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Abstract Summary Hepatitis C virus is positive-strand RNA virus and can replicate inside the liver, transmitted by apparent and inapparent parenteral procedures representing a frequent cause of liver disease worldwide. HCV exists as a multiple genotypes and is hyperendemic in Egypt. HCV infection causes acute symptoms in 15% of cases and not associated with jaundice. chronic infection develops in 85% of cases. Both acute and chronic HCV infection may affect the hepatic and extrahepatic tissues. There are a number of diagnostic tests for hepatitis C including: HCV antibody enzyme immunoassay or ELISA, recombinant immunoblot assay and quantitative HCV RNA polymerase chain reaction (PCR). HCV RNA can be detected by PCR typically one to two weeks after infection. 40-80% of HCV can clear with INF therapy and antiviral medications, no vaccine protects against HCV infection. Numerous extrahepatic disorders have been recognized in association with HCV infection among which dermatological disease occupy a central part. NAE was first described in 1996 by El-Darouti and Abou El Ela, it was presented as a cutaneous marker for HCV infection. NAE was initially classified as one of the necrolytic erythemas, a group which includes acrodermatitis enteropathica (associated most commonly with zinc deficiency), necrolytic migratory erythema (associated most commonly with glucoagonoma syndrome), pellagra (associated most commonly with niacin deficiency) and others. A lot of clinical and histologic similarities exist between these disease entities. Clinically, NAE is categorized into 3 phases; initial stage with a scaly erythematous papule or plaque with a deep red to violaceous center and a surrounding erythematous macule, fully developed stage with erythematous to violaceous lichenified plaques having sharply defined margins surmounted by adherent scales with finely mammillated surface in less scaly areas and occasional crusts over sites of necrosis, and late stage with progressively thinner lesions and increased hyperpigmentation. The distribution of the lesions is exclusively acral and the dorsal of the feet are the predominant site in all patients. Electron microscopic examination of lesional skin biopsy from necrolytic acral erythema shows no viral particles but only clumped tonofilaments. Most reported NAE cases are HCV positive as proven by ELISA and PCR. Liver enzymes are elevated in all cases. However, there are few cases reported with negative hepatitis C-virus infection. Several pathogenic mechanisms for NAE were postulated. NAE appears to be an immune mediated response in chronic HCV patients, associated with, lower C3 and C4 (complements C3 and C4), and higher frequency of positive ASMA (antismooth muscle antibody). Another postulated theory is low serum zinc levels. Lipopolysaccaride (LPS), a major signal transduction protein that accumulates in hepatic patients because of failure to detoxify, elevates in the plasma of HCV patients compared to controls. LPS significantly increases the cytokines beta interferon (IFN-ß) and interleukin-6 (IL-6) secretion from B cells. So, LPSstimulated hypozincemia is mediated, at least partly, by a cytokine-directed internal redistribution of zinc. The aim of this work is to assess the presence of HCV RNA in skin biopsy of Necrolytic acral erythema lesion since no other studies were done for this aim except for ElSummary 102 Ghandour et al. (2005) which was done on 5 patients only. To achieve this goal, 42 patients divided into two groups were recruited. The first group included 21 patients suffering from NAE and hepatitis C virus infection, and the other group included 21 HCV patients without any cutaneous manifestations. All patients and controls were subjected to full history taking, general and dermatological examination, and assessment of serum: Alanine amino transferase (ALT), Aspartate amino transferase (AST), total (Bilirubin) and alkaline phosphatase (ALK phos), skin biopsy taking and evaluation of the presence of HCV RNA in these biopsies by RT- PCR. No statistically significant difference was found between NAE and control group regarding age, sex, smoking, presence of HBV, ascites, bilharziasis, DM and regarding elevated liver enzymes. All patients in the NAE and control groups showed negative results regarding the detection of HCV RNA in the skin biopsies by PCR. In conclusion, although HCV may play a role in pathogenesis and development of cutaneous NAE, this is probably not through direct proliferation in NAE lesion. Further larger scale studies are needed for detection of HCV RNA by PCR in skin, with biopsies frozen as soon as possible to avoid destruction of the virus. Other investigations for the mechanism of association between HCV and NAE are warranted. |