DNA damage in human skin fibroblasts from patients with dermatitis herpetiformis.

Dermatitis herpetiformis (DH) and celiac disease (CD) are considered to be autoimmune diseases that share a specific trigger (gluten) and a common genetic background (HLA-DQ2/DQ8). However, the pathogenesis of DH is not yet fully understood and no data are available regarding a possible role of fibroblasts in this disease. The aim of this study was to assess baseline DNA damage in fibroblasts in DH-diagnosed patients vs. fibroblasts of controls without DH or CD. Primary fibroblast cultures were derived from dermal biopsies from DH patients and controls (without DH or CD). In vitro genotoxic damage was investigated using the comet assay and ɣH2AX test after different treatments (with 33mer peptide and digested gliadin [DG]) in order to investigate a correlation between oxidative stress (evaluated by reactive oxygen species formation) and glutathione content. Our results demonstrate a difference in baseline DNA damage between cutaneous fibroblasts of controls and DH patients, moreover, DNA damage significantly increased after exposure to gluten (DG and 33mer peptide) in fibroblasts from DH patients. DNA damage in fibroblasts from patients under dapsone treatment was similar to that of the control group. Our data indicate that oxidative stress and DNA damage may be characteristics of fibroblasts from DH patients who are not treated with dapsone, particularly after exposure to gliadin peptides.

Efficacy and Safety of Intralesional Methotrexate in the Treatment of a Large Keratoacanthoma of the Dorsal Hand in a 99-Year-Old Woman.

Several case reports and retrospective studies have demonstrated that intralesional methotrexate (MTX) could be a very effective and safe alternative treatment of keratoacanthoma (KA). Here, we report a rapid clinical efficacy of two intralesional MTX injections (total dose 40 mg) that were performed 1 week apart in the treatment of a large KA lesion of the dorsal hand in a 99-year-old woman. The lesion, with a 3-cm major axis diameter and a thickness of 2 cm with a central ulceration had rapidly appeared on the right dorsal hand. A 3-mm punch biopsy confirmed the diagnosis of a well-differentiated KA-type spinous cellular carcinoma. Due to the presence of comorbidities (arterial hypertension and atrial fibrillation) and chronic treatment with antihypertensive and oral anticoagulant drugs, treatment with intralesional MTX was proposed to the patient. Two intralesional MTX injections of 20 mg each were performed 1 week apart. A very fast resolution of the lesion was observed after the first injection. A week after the second injection a full resolution of the skin lesion was observed, with a nearly complete resolution of the central ulceration. The treatment was very well tolerated. No local or systemic side effects were observed. This case report confirms that intralesional MTX could be considered an effective and safe treatment of KA also in very old subjects.

Uncaria tomentosa.

Uncaria tomentosa (U. tomentosa) or uña de gato, a species of vine of Rubiaceae family, was used from centuries in various medical conditions. Although there are no randomized controlled trials or published human outcome studies, some conditions reportedly improved by U. tomentosa include osteoarthritis, rheumatoid arthritis, prostatitis, viral illnesses and cancer (acting as a non-specific immunomodulantign agent) and it may also have potential as an immunomodulating adaptogen in cellular aging. The understanding of some specific mechanisms of molecular action leads to the demonstration of various anti-inflammatory, immunostimulating and protective effects. These results bring the strong hypothesis that U. tomentosa could be effective in the topical treatment of dermatological manifestation, namely rosacea.