Hailey-Hailey disease successfully treated with vitamin D oral supplementation.

Hailey-Hailey disease (HHD) also known as familial benign chronic pemphigus is a rare autosomal dominant genodermatosis. HHD treatment is often not satisfactory and hence, various modalities of treatment have been tried. We describe the case of a 37-year-old woman with a 2 years history of macerated erythematous plaques along with erosions, fissures, and crusts located on axillae and submammary areas, successfully treated with only oral supplementation of vitamin D (800 I.U./die) for 3 months. We reported this case to suggest that oral vitamin D may be enumerated in the various treatments proposed for HHD so far due to its rapid efficacy on skin lesions and symptoms.

[Antidesmoglein antibodies in a patient with Hailey-Hailey disease]. / Détection d'anticorps antidesmogléines circulants chez un patient atteint de maladie de Hailey-Hailey.

BACKGROUND: Hailey-Hailey disease (HHD) is a rare hereditary disease in which the genetic defect is characterized by mutation in the ATP2C1 gene coding for a transmembrane calcium pump. It is generally considered a non-immunologic acantholytic dermatosis in which direct and indirect immunofluorescence studies are negative, unlike in autoimmune pemphigus. PATIENTS AND METHODS: We describe a case of HHD associated with antidesmoglein antibodies in a 53-year-old woman. The clinical symptoms and histology were typical of HHD. Antidesmoglein antibody tests were positive on several occasions and a difference was found between the two types of Elisa test performed (positive with the MBL kit, negative with the Euroimmun kit). DISCUSSION: The positive result for desmoglein antibodies could be due to unmasking of antigens by the mechanism of acantholysis. The specificity of the main desmoglein Elisa tests also requires discussion.

Non-Desmoglein Antibodies in Patients With Pemphigus Vulgaris.

Pemphigus vulgaris (PV) is a potentially life-threatening mucocutaneous autoimmune blistering disease. Patients develop non-healing erosions and blisters due to cell-cell detachment of keratinocytes (acantholysis), with subsequent suprabasal intraepidermal splitting. Identified almost 30 years ago, desmoglein-3 (Dsg3), a Ca2+-dependent cell adhesion molecule belonging to the cadherin family, has been considered the "primary" autoantigen in PV. Proteomic studies have identified numerous autoantibodies in patients with PV that have known roles in the physiology and cell adhesion of keratinocytes. Antibodies to these autoantibodies include desmocollins 1 and 3, several muscarinic and nicotinic acetylcholine receptor subtypes, mitochondrial proteins, human leukocyte antigen molecules, thyroid peroxidase, and hSPCA1-the Ca2+/Mn2+-ATPase encoded by ATP2C1, which is mutated in Hailey-Hailey disease. Several studies have identified direct pathogenic roles of these proteins, or synergistic roles when combined with Dsg3. We review the role of these direct and indirect mechanisms of non-desmoglein autoantibodies in the pathogenesis of PV.

Immunopathologic demonstration of MAC387+ UCHL1+ cells in bullous skin diseases.

Immunopathologic aspects of bullous skin diseases were studied in paraffin sections of thirty-three skin biopsy specimens utilizing monoclonal antibodies directed against histiocytes, helper/inducer T lymphocytes, and Langerhans cells in skin lesions. Laboratory examinations revealed that either more or fewer of the standard number of helper/inducer T lymphocytes (UCHL1+) were observed in the upper dermis in 84.8% of the cases examined, particularly in the various forms of pemphigus; histiocytes (MAC387+) were also found to occur in the upper dermis in 45.5% of the cases and blisters in 27.3% of the cases, particularly in pemphigus erythematosus and dermatitis herpetifomis. In 54.5% of all the cases, both UCHL1+ and MAC387+ cell infiltrates predominated in the upper dermis. These findings suggest that a cell-mediated immune response may also be important in the pathogenesis of bullous skin diseases. It may be possible that antigen from keratinocytes can produce ETAF, and that IL1 activating T lymphocytes and histiocytes also produce IL1 activating T cells, particularly helper/inducer T cells. Such activities would further promote the increase of B cell function and immunoglobulin synthesis.

Immunohistochemical distribution of CD44 and desmoplakin I & II in Hailey-Hailey's disease and Darier's disease.

The cell-surface glycoprotein CD44 is found on a wide variety of cells including epidermal cells. It is involved in cell to cell adhesion. Desmoplakin I & II are important components of the attachment plaque of desmosomes. In this study, we compared the distribution patterns of anti-CD44 and anti-desmoplakin I & II in Hailey-Hailey's disease and Darier's disease. In the normal skin, anti-CD44 stained the entire periphery of epidermal keratinocytes while anti-desmoplakin I & II produced dotted staining patterns along the periphery of epidermal keratinocytes. In Hailey-Hailey's disease and Darier's disease, the staining pattern of anti-CD44 on acantholized keratinocytes did not change, but anti-desmoplakin I & II lost their peripheral, dotted patterns and stained diffusely in the cytoplasm in most acantholytic cells. These results suggest that, in Hailey-Hailey's disease and Darier's disease, CD44 may be intact even in acantholytic cells but abnormalities of desmoplakin exist in such cells.

[A method of detecting soluble immune complexes in tissue biopsies]. / Sposob vyiavleniia rastvorimykh immunnykh kompleksov v bioptatakh tkanei.

Pretreatment of cryostat slices of tissue biopsy specimens with 30-50% water ethanol mixture increases the rate of detection of immune complexes in the intercellular substance of the epidermis to 100% in patients with acantholytic pemphigus. This method permitted the detection of immune complexes in all the examined cases with benign familial Hailey-Hailey pemphigus, which has never been reported heretofore. The authors believe that 30-50% water-ethanol mixture is capable of soft denaturation of proteins, stabilizes the slightly affine antibody-antigen relations, and aggregates soluble immune complexes into larger protein formations, this preventing their washing out from tissues.

Familial pemphigus vulgaris in mother and daughter.

BACKGROUND: Pemphigus vulgaris is an autoimmune disease in which genetics appears to be of basic importance. Although association with certain human leukocyte antigen (HLA) alleles has been found in some ethnic groups and individuals, no true disease susceptibility genes have been established, and familial cases are very unusual. METHODS: We report a Polish family with pemphigus vulgaris in the mother and daughter. The diagnosis was confirmed by cytologic, histologic, and immunofluorescence studies. RESULTS: The course was severe and the disease long-lasting in the mother, probably due to treatment with small doses of corticosteroids without immunosuppressive drugs. In the daughter, treated with larger doses of corticosteroids and azathioprine, the lesions regressed within 4 months, after which maintenance therapy was instituted with 10 mg of prednisone daily. The HLA studies performed in the daughter and her three children after the mother had died showed identical haplotypes in both the patient and the healthy children. The patient has given birth to a healthy child while still having a high titer of intercellular (IC) antibodies. CONCLUSIONS: The familial occurrence of pemphigus in first-degree relatives is suggestive of inherited susceptibility to the disease, transmitted as a dominant trait. The identical haplotypes in the healthy children of the patient favor the role of other, unknown factors required for the development of the disease in predisposed individuals.

Adhesion molecules and related proteins in Darier's disease and Hailey-Hailey disease.

We have used antibodies to plakoglobin and E-cadherin: the lectins, peanut agglutinin (PNA) and soybean agglutinin (SBA); and sera from patients with the autoimmune diseases pemphigus vulgaris (PV) or pemphigus foliaceus (PF), in an immunohistological study of Darier's disease and Hailey-Hailey disease. There was normal expression of plakoglobin, E-cadherin, lectins and pemphigus antigens at the periphery of keratinocytes in uninvolved skin. Clumps of plakoglobin were detected within acantholytic cells in Hailey-Hailey disease, whereas expression was diffuse in acantholytic cells in Darier's disease. This difference may reflect differences in the pathogenesis of acantholysis. E-cadherin expression was weak or absent at the periphery of some acantholytic cells; lectin binding was sometimes reduced around acantholytic cells, and pemphigus antibodies did not bind to the acantholytic cells involved skin in either disease. Internalization, conformational changes or proteolysis may alter the expression of extracellular epitopes by acantholytic cells.