Role of physical factors in the pathogenesis of bullous pemphigoid: Case report series and a comprehensive review of the published work.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease affecting mainly the elderly. The subtype of the disease induced by physical agents represents a rare and, therefore, insufficiently characterized form. In the present study, we aimed to contribute to a better understanding of the pathogenetic mechanisms involved in the onset of BP induced by different trigger factors. We have retrospectively analyzed nine cases of BP. All patients were characterized based on clinical, epidemiological and immunological parameters. For each case, the trigger factor involved was specified. In addition to our retrospective analysis, a comprehensive review of the 59 published cases was conducted, regarding the involvement of trigger factor in BP, and clinical, epidemiological and immunological data were collected. In the local study, conducted on nine patients diagnosed with BP, various trigger factors were identified: contrast substance injection, surgical procedure, mechanical trauma, insect bite, thermal burn, radiotherapy and ultraviolet exposure associated with pre-existing psoriasis. The autoantibodies from all patients were shown to activate granulocytes and induce dermal-epidermal split. Different hypotheses regarding the pathogenetic mechanism involving the trigger factors have been discussed. In regard of the pathogenetic mechanism, we believe that the most reliable hypothesis is that BP patients already have low titers of anti-basement membrane autoantibodies which activate the granulocytes. However, more studies are needed for a better understanding of the pathogenetic mechanism of the intervention of trigger factors.

Photodamaging effects of porphyrins and chitosan on primary human keratinocytes and carcinoma cell cultures.

BACKGROUND: Photodynamic therapy (PDT) is a non-surgical method for treating non-melanoma skin cancer and precancerous lesions which involves the activation of a photosensitizer by visible light to produce activated oxygen species within target cells, resulting in the destruction of the latter. The present study evaluates the effect of PDT on primary normal and basal cell carcinoma cultures in vitro. METHODS: Primary human keratinocytes and carcinoma cell cultures were exposed to various concentrations of 5,10,15,20-tetra-(para-methoxyphenyl) porphyrin (TMP) and its zinc compound (Zn-TMP) for 24 hours, with or without chitosan, and then irradiated using a PDT lamp (630 nm, 6 J/cm(2)). The effects of PDT were assessed using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay and an immunocytochemical method with Annexin V-FITC for detecting apoptosis. RESULTS: Both tested substances, TMP and Zn-TMP, had a phototoxic effect on primary human carcinoma cell cultures in concentrations of 1-100 µg/ml, which positively correlated with the concentration of the photosensitizer. There was no phototoxic effect on primary keratinocytes, probably because of the preferential accumulation of photosensitizing substances in tumoral cells. Administration of chitosan in association with photosensitizing substances increased cell viability compared with photosensitizers alone, exerting a cytoprotective effect. CONCLUSIONS: The study demonstrates that the photodynamic activity of TMP and its metalloporphyrin derivative is limited to primary human carcinoma cells and suggests that these porphyrins could be efficiently used in PDT in vivo.

Pemphigus vulgaris is the most common autoimmune bullous disease in Northwestern Romania.

BACKGROUND: Autoimmune bullous diseases are organ-specific diseases characterized by autoreactive T and B cells specific for structural proteins of the skin. The incidence and prevalence of autoimmune blistering diseases vary in different countries and their epidemiology has not yet been addressed in Romania. METHODS: In this study between 2001 and 2007, we prospectively investigated a total of 116 patients with autoimmune blistering diseases from the Northwestern region of Romania. The diagnosis was based on the clinical, histo- and immunohistological as well as serological findings. RESULTS: Pemphigus was the most common disease representing 58.6% of the case (68 cases); 40 cases (34.5%) were diagnosed with bullous pemphigoid (BP) and eight cases (6.9%) with other autoimmune sub-epidermal diseases. The incidence and prevalence of pemphigus diseases were four patients/1,000,000 inhabitants/year and 0.00248%, respectively. BP occurred in 2.5/1,000,000 inhabitants/year and its prevalence was 0.00146%. While the average onset age for pemphigus vulgaris was 53 years, BP patients were first diagnosed at a mean age of 73.6 years. CONCLUSION: The genetic background of the local population may explain why pemphigus occurs more commonly than BP in Northwestern Romania compared with the population of Western Europe. In addition, the shorter life expectancy in Romania (71.3 years) compared with Western Europe (>80 years) may contribute to this phenomenon.