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Notes: Background. Cutaneous necrotizing venulitis (CNV) is a clinical disorder associated with segmental inflammation and fibrinoid necrosis of the dermal venules. It usually presents clinically as palpable purpura, even sometimes as nodules, bullae, ulcers, and urticarial lesions. This form, when showing as leukocytoclastic vasculitis is apparently characterized by the tissue deposition of circulating immune complexes and by reduced cutaneous (cfa) and plasma (pfa) fibrinolytic activity due to reduced release of plasminogen activator (PA) from the venular endotheliocytes. Reduced cfa and pfa cause large amounts of fibrin deposits in both intra- and perivascular areas, which are able to magnify and self perpetuate the inflammatory processes following immune complex deposition. Methods. We have studied both the pfa and cfa potential (the maximum amount of PA released in the skin after certain stimuli) and the deposits of immunoglobulins, C3, and fibrin related antigen, before and after intradermal injection of histamine (a substance able to provoke endothelial release of PA), in three subjects affected by CNV before and 20 days after 10 mg/kg/day I.M. treatment with the fibrinolytic agent mesoglycan. Results. Cutaneous fibrinolytic activity and cfa potential, reduced prior to treatment, was normal after treatment, while the deposits of immunoglobulins (IgA, IgG and IgM), C3, and fibrin related antigen, detected with direct immune fluorescence (dif) showed similar findings before and after treatment. Conclusions. These data suggest that reduced cfa may play a major role in the pathogenesis of the immunologically mediated injury in cnv. The intraperivascular deposition of fibrin is favored. The fibrinolytic agent mesoglycan seems effective in restoring defective fibrinolysis in patients affected by cutaneous necrotizing venulitis, suggesting that in cases with reduced cutaneous fibrinolitic activity (or potential) the use of a fibrinolytic agent should be considered.

Notes: During a 4 year period, we observed three patients, aged 74, 47, and 55, with an average 12-year history of chronic itching and prickling skin discomfort. The dorsal and paimar surface of the hands and feet were involved without observable cutaneous lesions. We followed the patients for 1.5 years in our department. None of the subjects was dermographic, had personal or family history of atopy, or took drugs. The symptoms were not related to the degree of skin dryness, serum IgE levels, exercise, neoplasias, or high environmental temperature and low humidity caused by central heating or seasonal variations. No neurologic alterations were observed in a complete neurologic examination. Emotional upset did not induce symptoms. Upon psychiatric evaluation, the patients showed no alterations in their personality profile. Water exposure did not modify the symptoms. The wheals and pruritus induced by the intradermal injection of 1:10,000 histamine phosphate did not differ from those in three controls1 Immersion of one hand and foot for 5 days per week for 2 weeks in water at different temperatures (0–45°C) for varying lengths of time and the administration of one minimum erythemal dose of ultraviolet light (280–340 nm) to the controlateral part of the body three times per week for 3 weeks both failed to reduce the severity of the discomfort. Biopsy specimens were taken from the symptomatic skin of the three subjects and from three controls. The specimens were routinely stained with hematoxylineosin for mast cells, elastic fibers, and glycosaminoglycans. There were no significant differences between the two groups. Cutaneous fibrinolytic activity, which is due to the release of cutaneous plasminogen activators, was similar in both groups.2 Direct immuno-fluorescence staining (dif) for neuropeptides substance P (sp) (Fig. 1), vasointestinal polypeptide (vip), and calcitonin gene related peptide (CGRP) showed an increased number of pep-tidergic fibers in affected skin. After 2 weeks of three times daily application of 0.25% capsaicin in cold cream (8-methyl-N- vanillyl-6-nonenamide, known to interfere with the storage and release of neuropeptides), the symptoms disappeared completely, and neuropetidergic fibers were no longer de-tectable in the skin, as shown by dif.The application of cold cream alone on the contralateral part of the body did not modify DIF or the clinical symptoms. After suspension of capsaicin treatment, a relative to absolute refractory period of 10 to 18 days was observed, and the symptoms reappeared. Previous treatments with systemic Hi (with and without H2) antihistamines, antide-pressants, hypnotics, and topical corticosteroid prepara-tions did not achieve significant results. The increased number of neuropeptidergic fibers in the affected acral skin, the dramatic action of capsaicin in reducing the storage of neuropeptides in the same cutaneous fibers, and the com-plete disappearance of the clinical symptoms suggest that the cases reported here represent a distinct clinical entity, which could be called or described as neuropeptidergic acral dysesthesia.

Notes: Abstract Originally described as a product of the pituitary gland, propiomelanocortin (POMC) has recently been identified in other tissues, such as in human skin, where it may accumulate in response to various stimuli. Thus far, epidermal keratinocytes, as well as melanocytes and macrophages, have been shown to express POMC. This study investigated the expression of POMC mRNA in cultured dermal fibroblasts derived from either normal skin or keloids. Using Northern blot hybridization with a POMC cDNA generated by RT-PCR of mRNA isolated from cardiac muscle, we demonstrated that dermal fibroblasts express POMC, as significant levels of mRNA were detected in unstimulated cells in culture. POMC transcript steady-state levels were strongly reduced by transforming growth factor-β (TGF-β). whereas tumor necrosis factor-α (TNF-α) counteracted the effect of TGF-β and exerted a stimulatory activity on POMC mRNA levels. Reduction of POMC transcript levels by TGF-β was also observed in cultured keratinocytes. Clearly detectable levels of POMC mRNA were detected in cultured keloid-derived fibroblasts; however, little, if any, regulation by TGF-β was observed. These data represent the first demonstration of POMC expression by fibroblasts and down-regulation by TGF-β. Furthermore, our results indicate altered TGF-β regulation of POMC gene expression in keloid-derived fibroblasts suggesting that POMC may play a role in the pathogenesis of keloid formation.