Subject(s)
Estrogens/metabolism , Melanosis/etiology , Melanosomes/radiation effects , Ultraviolet Rays/adverse effects , Cell Culture Techniques , Cells, Cultured , Humans , Melanosomes/metabolism , Melanosomes/ultrastructure , Microscopy, Electron , Pilot Projects , Progesterone/metabolism , Skin/cytology , Skin/radiation effects , Skin/ultrastructureABSTRACT
BACKGROUND: Due to the very short T2 of its components, the normal anatomy of Achilles enthesis is impossible to define with "conventional" long echo time (TE) T2 sequences. However, this is a common site affected by rheumatologic disease. Early abnormalities related to inflammatory processes are impossible to detect in this location. PURPOSE: To assess the feasibility of a 3D-UTE (ultrashort echo time) sequence to evaluate normal and pathological Achilles entheses, determining both anterior fibrocartilaginous and posterior collagenic portions at 4.7T, in a rat model of spondyloarthropathy (SpA) with histological correlation. To assess whether this sequence detects SpA enthesopathy prior to long TE T2 sequences, enabling disease monitoring. STUDY TYPE: Prospective case-control study. ANIMAL MODEL: Twelve immunocompetent Wistar male rats imaged before (controls); the model was induced in eight rats (16 tendons) imaged at day 6, day 13, and day 21 with regular sacrifice for ex vivo imaging and histological correlation. FIELD STRENGTH: 4.7T Bruker Biospec Systems. 3D balanced steady-state free precession (bSSFP) and 3D-UTE sequences, performed at baseline (day 0, n = 12 animals / 24 tendons), day 6 (n = 8/16), 13 (n = 4/8), and day 21 (n = 2/4). ASSESSMENT: Visual analysis and signal intensity measurements (signal to noise ratio, SNR) of both bSSFP and UTE images were performed by two independent musculoskeletal radiologists at different locations of the Achilles enthesis and preinsertional area. STATISTICAL TESTS: Normal and pathological rat values were compared by Wilcoxon signed-rank tests, as well as interobserver differences. MRI findings were compared against histological data. RESULTS: The 3D-UTE sequence identified the anterior fibrocartilage and posterior collagenic areas of Achilles entheses in all cases. Visual analysis and signal intensity measurements distinguished SpA-affected entheses from healthy ones at days 6 and 13 (P = 0.002 and P = 0.006, respectively). Neither the normal anatomy of the enthesis nor its pathological pattern could be identified on T2 bSSFP sequences. DATA CONCLUSION: Unlike bSSFP T2 sequences, 3D-UTE sequences enable visualization of normal enthesis anatomy and early detection of abnormalities in pathological conditions. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:127-135.
Subject(s)
Achilles Tendon/diagnostic imaging , Fibrocartilage/diagnostic imaging , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Spondylarthropathies/diagnostic imaging , Animals , Disease Models, Animal , Feasibility Studies , Inflammation , Male , Rats , Rats, Wistar , Tendons/diagnostic imagingABSTRACT
Allograft pathology, antibody-tissue interaction as demonstrated by C4d deposition and serological evidence of donor-specific antibodies (DSA) are the cardinal diagnostic features of antibody-mediated lesions (AML) in kidney transplantation. However, discrepancy between histological and serological findings is common, and more reliable diagnostic tools are called for. Here, we asked whether the in situ detection of DSA could serve as marker for AML. To that end, we applied the anti-HLA single antigen flow bead assay to eluates from 51 needle core graft biopsies performed for cause. Intragraft antibody profiles were correlated to serum DSA (sDSA), histological data and transplant outcome. The prevalence and the mean number of intragraft DSA (gDSA) were lower than that of sDSA (15/51 gDSA+ vs. 37/51 sDSA+ patients; 1.64 gDSA vs. 2.24 sDSA per patient). DSA were detected in all anti-HLA antibody-positive biopsies (15/15). The presence of gDSA was significantly associated with (1) microcirculation lesions taken individually (g, cg) and analyzed in functional clusters (ptc + g + cg > 0, cg + mm > 0), (2) C4d positivity and (3) a worse short-term transplant outcome (p = 0.05). These associations were not found for patients presenting only sDSA. Taken together, these results indicate that gDSA is a severity marker of antibody-mediated pathogenic process.
Subject(s)
Graft Rejection/diagnosis , HLA Antigens/metabolism , Isoantibodies/blood , Kidney Diseases/pathology , Kidney Transplantation/adverse effects , Tissue Donors , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Survival , Humans , Kidney Diseases/mortality , Kidney Diseases/surgery , Male , Middle Aged , Retrospective Studies , Risk Factors , Transplantation, HomologousABSTRACT
Hepatitis E virus (HEV) has been identified as a cause of chronic viral hepatitis in immunocompromised patients. Some glomerular diseases were found to be associated with this infection. We report the first case, to our knowledge, of a kidney transplant recipient who developed an HEV infection and de novo membranous nephropathy (MN) concomitantly. The patient displayed a hepatic cytolysis first and a nephrotic syndrome occurred 3 months later. HEV infection was diagnosed upon positive polymerase chain reaction on plasma and stool samples, and renal allograft biopsy revealed de novo MN. Typical causes of MN were definitively excluded. A 3-month course of ribavirin monotherapy allowed the patient to mount a sustained viral response that was rapidly followed by complete remission of the nephrotic syndrome. The chronology of the onset and remission of both diseases is highly suggestive of a causal relationship between hepatitis E and MN.
Subject(s)
Glomerulonephritis, Membranous/virology , Hepatitis E/complications , Kidney Transplantation , Hepatitis E/drug therapy , Humans , Male , Middle AgedABSTRACT
The combination of skin ablation and 5-Fluorouracil (5-FU) ointment was previously tried in the treatment of vitiligo, and good results were specifically reported in glabrous skin without follicular melanocyte reservoirs. Methods. This study was carried out on the skins of seven guinea pigs: three were treated with mechanical dermabrasion plus topical 5-FU in an achromic area contiguous to a pigmented area; two were treated by only dermabrasion in a similar area; and two were treated by topical 5-FU alone. Clinical, histological, and ultrastructural studies were performed over two months. Results. In guinea pigs treated with dermabrasion plus 5-FU, we observed firstly a delay of wound healing with an obvious inflammatory reaction, and, after two months, evident pigment spread from the pigmented into the achromic area. After six months, we noticed black hair regrowing in the achromic area. Pigment spread was not seen in the guinea pigs skin treated by either dermabrasion or topical 5-FU. We suggest that the inflammatory mediators and enzymes (metalloproteinases), which are locally released over a long time, could stimulate and facilitate melanocyte proliferation and migration through the enlarged intercellular spaces of the epidermis. This sequence of events may be applied to vitiligo patients treated with 5-FU on ablated lesions.
ABSTRACT
BACKGROUND: Imatinib mesylate is a potent inhibitor of platelet-derived growth factor and transforming growth factor-ß signalling pathways which may play a role in systemic sclerosis (SSc)-associated skin changes. OBJECTIVES: We aimed primarily at assessing the efficacy of imatinib mesylate in scleroderma skin fibrosis. METHODS: We performed a phase II double-blinded trial on patients with scleroderma with either morphoea involving > 20% of body surface area or SSc with extensive skin involvement: modified Rodnan Skin Score (mRSS) ≥ 20/51. Each patient was randomized to receive either imatinib mesylate 400 mg or placebo daily for a total of 6 months, and then was followed up 6 months after therapy discontinuation. Skin fibrosis was assessed by mRSS and measurement of the dermal thickness using skin biopsies performed at inclusion and at 6 months of treatment. In addition, quality of life (Dermatology Life Quality Index and modified Health Assessment Questionnaire for Scleroderma) was recorded at each visit, and pulmonary function before and after intervention. RESULTS: Twenty-eight patients were included in the study with a mean age of 48·9 years (range 30-71): 25 had a diagnosis of a SSc and three of diffuse cutaneous scleroderma. Demographic data, frequency of organ involvement of SSc and mRSS were comparable between groups. At 6 months, the proportion of variation of mRSS from inclusion was not statistically significantly different between the two groups (median +0·10 in imatinib group vs. -0·16 in placebo group, P = 0·098). Similarly, changes in dermal thickness, quality of life and diffusion capacity for carbon monoxide were not significantly different between groups. CONCLUSIONS: This study failed to demonstrate the efficacy of imatinib 400 mg daily to improve skin fibrosis of diffuse scleroderma after 6 months of treatment based on validated outcome measurements.
Subject(s)
Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Scleroderma, Diffuse/drug therapy , Skin/pathology , Adult , Aged , Benzamides , Double-Blind Method , Female , Fibrosis/drug therapy , Humans , Imatinib Mesylate , Male , Middle Aged , Platelet-Derived Growth Factor/metabolism , Quality of Life , Scleroderma, Diffuse/metabolism , Transforming Growth Factor beta/metabolism , Treatment OutcomeABSTRACT
Infantile digital fibromatosis or inclusion body fibromatosis is a rare, benign fibroproliferative lesion with recurrent potential that occurs on the digits of infants. A highly characteristic morphologic finding is the presence of paranuclear inclusion within the tumoral cells. We report here a case occurring in an 8-month-old infant with 2 asynchronous lesions of the toes.
Subject(s)
Fibroma/diagnosis , Fibroma/genetics , Foot Diseases/diagnosis , Foot Diseases/genetics , Inclusion Bodies/pathology , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/genetics , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Toes , Child, Preschool , Fibroma/pathology , Fibroma/surgery , Follow-Up Studies , Foot Diseases/surgery , Humans , Infant , Male , Neoplasms, Multiple Primary/pathology , Neoplasms, Multiple Primary/surgery , Skin/pathology , Skin Neoplasms/pathology , Skin Neoplasms/surgeryABSTRACT
Waldenström macroglobulinemia is defined by a bone marrow lymphoplasmacytic infiltration associated with serum IgM monoclonal gammopathy. Specific properties of the IgM gammopathy induce the main clinical manifestations revealing the disease: hyperviscosity syndrome, autoimmune peripheral neuropathy, cryoglobulinemia or hemolysis, and exceptional skin deposit such as macroglobulinosis cutis that we here report. Physicians should be aware of these clinical manifestations to avoid diagnostic delay.
Subject(s)
Skin Diseases, Papulosquamous/etiology , Waldenstrom Macroglobulinemia/diagnosis , Humans , Male , Middle AgedABSTRACT
Elastic fibers are composed of microfibrils containing fibrillin-1 and an elastic component, elastin. Microfibrils may not be associated with elastin. In the adult liver, fibrillin-1 and elastin are coexpressed within the stroma and portal tracts vessel walls. Fibrillin-1 is expressed alone around the bile ducts and within the Disse space. There is little work that has studied the elastic fiber organization during the fÅtal liver development. Here, we studied the expression of fibrillin-1 and elastin by immunohistochemistry on 20 cases of fÅtal liver. During the development of the portal tract, the two components are coexpressed on interstitial elastic fibers and within vessel walls. Fibrillin-1 is expressed alone around the bile structures during their maturation. Unlike adult liver, fibrillin-1 is expressed on thin and very irregular microfibrils within the Disse space. Our study shows that the elastic matrix development in the portal tract follows the development of the different structures, notably biliary structures. In the Disse space, microfibrils are not continuous. Their maturation may be in relation with the change of the hepatic blood flow after birth.
Subject(s)
Elastic Tissue , Elastin/biosynthesis , Liver/embryology , Microfilament Proteins/biosynthesis , Elastin/analysis , Fibrillin-1 , Fibrillins , Humans , Immunohistochemistry , Liver/metabolism , Microfilament Proteins/analysisABSTRACT
BACKGROUND: Psoriasiform eruptions occur in association with antitumour necrosis factor (TNF)-alpha treatments in autoinflammatory diseases. The major reported clinical presentation is palmoplantar pustulosis, sometimes accompanied with plaque-like psoriasis. In some reports, histological findings suggest psoriasis whereas others favour a lichenoid drug reaction. We present a case series with a comprehensive clinical, histopathological and immunohistochemical study. OBJECTIVES: To investigate the mechanism involved in psoriasiform eruptions in patients receiving anti-TNF-alpha inhibitors. METHODS: Between July 2004 and May 2008, 13 patients with psoriasiform eruptions arising under anti-TNF-alpha treatment were enrolled in the study. Punch biopsy specimens of lesions were processed for standard and immunohistochemical analyses using antibodies against CD3, CD4, CD8, CD20, CD1a, KP1, CXCR3, CXCL9, Tia1 and MxA, which is specifically induced by type I interferons (IFNs). Additionally, we analysed biopsies from lesional skin of patients with cutaneous discoid lupus erythematosus, lichen planus and psoriasis. Control biopsies were taken from unaffected skin. RESULTS: All patients developed psoriasiform plaques on the body accompanied with palmoplantar keratoderma or pustulosis in three patients. Histological and immunohistochemical findings showed a psoriasiform pattern with focal lichenoid and spongiotic features. We detected strong production of the MxA protein in inflammatory cells, indicating involvement of type I IFNs, and the expression was higher than in control psoriasis samples. Expression of MxA was closely associated with the recruitment of CXCR3+ lymphocytes in the skin bearing markers of cytotoxic capacity. CONCLUSIONS: Results support the hypothesis that psoriasiform eruptions are a new model of drug reaction characterized by an increased expression of type I IFNs induced by anti-TNF-alpha.
Subject(s)
Cytokines/metabolism , Drug Eruptions/etiology , Psoriasis/chemically induced , Receptors, Chemokine/immunology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Adult , Aged , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Biopsy , Etanercept , Female , Humans , Immunoglobulin G/therapeutic use , Immunohistochemistry , Infliximab , Interferon-alpha/metabolism , Lichen Planus/immunology , Lichen Planus/pathology , Lupus Erythematosus, Discoid/immunology , Lupus Erythematosus, Discoid/pathology , Lymphocytes/metabolism , Male , Middle Aged , Psoriasis/immunology , Psoriasis/pathology , Receptors, Chemokine/metabolism , Receptors, Tumor Necrosis Factor/therapeutic useABSTRACT
Actinomycosis is an unusual and unrecognized cause of spinal cord compression of infectious origin. We report the case of a 57-year-old immunocompetent woman admitted for sub-acute lower limb ataxia. The diagnosis of spinal cord compression secondary to actinomyces infectious arthritis was established. Surgical decompression and long-term antibiotic treatment enabled complete recovery. Data from the literature indicate that actinomycosis is a potential cause of several neurological manifestations. Unusual but treatable, actinomycosis is a potential alternative when the main etiologies have been ruled out.
Subject(s)
Actinomycosis/complications , Spinal Cord Compression/etiology , Spinal Cord Compression/surgery , Actinomycosis/drug therapy , Actinomycosis/pathology , Anti-Bacterial Agents/therapeutic use , Arthritis, Infectious/pathology , Ataxia/etiology , Decompression, Surgical , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Spinal Cord/pathology , Spinal Cord Compression/pathology , Tomography, X-Ray ComputedABSTRACT
Familial Tumoral Calcinosis (FTC) is a rare autosomal recessive disorder of the phosphocalcic metabolism caused by mutations in the FGF23 or GALNT3 genes. We have identified a Beninese family in which two brothers present FTC caused by a homozygous A>T transversion at the acceptor splice site in intron 1 of GALNT3 gene. We report on the clinical, biochemical, histopathological and molecular spectrum of the disorder in this family. The particularly severe phenotype, the amelogenesis imperfecta, and the carbapatite deposit observed in these patients, seem to be characteristic of our observations.
Subject(s)
Black People/genetics , Calcinosis/genetics , Joint Diseases/genetics , Mutation , N-Acetylgalactosaminyltransferases/genetics , Adolescent , Adult , Amelogenesis Imperfecta/genetics , Amelogenesis Imperfecta/pathology , Apatites/blood , Benin , Calcinosis/pathology , Fibroblast Growth Factor-23 , Humans , Hyperphosphatemia/genetics , Hyperphosphatemia/pathology , Joint Diseases/pathology , Male , Pedigree , Siblings , Polypeptide N-acetylgalactosaminyltransferaseABSTRACT
BACKGROUND: Scleroderma skin overexpresses the platelet-derived growth factor receptor beta-subunit (PDGFR-beta) in dermal vessels and PDGFR-beta messenger RNA in cultured fibroblasts. Moreover, increased levels of PDGF and stimulatory autoantibodies to PDGFR have been identified in the serum of scleroderma patients. OBJECTIVE: Imatinib being an inhibitor of tyrosine kinase receptors such as PDGFR, its effect on scleroderma fibroblasts was evaluated in vitro as a preclinical therapeutic step. METHODS: The effect of imatinib on fibroblasts grown from normal or involved/uninvolved scleroderma skin was studied by Western blot and the methyltetrazolium test. The pattern of distribution of PDGFR-beta in scleroderma versus normal skin was studied by immunohistochemistry. RESULTS: In vitro, imatinib inhibited the proliferation of normal dermal and scleroderma fibroblasts at least partly via the inhibition of the phosphorylation of PDGFR. PDGFR-beta was expressed in the epidermis and adnexae in 5 lesional scleroderma biopsies and not in controls. CONCLUSION: This study suggests that imatinib can serve as therapy to limit dermal fibroblast proliferation in scleroderma.
Subject(s)
Fibroblasts/drug effects , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Scleroderma, Systemic/drug therapy , Skin/cytology , Adolescent , Adult , Aged , Aged, 80 and over , Benzamides , Blotting, Western , Cell Proliferation/drug effects , Cells, Cultured , Female , Fibroblasts/cytology , Fibroblasts/metabolism , Humans , Imatinib Mesylate , Immunohistochemistry , Male , Middle Aged , Protein-Tyrosine Kinases/antagonists & inhibitors , Receptor, Platelet-Derived Growth Factor beta/biosynthesis , Receptor, Platelet-Derived Growth Factor beta/drug effects , Scleroderma, Systemic/metabolism , Scleroderma, Systemic/pathology , Skin/drug effects , Skin/metabolism , Treatment OutcomeSubject(s)
Granuloma Annulare/pathology , Child , Female , Hand Dermatoses/pathology , Humans , Leg Dermatoses/pathology , ThoraxABSTRACT
BACKGROUND: Idiopathic facial aseptic granuloma (IFAG) was recently described in a single-centre retrospective study as a skin condition that occurs specifically in childhood. OBJECTIVES: To improve our epidemiological, clinical and pathological knowledge on IFAG, to search for an infectious aetiology, and to assess therapeutic recommendations. METHODS: Children presenting with one or several acquired nodules on the face, lasting for at least 1 month, with no evidence of any other recognizable clinical entity such as infantile acne, pilomatrixoma, furuncle, tumour or vascular malformation, were enrolled in a prospective multicentre study from June 2001 to June 2004, involving the main French paediatric dermatology outpatient units. We recorded clinical details about the nodule and its duration, ultrasound study pattern, cultures for bacteria and mycobacteria, and Bartonella henselae and Afipia felis antibody testing. RESULTS: Thirty children (17 boys and 13 girls, mean age 3.8 years) were enrolled. Ultrasound studies revealed a solid well-demarcated hypoechoic lesion without calcium deposit. Cultures for bacteria were negative in 70% of cases. Cultures for mycobacteria and cat scratch disease serologies were negative. Antibiotic therapy was ineffective; the lesion healed spontaneously with a mean duration of 11 months. Histological examination, performed in five cases, showed a chronic dermal lymphohistiocytic granuloma with numerous foreign body-type giant cells. CONCLUSIONS: IFAG is characterized by a painless facial nodule, presenting as a single lesion localized on the cheek, with a prolonged course but spontaneous healing. Oral or local antibiotics are usually ineffective. Regarding the pathophysiology, our study rules out a primary infectious disease, and allows considering IFAG either as a granulomatous process appearing around an embryological residue or as a manifestation to include in the spectrum of granulomatous rosacea in childhood.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Facial Dermatoses/pathology , Granuloma/pathology , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Prospective Studies , Treatment OutcomeABSTRACT
Senile lentigo is a common component of photoaged skin. It is characterized by hyperpigmented macules which affect chronically irradiated skin mostly after the age of 50. This study was undertaken to assess the morphology of senile lentigo on the dorsum of the hands. A systematic comparison between lesional and perilesional skin using histology and transmission electron microscopy was done to determine whether melanocytes or keratinocytes are affected in the evolution of lesions and which tissue structure is modified. The histology study showed that lesional skin is characterized by a hyperpigmented basal layer and an elongation of the rete ridges, which seem to drive deeply into the dermis. The epidermis contained clusters of keratinocytes, which retained and accumulated the melanin pigment. Electron microscopy studies showed important modifications in the lesional skin ultrastructure in comparison with perilesional skin. In melanocytes from perilesional and lesional skin, we observed normal size melanosomes at all stages of maturation in the cytoplasm and in migration within dendrites. No pigment accumulation was observed. However, the morphology of melanocytes in lesional skin revealed an activated status with numerous mitochondria and a well-developed endoplasmic reticulum, which could reflect intense protein synthesis. In basal keratinocytes from lesional skin, we observed numerous melanosome complexes called polymelanosomes, which formed massive caps on the nuclei. Observations in colored semi-thin sections also revealed perturbed structures in the basal layer region, which could explain the skin perturbation. Indeed, we observed keratinocytes that presented important microinvaginations and pendulum melanocytes, which sank into the dermis, beneath the basal layer of keratinocytes. These cell modifications seemed to be due to a perturbation of the dermal-epidermal junction, which appeared disorganized and disrupted and could directly disturb the basal support of the cells.
Subject(s)
Lentigo/pathology , Skin/pathology , Skin/ultrastructure , Aged , Aged, 80 and over , Biopsy , Cell Count , Dermis/pathology , Dermis/ultrastructure , Female , Hand/pathology , Humans , Immunohistochemistry , Lentigo/diagnosis , Male , Melanocytes/pathology , Melanocytes/ultrastructure , Microscopy, Electron , Middle Aged , Tissue EmbeddingABSTRACT
BACKGROUND: Hereditary mucoepithelial dysplasia is a dominantly inherited disease, mainly characterized by chronic mucosal lesions associated with keratitis, non-scarring alopecia, keratosis pilaris and perineal intertrigo. Since the original report by Witkop, this condition has been considered to be a disorder of desmosome/gap junction formation, but there has been no ex vivo investigation of these components using genetic and immunolabelling techniques. OBJECTIVES: To perform light and immunoelectron microscopic studies, and partial genetic analysis on five patients in a family and three sporadic cases and to point out similarities of this rare disorder with chronic mucocutaneous candidiasis and other follicular keratosis syndromes, i.e. ichthyosis follicularis-alopecia-photophobia (IFAP), keratitis-ichthyosis-deafness (KID) and Siemens syndromes. METHODS: Biopsies from the involved oral mucosa and armpit skin of patient 1 were prepared for standard histopathology, electron microscopy and immunocytochemistry. Microsatellite genotyping was performed in three affected family members. Direct sequencing after polymerase chain reaction amplification of the entire coding region was performed. RESULTS: A 14-year-old male had recurrent keratitis, widespread keratosis pilaris, perineal intertrigo, hypotrichosis and oral mucosal involvement. A similar phenotype was noted in four members of his family and in three sporadic cases. Histological examination of oral mucosa and skin samples showed a psoriasiform pattern, dyskeratotic features and cytoplasmic vacuoles. Expression of connexins (Cx), desmosomal, adherens junction and cytoskeleton proteins (Cx 26, 32 and 43, desmogleins 1 and 2, plakoglobin, desmoplakins I-II, plakophilin 1, beta-catenin, E-cadherin, keratins, beta-tubulin, vimentin and actin) was normal. Ultrastructural studies showed a reduced number of desmosomes. Dyskeratotic cells exhibited internalized gap junctions, long filamentous inclusions reactive with antikeratin antibodies, and bundles of perinuclear fibres resembling clear tonofilaments. Genetic analysis in the studied family excluded the desmosomal cadherins in chromosome 18q12 as candidate genes. CONCLUSIONS: A diagnosis of hereditary mucoepithelial dysplasia should be strongly suggested by the triad of non-scarring alopecia, well-demarcated erythema of oral mucosa and psoriasiform perineal rash, after exclusion of the clinically related follicular keratosis syndromes. Defective expression of cytoskeleton elements and/or a modification of mechanisms regulating junction-cytoskeleton assembly may be primarily responsible for impaired epithelial cohesion.