Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients

Colors in atypical nevi: a computer description reproducing clinical assessment

Background/purpose: Atypical nevi (AN) share some dermoscopic features with early melanoma (MM), and computer elaboration of digital images could represent a useful support to diagnosis to assess automatically colors in AN, and to compare the data with those referring to clearly benign nevi (BN) and MMs. Methods: An image analysis program enabling the numerical description of color areas in melanocytic lesions was used on 459 videomicroscopic images, referring to 76 AN, 288 clearly BN and 95 MMs. Results: Black, white and blue-gray were more frequently found in AN than in clearly BN, but less frequently than in MMs. Color area values significantly differed between the three groups. Conclusion: The clinical-morphological interpretation of the numerical data, based on the mathematical description of the aspect and distribution of different color areas in different lesion types may contribute to the characterization of AN and their distinction from MMs