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Sarcoidosis is a systemic granulomatous disease characterized by the presence of non-caseating granulomas. Its etiology remains obscure. A plausible hypothesis suggests that a complex interplay of host factors, infectious processes, and non-infectious environmental factors, matched with a susceptible genetic background, results in a pathway that leads to systemic granulomatous inflammation. Although presentations of sarcoidosis vary enormously, multi-organ involvement is a common feature. Cutaneous involvement occurs in about 25% of patients with protean manifestations and variable prognoses. Skin manifestations are divided into specific lesions with histopathologically evident non-caseating granulomas and nonspecific lesions arising from a reactive process that does not form granulomas. A peculiar form of cutaneous sarcoidosis is represented by sarcoidal lesions at sites of trauma that has caused scarring. The pathogenesis of scar sarcoidosis remains unknown. Scar sarcoidosis is also associated with herpes zoster infection, surgery, and tattooing. Such heterogeneous events, along with those at the sites of chronic lymphedema, thermal burns, radiation dermatitis, and vaccinations, occur on areas of vulnerable skin labeled "immunocompromised districts". Numerous options are available for the treatment of cutaneous sarcoidosis. Although corticosteroids remain the treatment of choice for initial systemic therapy, other nonsteroidal agents have proven effective and therefore useful for long-term management. Tumor necrosis factor-α antagonists such as infliximab may have a role in the treatment of cutaneous sarcoidosis, especially in refractory cases that are resistant to standard regimens. Elucidation of the relationship of sarcoidal granulomas with malignancy and immunity may facilitate a better understanding of some pathomechanisms operating in neoplastic and immunity-related disorders.

Background There have been reports suggesting the involvement of environmental factors in the disease process of pemphigus. Factors suggested include exposure to pesticides or certain drugs. Objective To analyze the association of pemphigus with environmental exposure to various agents, including smoking, recreational and occupational insults, drugs, and food. Design and setting In-person interviews of pemphigus patients and control subjects were conducted by trained medical investigators using a structured questionnaire. Questions included occupational, behavioral, medical, and qualitative food frequency details. The multicenter study was conducted at outpatient services of teaching hospitals in Bulgaria, Brazil, India, Israel, Italy, Spain, and the USA. Participants A total of 126 pemphigus patients (55 men, 71 women; age, 54 ± 17 years) and 173 healthy controls (87 men, 86 women; age 50 ± 19 years) were interviewed in the period between October 1, 1999 and March 31, 2000. The diagnosis of pemphigus was based on clinical, histologic, immunohistologic, and immunohistochemical criteria. The disease duration was 2–27 years (8.4 ± 7.2 years). Individuals with skin diseases other than pemphigus were selected as control subjects. Main outcome measure Information on drugs, foods, and occupational, environmental, constitutional, and other possible risk factors was analyzed by t-tests and chi-squared tests as applicable. A multivariate logistic regression model was applied to the data to study simultaneously the independent relationship between each risk factor and pemphigus vulgaris. Results The risk for pemphigus vulgaris was lower for ex-smokers and current smokers than for patients who had never smoked. Exposure to pesticides and occupational exposure to metal vapor were associated with an increased risk of pemphigus. Pemphigus patients had more pregnancies than controls. There were differences in environmental factors between countries, with exposure to gardening materials and pesticides being highest among patients from Bulgaria, followed by Israel. Disease characteristics also exhibited differences between countries. Bulgarian patients less frequently had oral mucous membrane lesions: 66% compared to 92% for Israeli patients and 83% for Italians. The distribution of the disease in skin and mucous membranes was similar among patients from all countries. Exclusive skin involvement was seen in 50% of patients, mucous membranes alone in 23% of patients, and both skin and mucous membranes in 27% of patients. Conclusions The beneficial effect of smoking on pemphigus might be explained by its effect on the immune system. In addition, smoking has an antiestrogenic effect, while pesticides have an estrogenic effect. The lower numbers of smokers among patients, the higher exposure rates to pesticides, and the higher number of female patients who had been pregnant may point to the contribution of estrogens to the disease process. It remains to be determined whether measures, such as avoiding exposure to pesticides or metal vapor, may be beneficial in the clinical context. As the present study was a survey, more definitive studies should be conducted to validate the results.

Background Exogenous factors, such as certain drugs, may be involved in the induction of pemphigus. Other offenders sharing a similar chemical composition to these drugs may also play a role. Tannins with their considerable biologic activity were suggested as possible factors. To substantiate the role of tannins in the pathomechanism of pemphigus, the present study examined the acantholytic potential of tannins in vitro. Methods Normal human breast skin from patients without any bullous disease was cultured for 3 days in the presence of tannic acid at concentrations of 0.02, 0.05, 0.1, 0.25, 0.5, 1.0, and 2.0 m m. The effect of the tannic acid was microscopically examined in a blind fashion by three independent investigators. Results In addition to the cytotoxic effect, tannic acid caused marked acantholytic changes, with a clear suprabasal cleavage and intraepidermal acantholytic cells. The acantholytic changes were the most constant and specific effects. They were constantly observed at 1.0 and 2.0 m m, whereas lower concentrations showed changes only in some of the explants. The concentrations needed to exert this effect were notably low. There was a remarkable variability among the subjects who had provided the explants. Conclusions The results suggest a possible role of tannin in the disease process of pemphigus. The tannin acantholytic potential was much greater than the potential of known acantholytic drugs, such as penicillamine and captopril. The interindividual variability in susceptibility to acantholysis may explain the variability in the individual potential for developing pemphigus.

Background A variety of drugs have been implicated in the onset and exacerbation of pemphigus and bullous pemphigoid. The demonstration of biochemical acantholysis in skin explants to various drugs in the absence of autoantibodies, in which the tested drugs evoke a biochemical reaction that leads to desmosomal function loss, may be a valuable adjunct to patient management by confirming the suspicion of drug-related pemphigus or bullous pemphigoid. Objective To determine whether a skin explant model might serve as a possible in vitro correlate of drug-induced pemphigus and pemphigoid-like effects related to the calcium channel blocker nifedipine. Methods Normal human breast skin obtained from nonpemphigus and nonpemphigoid patients undergoing mastectomy was cultured with nifedipine at final concentrations of 2, 4, and 8 mm. The drug effect on skin explants evidenced by morphologic changes was evaluated by microscopy by three observers. Results Five out of seven explants cultured with nifedipine at concentrations ranging from 2 to 8 mm exhibited obvious morphologic changes of two types: intraepithelial (or pemphigus-type) splittings and subepithelial (or pemphigoid-type) splittings. Two explants showed no acantholysis and no subepithelial splittings. Control cultures without polyethylene glycol 200 (PEG) showed no changes. Skin control samples cultured in medium supplemented with 10% PEG displayed vacuolar degeneration throughout the entire epidermis, but no sign of cell–cell dyshesion or dermo-epidermal detachment. Conclusions A type of skin susceptibility to nifedipine may be genetically determined, with some nifedipine-treated patients developing an acantholytic reaction and others a subepidermal bullous eruption.

The occurrence of a new skin disorder exactly at the site of another one, already healed and unrelated, was first described in 1955. In 1985, Wolf et al. recognized that we are dealing with a dermatologic phenomenon and established a precise definition for this phenomenon. Fifty-eight cases corresponding to the definition of this phenomenon have been reported until now.The new phenomenon, for which the term "isotopic response" has been suggested, has been defined. Cases corresponding to the definition have been analyzed with special emphasis on the diseases involved, the time intervals, and the locations of the diseases. Eight new cases are described.A total of 58 cases of isotopic response have been described. The first disease in most of the patients was herpes zoster; in three cases it was herpes simplex, in two varicella, and in one, thrombophlebitis. The second disease, which appeared exactly at the site of the first, already healed disease, was in most reported cases a carcinoma (26 cases, in particular 15 cases of breast carcinoma, 5 basal cell carcinomas (BCC), 4 squamous cell carcinomas (SCC), 2 basosquamous carcinomas), or granuloma annulare (16 cases). Additional diseases were Kaposi's sarcoma (2 cases), pseudolymphoma (2 cases), sarcoid (2 cases), tinea (2 cases), tuberculoid and vasculitis granuloma (1 case), angiosarcoma, metastasis, Bowen's disease, lymphoma, leukemia cutis, and acne (1 case each). The diseases did not show any predilection for a particular location. The interval between the first and second disease was extremely variable (ranging from days to years) and showed no particular features. In the eight additional cases described in the present report, the first disease was herpes simplex (6 cases) or herpes zoster (2 cases). The second disease was viral warts (3 cases) or squamous cell carcinoma (2 cases). Additional diseases were furunculosis, contact dermatitis, and molluscum contagiosum (1 case each).The new term, "isotopic response," describes the occurrence of a new skin disorder at the site of another, unrelated, and already healed skin disease. It is suggested that the term "isotopic response" be included in the lexicon (glossary) of dermatology. Introducing the new term and classifying all the cases under a single key word, will make it possible to locate and collect them easily and to search for the mechanism underlying this phenomenon.