A novel 105-kDa lamina lucida autoantigen: association with bullous pemphigoid.

Several cases have been reported of patients with immunemediated subepidermal blistering disorders whose autoantibodies react to antigens present on both the dermal and epidermal side of 1 M NaCl-split skin. In this report, we identify, localize, and characterize the basement membrane zone antigen corresponding to the dermal staining in a patient whose serum stains both the dermal and epidermal side of 1 M NaCl-split skin. This patient's serum contains autoantibodies directed against a 105-kilodalton(kDa) dermal antigen and the 230-kDa epidermal (bullous pemphigoid) antigen. This novel 105-kDa protein was previously identified as the sole antigen in another patient with a unique bullous disease whose autoantibodies were directed against only the dermal side of 1 M NaCl-split skin. This 105-kDa antigen was identical by one- and two-dimensional immunoblot analysis in these two patients. By immunoblot analysis, autoantibodies from our patient labeled a 105-kDa protein within various extracts of human skin basement membrane. Immunoblot analyses using epitope-selected autoantibodies directed against the 105-kDa protein demonstrated that this antigen is independent and distinct from other known basement membrane antigens. The 105-kDa antigen is an extracellular matrix component of the basement membrane, which is synthesized and secreted by both keratinocytes and fibroblasts. Identical electrophoretic migration of cellular and secreted forms of the protein suggested there is no major post-translational modification of the protein. Immunomapping of normal human skin fractured through the dermal-epidermal junction by incubation in 1 M NaCl or by suction blistering demonstrated that the location of the 105-kDa antigen within the basement membrane zone is between the bullous pemphigoid antigens and two other lamina lucida components, laminin and nicein. These data demonstrate clearly that a subepidermal autoimmune bullous disease may have autoantibodies directed against two distinct components of the dermal-epidermal junction.

Hepatonecrosis resulting from parenteral gold therapy in pemphigus vulgaris.

A patient who had pemphigus vulgaris received therapy with gold thiomalate in addition to dexamethasone. Three weeks after the initiation of parenteral gold the patient developed acute hepatitis. Causes other than gold toxicity were ruled out, and the patient recovered completely after discontinuation of gold therapy. This is the first case of acute hepatonecrosis resulting from gold therapy of pemphigus to be reported in the dermatologic literature.

Pruritic urticarial papules and plaques of pregnancy and its relationship to maternal-fetal weight gain and twin pregnancy.

Thirty women who were seen at our institution between 1984 and 1988 for pruritic urticarial papules and plaques of pregnancy (PUPPP) were retrospectively evaluated and interviewed. We found a significantly increased maternal weight gain and newborn birth weight in patients with PUPPP, compared with age and parity-matched controls. The average weight gain during pregnancy was 18.1 +/- 0.9 (SEM) kg for the patients with PUPPP (excluding twin gestations) and 14.6 +/- 1.0 kg for the controls. The mean newborn birth weight was 3.6 +/- 0.09 kg for the PUPPP group and 3.3 +/- 0.08 kg for the control group. There were three twin pregnancies (10%), compared with the twin gestation rate at our institution of 1.6%. Therefore, based on our findings of an increased maternal weight gain and neonatal birth weight, an increased twin rate, and an abdominal eruption that occurs in primigravidas in their third trimester of pregnancy, we suggest that abdominal distention or a reaction to it may play a role in the development of PUPPP.

Transplacentally transferred dermatoses.

Transplacentally transferred dermatoses (TTDs) are cutaneous diseases that are transmitted from mother to fetus through the placental circulation. The uniqueness of the maternal-placental-fetal interaction provides many helpful opportunities to enhance our understanding of the pathogenesis and course of these diseases.

Treatment of mucocutaneous herpes simplex infections with acyclovir.

Topical acyclovir speeds healing and decreases viral shedding and pain in immunocompromised patients with chronic, ulcerative herpetic lesions; it may be used when one does not wish to add another systemic drug. In severe first-episode and life-threatening infections, acyclovir may be administered intravenously for 7 to 10 days. In milder and non-life-threatening first-episode infections, acyclovir may be given orally in a dosage of 200 mg five times a day for 10 days. With these doses, healing is 50% faster and viral shedding stops 90% sooner. Acyclovir given early during first-episode infections, especially true primary infections, may decrease immune responses to the virus, but these usually become normal later. Fewer than six recurrences a year may be managed by 200 mg acyclovir orally five times a day for 5 days beginning as soon as symptoms appear. More than six recurrences a year, often every month, may be managed by continuous suppressive oral acyclovir therapy. Kaposi's varicelliform eruption responds to acyclovir given orally or intravenously depending on circumstances. Primary and recurrent herpetic whitlow respond to acyclovir.

Pulling boat hands: a unique dermatosis from coastal New England.

We report a previously unrecognized hand dermatosis, pulling boat hands (PBH), occurring in thirteen participants at the Outward Bound School on Hurricane Island, Maine. Painful and pruritic macules, plaques, and vesicles developed exclusively while subjects lived aboard a pulling boat, the school's open rowing/sailing craft. Nine of those affected were women and eight had Raynaud's phenomenon or vasospasm. These subjects experienced thirty episodes of PBH during May through October, 1978 to 1982. Histopathology revealed a superficial and deep lymphohistiocytic perivascular infiltrate, subepidermal blister formation, red blood cell extravasation, and dermal capillary thrombosis compatible with cold injury to the skin. All patients experienced prolonged percussion to their hands while rowing as well as a continuous environmental exposure to cold air, wind, humidity, ocean spume, and precipitation. These clinical, histopathologic, and environmental findings suggest a unique syndrome that combines the vascular effects of mechanical trauma from rowing with those of nonfreezing cold injury.

Hirsutism: evaluation and treatment.

Hirsutism, a troublesome cosmetic problem, may also be a sign of serious systemic disease that can be screened for by means of the patient's history, physical examination, and certain basic blood tests. Most patients with functional hirsutism have elevated production rates of testosterone, elevated metabolic clearance rates of testosterone, depressed levels of sex hormone-binding globulin, and elevated levels of serum-free testosterone and hair follicle sensitivity. Once a neoplastic source is ruled out and hirsutism established as functional, essentially empiric treatment, including low-dose dexamethasone, oral contraceptives, and spironolactone, has proved to be effective.

Multicentric reticulohistiocytosis and cancer: a case report and review of the literature.

Multicentric reticulohistiocytosis (MR) is a syndrome characterized by papulonodular skin lesions, a debilitating polyarthritis, and characteristic histologic findings. It is a rare disorder with only 82 cases reported. Twenty-eight percent had an associated neoplasm. Hematologic malignancies (four) and neoplasms arising from the breast (four), cervix (three), stomach (three), ovary (two), colon (two), lung (one), pleura (one), and from an unknown source (two) were all seen associated with MR. Eleven cases (including our own) were available for review. The papulonodular skin involvement was the initial manifestation (alone or concurrent with the polyarthritis) in 90% of our cases. The diagnosis of MR preceded that of the associated neoplasm in 73% of the cases. A case report is presented illustrating the relapse of MR before the clinical relapse of the associated tumor, and the response of both the tumor and MR to combination chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone when prednisone and aspirin alone failed to relieve the symptoms of MR. Steroids were not beneficial in the patients reviewed. The best management of MR associated with a neoplasm is the best management of the primary neoplasm. Cytotoxic chemotherapy including cyclophosphamide should be considered if there is progression of the MR in order to control the symptoms of MR and prevent a progressive debilitating arthritis.

Local immune response in basal cell carcinoma: characterization by transmission electron microscopy and monoclonal anti-T6 antibody.

We examined lesional and perilesional skin from nine basal cell carcinomas occurring in six patients to determine the role of local immunity in the pathogenesis of these neoplasms. Marked hyperplasia of Langerhans cells and indeterminate cells as defined by monoclonal anti-T6 antibody was observed in lesional and perilesional skin of most specimens. Ultrastructurally, Langerhans cells were observed in the dermis and above the basement membrane zone where mitotic activity was documented. Apposition of Langerhans cells and indeterminate cells with degenerating and necrotic neoplastic keratinocytes and with exocytotic lymphocytes was frequently encountered. Zonal necrosis of carcinoma cells was often immediately peripheral to exocytotic lymphoid cells. These observations support the contention that an active local immunologic response is related to the biologic behavior of some basal cell carcinomas.

The Nikolsky sign.

The well known Nikolsky sign has long been associated with clinical diagnosis of the pemphigus group of diseases. The literature has been reviewed on the origin and application of this physical sign, and its clinical usefulness is assessed herein. A wide variety of dermatologic disease states associated with this sign was found as well as sigificant disparity about the definition of a positive sign. Little documentation was found to substantiate these large variations.

6-Thioguanine resistant peripheral blood lymphocytes in humans following psoralen, long-wave ultraviolet light (PUVA) therapy.

A recently described method that enumerates variant 6-thioguanine resistant peripheral blood lymphocytes present in vivo in man as a potential marker of somatic cell mutations occurring in vivo was used to study 18 psoriatic patients receiving PUVA therapy, 16 conventinally treated psoriatic patients, 10 vitiligo patients receiving PUVA therapy and 7 untreated individuals with vitiligo. Variant lymphocyte frequencies determined for these individuals were compared with those determined for groups of 10 concurrent and 63 cumulative healthy control individuals. Variant frequencies were elevated in psoriatic and vitiligo patients receiving PUVA therapy and in conventionally-treated psoriatic patients. They were not elevated over control values in untreated vitiligo patients.