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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 -
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 -
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 -
Journal of the American Academy of... Oct 2020Antineoplastic agents that use the immune system have revolutionized cancer treatment. Specifically, implementation of immune checkpoint inhibitors, monoclonal... (Review)
Review
Antineoplastic agents that use the immune system have revolutionized cancer treatment. Specifically, implementation of immune checkpoint inhibitors, monoclonal antibodies that block cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein 1, or programmed cell death ligand 1 show improved and sustained responses in patients with cancer. However, these agents are associated with a plethora of adverse events, many manifesting in the skin. As the clinical application of cancer immunotherapies expands, understanding the clinical and histopathologic features of associated cutaneous toxicities becomes increasingly important to dermatologists, oncologists, and pathologists to ensure timely diagnosis and appropriate care. This review discusses cutaneous reactions to immune checkpoint inhibitors, focusing on histopathologic features.
Topics: Acantholysis; Alopecia; Drug Eruptions; Humans; Immune Checkpoint Inhibitors; Keratinocytes; Lichenoid Eruptions; Nevus, Pigmented; Panniculitis; Pemphigoid, Bullous; Pruritus; Psoriasis; Stevens-Johnson Syndrome; Vitiligo
PubMed: 32360716
DOI: 10.1016/j.jaad.2020.04.105 -
Frontiers in Immunology 2022Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease of the skin. First-line treatment of systemic corticosteroids may cause serious...
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease of the skin. First-line treatment of systemic corticosteroids may cause serious adverse events. Rituximab, omalizumab, and dupilumab should be explored as alternative treatment options to improve outcomes.
OBJECTIVE
To systematically review the rituximab, omalizumab, and dupilumab treatment outcomes in bullous pemphigoid.
METHODS
A PubMed, Embase, Web of Science, and Cochrane library search were conducted on March 10, 2022. A total of 75 studies were included using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
RESULTS
Use of rituximab (n=122), omalizumab (n=53) and dupilumab (n=36) were reported in 211 patients with BP. Rituximab led to complete remission in 70.5% (n=86/122) and partial remission in 23.8% (n=29/122) of patients within 5.7 months, with a recurrence rate of 20.5% (n=25/122). 9.0% (n=11/122) of patients died and infection (6.6%, n=8/122) was the most common adverse event. Omalizumab led to complete remission in 67.9% (n=36/53) and partial remission in 20.8% (n=11/53) of patients within 6.6 months, with a recurrence rate of 5.7% (n=3/53). 1.9% (n=1/53) of patients died and thrombocytopenia (1.9%, n=1/53) was observed as the most common adverse event. Dupilumab led to complete remission in 66.7% (n=24/36) and partial remission in 19.4% (n=7/36) of patients within 4.5 months of treatment without any reported adverse events, with a recurrence rate of 5.6% (n=2/36).
CONCLUSIONS
Rituximab, omalizumab, and dupilumab have similar clinical benefits for BP patients. However, rituximab resulted in higher recurrence rates, adverse events, and mortality rates.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022316454.
Topics: Antibodies, Monoclonal, Humanized; Humans; Omalizumab; Pemphigoid, Bullous; Rituximab; Treatment Outcome
PubMed: 35769474
DOI: 10.3389/fimmu.2022.928621 -
Anais Brasileiros de Dermatologia 2022Epidermolysis bullosa acquisita is a rare autoimmune disease, characterized by the synthesis of anti-collagen VII autoantibodies, the main component of hemidesmosome...
Epidermolysis bullosa acquisita is a rare autoimmune disease, characterized by the synthesis of anti-collagen VII autoantibodies, the main component of hemidesmosome anchoring fibrils. The antigen-antibody binding elicits a complex inflammatory response, which culminates in the loss of dermo-epidermal adhesion of the skin and/or mucous membranes. Skin fragility with bullae, erosions, and milia in areas of trauma characterizes the mechanobullous form of the disease. In the inflammatory form of epidermolysis bullosa acquisita, urticarial inflammatory plaques with tense bullae, similar to bullous pemphigoid, or mucosal lesions can determine permanent scars and loss of functionality in the ocular, oral, esophageal, and urogenital regions. Due to the similarity of the clinical findings of epidermolysis bullosa acquisita with other diseases of the pemphigoid group and with porphyria cutanea tarda, the diagnosis is currently confirmed mainly based on the clinical correlation with histopathological findings (pauci-inflammatory subepidermal cleavage or with a neutrophilic infiltrate) and the demonstration of the presence of anti-collagen VII IgG in situ by direct immunofluorescence, or circulating anti-collagen VII IgG through indirect immunofluorescence and/or ELISA. There is no specific therapy for epidermolysis bullosa acquisita and the response to treatment is variable, usually with complete remission in children and a worse prognosis in adults with mucosal involvement. Systemic corticosteroids and immunomodulators (colchicine and dapsone) are alternatives for the treatment of mild forms of the disease, while severe forms require the use of corticosteroid therapy associated with immunosuppressants, intravenous immunoglobulin, and rituximab.
Topics: Adult; Autoantibodies; Autoimmune Diseases; Blister; Child; Epidermolysis Bullosa Acquisita; Humans; Immunoglobulins, Intravenous; Pemphigoid, Bullous
PubMed: 35701269
DOI: 10.1016/j.abd.2021.09.010 -
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