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Medicina (Kaunas, Lithuania) Oct 2021The pemphigoid family of dermatoses is characterized by autoimmune subepidermal blistering. The classic paradigm for pemphigoid, and the most common member, is bullous... (Review)
Review
The pemphigoid family of dermatoses is characterized by autoimmune subepidermal blistering. The classic paradigm for pemphigoid, and the most common member, is bullous pemphigoid. Its variable clinical presentation, with or without frank bullae, is linked by significant pruritus afflicting the elderly. Mucous membrane pemphigoid is an umbrella term for a group of subepidermal blistering dermatoses that favor the mucosal membranes and can scar. Epidermolysis bullosa acquisita is a chronic blistering disorder characterized by skin fragility, sensitivity to trauma, and its treatment-refractory nature. Clinicians that encounter these pemphigoid disorders may benefit from an overview of their clinical presentation, diagnostic work-up, and therapeutic management, with an emphasis on the most frequently encountered pemphigoid disease, bullous pemphigoid.
Topics: Aged; Humans; Mucous Membrane; Pemphigoid, Bullous; Skin Diseases, Vesiculobullous
PubMed: 34684098
DOI: 10.3390/medicina57101061 -
Anais Brasileiros de Dermatologia 2019Bullous pemphigoid is the most frequent autoimmune bullous disease and mainly affects elderly individuals. Increase in incidence rates in the past decades has been... (Review)
Review
Bullous pemphigoid is the most frequent autoimmune bullous disease and mainly affects elderly individuals. Increase in incidence rates in the past decades has been attributed to population aging, drug-induced cases and improvement in the diagnosis of the nonbullous presentations of the disease. A dysregulated T cell immune response and synthesis of IgG and IgE autoantibodies against hemidesmosomal proteins (BP180 and BP230) lead to neutrophil chemotaxis and degradation of the basement membrane zone. Bullous pemphigoid classically manifests with tense blisters over urticarial plaques on the trunk and extremities accompanied by intense pruritus. Mucosal involvement is rarely reported. Diagnosis relies on (1) the histopathological evaluation demonstrating eosinophilic spongiosis or a subepidermal detachment with eosinophils; (2) the detection of IgG and/or C3 deposition at the basement membrane zone using direct or indirect immunofluorescence assays; and (3) quantification of circulating autoantibodies against BP180 and/or BP230 using ELISA. Bullous pemphigoid is often associated with multiple comorbidities in elderly individuals, especially neurological disorders and increased thrombotic risk, reaching a 1-year mortality rate of 23%. Treatment has to be tailored according to the patient's clinical conditions and disease severity. High potency topical steroids and systemic steroids are the current mainstay of therapy. Recent randomized controlled studies have demonstrated the benefit and safety of adjuvant treatment with doxycycline, dapsone and immunosuppressants aiming a reduction in the cumulative steroid dose and mortality.
Topics: Aged; Autoimmunity; Diagnosis, Differential; Fluorescent Antibody Technique; Humans; Pemphigoid, Bullous; Steroids
PubMed: 31090818
DOI: 10.1590/abd1806-4841.20199007 -
Biomolecules Oct 2020Bullous pemphigoid (BP) is the most frequent autoimmune subepidermal blistering disease provoked by autoantibodies directed against two hemidesmosomal proteins: BP180... (Review)
Review
Bullous pemphigoid (BP) is the most frequent autoimmune subepidermal blistering disease provoked by autoantibodies directed against two hemidesmosomal proteins: BP180 and BP230. Its pathogenesis depends on the interaction between predisposing factors, such as human leukocyte antigen (HLA) genes, comorbidities, aging, and trigger factors. Several trigger factors, such as drugs, thermal or electrical burns, surgical procedures, trauma, ultraviolet irradiation, radiotherapy, chemical preparations, transplants, and infections may induce or exacerbate BP disease. Identification of predisposing and trigger factors can increase the understanding of BP pathogenesis. Furthermore, an accurate anamnesis focused on the recognition of a possible trigger factor can improve prognosis by promptly removing it.
Topics: Causality; Comorbidity; Disease Susceptibility; Drug-Related Side Effects and Adverse Reactions; Gene-Environment Interaction; Genetic Predisposition to Disease; HLA Antigens; Humans; Infections; Pemphigoid, Bullous; Prognosis; Risk Factors
PubMed: 33050407
DOI: 10.3390/biom10101432 -
Journal of the European Academy of... Oct 2022Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and...
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life.
OBJECTIVES AND METHODOLOGY
The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included.
RESULTS
Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations.
CONCLUSIONS
The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice.
Topics: Adrenal Cortex Hormones; Aged; Blister; Dermatology; Humans; Pemphigoid, Bullous; Quality of Life; Venereology
PubMed: 35766904
DOI: 10.1111/jdv.18220 -
Annual Review of Pathology May 2016Pemphigus and bullous pemphigoid are autoantibody-mediated blistering skin diseases. In pemphigus, keratinocytes in epidermis and mucous membranes lose cell-cell... (Review)
Review
Pemphigus and bullous pemphigoid are autoantibody-mediated blistering skin diseases. In pemphigus, keratinocytes in epidermis and mucous membranes lose cell-cell adhesion, and in pemphigoid, the basal keratinocytes lose adhesion to the basement membrane. Pemphigus lesions are mediated directly by the autoantibodies, whereas the autoantibodies in pemphigoid fix complement and mediate inflammation. In both diseases, the autoantigens have been cloned and characterized; pemphigus antigens are desmogleins (cell adhesion molecules in desmosomes), and pemphigoid antigens are found in hemidesmosomes (which mediate adhesion to the basement membrane). This knowledge has enabled diagnostic testing for these diseases by enzyme-linked immunosorbent assays and dissection of various pathophysiological mechanisms, including direct inhibition of cell adhesion, antibody-induced internalization of antigen, and cell signaling. Understanding these mechanisms of disease has led to rational targeted therapeutic strategies.
Topics: Animals; Humans; Pemphigoid, Bullous; Pemphigus
PubMed: 26907530
DOI: 10.1146/annurev-pathol-012615-044313 -
Acta Dermato-venereologica Aug 2020Bullous pemphigoid is an autoimmune subepithelial disease characterised by pruritus followed by urticarial plaques and finally bullae on the skin and mucosa....
Bullous pemphigoid is an autoimmune subepithelial disease characterised by pruritus followed by urticarial plaques and finally bullae on the skin and mucosa. Drug-associated bullous pemphigoid (DABP) is a term used to describe instances of bullous pemphigoid demonstrating clinical, histological, or immunopathological features identical or similar to those of the idiopathic form of bullous pemphigoid, associated with the systemic ingestion, or topical application of particular drugs. In this study, we conducted a comprehensive search of the literature according to PRISMA guidelines and a total of 170 publications were included in the final qualitative analysis. In conclusion, 89 drugs were implicated in DABP. The strongest evidence for DABP is seen with gliptins, PD-1/PD-L1 inhibitors, loop diuretics, penicillin and derivatives. An appreciation of the medications associated with bullous pemphigoid enables clinicians to identify potential cases of DABP earlier and cease the offending medication.
Topics: Blister; Humans; Pemphigoid, Bullous; Pharmaceutical Preparations; Pruritus; Skin
PubMed: 32176310
DOI: 10.2340/00015555-3457 -
Frontiers in Immunology 2021Bullous pemphigoid (BP) is an autoimmune blistering disorder that predominantly affects the elderly. As the main treatment for BP, systemic corticosteroids are often... (Comparative Study)
Comparative Study
BACKGROUND
Bullous pemphigoid (BP) is an autoimmune blistering disorder that predominantly affects the elderly. As the main treatment for BP, systemic corticosteroids are often limited by their side effects. Safer treatment modalities are therefore needed. Dupilumab is a biologic agent used to treat BP in recent years.
METHODS
Medical records of patients with moderate-to-severe BP were retrospectively reviewed. Twenty-four patients were included (follow-up period: 32 weeks), eight of whom received dupilumab in combination with methylprednisolone and azathioprine (dupilumab group) while the other 16 patients received methylprednisolone and azathioprine (conventional group). Response to dupilumab was evaluated by comparison of several parameters (time to stop new blister formation, time to reduce the systemic glucocorticoids to minimal dose, and total amount of methylprednisolone).
RESULTS
The median age of patients in the dupilumab and conventional groups were 64.50 years (range: 22-90 years) and 64.50 years (range: 17-86 years), respectively. The median duration of disease before admission in the dupilumab group was 2 months (range: 1-240 months) and 2.5 months (range: 1-60 months) in the conventional group. The median time to stop new blister formation was 8 days (range: 1-13 days) and 12 days (range: 5-21 days) in patients of the dupilumab and conventional groups, respectively ( = 0.028 by Kaplan-Meier analysis). In addition, the median time to reduce the systemic glucocorticoids to minimal dose (methylprednisolone 0.08 mg/kg/day) was 121.5 and 148.5 days for the dupilumab and conventional therapy groups, respectively ( = 0.0053 by Kaplan-Meier analysis). The median total amount of methylprednisolone (at the time of reaching the minimal dose) used in the dupilumab group was 1,898 mg (range: 1,624-2,932 mg) while the cumulative dose of conventional group was 2,344 mg (range: 1,708-4,744 mg) ( = 0.036 by Mann-Whitney test). The median total amount of azathioprine (at the time of reaching the minimal dose) used in dupilumab group was 8,300 mg (range: 7,100-10,400 mg) while the total dose of conventional group was 10,300 mg (range: 8,900-14,400 mg) ( = 0.0048 by Mann-Whitney test). No adverse event related to dupilumab was recorded.
CONCLUSIONS
Dupilumab in addition to methylprednisolone and azathioprine seems superior to methylprednisolone/azathioprine alone in controlling disease progression and accelerating the tapering of glucocorticoids.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Azathioprine; Drug Tapering; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Methylprednisolone; Middle Aged; Pemphigoid, Bullous; Remission Induction; Retrospective Studies; Severity of Illness Index; Skin; Time Factors; Treatment Outcome; Young Adult
PubMed: 34721404
DOI: 10.3389/fimmu.2021.738907 -
Medicina (Kaunas, Lithuania) Apr 2021Dyshidrosiform bullous pemphigoid is a variant of bullous pemphigoid. At least 84 patients with dyshidrosiform bullous pemphigoid have been described. Dyshidrosiform... (Review)
Review
Dyshidrosiform bullous pemphigoid is a variant of bullous pemphigoid. At least 84 patients with dyshidrosiform bullous pemphigoid have been described. Dyshidrosiform bullous pemphigoid usually presents with pruritic blisters in elderly individuals; the hemorrhagic or purpuric lesions on the palms and soles can be the only manifestation of the disease. However, bullae may concurrently or subsequently appear on other areas of the patient's body. Patients typically improve after the diagnosis is established and treatment is initiated. The mainstay of therapy is systemic corticosteroids, with or without topical corticosteroids, and systemic dapsone or immunosuppressants. Drug-related or nickel-induced dyshidrosiform bullous pemphigoid improves after stopping the associated agent; however, systemic therapy has also been required to achieve resolution of the blisters. Similar to classic bullous pemphigoid, neurologic conditions and psychiatric disorders have been observed in dyshidrosiform bullous pemphigoid patients. The new onset of recurrent or persistent blisters on the palms, soles, or both of an elderly individual should prompt the clinician to consider the diagnosis of dyshidrosiform bullous pemphigoid.
Topics: Aged; Humans; Immunosuppressive Agents; Pemphigoid, Bullous
PubMed: 33924249
DOI: 10.3390/medicina57040398 -
Indian Journal of Dermatology,... 2011Bullous pemphigoid (BP) is a relatively common autoimmune vesicobullous disease encountered in India. It is a subepidermal bullous disorder most commonly seen in the... (Review)
Review
Bullous pemphigoid (BP) is a relatively common autoimmune vesicobullous disease encountered in India. It is a subepidermal bullous disorder most commonly seen in the elderly and manifests as tense blisters on urticarial base, predominantly over flexures, and is associated with pruritus. The diagnosis can be confirmed by histology, direct and indirect immunofluorescence. Several new diagnostic techniques have also been developed. Treatment of BP is based on the extent and rate of progression of the disease. Several topical and systemic anti-inflammatory and immunosuppressive agents have been used with variable results.
Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Humans; Immunosuppressive Agents; India; Pemphigoid, Bullous
PubMed: 21727692
DOI: 10.4103/0378-6323.82398 -
Frontiers in Immunology 2022This study aimed to investigate the clinical features of biologics-induced bullous pemphigoid (BP) and the therapeutic effects of those agents for BP, exploring the... (Review)
Review
OBJECTIVE
This study aimed to investigate the clinical features of biologics-induced bullous pemphigoid (BP) and the therapeutic effects of those agents for BP, exploring the underlying pathophysiological mechanisms.
METHODS
We searched PubMed, Web of Science, and Elsevier for studies involving pemphigoid patients treated with or induced by identical biologics published in English from January 2009 to April 2022.
RESULTS
Seventeen cases of drug-induced BP associated with anti-tumor necrosis factor (aTNF)-α therapies, one with interleukin (IL)-17 inhibitors, and seven with IL-12/IL-23 or IL-23 inhibitors were enrolled. Time to cutaneous toxicity varied among different types of agents, and the characteristics of clinical examinations were similar to idiopathic BP. Discontinuation of the culprit drugs and initiation of topical or systemic corticosteroids were adequate in most cases. Several monoclonal antibodies above have also been reported for the treatment of refractory or recurrent BP, especially concurrent with psoriasis.
CONCLUSION
Biologics for immune-related diseases, including TNF-α, IL-17, and IL-12/IL-23 or IL-23 inhibitors, can both induce and treat BP, which might be associated with a helper T cells Th1/Th2 imbalance, complicated inflammatory networks, and a specific individual microenvironment, suggestive of a new perspective on the therapeutic algorithms of BP. There have been numerous reports about biologics inducing or treating BP. We have taken note of this phenomenon and focused on biologics with both pathogenetic and therapeutic effects on BP. Our review summarized the clinical characteristics of associated cases, trying to figure out the underlying mechanisms of this paradoxical phenomenon and to provide an integrated perspective and new therapeutic alternatives for BP.
Topics: Humans; Pemphigoid, Bullous; Biological Products; Antibodies, Monoclonal; T-Lymphocytes, Helper-Inducer; Interleukin-12
PubMed: 36685489
DOI: 10.3389/fimmu.2022.1050373