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OBJECTIVE: To evaluate the effect of all-trans retinoic acid (ATRA) as treatment for chemotherapy-induced peripheral neuropathy in an experimental animal model and in a randomized, double-blinded, controlled trial in patients with non-small-cell lung cancer (NSCLC). METHODS: Forty male Wistar rats were randomized in 5 groups: group A, control; groups B and C, treated with cisplatin; and groups D and E, treated with paclitaxel. ATRA (20 mg/kg PO) was administered for 15 days in groups C and E. We evaluated neuropathy and nerve regeneration-related morphologic changes in sciatic nerve, the concentration of nerve growth factor (NGF), and retinoic acid receptor (RAR)-α and RAR-ß expression. In addition, 95 patients with NSCLC under chemotherapy treatment were randomized to either ATRA (20 mg/m(2)/d) or placebo. Serum NGF, neurophysiologic tests, and clinical neurotoxicity were assessed. RESULTS: The experimental animals developed neuropathy and axonal degeneration, associated with decreased NGF levels in peripheral nerves. Treatment with ATRA reversed sensorial changes and nerve morphology; this was associated with increased NGF levels and RAR-ß expression. Patients treated with chemotherapy had clinical neuropathy and axonal loss assessed by neurophysiology, which was related to decreased NGF levels. ATRA reduced axonal degeneration demonstrated by nerve conduction velocity and clinical manifestations of neuropathy grades ≥2. CONCLUSIONS: ATRA reduced chemotherapy-induced experimental neuropathy, increased NGF levels, and induced RAR-ß expression in nerve. In patients, reduction of NGF in serum was associated with the severity of neuropathy; ATRA treatment reduced the electrophysiologic alterations. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that ATRA improves nerve conduction in patients with chemotherapy-induced peripheral neuropathy.

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BACKGROUND: In 1952, a Brazilian dermatologist, Oswaldo Costa, described a dermatosis characterized by accentuation of the cutaneous folds on the knuckles of both hands and small horny papules on the thenar eminences, posterior surface of the wrists, and the interdigital space between thumb and index finger; he called this entity acrokeratoelastoidosis. Other similar entities, such as focal acral hyperkeratosis and marginal keratoelastoidosis, have been described. The features of the different types of lenticular acral keratosis are discussed. MATERIALS AND METHODS: Fifteen patients with lenticular acral keratosis and five controls were studied clinically and pathologically. The skin biopsies were processed for light and transmission electron microscopy. The clinical data were reviewed, and the following variables were recorded: age, sex, distribution and morphology of the lesions, history of exposure to sunlight and objective evidence of photodamage, familial incidence, occupation and hobbies, time of evolution, and response to previous treatments. The results were compared with samples taken at autopsy from five women without dermatoses. RESULTS: All patients were women, with flat, keratotic papules located on the transition between the dorsal and volar surfaces of the fingers and hands. Histologically, there was an increased amount of elastic fibers, which were coarse and tortuous, and appeared to be interrupted in some areas. In contrast, there were sparse, thin fibers in the mid and deep dermis in the skin of controls. Transmission electron microscopy of these papules showed enlarged, thickened elastic fibers, with deposits of electron-dense, coarse clumps. CONCLUSIONS: Our cases do not seem to correspond to any of the three entities which are manifested clinically by acral keratotic plaques. All of these women washed clothes by hand on a stone washboard for many hours every day. As there is no clinical or histologic evidence of actinic damage, chronic trauma seems to be the cause of the dermatosis in this type of patient. We propose the term "occupational lenticular acral keratosis" for our cases.

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To study peripheral nerves changes in chronic alcoholism and in malnutrition, we examined ultrastructurally the distal nerve branches of the digits of rats treated with four different dietary schemes, as follows: controls (n = 22), fed standard rodent diet plus water ad libitum; alcoholism (n = 12), fed the standard diet and 2-12% ethanol in drinking water; malnutrition (n = 21), fed with corn tortillas instead of standard diet; and alcoholism and malnutrition combined (n = 22). After 10 months under these conditions, a proportion of animals from each group were sacrificed. The remaining rats of the malnutrition and alcoholism alone groups were deferred a standard diet. The combined alcohol + malnutrition group was subdivided into standard diet, malnutrition and ethanol. After a further 4 months under these new conditions, the animals were sacrificed. Ultrastructural examination of limb distal nerve branches showed that glycogen-like particles were more common in malnourished animals, whereas remyelinating axons were more numerous in ethanol-treated rats. Bands of regeneration were present in both groups, but were more common in animals treated with ethanol. These features decreased significantly when the respective nutritional factor was reversed. The results confirm that ethanol plays a definitive role in the development of alcoholic neuropathy and that malnutrition accentuates, the histopathological abnormalities.

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