Keratitis-ichthyosis-deafness syndrome, atypical connexin GJB2 genemutation, and peripheral T-cell lymphoma: more than a random association?

Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital disorder characterized by a variety of skin lesions— that is, palmoplantar keratoderma, thickening of the skin, and erythematous verrucous lesions—neurosensorial hypoacusia, and keratitis with a variable degree of visual impairment. Both sporadic and familial forms of the syndrome have been described, the latter usually showing a dominant pattern of inheritance. The molecular lesion responsible for the syndrome typically involves the connexin 26 (Cx26) gene (GJB2). Most patients display the heterozygous c.148G→A mutation causing the substitution of an aspartic acid for an asparagine at position 50 (p.Asp50Asn), while a few of them show the c.50C→T mutation, implying the substitution of a serine for a phenylalanine at position 17 (p.Ser17Phe). However, even a mutation in the connexin 30 (Cx30) gene (GJB6) has been found in a typical KID patient, thus suggesting a genetic heterogeneity of the syndrome. As connexins are a large family of small integral membrane proteins which influence tissue cornification by modulating the establishment of direct cell-cell communication through gap junction channels, it is likely that defects involving this class of proteins are at the basis of the wellknown increased incidence of squamous cell carcinoma in KID patients

Classical Kaposi's sarcoma in north-east Sardinia: an overview from 1977 to 1991.

The incidence of classical Kaposi's sarcoma in 1977-91 was studied in north-east Sardinia. In this period, 160 new cases were observed in a defined area, of which 124 were in males. This represented a standardised incidence of the disease of 1.58/100,000 inhabitants per year (2.43 for males and 0.77 for females). This is the highest incidence of classical Kaposi's sarcoma so far recorded. The incidence increased with age, particularly after the age of 70 in males

Bullous lesions at polyethylene glycol interferon-alpha-2a inoculation site in a hepatitis C virus-infected subject.

Sir, The recent introduction of polyethylene glycol interferon (PEG-IFN) for treatment of hepatitis C virus (HCV) has led to reports of both widespread and localized dermatological manifestations as side-effects. Widespread manifestations comprise hair loss, pruritus, generalized eczema, hyperpigmentation tongue, vitiligo and cutaneous sarcoidosis (1–4). Localized manifestations include cutaneous ulcerations and cutaneous local necrosis at the inoculation site, with both non-pegylated IFN (5) and PEG-IFN-α-2b (6, 7). We report here a case of bullous lesion at the inoculation site of PEG-IFN-α-2a in a patient with chronic HCV-correlated hepatopathy

High prevalence of antibodies to human herpesvirus 8 in relatives of patients with classic Kaposi's sarcoma from Sardinia

A survey for antibodies to a recombinant small viral capsid antigen (sVCA) of human herpesvirus type 8 (HHV‐8) was conducted in Sardinia, one of the world's highest incidence areas for classic Kaposi's sarcoma (KS). Prevalence of antibodies to HHV‐8 sVCA was greatest in patients with KS (95%), followed by family members (39%) and a Sardinian control population age‐ and sex‐matched to the relatives (11%). Within families, prevalence of antibodies was about equal among spouses, children, and siblings of KS patients, a finding that raises the possibilities of intrafamilial person‐to‐person or vertical transmission. Antibodies were detected 2–3 times more frequently in males than in females. The data show that prevalence of antibodies to HHV‐8 sVCA correlates with the distribution of classic KS in a high‐ incidence area. Clustering of seroprevalence within some families suggests the presence of familial risk factors for active HHV‐8 infection

cutaneous mycobacterium chelonae infection in a presumably immunocompetent host

8. Parslew R, Lewis-Jones MS. Localized unilateral hyper13. Mayou SC, Black MM, Russell Jones R. Sudoriferous hamartoma. Clin Exp Dermatol 1988; 13: 107–108. hidrosis secondary to an eccrine naevus. Clin Exp 14. Pippione M, Depaoli MA, Sartoris S. Naevus eccrine. Dermatol 1997; 22: 246–247. Dermatologica 1976; 152: 40–46. 9. Martius I. Lokalisierte ekkrine schweibdrusennavus mit 15. Hong CE, Lee SH. Multiple eccrine nevus with depressed hyperfunktion. Dermatol Wochenschr 1954; 130: 1016. patches. Yosei Med J 1997; 38: 60–62. 10. Chan P, Kao GF, Pierson DL, Rodman OG. Episodic 16. Kopera D, Soyer HP, Kerl H. Human eccrine hamartoma hyperhidrosis on the dorsum of hands. J Am Acad of forearm-antebrachial organ of the ringtailed Lemur Dermatol 1985; 12: 937–942. ( lemur catta). A posssible phylogenetic relationship? Am 11. Bingel G, Ertle T. Naevus sudoriferus. Z Hautch 1985; J Dermatopathol 1994; 16: 275–279. 60: 372. 17. Nightingale KJ, Newman P, Davies MG. A function12. Van de Kerkhof PJCM, Den Arend JAJC, Bousema MT, ing hamartoma associated with Down's syndrome Strolz E. Localized unilateral hyperhidrosis. Br J Dermatol (46,xx,–21,+ t(21q21q). Clin Exp Dermatol 1998; 23: 264–266. 1987; 177: 779–782

Environmental factors influence the rate of human herpesvirus type 8 infection in a population with high incidence of classic Kaposi sarcoma

High prevalence of human herpesvirus type 8 (HHV-8) infection has been reported on the island of Sardinia. Among emigrants from Sardinia, rates of HHV-8 infection are lower than they are in Sardinia and are similar to those observed in the local population. Thus, environmental factors seem to play a relevant role in affecting the prevalence of HHV-8 infection

skin reaction in antiviral therapy for chronic hepatitis c a role for polyethylene glycol interferon

In the past decade, different modalities of antiviral therapy have been adopted aimed at eradicating hepatitis C virus infection. Initially, interferon was used in monotherapy, then interferon combined with ribavirin and amantadine. Recently, interferon has been conjugated with polyethylene glycol to allow optimization of its pharmacokinetic properties and to improve its antiviral activity. This study focused on the characteristics of the skin reactions that we observed in 27 patients with naive hepatitis C who received polyethylene glycol interferon-ribavirin-amantadine or polyethylene glycol interferon-ribavirin and in 10 previous non-responders to interferon monotherapy who were retreated with triple therapy. In 9 patients (7 on triple therapy) dermatitis-like lesions were observed, and in 5 the severity of the lesions necessitated withdrawal from therapy

Merkel cell carcinoma: a population-based study on mortality and the association with other cancers

Few population-based epidemiological data are available on Merkel cell carcinoma (MCC), a rare lethal non-melanoma skin cancer. We analysed multiple-cause-of-death records to describe MCC mortality and trends and the association with other primary cancers. We reviewed all 6,713,059 death certificates in Italy (1995-2006) to identify those mentioning MCC. We evaluated the association with other primary cancers by calculating the ratio of observed to expected deaths, using a standardized mortality ratio (SMR)-like analysis. We also evaluated the geographic distribution of deaths. We identified 351 death certificates with the mention of MCC. The age-adjusted mortality was 0.031/100,000, with a significant trend of increase and a slight north-south gradient. There was a significant deficit for solid cancers (SMR = 0.15) and a non-significant excess for lymphohematopoietic malignancies (SMR = 1.62). There were significant excesses for chronic lymphocytic leukemia (SMR = 4.07) and Waldenstrom's macroglobulinemia (SMR = 27.2) and a non-significant excess for chronic myeloid leukemia (SMR = 5.12). The increase in MCC mortality reflects the incidence trend in the literature. The association with chronic lymphocytic leukemia confirms the importance of immunologic factors in MCC. Regarding Waldenstrom's macroglobulinemia, an association with MCC has never been reported

Incidence of Human Herpesvirus 8 (HHV-8) infection among HIV-uninfected individuals at high risk for sexually transmitted infections

<p>Abstract</p> <p>Background</p> <p>The occurrence of, and risk factors for, HHV-8 infection have yet to be definitively determined, particularly among heterosexual individuals with at-risk behavior for sexually transmitted infections (STI). The objective of this study was to estimate the incidence and determinants of HHV-8 infection among HIV-uninfected individuals repeatedly attending an urban STI clinic.</p> <p>Methods</p> <p>Sera from consecutive HIV-uninfected individuals repeatedly tested for HIV-1 antibodies were additionally tested for HHV-8 antibodies using an immunofluorescence assay. To identify determinants of HHV-8 infection, a nested case-control study and multivariate logistic regression analysis were performed.</p> <p>Results</p> <p>Sera from 456 HIV-uninfected individuals (224 multiple-partner heterosexuals and 232 men who have sex with men (MSM]) were identified for inclusion in the study. The HHV-8 seroprevalence at enrollment was 9.4% (21/224; 95% C.I.: 6.0–14.2%) among heterosexuals with multiple partners and 22.0% (51/232; 95% C.I.: 16.9–28.0%) among MSM. Among the 203 multiple-partner heterosexuals and 181 MSM who were initially HHV-8-negative, 17 (IR = 3.0/100 p-y, 95% C.I.: 1.9 – 4.8) and 21 (IR = 3.3/100 p-y, 95% C.I:.2.1 – 5.1) seroconversions occurred, respectively. HHV-8 seroconversion tended to be associated with a high number of sexual partners during the follow-up among MSM (> 10 partners: AOR = 3.32 95% CI:0.89–12.46) and among the multiple-partner heterosexuals (> 10 partner; AOR = 3.46, 95% CI:0.42–28.2). Moreover, among MSM, HHV-8 seroconversion tended to be associated with STI (AOR = 1.80 95%CI: 0.52–7.96).</p> <p>During the study period the HIV-1 incidence was lower than that of HHV-8 among both groups (0.89/100 p-y among MSM and 0.95/100 p-y among multiple-partner heterosexuals).</p> <p>Conclusion</p> <p>The large difference between the incidence of HHV-8 and the incidence of HIV-1 and other STIs may suggest that the circulation of HHV-8 is sustained by practices other than classical at-risk sexual behavior.</p