Intercellular Pattern Research Articles

A deep learning approach for Direct Immunofluorescence pattern recognition of Autoimmune Bullous Diseases.

Artificial intelligence (AI) is reshaping healthcare, using machine and deep learning to enhance disease management. Dermatology has seen improved diagnostics, particularly in skin cancer detection, through the integration of AI. However, the potential of AI in automating immunofluorescence imaging for autoimmune bullous skin diseases remains untapped. While direct immunofluorescence (DIF) supports diagnosis, its manual interpretation can hinder efficiency. The use of deep learning to automatically classify DIF patterns, including the Intercellular Pattern (ICP) and the Linear Pattern (LP), holds promise for improving the diagnosis of autoimmune bullous skin diseases. The objectives of this study are to develop AI algorithms for automated classification of autoimmune bullous skin disease DIF patterns, such as ICP and LP. This aims to enhance diagnostic accuracy, streamline disease management, and improve patient outcomes through deep learning-driven immunofluorescence interpretation. We collected immunofluorescence images from skin biopsies of patients suspected of AIBD between January 2022 and January 2024. Skin tissue was obtained via 5-mm punch biopsy, prepared for direct immunofluorescence. Experienced dermatologists classified the images into three classes: ICP, LP, and negative. To evaluate our deep learning approach, we divided the images into training (436) and test sets (93). We employed transfer learning with pre-trained deep neural networks and conducted 5-fold cross-validation to assess model performance. Our dataset's class imbalance was addressed using weighted loss and data augmentation strategies. The models were trained for 50 epochs using Pytorch, achieving an image size of 224x224 for both CNNs and the Swin Transformer. Our study compared six CNNs and the Swin transformer for AIBDs image classification, with the Swin transformer achieving the highest average validation accuracy of 98.5%. On a separate test set, the best model attained an accuracy of 94.6%, demonstrating 95.3% sensitivity and 97.5% specificity across AIBDs classes. Visualization with Grad-CAM highlighted the model's reliance on characteristic patterns for accurate classification. The study highlighted CNN's accuracy in identifying DIF features. This approach aids automated analysis and reporting, offering reproducibility, speed, data handling, and cost-efficiency. Integrating deep learning in skin immunofluorescence promises precise diagnostics and streamlined reporting in this branch of dermatology.

An unusual presentation of pemphigus foliaceus following COVID‐19 vaccination

An unusual presentation of pemphigus foliaceus following COVID‐19 vaccination

Syphilitic paronychia: a diagnostic challenge

A 28-year- old HIV-negative male patient presented with a 2-month history of painful inflamed nodules on the tip of his left index and right third finger (figure 1). A biopsy...

Dynamics of hydraulic and contractile wave-mediated fluid transport during Drosophila oogenesis

From insects to mice, oocytes develop within cysts alongside nurse-like sister germ cells. Prior to fertilization, the nurse cells' cytoplasmic contents are transported into the oocyte, which grows as its sister cells regress and die. Although critical for fertility, the biological and physical mechanisms underlying this transport process are poorly understood. Here, we combined live imaging of germline cysts, genetic perturbations, and mathematical modeling to investigate the dynamics and mechanisms that enable directional and complete cytoplasmic transport in Drosophila melanogaster egg chambers. We discovered that during "nurse cell (NC) dumping" most cytoplasm is transported into the oocyte independently of changes in myosin-II contractility, with dynamics instead explained by an effective Young-Laplace law, suggesting hydraulic transport induced by baseline cell-surface tension. A minimal flow-network model inspired by the famous two-balloon experiment and motivated by genetic analysis of a myosin mutant correctly predicts the directionality, intercellular pattern, and time scale of transport. Long thought to trigger transport through "squeezing," changes in actomyosin contractility are required only once NC volume has become comparable to nuclear volume, in the form of surface contractile waves that drive NC dumping to completion. Our work thus demonstrates how biological and physical mechanisms cooperate to enable a critical developmental process that, until now, was thought to be mainly biochemically regulated.

Plucked Hair as a Substrate for Indirect Immunofluorescence in Cases of Pemphigus Vulgaris.

Introduction:Indirect immunofluorescence (IIF) is used to determine the circulating autoantibodies in cases of Pemphigus. For IIF in Pemphigus several substrates had been used. This study was done to determine whether plucked hair can be utilized as a substrate for IIF in cases of Pemphigus. Aim & Objectives: To determine the efficacy of utilizing the plucked hair as a substrate for indirect immunofluorescence among patients with Pemphigus vulgaris.Methodology:Thirty two consecutive patients with active and fresh diagnosed cases of pemphigus vulgaris (PV) who did not undergo any treatment and those patients who had positive DIF findings of characteristic fish net or chicken wire pattern of intercellular IgG deposits in the epidermis of perilesional skin were included in the study. A total of 32 control subjects without any auto immune disorders were selected and the blood samples were taken from these patients for IIF analysis. Anagen hair were collected from the healthy volunteers without pemphigus in the same way as for trichogram. Telogen hair were obtained by combing the hair and collecting the loose strands of hair on the comb and further confirmed under microscope. Three hairs each of anagen and telogen stage were collected from each subject to be utilized as a substrate for IIF.Results:Out of 32 samples 20 samples showed positive results for Ig G alone and 5 samples showed positivity for Ig G and C3. One sample showed positivity for C3alone. All these 26 samples were considered to have positive IIF test based on the intercellular pattern of deposit. Positive IIF results were observed in anagen hair samples and were negative in all the telogen hair samples. Six anagen hair samples did not show any positive findings in IIF for the study group. All the 32 control samples showed negative reports in IIF.Conclusion:In conclusion, IIF microscopy on plucked hair as a substrate is a more sensitive immunoassay for the detection of circulating intercellular autoantibodies in PV and the lower negative predictive value of this substrate is a limitation. Further large scale studies might provide better information regarding the practical utility.

Structural and biochemical characterization of the C₃-C₄ intermediate Brassica gravinae and relatives, with particular reference to cellular distribution of Rubisco.

On the basis of its CO2 compensation concentration, Brassica gravinae Ten. has been reported to be a C3–C4 intermediate. This study investigated the structural and biochemical features of photosynthetic metabolism in B. gravinae. The cellular distribution of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) was also examined in B. gravinae, B. napus L. (C3), Raphanus sativus L. (C3), and Diplotaxis tenuifolia (L.) DC. (C3–C4) by immunogold electron microscopy to elucidate Rubisco expression during the evolution from C3 to C3–C4 intermediate plants. The bundle sheath (BS) cells of B. gravinae contained centrifugally located chloroplasts as well as centripetally located chloroplasts and mitochondria. Glycine decarboxylase P-protein was localized in the BS mitochondria. Brassica gravinae had low C4 enzyme activities and high activities of Rubisco and photorespiratory enzymes, suggesting that it reduces photorespiratory CO2 loss by the glycine shuttle. In B. gravinae, the labelling density of Rubisco was higher in the mesophyll chloroplasts than in the BS chloroplasts. A similar cellular pattern was found in other Brassicaceae species. These data demonstrate that, during the evolution from C3 to C3–C4 intermediate plants, the intercellular pattern of Rubisco expression did not change greatly, although the amount of chloroplasts in the BS cells increased. It also appears that intracellular variation in Rubisco distribution may occur within the BS cells of B. gravinae.

The use of C3d and C4d immunohistochemistry on formalin-fixed tissue as a diagnostic adjunct in the assessment of inflammatory skin disease

Direct immunofluorescent (DIF) testing defines an important diagnostic adjunct in the classification of various inflammatory skin conditions; it requires fresh tissue, a laboratory equipped to perform the procedure, and a pathologist skilled in its interpretation. Although advances have been made in the development of antibodies that can be applied to paraffin-embedded tissue, there has been no reported success on the application of paraffin tissue-based immunohistochemistry as a potential substitute for DIF testing on skin biopsy material. We applied C3d and C4d immunohistochemistry on paraffin-embedded, formalin-fixed tissue to define a potential application of these two antibodies as a diagnostic adjunct in the evaluation of various inflammatory skin diseases. A natural language search identified cases submitted for both light microscopic and DIF studies from July 2006 to August 2007. We prospectively included similar cases encountered from August 2007 to March 2008. We correlated the C3d and C4d staining pattern with the DIF and light microscopic findings. All cases of scarring discoid lupus erythematosus (LE) (20/20) and systemic LE (5/5) showed prominent granular C3d along the dermoepidermal junction (DEJ) and a positive lupus band test result in the latter by DIF. All systemic LE cases demonstrated granular DEJ C4d with C3d or C4d in blood vessels (BV). There was a negative lupus band test result without DEJ C3d or C4d in all cases of subacute cutaneous lupus erythematosus (SCLE) (15/15). There were, however, deposits of C4d within epidermal keratinocytes (7/7), corresponding to IgG decoration of keratinocytes by DIF and the presence of anti-Ro antibodies. Dermatomyositis cases showed prominent mural C3d and C4d in BV corresponding to C5b-9 by DIF (12/12) and one case of hydroxyurea-induced dermatomyositis lacked this staining. Although by DIF all dermatomyositis cases had a negative lupus band test result, 25% of cases showed staining for C3d along the DEJ (3/9). Bullous pemphigoid cases demonstrated homogenous DEJ C3d (17/17) whereas C4d was characteristically negative; there was 100% concordance with linear IgG and C3d by DIF. Eighty two percent of pemphigus cases demonstrated prominent intercellular C3d and C4d, roughly mirroring the intercellular pattern for IgG and complement seen by DIF (9/11). Porphyria cases showed homogeneous and granular C3d (11/11) and C4d (7/11), mirroring the vascular immunoglobulin and C5b-9 by DIF. All cases of urticarial (5), leukocytoclastic (6), and lymphocytic (1) vasculitis exhibited prominent mural C3d and C4d in BV, whereas Henoch-Schönlein purpura (10/10) showed primarily mural BV C3d without C4d, with IgA by DIF. Three cases of relapsing polychondritis showed C3d and C4d within chondrocyte nuclei (3/3), in contrast to negative staining in chondrodermatitis nodularis helicis (0/2). Hypersensitivity reactions were negative for C3d and C4d. The small sample size in each category is a limitation. The lack of literature precedent with regard to immunohistochemical assessment of extracellular antigens on paraffin-embedded tissue in skin samples is another limitation of this study. When correlated with the light microscopic and clinical findings, the C3d and C4d assay has significant application in the assessment of select inflammatory skin diseases including vasculopathic conditions, collagen vascular disease, and autoimmune vesiculobullous disorder. It may prompt further DIF testing or, in some instances, may even define a reasonable substitute for DIF and/or add to the morphologic assessment of a biopsy specimen submitted for routine light microscopic assessment primarily in the setting of autoimmune vesiculobullous disease and collagen vascular disease.

Coexistence of IgA antibodies to desmogleins 1 and 3 in pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus

Pemphigus is a bullous mucocutaneous autoimmune disease characterized by IgG autoantibodies to desmoglein (Dsg) 1 and/or Dsg3. Occasionally direct immunofluorescence of pemphigus skin reveals IgA depositions with an intraepidermal intercellular pattern in addition to the IgG deposition. To investigate if pemphigus patients, in addition to having IgG autoantibodies, also generate IgA antibodies to Dsg1 and/or Dsg3. Sera of 100 pemphigus patients and 36 bullous pemphigoid controls were tested by IgA enzyme-linked immunosorbent assay (ELISA) to the recombinant extracellular domains of Dsg1 and Dsg3. The patients were selected on clinical grounds and positive IgG ELISA index values for Dsg1 and/or Dsg3. They were divided into four groups: patients having IgG to only Dsg1 (n=34), patients having IgG to both Dsg1 and Dsg3 (n=31), patients having IgG to only Dsg3 (n=27) and patients who had paraneoplastic pemphigus (PNP) (n=8). IgA antibodies to Dsg1 were found in 13 (38%) of the patients with IgG to Dsg1, in five (16%) of the patients with IgG to both Dsg1 and Dsg3, in four (15%) of the patients with IgG to Dsg3 and in none of the PNP patients. IgA antibodies to Dsg3 were found in one (3%) of the patients with IgG to Dsg1, in 18 (58%) of the patients with IgG to both Dsg1 and 3, in 18 (67%) of the patients with IgG to Dsg3, and in four (50%) of the PNP patients. Immunofluorescence analysis demonstrated intraepidermal intercellular staining IgA antibodies in serum and intercellular IgA deposits in skin of IgA ELISA-positive patients, although to a lesser extent than by ELISA. This study shows that in a considerable number of supposedly IgG-mediated pemphigus patients IgA to Dsg1 and Dsg3 is also present. In most cases the antigen specificity of the IgA follows the antigen specificity of the IgG, although in a small number of cases IgA is present against the Dsg not recognized by IgG.

IgA‐Pemphigus – Vorkommen von Anti‐Desmocollin‐1‐und Anti‐Desmoglein‐1‐Antikörpern bei einem Patienten

Background: IgA pemphigus is a rare pustular autoimmune disease with exclusive IgA anti-keratinocyte cell surface antibody reactivity. Two subtypes have been discerned: in the subcorneal pustular dermatosis type, desmocollin 1 has been identified as a targeted autoantigen, while in few cases of the intraepidermal neutrophilic type, IgA anti-desmoglein 1 or IgA anti-desmoglein 3 reactivity has been demonstrated. Patients and Methods: A 48-year-old white male presented with generalized large confluent pustules. Skin pathology was assessed by histology and direct immunofluorescence analysis. IgG/lgA autoantibodies against desmoglein 1/3 and desmocollin 1 were measured by ELISA and indirect immunofluorescence using desmocollin 1 cDNA-transfected COS7 cells, respectively. Results: Histopathology revealed subcorneal pustules and direct immunofluorescence microscopy exclusively showed in vivo bound IgA with an intercellular pattern in the epidermis. Desmocollin 1 was identified as a target of IgA autoantibodies by indirect immunofluorescence microscopy utilizing desmocollin 1 cDNA-transfected COS7 cells. In addition, IgA anti-desmoglein 1 reactivity was demonstrated by ELISA. Neither IgA anti-desmoglein 3 nor IgG anti-desmoglein 1/3 autoantibodies were present. Conclusions: Both desmocollin 1 and desmoglein 1 were autoantigens in this patient with IgA pemphigus and a distinct clinical presentation. To our knowledge, this is the first IgA pemphigus case with dual autoantibody reactivity.

IgA pemphigus – Occurrence of anti‐Desmocollin 1 and anti‐Desmoglein 1 antibody reactivity in an individual patient

IgA pemphigus is a rare pustular autoimmune disease with exclusive IgA anti-keratinocyte cell surface antibody reactivity. Two subtypes have been discerned: in the subcorneal pustular dermatosis type, desmocollin 1 has been identified as a targeted autoantigen, while in few cases of the intraepidermal neutrophilic type, IgA anti-desmoglein 1 or IgA anti-desmoglein 3 reactivity has been demonstrated. A 48-year-old white male presented with generalized large confluent pustules. Skin pathology was assessed by histology and direct immunofluorescence analysis. IgG/IgA autoantibodies against desmoglein 1/3 and desmocollin 1 were measured by ELISA and indirect immunofluorescence using desmocollin 1 cDNA-transfected COS7 cells, respectively. Histopathology revealed subcorneal pustules and direct immunofluorescence microscopy exclusively showed in vivo bound IgA with an intercellular pattern in the epidermis. Desmocollin 1 was identified as a target of IgA autoantibodies by indirect immunofluorescence microscopy utilizing desmocollin 1 cDNA-transfected COS7 cells. In addition, IgA anti-desmoglein 1 reactivity was demonstrated by ELISA. Neither IgA anti-desmoglein 3 nor IgG anti-desmoglein 1/3 autoantibodies were present. Both desmocollin 1 and desmoglein 1 were autoantigens in this patient with IgA pemphigus and a distinct clinical presentation. To our knowledge, this is the first IgA pemphigus case with dual autoantibody reactivity.

A complicated blistering disease case demonstrating the usefulness of immunoblotting and ELISA for the diagnosis of immunobullous diseases

A 51 year old female was referred for evaluation of a transient pruritic blistering eruption located on the trunk and extremities. She had a complicated medical background including rheumatoid arthritis and drug‐induced lupus erythematosus from the TNF blocker adalimubab. Her medications included prednisone 4 mg/day and hydroxychloroquine 400 mg/day. On examination a few large tense blisters were noted and the Nikolsky sign was negative.A routine skin biopsy showed intraepidermal vesicles, eosinophilic spongiosis and significant subepidermal oedema, but no acantholysis. Direct immunofluorescence (DIF) showed IgG depositions in an intercellular pattern in the upper epidermis, and IgM depositions in a granular pattern at the dermo‐epidermal junction. Indirect immunofluorescence on monkey oesophagus and rat bladder was negative, whereas salt‐split skin showed positive staining for IgG in the roof of the blister.As it was difficult to establish a unifying diagnosis given these clinical and histopathological features, the auto‐antigenic targets were studied by ELISA and immunoblotting techniques. ELISA showed IgG reactivity to the 165 kd desmoglein 1 antigen, but not to desmoglein 3. Immunoblotting to basement membrane components was negative. These results supported a unifying final diagnosis of pemphigus foliaceus. She has been treated with minomycin and topical corticosteroids and has had a benign course.This case demonstrates the concurrence of multiple serious autoimmune diseases, which represent an ongoing diagnostic and management challenge. Although the molecular pathogenesis of autoimmune blistering diseases is well understood, clinico‐pathological correlation may not always be achieved with routine dermatohistopathology and immunofluorescence examination. This case demonstrates the utility of additional molecular techniques in differentiating blistering diseases, which has important implications for management and prognosis.

Loss of Desmoplakin Tail Causes Lethal Acantholytic Epidermolysis Bullosa

The cytoplasmic plaque protein desmoplakin (DP), which is located in desmosomes, plays a major role in epithelial and muscle cell adhesion by linking the transmembrane cadherins to the cytoplasmic intermediate filament network. Mutations of DP may cause striate palmoplantar keratoderma, arrhythmogenic right ventricular dysplasia, skin fragility/woolly hair syndrome, Naxos-like disease, and Carvajal syndrome. DP must be indispensable, because DP-/- mice are early abortive. Here, we report a patient with severe fragility of skin and mucous membranes caused by genetic truncation of the DP tail. The new phenotype is lethal in the neonatal period because of immense transcutaneous fluid loss. The phenotype also comprised universal alopecia, neonatal teeth, and nail loss. Histology showed suprabasal clefting and acantholysis throughout the spinous layer, mimicking pemphigus. Electron microscopy revealed disconnection of keratin intermediate filaments from desmosomes. Immunofluorescence staining of DP showed a distinct punctate intercellular pattern in the patient's skin. Protein analysis revealed expression of truncated DP polypeptides. Mutational analysis of the patient demonstrated compound heterozygosity for two DP mutations, 6079C-->T (R1934X) and 6370delTT, respectively. Aberrant mRNA transcripts that predict premature termination of translation with loss of the three intermediate filament-binding subdomains in the DP tail were detected by RT-PCR. The new dramatic phenotype, which we named "lethal acantholytic epidermolysis bullosa," underscores the paramount role of DP in epidermal integrity.

Structural and biochemical dissection of photorespiration in hybrids differing in genome constitution between Diplotaxis tenuifolia (C3-C4) and radish (C3).

We compared the structural, biochemical, and physiological characteristics involved in photorespiration of intergeneric hybrids differing in genome constitution (DtDtR, DtDtRR, and DtRR) between the C(3)-C(4) intermediate species Diplotaxis tenuifolia (DtDt) and the C(3) species radish (Raphanus sativus; RR). The bundle sheath (BS) cells in D. tenuifolia included many centripetally located chloroplasts and mitochondria, but those of radish had only a few chloroplasts and mitochondria. In the hybrids, the numbers of chloroplasts and mitochondria, the ratio of centripetally located organelles to total organelles, and the mitochondrial size in the BS cells increased with an increase in the constitution ratio of the Dt:R genome. The P-protein of glycine decarboxylase (GDC) was confined to the BS mitochondria in D. tenuifolia, whereas in radish, it accumulated more densely in the mesophyll than in the BS mitochondria. In the hybrids, more intense accumulation of GDC in the BS relative to the mesophyll mitochondria occurred with an increase in the Dt:R ratio. These structural and biochemical features in the hybrids were reflected in the gas exchange characteristics of leaves, such as the CO(2) compensation point. Our data indicate that the leaf structure, the intercellular pattern of GDC expression, and the gas exchange characteristics of C(3)-C(4) intermediate photosynthesis are inherited in the hybrids depending on the constitution ratio of the parent genomes. Our findings also demonstrate that the apparent reduced photorespiration in C(3)-C(4) intermediate plants is mainly due to the structural differentiation of mitochondria and chloroplasts in the BS cells combined with the BS-dominant expression of GDC.

Carotenoderma--a review of the current literature.

Carotenoderma--a review of the current literature.

Novel Human α9 Acetylcholine Receptor Regulating Keratinocyte Adhesion is Targeted by Pemphigus Vulgaris Autoimmunity

Pemphigus vulgaris (PV) is a potentially fatal autoimmune mucocutaneous blistering disease. It was assumed that PV is caused by anti-desmoglein (Dsg) 3 autoimmunity because absorption of PV sera with a chimeric baculoprotein containing the Dsg 3 and IgG1 portions, rDsg3-Ig-His, eliminated disease-causing antibodies. In this study we demonstrate that rDsg3-Ig-His adsorbs out autoantibodies to different keratinocyte antigens, including a non-Dsg 3 130-kd polypeptide. Because the pool of disease-causing PV IgGs contains antibodies against the keratinocyte acetylcholine receptor (AChR), we sought to identify the targeted receptor(s). Preincubation of monkey esophagus with PV antibodies blocked specific staining of the keratinocyte cell membrane with rabbit monoepitopic antibody to alpha9 AChR, indicating that this first of its kind AChR with dual, muscarinic and nicotinic pharmacology is targeted by PV autoimmunity. Anti-alpha9 antibody stained keratinocytes in a fishnet-like intercellular pattern, and visualized a single band at approximately 50 kd in Western blots of keratinocyte membrane proteins. Using step-by-step reverse transcription polymerase chain reactions with primers based on known alpha9 sequence regions, we identified the complete reading frame of human alpha9. Its amino acid sequence showed 85% similarity with rat alpha9. Treatment of keratinocyte monolayers with anti-alpha9 antibody induced pemphigus-like acantholysis, which could be reversed either spontaneously or by using the cholinergic agonist carbachol. We conclude that alpha9 is coupled to physiological regulation of keratinocyte adhesion, and its interaction with PV IgG may lead to blister development.

Anomalous Diffusion of Solar Magnetic Elements

The diffusion properties of photospheric bright points associated with magnetic elements (magnetic bright points) in the granulation network are analyzed. We find that the transport is subdiffusive for times less than 20 minutes but normal for times larger than 25 minutes. The subdiffusive transport is caused by the walkers being trapped at stagnation points in the intercellular pattern. We find that the distribution of waiting times at the trap sites obeys a truncated Levy type (power-law) distribution. The fractal dimension of the pattern of sites available to the random walk is less than 2 for the subdiffusive range and tends to 2 in the normal diffusion range. We show how the continuous time random walk formalism can give an analytical explanation of the observations. We simulate this random walk by using a version of a phenomenological model of renewing cells introduced originally for supergranules by Simon, Title, & Weiss. We find that the traps that cause the subdiffusive transport arise when the renewed convection cell pattern is neither fixed nor totally uncorrelated from the old pattern, as required in Leighton's model, but in some intermediate state between these extremes.

Human Skin/SCID Mouse Chimeras as an In Vivo Model for Human Cutaneous Mast Cell Hyperplasia

Human skin xenografted to mice with severe combined immunodeficiency syndrome (SCID) was evaluated to determine the integrity and fate of human dermal mast cells. There was an approximately 3-fold increase in number of dermal mast cells by 3 mo after engraftment (p < 0.05). These cells were responsive to conventional mast cell secretagogues and were confirmed to be of human origin by ultrastructural characterization of granule substructure and by reactivity for the human mast cell proteinase, chymase. CD1a+ Langerhans cells, also bone marrow-derived cells, failed to show evidence of concomitant hyperplasia, and increased mast cell number was not associated with alterations in number of dermal vascular profiles identified immunohistochemically for human CD31. RT-PCR analysis demonstrated human but not murine stem cell factor (SCF; also termed mast cell growth factor, c-kit ligand) mRNA in xenografts. Epidermal reactivity for stem cell factor protein shifted from a cytoplasmic pattern to an intercellular pattern by 3 mo after engraftment, suggesting a secretory phenotype, as previously documented for human cutaneous mastocytosis. The majority (>90%) of mast cells demonstrated membrane reactivity for human SCF at the time points of peak hyperplasia. These data establish SCID mouse recipients of human skin xenografts as a potential in vivo model for cutaneous mast cell hyperplasia.

Paraneoplastischer Pemphigus

Paraneoplastic pemphigus (PP) is a newly reported autoimmune disease, which is always associated with an underlying neoplasia. It is characterized by painful mucosal erosions and ulcerations, and by polymorphous skin lesions reminiscent of erythema multiforme, pemphigus vulgaris and lichen planus pemphigoides. These patients have autoantibodies that bind to a distinct complex of epidermal proteins, including desmoplakin I (250 kD), major bullous pemphigoid antigen (230 kD), desmoplakin II (210 kD) and a 190-kD and a 170-kD protein, neither of which has yet been further characterized. Histological findings include acantholysis, epidermal cell necrosis, vacuolar interface changes and, sometimes, lichenoid infiltrates of the upper dermis. Direct immunofluorescence shows an intercellular deposition of immunoreactants in the epidermis and granular deposits at the dermal-epidermal junction. Indirect immunofluorescence with rodent bladder as substrate shows an intercellular pattern. This method is the most convenient and cost-effective method of screening for PP, since antigens of both pemphigus vulgaris and pemphigus foliaceus are not expressed in this tissue.

Paraneoplastic pemphigus: A distinct autoimmune vesiculobullous disorder associated with neoplasia

A vesiculobullous disease termed paraneoplastic pemphigus with distinct autoantibodies was newly described in 1990. All reported cases have occurred in patients with a history of neoplasia, including lymphoma, chronic lymphocytic leukemia, poorly differentiated sarcoma, and benign thymoma. As in pemphigus vulgaris, intraepithelial clefts with acantholysis are noted hisopathologically, and intercellular binding of immunoreactants is seen with direct immunofluorescence studies of mucous membrane and skin biopsies. However, immunoreactants may also be found along the basement membrane zone in paraneoplastic pemphigus. Indirect immunofluorescence using rat bladder epithelium as substrate shows an intercellular pattern that appears to be highly specific for paraneoplastic pemphigus. We report a patient with non-Hodgkins lymphoma of 8 years duration who developed severe erosive stomatitis and lichenoid dermatitis after receiving chemotherapy for a relapse of lymphoma. Her case illustrates the typical features of the disorder described as paraneoplastic pemphigus. Neoplasia-associated pemphigus may be a more precise term for this disorder because the course of the blistering eruption does not always parallel the course of the underlying cancer. The clinical features, histopathologic findings, and immunofluorescence findings of this unique syndrome are reviewed.

Immunohistochemical Expression of Epidermal Growth Factor Receptors in Nuclei of a Subpopulation of Keratinocytes and Sweat Gland Cells

We have raised a polyclonal antibody to the 170-kD epidermal growth factor receptor. We found an intercellular pattern of immunoreactivity in the epidermis as well as a positivity of the cytoplasm of keratinocytes and eccrine secretory cells. In some samples, a nuclear labelling was evidenced in these type of cells. There is a close resemblance in the topographical distribution of these cells with nuclear labelling and those synthesizing DNA under phytohaemagglutinin stimulation.