NEUROPEPTIDERGIC ACRAL DYSESTHESIA: A NEW ENTITY
Authors: LOTTI TORELLO , TSAMPAU DIONIGI , TEOFOLI PATRIZIA , BENCI MAURIZIO , GHERSETICH ILARIA , DAHM MICHAEL , CAPPUGI PIETRO , PANCONESI EMILIANO 
Published: May 2007

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.