Recent rapid advances in basic reseach for various autoimmune bullous dermatoses have provided us with many insights into their pathomechanisms. In particular, a recently developed enzyme-linked immunosorbent assay (ELISA) for desmogleins 1 and 3 (Dsg1 and Dsg3), the antigens for pemphigus foliaceus (PF) and pemphigus vulgaris (PV), respectively, has provided great progress in the diagnosis and classification of pemphigus, as well as in the understanding of its pathomechanisms. The study of the anti-Dsg1 and Dsg3 antibodies indicated that there are two different types of PV; i.e., the mucosal dominant type and the mucocutaneous type. In addition, the desmoglein compensation theory, which has been proposed by Dr. Stanley and Dr. Amagai, can reasonably explain the different depths of skin lesions and the different occurrences of skin and oral mucosal lesions between PV and PF. In bullous pemphigoid (BP), the NC16a domain of BP180 has been shown to play an important role in blister formation, while the role of the other BP antigen, BP230, is not clear. Mucous membrane pemphigoid (MMP) is heterogeneous, and several distinct proteins have been shown as candidates. Most MMP cases react with BP180, particularly with its C-terminal domain. A lesser number of MMP cases react with laminin 5. Because the patients react with BP180 and laminin 5 can not be distinguished clinically, the epitopes in BP180 and laminin 5 are considered to be present at similar sites. Various autoimmune bullous diseases, including several types of pemphigus and pemphigoid, are the only diseases, in which the pathogenic roles of circulating autoantibodies have been confirmed by newborn mouse animal models. Therefore, such studies on the pathophysiology of pemphigus and pemphigoid should be extremely important as paradigms for the research into various types of autoimmune diseases in other fields.
Recent investigations from several laboratories, including our own, have demonstrated that the skin has the capacity to produce corticotropin-releasing factor (CRF) and proopiomelanocortin (POMC) peptides and that it can express the corresponding receptors (CRF-R and MC-R). Ultraviolet (UV) irradiation and administration of proinflammatory cytokines have been reported to increase the expression of the genes for CRF and POMC in cultured keratinocytes and melanocytes. UV irradiation of the whole body is also known to increase the level of circulating POMC peptides in the blood. In addition, administration of CRF has been found to promote production of POMC peptides and corticosteroids simultaneously in cultured melanocytes and fibroblasts. Based on these observations, it has been postulated that a system equivalent to the hypothalamicpituitary-adrenal axis might operate locally in the skin as a coordinator and executor of peripheral responses to stress. We found that systemic stress (foot shock stress and psychological stress) aggravated contact dermatitis in rat skin, prolonged the telogen stage, and delayed the subsequent anagen induction in the murine hair cycle. It is noteworthy that these effects were mediated by the actions of CRF in the skin. Therefore we propose that the skin contributes to maintaining homeostasis of the living body through its own stress response system and that CRF is a key factor of modifying cutaneous function under systemic stress conditions.
For the treatment of metastatic melanoma, chemotherapy and immunotherapy are commonly used, but the long term prognosis is generally unfavorable, because of the low sensitivity of tumor cells to such therapies. However, 18 patients with lung metastases from cutaneous malignant melanoma who were surgically treated in our institute experienced generally favorable outcomes. We report the details of these 18 cases and discuss the most appropriate therapy. Between 1984 and 2003, 18 patients underwent surgery for lung metastases from cutaneous malignant melanoma. Their clinical features were examined and compared with those in patients with only lung metastases who did not undergo surgery. The median disease-free interval of patients with surgical treatment was longer than that of patients without surgical treatment. Patients with lung metastases only, less than 4 metastatic foci and disease free intervals of more than 12 months after initial treatment were found to be good candidates for surgical treatment for lung metastases, even though metastatic foci were found in both lungs. Watchful waiting for the evaluation of tumor growth for 3 months is another option when deciding on the employment of surgical treatment for lung metastases.
A 38-year-old male presented with edematous macules, papules and target lesions over the whole body and pharyngeal pain. A toxic eruption was suspected, but treatment with oral administration of corticosteroids and antibiotics was unsuccessful. Ten days later, the lesions developed into erythemas with thick scales. Histological examination showed mounds of parakeratosis with neutrophils and dilated blood vessels at the tips of the dermal papillae, compatible with early psoriasis. At this point, a diagnosis of guttate psoriasis was made. Therefore, oral PUVA therapy was started, and the skin lesions disappeared 2 months later. The edematous erytemas at the beginning of the disease suggested an initial psoriatic eruption.
There are no detailed clinical practice guidelines for neck dissection of skin cancers located in the head and neck. Here we report our cases and examine how and which lymph node groups should be dissected. From January of 1984 to December of 2003, we performed neck dissections or sentinel node biopsies of 24 cases with head and neck malignant melanoma. We ordinarily perform selective neck dissection, except in advanced cases. We describe the levels or sublevels removed according to the location of the primary lesion. Our choices of operation and regions of dissection are considered to be appropriate at present, but future revisions and reevaluations are expected as cases accumulate. The next problem will be to determine the range of operation and adaptation, depending on the kind of skin cancer and degree of progression.