Autoimmune Blistering Dermatoses Research Articles

Immunomorphological insights into clinical variants of bullous pemphigoid in Moscow Region patients

Bullous pemphigoid is an autoimmune blistering dermatosis in which the pathogenesis is primarily characterized by the production of autoantibodies IgG and IgE against hemidesmosomal proteins (BP180 and BP230) and the disruption of T-cell immune response regulation. The classical understanding of the clinical course of bullous pemphigoid has undergone significant transformation in recent years due to the identification of numerous conditions that do not exhibit typical clinical presentations but are diagnosed as bullous pemphigoid based on immunofluorescence’s results. Often, when an atypical clinical form of bullous pemphigoid develops, a specialist physician may not have grounds to include bullous pemphigoid in the differential diagnosis. Consequently, specific diagnostic tests (such as immunomorphological examinations of skin biopsies) that would allow for the verification of this blistering dermatosis are not performed for the patient. Clearly, due to the absence of an accurate diagnosis, patients do not receive the necessary therapy. There is currently no information in the world literature regarding the frequency of atypical forms of bullous pemphigoid. However, it is known that bullous pemphigoid is a relatively common blistering dermatosis in the population of European countries, with a prevalence ranging from 2.4 to 66 cases per million people, depending on the region.

Metronidazole-induced linear immunoglobulin A disease in a patient suffering from ulcerative colitis: a case report and focused review of the literature

Linear immunoglobulin (Ig) A disease (LAD) is a rare autoimmune blistering dermatosis caused by linear deposition of IgA1 along the dermoepidermal junction of skin and mucosae. It can affect both children and adults. Although idiopathic in most cases, it can also be associated with infections, malignancies, or drug administration. Among medications, antibiotics are most commonly responsible, particularly vancomycin. We report the case of a 51-year-old female patient who developed mucocutaneous LAD after oral metronidazole administration, which was confirmed by histopathological examination and direct immunofluorescence of one of the bullous lesions. Lesions rapidly cleared after metronidazole discontinuation and a short course of oral methylprednisolone and dapsone. To our knowledge, this is the third reported case of metronidazole-induced LAD, and the first in which metronidazole was not administered in combination with other antibiotics such as ceftriaxone.

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.

Gestational pemphigoid

Pemphigoid gestationis is a rare, autoimmune blistering dermatosis. It is unique in that it is diagnosed primarily in association with pregnancy. Autoantibodies against placental BP180 (also known as BPAG2 or collagen XVII) cause damage to the skin basement membrane, resulting in severe itching and blistering rash over the body and the extremities.

Pemphigus végétant

Intraepithelial autoimmune blistering dermatoses are a rare group of skin disorders characterized by the intraepithelial disruption of intercellular connections through the action of autoantibodies. The first article in this continuing medical education series explores the background, epidemiology, clinical features, and diagnostic criteria of each of the major intraepithelial autoimmune blistering dermatoses, including pemphigus foliaceus, pemphigus erythematosus, pemphigus herpetiformis, fogo selvagem, pemphigus vulgaris, pemphigus vegetans, drug-induced pemphigus, IgA pemphigus, IgG/IgA pemphigus, and paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome.

Anti-p200 pemphigoid: clinical, diagnostic and therapeutic aspects

Anti-p200 pemphigoid is a rare autoimmune blistering dermatosis. The clinical course is heterogeneous. Typically, immunoglobulin G (IgG) antibodies are found on the floor of salt-split skin, which differentiates p200 pemphigoid from bullous pemphigoid. It is necessary to perform immunoblotting and enzyme-linked immunosorbent assays (ELISA) to confirm the diagnosis. Small amounts of dapsone are often sufficient for disease control. The clinical and diagnostic characteristics of anti-p200 pemphigoid and the principles of treatment are presented exemplified by two case reports.

BP180 Is Critical in the Autoimmunity of Bullous Pemphigoid.

Bullous pemphigoid (BP) is by far the most common autoimmune blistering dermatosis that mainly occurs in the elderly. The BP180 is a transmembrane glycoprotein, which is highly immunodominant in BP. The structure and location of BP180 indicate that it is a significant autoantigen and plays a key role in blister formation. Autoantibodies from BP patients react with BP180, which leads to its degradation and this has been regarded as the central event in BP pathogenesis. The consequent blister formation involves the activation of complement-dependent or -independent signals, as well as inflammatory pathways induced by BP180/anti-BP180 autoantibody interaction. As a multi-epitope molecule, BP180 can cause dermal–epidermal separation via combining each epitope with specific immunoglobulin, which also facilitates blister formation. In addition, some inflammatory factors can directly deplete BP180, thereby leading to fragility of the dermal–epidermal junction and blister formation. This review summarizes recent investigations on the role of BP180 in BP pathogenesis to determine the potential targets for the treatment of patients with BP.

Clinical evaluation of a multiparametric ELISA as a rapid tool for routinely diagnosing IgG-mediated autoimmune blistering dermatoses in ethnic Slavs.

Technical innovation of autoimmune blistering dermatoses (ABDs) diagnosis aimed at multiplex approach. Two multiparametric ELISA tests are commercially available for ABDs serology. The aim was to compare diagnostic accuracy of multiparametric and monospecific ELISAs and to examine the diagnostic value/agreement of multivariant ELISA in compliance with traditional diagnostic setup for ABDs. In total, 128 sera from suspected ABDs patients were studied (27 sera in order to compare ELISAs). Multivariant ELISA (detection of IgG against desmoglein 1 and 3 - DSG1/3; BP180, BP230, envoplakin, type VII collagen), monovariant ELISA, and statistical analysis were performed. With the use of sera from patients with suspected ABDs, the multiparametric ELISA yield an agreement of 84% with traditional stepwise diagnostics. Multivariant ELISA with BP180 and BP230 showed 87.5% and 80% sensitivity, 87.5% and 91% specificity, 87.5% reliability as well as 87.5% and 80% positive predictive value, 87.5% and 91% negative predictive value, respectively, in relation to monospecific ELISA. Multivariant ELISA with DSG1 and DSG3 showed 50% and 80% sensitivity, 100% and 80% specificity, 85% and 80% reliability as well as 100% and 57% positive predictive value, 82% and 92% negative predictive value, respectively, in relation to monospecific ELISA. A better rate of agreement was observed among ELISA systems with BP180 and BP230, than with ELISA systems with DSG1 and DSG3. Multivariant ELISA test combined with clinical examinations and DIF is recommended as a minimal approach to diagnosing ABDs in ethnic Slavs.

Pemphigus foliaceus complicated by Kaposi varicelliform eruption and bilateral herpes simplex keratitis

Abstract Pemphigus foliaceus (PF) is a chronic autoimmune blistering dermatosis (ABD) that often involves the face, scalp and trunk. Kaposi's varicelliform eruption (KVE) is a viral vesicular dermatosis that rarely complicates ABD. In addition, KVE infrequently causes ocular involvement including herpes simplex keratitis (HSK). Timely diagnosis of KVE may be difficult in patients with PF due to their overlapping clinical features. In this report, we described a 79-year-old female with PF complicated by KVE and bilateral HSK. This report reminds physicians that KVE should be considered in patients with refractory PF and other ABD.

Reviewing putative industrial triggering in pemphigus: cluster of pemphigus in the area near the wastewater treatment plant.

A range of pemphigus is relatively rare potentially fatal group of autoimmune blistering dermatoses. Usually, there is no apparent triggering, while in some predisposed patients there are alleged environmental/industrial inducing factors. In a short time period (4 years), we diagnosed 3 novel cases of pemphigus (1 pemphigus vulgaris, 1 pemphigus foliaceus and 1 shift from pemphigus foliaceus into pemphigus vulgaris) at a clinical and laboratory level (ELISA, immunofluorescence studies). We discuss a possible common inducing mechanism as these patients inhabit one estate of the Poznan suburbia (Kozieglowy, population < 12,000), Greater Poland district, Poland, and review literature data on alleged pemphigus triggers. To the best of our knowledge, this is the first report exploring the putative association between pemphigus diseases and wastewater treatment plant waterborne or volatile by-products in the vicinity of such a facility.

Neurodegenerative disorders, bullous pemphigoid and psoriasis: a comparative study in ethnic Poles indicates that Parkinson's disease is more relevant to bullous pemphigoid.

IntroductionBullous pemphigoid (BP) is an autoimmune blistering dermatosis of the elderly with autoimmunity to hemidesmosomal proteins, BP180 and BP230, which are expressed also in neuronal tissue.AimThe aim here was to retrospectively compare the prevalence of neurodegenerative disorders (ND), particularly Parkinson’s disease (PD), unspecified conditions manifesting as dementia and stroke, in two groups of ethnic Poles, with BP and with psoriasis (Ps), in order to obtain data whether BP is more prone to coexist with ND than Ps in the elderly. Psoriasis was chosen in this comparative study as it was considered to be a paradigm of cutaneous disease with systemic manifestations.Material and methodsThe available medical records of 96 BP patients and 149 Ps patients over 70 years of age were analyzed for the presence of ND.ResultsThere were no statistically significant differences in prevalence of ND without specifying the type and ND types analyzed between BP and Ps groups, except for a higher prevalence of PD in the BP group.ConclusionsThus, regarding population aging and increasing incidence and prevalence of BP corresponding with that phenomenon in various ethnicities, it appears justified to expand studies of a possible immunopathogenic relationship, appearing to be PD-related, between BP and ND.

045 Blue light-emitting diode technology-operated microscopy is superior to laser scanning confocal microscopy and short arc mercury lamp-operated microscopy for routine diagnostics of subepidermal autoimmune blistering dermatoses with direct immunofluorescence

045 Blue light-emitting diode technology-operated microscopy is superior to laser scanning confocal microscopy and short arc mercury lamp-operated microscopy for routine diagnostics of subepidermal autoimmune blistering dermatoses with direct immunofluorescence

Bullous pemphigoid and neurodegenerative diseases: a study in a setting of a Central European university dermatology department.

Bullous pemphigoid (BP) is an autoimmune blistering dermatosis of the elderly mediated by IgG and IgE antibodies to skin hemidesmosomal proteins, BP180 and/or BP230, that occur physiologically also in neuronal tissue. It was reported that BP is associated with neurodegenerative diseases (ND). We performed a retrospective study in a setting of a Central European university dermatology department on prevalence of ND in 94 BP patients. 26 out of 94 BP patients had at least one ND. ND included: Parkinson’s disease, dementia, stroke, hear loss, tinnitus, blindness, vertigo, neurosyphilis, systemic sclerosis, and epilepsy. Since population aging is conceivably responsible for the rising number of BP cases as a result of immunosenescence-related phenomena, the plausible BP-specific immunopathogenetic relationship between BP and ND deserves to be further experimentally explored.

Lichen planus pemphigoides: report of four new cases with literature review

Lichen planus pemphigoides (LPP) is a rare autoimmune blistering dermatosis of the pemphigoid family of diseases; it is characterized by development of vesiculobullous lesions on or adjacent to areas of lichen planus. LPP primarily affects the skin with 37% of cases also affecting oral mucosa; oral involvement alone is rare. Epitope spread, a theory that inflammation releases previously sequestered antigens leading to an autoimmune response, is hypothesized to contribute to the pathophysiology of this disease.

Recombinant human IgA1 and IgA2 autoantibodies to type VII collagen induce subepidermal blistering ex vivo.

Subepidermal autoimmune blistering dermatoses (AIBD) are prototypic autoantibody-mediated diseases. In epidermolysis bullosa acquisita (EBA), an autoimmune disease with severe and chronic skin blistering, autoantibodies are directed against type VII collagen. IgG is the predominant autoantibody isotype of EBA, the pathogenicity of which has been demonstrated in a variety of in vivo and ex vivo disease models. In contrast, there is not much evidence for the pathogenicity of IgA, which may appear as the only autoantibody isotype in some EBA patients. To investigate the pathogenic potential of IgA autoantibodies, we generated chimeric V gene-matched human IgA1, IgA2, and control IgG1 autoantibodies directed against type VII collagen. Immobilized immune complexes containing the rIgA1 and rIgA2 autoantibodies induced the dose-dependent release of reactive oxygen species from neutrophil granulocytes, a precondition for blister formation. Moreover, both rIgA1 and rIgA2 induced leukocyte-dependent dermal-epidermal separation in cryosections of human skin. In contrast with rIgG1, neither rIgA1 nor rIgA2 was capable of inducing complement deposition at the dermal-epidermal junction. Because complement activation is a prerequisite for blister induction, this lack of function compared with IgG1 may be compensated for by the stronger activation of neutrophil granulocytes by both IgA1 and IgA2. For IgG-mediated AIBD, immunoadsorption therapy is a convenient treatment modality for the removal of pathogenic autoantibodies, particularly in treatment-resistant cases. The results of this study show the pathogenic potential of IgA autoantibodies and support the development of adsorber matrices for IgA-mediated AIBD.

Cost-effective algorithm for the differentiation of IgG-mediated subepidermal autoimmune blistering dermatoses

Cost-effective algorithm for the differentiation of IgG-mediated subepidermal autoimmune blistering dermatoses

Case for diagnosis

Pemphigoid gestationis is a rare, autoimmune blistering dermatosis of pregnancy. No increase in fetal or maternal mortality has been demonstrated, but a greater prevalence of premature and small-for-gestationalage babies has been reported. Topical and systemic corticosteroids and antihistamines are the manstay of treatment. The authors report a case of a 27-year-old woman at 28-weeks gestation with sudden onset of pruriginous vesicles and blisters in the abdomen and limbs. Systemic corticosteroids were introduced and maintained throughout gestation to prevent flares and tapered after the birth of a healthy child.

Autoimmune blistering dermatoses as systemic diseases

Autoimmune blistering dermatoses are examples of skin-specific autoimmune disorders that can sometimes represent the cutaneous manifestation of a multiorgan disease due to potential common pathogenic mechanisms. As soon as a distinct autoimmune blistering dermatosis is diagnosed, it is imperative to consider its potential systemic involvement, as well as the autoimmune and inflammatory conditions that are frequently associated with it. In paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome, the internal organs (particularly the lungs) are affected by the autoimmune injury. Pemphigus erythematosus may manifest with overlapping serologic and immunohistologic features of lupus erythematosus. In patients with bullous pemphigoid, there is a greater prevalence of neurologic disease, possibly caused by cross-reactivity of the autoantibodies with isoforms of bullous pemphigoid antigens expressed in the skin and brain. Anti-laminin 332 pemphigoid shows an increased risk for adenocarcinomas. Patients with anti-p200 pemphigoid often suffer from psoriasis. A rare form of pemphigoid with antibodies against the α5 chain of type IV collagen is characterized by underlying nephropathia. Particularly interesting is the association of linear IgA disease or epidermolysis bullosa acquisita with inflammatory bowel disease. Dermatitis herpetiformis is currently regarded as the skin manifestation of gluten sensitivity. Bullous systemic lupus erythematosus is part of the clinical spectrum of systemic lupus erythematosus, a prototypic autoimmune disease with multisystem involvement.

Spectrum of autoimmune blistering dermatoses in Tunisia: an 11‐year study and a review of the literature

Autoimmune bullous dermatoses (ABD) are a rare but significant group of cutaneous disorders posing great diagnostic and therapeutic challenges to the treating dermatologist. Few surveys have been carried out to describe the whole spectrum of ABD in a region. To determine the clinicoepidemiological features of various ABD. We retrospectively recruited all ABD cases seen during an 11-year period (1997-2007). One hundred and seventy-four patients were involved (16.3 cases/year). Pemphigus was observed to be the most common ABD (53%), with the majority being pemphigus vulgaris (61%) vs. 36% of pemphigus foliaceus (Tunisian pemphigus). Most epidemiological surveys have focused on a single or just one group of ABD. In our series, pemphigus foliaceus was relatively more prevalent than in occidental data. The frequencies of subepidermal immunobullous dermatoses in our study were in agreement with those in the literature.

Rituximab for treatment-refractory pemphigus and pemphigoid: A case series of 17 patients

Rituximab has been increasingly used in autoimmune blistering dermatoses, mainly in pemphigus. However, only a few larger case series are available on this subject and information on the efficacy of retreatment with rituximab during relapses is lacking. We sought to determine efficacy and adverse effects of adjuvant rituximab. Seventeen patients with refractory autoimmune blistering dermatoses (pemphigus vulgaris [PV], n= 8; pemphigus foliaceus [PF], n= 2; bullous pemphigoid [BP], n= 2; mucous membrane pemphigoid, n=5) were treated 4 times with rituximab at an individual dose of 375 mg/m(2) in weekly intervals or twice with 1000 mg 2 weeks apart. Six of 8 patients with a relapse after this regimen received rituximab again twice with 1000 mg in a 2-week interval. All lesions cleared in 14 patients (7 PV, two PF, two BP, 3 mucous membrane pemphigoid), whereas partial healing was found in 3 others (one PV, two mucous membrane pemphigoid). Relapses occurred in 8 patients (5 PV, two PF, one BP). Retreatment with rituximab again resulted in complete (two PV, one PF, one BP) or partial (two PV) remission. Serious side effects associated with rituximab were not observed. Rituximab has been combined with various other immunosuppressive or immunomodulatory treatments. Adjuvant rituximab is effective and well tolerated not only in patients with pemphigus but also with pemphigoid. Efficacy and safety of rituximab are maintained when it is readministered during relapses.