Hydroxyurea is an antimetabolite agent used in the treatment of myeloproliferative disorders and sickle cell anaemia. Although hydroxyurea is relatively well tolerated, adverse effects often involve skin and mucous membrane during long-term therapy. A group of 510 patients affected by chronic myeloid leukaemia from 1977 to 1998 has been considered. Only 158 patients were treated with hydroxyurea and fulfilled inclusion/exclusion criteria of this study. A spectrum of severe cutaneous and mucosal changes (inflammatory and neoplastic) was seen in about 13% of patients (21 patients out of 158) and was studied in detail. Cutaneous and mucosal atrophy were observed in all 21 patients. Skin atrophy was often characterized by numerous telangiectases, especially on legs and on sun-exposed sites (16/21). Cutaneous, mucosal and nail hyperpigmentation was evident, albeit with variable extent, in 10 of the 21 patients. Severe stomatitis and glossitis with flattening of papillae were another common finding. Five patients, who received a particularly long treatment with hydroxyurea, developed squamous-cell neoplasms on sun-exposed sites (both squamous-cell carcinomas and keratoacanthomas). Acral changes were characteristic and constant, including acral erythema (21/21), dermatomyositis-like changes on the dorsa of hands (7/21), ulcers localized on acral areas of legs, on genitalia and oral mucosae (20/21). The frequency and the variety of these muco-cutaneous changes are reported and the mechanisms by which hydroxyurea may induce this muco-cutaneous syndrome-like group of changes, are proposed.

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Background: Most immunogenetic studies restrict the location of the susceptibility gene for psoriasis to the HLA-C locus. Objective: The present study evaluates the amino acid sequences of the HLA-C binding groove associated with the disease in a restricted population of Italian descent: Pavia, Northern Italy. Method: Forty patients, affected by psoriasis, underwent genomic analysis of exons 2 and 3 of the HLA-C gene by means of the PCR-SSP technique. Results: The HLA-C*0602 gene frequency was significantly higher in patients with respect to 122 sex-, age- and ethnically matched controls (25 vs. 8.6%, χ² = 14.65, p = 0.000129). This frequency rose to 39.5% in patients with a family history positive for psoriasis. In particular, 4 amino acid substitutions were shown to be crucial for the predisposition to the disease, namely Ala 73 and Asn 77 (located in the C pocket of the antigen binding groove), Lys 80 in the F pocket and Asp 90 in the outer loop of the molecule. This peculiar motif, entirely located in the α₁-domain of the HLA-C molecule, was characteristic of psoriatic patients being present in 77.5% of the cases against the 50.82% of controls (χ² = 8.77; p = 0.0031). Homozygosity for the amino acids considered at these residues was found in 15% of patients and in 0% of controls (χ² = 20.74, p = 0.0000053). Conclusion: The most important results emerging from this study indicate that Ala 73, Asn 77, Lys 80 and Asp 90 together form a motif restricted to few pathogenic peptides to be studied in the near future.