BACKGROUND: Patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy frequently display cutaneous alterations such as acquired ichthyosis. OBJECTIVES: Elucidation of the pattern of acquired ichthyosis in HTLV-I-associated myelopathy. METHODS: Skin fragments from 10 patients with HTLV-I-associated myelopathy presenting with acquired ichthyosis were assessed by histopathological and immunohistochemical tests. We used anticytokeratin antibodies related to normal keratinization (K1/K10), and others related to cutaneous conditions such as activation, migration and hyperproliferation of keratinocytes (K6/K16), and involucrin, a precursor protein in the formation of the protein envelope in keratinocytes. For quantification of the proliferating basal and parabasal cells the anti-Ki-67 antibody was employed. RESULTS: On light microscopy, all skin specimens displayed orthokeratotic hyperkeratosis and hypogranulosis. Three of them presented focal parakeratosis. A slight to moderate perivascular infiltrate of mononuclear lymphocytes was observed in seven cases, three of which showed discrete spongiosis with epidermotropism of lymphocytes. All fragments displayed coexpression of K1, K10 and K16 in the suprabasal layers. Expression of involucrin was also observed in all cases, in the upper spinous and granular layers. Focal expression of K6 was observed in three cases, under a parakeratotic area. The mean number of Ki-67+ basal and parabasal cells was 3.5 cells per mm, similar to that in control skin. CONCLUSIONS: In acquired ichthyosis related to HTLV-I-associated myelopathy, histopathology revealed orthokeratotic hyperkeratosis and a perivascular inflammatory infiltrate of mononuclear lymphocytes, with areas of parakeratosis and foci of epidermotropism in rare cases. The expression profiles of K1, K10 and involucrin were similar to those in normal skin. The diffuse coexpression of K16 with K1 and K10 throughout the analysed epidermis, as well as the occurrence of restricted areas of parakeratosis expressing K6, indicate the presence of keratinocyte activation with induction of the alternative keratinization pathway, probably dependent on the cytokines liberated by the mononuclear cells of the dermal inflammatory infiltrate infected with HTLV-I. The absence of acanthosis and of increased cellular kinetics, as shown by the low rate of Ki-67 antigen expression, allow the inference that the pattern of acquired ichthyosis related to HTLV-I-associated myelopathy may be retentional. The observation of foci of parakeratosis expressing K6 in three specimens suggests that, at least in certain areas and in some cases, interference with epidermal differentiation and maturation occurs.
BACKGROUND:Patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy frequently display cutaneous alterations such as acquired ichthyosis. OBJECTIVES: Elucidation of the pattern of acquired ichthyosis in HTLV-I-associated myelopathy. METHODS: Skin fragments from 10 patients with HTLV-I-associated myelopathy presenting with acquired ichthyosis were assessed by histopathological and immunohistochemical tests. We used anticytokeratin antibodies related to normal keratinization (K1/K10), and others related to cutaneous conditions such as activation, migration and hyperproliferation of keratinocytes (K6/K16), and involucrin, a precursor protein in the formation of the protein envelope in keratinocytes. For quantification of the proliferating basal and parabasal cells the anti-Ki-67 antibody was employed. RESULTS: On light microscopy, all skin specimens displayed orthokeratotic hyperkeratosis and hypogranulosis. Three of them presented focal parakeratosis. A slight to moderate perivascular infiltrate of mononuclear lymphocytes was observed in seven cases, three of which showed discrete spongiosis with epidermotropism of lymphocytes. All fragments displayed coexpression of K1, K10 and K16 in the suprabasal layers. Expression of involucrin was also observed in all cases, in the upper spinous and granular layers. Focal expression of K6 was observed in three cases, under a parakeratotic area. The mean number of Ki-67+ basal and parabasal cells was 3.5 cells per mm, similar to that in control skin. CONCLUSIONS: In acquired ichthyosis related to HTLV-I-associated myelopathy, histopathology revealed orthokeratotic hyperkeratosis and a perivascular inflammatory infiltrate of mononuclear lymphocytes, with areas of parakeratosis and foci of epidermotropism in rare cases. The expression profiles of K1, K10 and involucrin were similar to those in normal skin. The diffuse coexpression of K16 with K1 and K10 throughout the analysed epidermis, as well as the occurrence of restricted areas of parakeratosis expressing K6, indicate the presence of keratinocyte activation with induction of the alternative keratinization pathway, probably dependent on the cytokines liberated by the mononuclear cells of the dermal inflammatory infiltrate infected with HTLV-I. The absence of acanthosis and of increased cellular kinetics, as shown by the low rate of Ki-67 antigen expression, allow the inference that the pattern of acquired ichthyosis related to HTLV-I-associated myelopathy may be retentional. The observation of foci of parakeratosis expressing K6 in three specimens suggests that, at least in certain areas and in some cases, interference with epidermal differentiation and maturation occurs.
Authors: Denise Utsch Gonçalves; Fernando Augusto Proietti; João Gabriel Ramos Ribas; Marcelo Grossi Araújo; Sônia Regina Pinheiro; Antônio Carlos Guedes; Anna Bárbara F Carneiro-Proietti Journal: Clin Microbiol Rev Date: 2010-07 Impact factor: 26.132