoantibodies against keratinocyte muscarinic and nicotinic acetylcholine receptors, as well as the annexin-like molecule pemphaxin that also binds ACh, in the immunopathogenesis of PV. The identification of targets in this disease is important, as they may lead to novel diagnostic and therapeutic options in the future for this potentially deadly disease.

Autoimmune blistering skin diseases triggered by COVID-19 vaccinations: An Australian case series.

Autoimmune blistering skin diseases (AIBD) can be induced or flared by a multitude of sources, however, there have been some reports suggesting that this occurrence is due to COVID-19 vaccinations. At a single academic blistering disease centre in Sydney, Australia, a retrospective review was conducted, identifying 59 patients with AIBD seen between February 2021 and November 2022. Secondary to recent COVID-19 vaccination, four patients had induction of bullous pemphigoid, three patients had a flare of pre-existing bullous pemphigoid, one patient had induction of pemphigus, and two patients had a flare of pre-existing pemphigus vulgaris. This adds to our understanding of the role of vaccinations in the activity of AIBD.

Lisinopril prevents bullous pemphigoid induced by dipeptidyl peptidase 4 inhibitors via the Mas receptor pathway.

Recent studies have suggested that dipeptidyl peptidase 4 (DPP4) inhibitors increase the risk of development of bullous pemphigoid (BP), which is the most common autoimmune blistering skin disease; however, the associated mechanisms remain unclear, and thus far, no therapeutic targets responsible for drug-induced BP have been identified. Therefore, we used clinical data mining to identify candidate drugs that can suppress DPP4 inhibitor-associated BP, and we experimentally examined the underlying molecular mechanisms using human peripheral blood mononuclear cells (hPBMCs). A search of the US Food and Drug Administration Adverse Event Reporting System and the IBM® MarketScan® Research databases indicated that DPP4 inhibitors increased the risk of BP, and that the concomitant use of lisinopril, an angiotensin-converting enzyme inhibitor, significantly decreased the incidence of BP in patients receiving DPP4 inhibitors. Additionally, in vitro experiments with hPBMCs showed that DPP4 inhibitors upregulated mRNA expression of MMP9 and ACE2, which are responsible for the pathophysiology of BP in monocytes/macrophages. Furthermore, lisinopril and Mas receptor (MasR) inhibitors suppressed DPP4 inhibitor-induced upregulation of MMP9. These findings suggest that the modulation of the renin-angiotensin system, especially the angiotensin1-7/MasR axis, is a therapeutic target in DPP4 inhibitor-associated BP.

Clinical and immunopathological characteristics of autoimmune blistering skin diseases

Clinical and immunopathological characteristics of autoimmune blistering skin diseases

Cytoskeletal anchorage of different Dsg3 pools revealed by combination of hybrid STED/SMFS-AFM

Desmoglein 3 (Dsg3) is a desmosomal cadherin mediating cell adhesion within desmosomes and is the antigen of the autoimmune blistering skin disease pemphigus vulgaris. Therefore, understanding of the complex desmosome turnover process is of high biomedical relevance. Recently, super resolution microscopy was used to characterize desmosome composition and turnover. However, studies were limited because adhesion measurements on living cells were not possible in parallel. Before desmosomal cadherins are incorporated into nascent desmosomes, they are not bound to intermediate filaments but were suggested to be associated with the actin cytoskeleton. However, direct proof that adhesion of a pool of desmosomal cadherins is dependent on actin is missing. Here, we applied single-molecule force spectroscopy measurements with the novel single molecule hybrid-technique STED/SMFS-AFM to investigate the cytoskeletal anchorage of Dsg3 on living keratinocytes for the first time. By application of pharmacological agents we discriminated two different Dsg3 pools, only one of which is anchored to actin filaments. We applied the actin polymerization inhibitor Latrunculin B to modify the actin cytoskeleton and the PKCα activator PMA to modulate intermediate filament anchorage. On the cellular surface Dsg3 adhesion was actin-dependent. In contrast, at cell–cell contacts, Dsg3 adhesion was independent from actin but rather is regulated by PKC which is well established to control desmosome turn-over via intermediate filament anchorage. Taken together, using the novel STED/SMFS-AFM technique, we demonstrated the existence of two Dsg3 pools with different cytoskeletal anchorage mechanisms.

A Case of Pemphigus Vulgaris in a Patient with Human Immunodeficiency Virus

Pemphigus vulgaris is the most common variant of autoimmune chronic blistering skin diseases. Its appearance in patients infected with acquired immunodeficiency virus (HIV) is rare. A 40-year-old woman is reported, who presented skin lesions in 90% of the body surface, characterized by blisters of 3 to 4 cm that, when broken, left denuded areas, excoriations and pruritic meliceric crusts. A skin biopsy was performed that showed a characteristic pattern of pemphigus vulgaris. Elisa for HIV positive. She evolved with septic shock and died 72 hours later. Understanding the relationship between HIV and autoimmune blistering disorders can help guide the therapeutic and prognostic management of these patients. Proposed mechanisms include molecular mimicry, polyclonal B-cell stimulation, and highly active antiretroviral therapy possibly associated with immune restoration. Clinically, these patients may present limited mucosal symptoms or develop multiple erosions that may spread, merge, and progress to exfoliative erythroderma. Glucocorticoids serve as the first line of management; however, they can have important adverse effects such as infectious complications that pose a therapeutic challenge for the doctor and could influence mortality.

Ocular surface disorders affect quality of life in patients with autoimmune blistering skin diseases: a cross-sectional study

BackgroundAutoimmune blistering skin diseases (AIBD) are a group of rare chronic autoimmune diseases which are associated with ocular surface diseases especially dry eye disease. This study is designed to investigate the relationship between ocular surface disorders and quality of life among patients with autoimmune blistering skin diseases.MethodsTwenty-four AIBD patients (18 pemphigus and 7 pemphigoid) and twenty-five non-AIBD controls were included. Ocular surface disease index (OSDI), ocular surface evaluation, including slit-lamp examination, Schirmer I test, tear break-up time, corneal fluorescein staining, lid-parallel conjunctival folds, meibomian gland evaluation, presence of symblepharon and corneal opacity were assessed. Life quality was evaluated by multiple questionnaires, including Medical Outcomes Study 36-Item Short Form Questionnaire (SF-36), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Ocular surface tests and quality of life were compared between AIBD patients and non-AIBD controls. In the AIBD patients, the associations between ocular surface parameters and quality of life were also evaluated.Results92% of AIBD patients and 87.5% of age- and sex-matched non-AIBD controls were diagnosed with dry eye in this study. Compared with non-AIBD controls, AIBD patients reported lower SF-36 scores (P < 0.05) and severer OSDI, Schirmer I test, tear break-up time, corneal fluorescein staining, presence of symblepharon and corneal opacity measures (P < 0.05). OSDI, Schirmer I test were correlated with SF-36 composite scores or scores on the SF-36 subscales.ConclusionsAIBD patients experience reduced quality of life and more severe ocular surface disorders including dry eye, symblepharon and corneal opacity. Early treatments of dry eye and collaborations among multidisciplinary physicians are necessary in patients with AIBD.

Role of Rituximab in the Treatment of Pemphigus Vulgaris: Patient Selection and Acceptability

Anti-CD20 monoclonal antibody rituximab is an approved adjuvant treatment, in combination with oral corticosteroids, for patients with pemphigus vulgaris, a severe and potentially life-threatening autoimmune blistering skin disorder. Updated approaches to the management of pemphigus vulgaris support rituximab as a first-line adjuvant treatment to induce remission early in the course of disease; however, its feasibility in the clinical setting is often reduced by a series of limitations, including high cost of this biological drug, physician and patient concern for the risk of adverse reactions, and uncertainty regarding the optimum dosing and schedule of administration. The standard approved rituximab dosages, which are derived from lymphoma protocols, have been recognized to exceed the effective dose required for inducing B cell depletion, since the B cell burden in pemphigus vulgaris is much lower than in lymphoproliferative disorders. To overcome these limitations, recent research has investigated alternative regimens of rituximab, using lower doses of the drug. Moreover, differences in patient and disease characteristics that are highlighted in the literature strongly suggest that therapy should be tailored individually on a case-by-case basis: personalized treatment schedules may be necessary to optimize response to treatment and tolerability in different subjects, with the possibility of repeated infusions for severe forms and in case of relapse. Finally, low-dose regimens of rituximab were suggested to be favorable during the COVID-19 pandemic by providing a lesser degree of immune cell depletion while retaining a sufficient response. In conclusion, the current literature suggests that lower-dose regimens of rituximab are not only tolerable and cost-effective but may also be associated with a positive response in pemphigus vulgaris, comparable to that achieved with higher doses especially in early disease. Further evidence from rigorous clinical trials will be required to optimize lower-dose regimens of RTX and establish their position within the treatment scenario of pemphigus vulgaris.