tretinoin and Pemphigus

The efficient treatment of pemphigus with no certain side effect remained a controversial issue. Although there are various options for controlling disease severity, the majority of them may cause serious side effects. Retinoic acid (RA), an active metabolite converted from vitamin A, plays an active role in immune functions. Effects of RA, especially all-trans-Retinoic Acid (ATRA) on different types of cells involved in immune responses were analyzed in vitro and in vivo. RAs could affect the differentiation of T helper (Th) cells, B cells responses, stabilization of both natural regulatory T cells (nTregs) and regulatory B cells (Bregs) populations, and regulating the expression of critical genes in immune responses. The role of RA, based on major immune cells involved in pemphigus has not been addressed so far. In this study, we sought to determine the possible effects of RA, with a special focus on ATRA in pemphigus. All the evidences of ATRA effects on the immune system were collected and their association with the pemphigus was analyzed. According to the previous results, ATRA causes a decline in Th17 populations; increase in CD4+ induced regulatory T cells (iTregs), stabilization of nTregs, and promotion of suppressive B cells, which are critical in the improvement of pemphigus. Nevertheless, it also causes shifting of the Th1:Th2 balance toward Th2 cells, which is not favorable for pemphigus patients. In conclusion, ATRA acts via different ways in pemphigus. Due to increase in the suppressive function via iTregs, nTregs, and Bregs, it is suggested that patients with pemphigus may benefit from systemic ATRA therapy. To clarify this issue, further studies, such as clinical trials are needed.

Topics: Animals; B-Lymphocytes, Regulatory; Glutamates; Humans; Immunity, Humoral; Immunosuppression Therapy; Pemphigus; T-Lymphocytes, Regulatory; Th1-Th2 Balance; Th17 Cells; Th2 Cells; Tretinoin

Pemphigus herpetiformis is an unusual variant of the pemphigus group, showing acantholytic bulla formation together with marked eosinophilic spongiosis. The clinical picture shows erythematous and pruritic papulovesicular bullous lesions affecting the skin and the oral mucosa. It most closely resembles dermatitis herpetiformis or bullous pemphigoid. In contrast, the presence of acantholysis and of antiepithelial antibodies indicate pemphigus. Three patients, all women, showing this unusual variant of pemphigus, were seen during the last 3 years, a fourth is reported here. One patient responded well to dapsone; the three others did not. Oral treatment with aromatic retinoid (Ro 10-9359) was clearly effective in the last patient, leading to full remission of the skin lesions in a few days. The oral mucosa improved only partly. Discontinuation of the aromatic retinoid treatment and replacement of the drug by placebo was followed by a relapse both of mucosal and skin lesions. Aromatic retinoid possibly inhibits eosinophilic migration into the epidermis and impedes acantholysis associated with this phenomenon.

Topics: Acantholysis; Eosinophilia; Etretinate; Female; Humans; Middle Aged; Pemphigus; Tretinoin

Vitamin A and its derivatives (retinoids) have both profound effects on epidermal differentiation and beneficial therapeutic effects in various dermatologic diseases. In order to understand these effects, much work has been done with cultured keratinocytes, which show specific morphologic, cellular, and biochemical changes modulated by retinoids. In an attempt to further define specific molecular effects of retinoids in cultured human keratinocytes, we studied the expression of pemphigus (P) and pemphigoid (BP) antigens by human keratinocytes cultured with retinoic acid (RA) in concentrations which modulated differentiation. Cultures of human keratinocytes in medium with 10% delipidized fetal bovine serum (vitamin A-depleted medium) demonstrated areas of extensive differentiation with flattened stratifying cells, keratohyaline granules, and an anucleate stratum corneum-like superficial layer. These cells also synthesized a 67 kd keratin, characteristic of well-differentiated epidermis. In contrast, cultures of human keratinocytes in the same medium supplemented with (10(-7) M, 3 X 10(-7) M, or 10(-6) M) RA demonstrated less differentiated small cuboidal cells that were stratified but did not form an anucleate layer or keratohyaline granules, and did not synthesize the 67 kd keratin. In order to detect P and BP antigens in these cultures, we used indirect immunofluorescence. In vitamin A-depleted cultures, P antigen either was not detected or was seen focally on the cell surface of basal cells. BP antigen was seen on the basal pole of the basal cells, approximating its in vivo location. In RA-treated cells, P antigen was seen on the cell surface of most of the cells, and BP antigen was seen throughout the cytoplasm of the basal cells. In order to study the expression of newly synthesized antigens, we radiolabeled cultures with 14C-amino acids and quantitatively immunoprecipitated the antigens, which were then identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis. We detected a major decrease in newly synthesized P antigen precipitated from extracts of vitamin A-depleted cells compared to RA-supplemented cells, whereas amounts of newly synthesized BP antigen were about the same. Taken together these data demonstrate that RA, at concentrations that decrease differentiation of cultured human keratinocytes, increases the expression of P antigen and changes the subcellular location of BP antigen.

Topics: Antigens; Cells, Cultured; Fluorescent Antibody Technique; Humans; Keratins; Pemphigoid, Bullous; Pemphigus; Skin; Skin Diseases, Vesiculobullous; Tretinoin; Vitamin A

Topics: Adult; Female; Humans; Isomerism; Isotretinoin; Pemphigus; Tretinoin

Topics: Etretinate; Humans; Male; Middle Aged; Pemphigus; Tretinoin

Topics: Adolescent; Aged; Anti-Bacterial Agents; Child; Cryosurgery; Darier Disease; Elastic Tissue; Epidermolysis Bullosa; Female; Humans; Impetigo; Larva Migrans; Lichen Planus; Male; Middle Aged; Papilloma; Pemphigus; Skin Diseases; Tongue Neoplasms; Tretinoin