Global burden of skin disease in the elderly: a grand challenge to skin health.

Skin diseases, as estimated in the global burden of disease study 2010, are a significant health problem in all global regions and many of those analyzed in this study show an increasing burden over recent years, extending into old age. Some of the conditions which have the highest impact on the elderly include non-melanoma skin cancer and skin ulceration, but bacterial skin infection, fungal disease or pruritus are all significant problems. With predicted changes in demography and a higher proportion of individuals above the age of 80 in the coming years concentrating new resources on gathering better data and devising preventative, therapeutic and palliative strategies is a priority.

Screening for asymptomatic carriage of Trichophyton tonsurans in household contacts of patients with tinea capitis: results of 209 patients from South London.

BACKGROUND: There is currently an epidemic of tinea capitis in urban areas of developed countries caused by Trichophyton tonsurans. Recurrence or re-infection with dermatophyte is not uncommon after adequate oral treatment. Asymptomatic carriers who are household contacts may partly explain this observation by forming a reservoir for infection. PATIENTS/METHODS: Two-hundred and nine household contacts of patients with tinea capitis were examined and screened for asymptomatic carriage of dermatophyte. RESULTS: Only 7.2% had clinically evident disease yet 44.5% had silent fungal carriage on the scalp. Children under 16 years were much more likely to be carriers than adults (P < 0.001) and males were less likely than females to be affected (P < 0.01). CONCLUSION: This evidence poses questions about factors relevant in transmission of dermatophytes. The authors propose that all household contacts of patients with tinea capitis should be offered screening to eradicate a potential reservoir of infection.

A novel case of linear syringomatous hamartoma.

A 4-year-old girl presented with a linear, indurated area of dusky erythema and hyperpigmentation down the left leg, present since birth. Histology suggested syringomata. The clinical course and appearances suggest a novel entity for which we have coined the term 'linear syringomatous hamartoma'.

Trends in the presentation of cutaneous malignant melanoma over three decades at King's College Hospital, London.

The aim of this study was to examine trends in the presentation of cutaneous malignant melanoma at King's College Hospital (KCH) over the last three decades (1970-2000). KCH was one of seven centres that participated in the 1987 Cancer Research Campaign (CRC) publicity campaign aimed at promoting earlier self-recognition of melanoma. Data included patient age at presentation, sex, tumour site, Breslow thickness and histological subtype. The late 1980s saw a threefold increase in the annual number of melanomas and an eightfold increase in thin melanomas compared to the 1970s. The increase occurred in both sexes and was particularly marked after the CRC campaign but numbers had already begun to increase prior to this. The increase has predominantly been thin (Breslow < 1.5 mm) tumours of the superficial spreading variety with a resultant fall in mean Breslow thickness. There has been a decline in the annual number of melanomas since the peak in 1992 which is not explained by increased proportion of in situ tumours. The CRC campaign may have contributed to the documented increase in thin tumours but this trend had begun prior to 1987 suggesting factors other than public awareness and earlier presentation are important. It is encouraging that the number of melanomas has declined over the last 5 years at KCH but it is yet to be seen whether this reflects a real decrease in the incidence of melanoma.

Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency.

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.

Cutaneous Rosai-Dorfman disease.

We report a patient with purely cutaneous Rosai-Dorfman disease (RDD) who presented with a solitary, asymptomatic plaque on the back of her left thigh, with characteristic, large histiocytoid cells exhibiting emperipolesis histologically. Cutaneous lesions occur in 27% of patients with lymph node involvement in RDD however purely cutaneous disease has only been reported on 18 previous occasions. The aetiology is unknown, although it is though to be a reactive disorder rather than neoplastic, possibly an immunological response to an infectious agent.

Serum S-100 protein: a potentially useful prognostic marker in cutaneous melanoma.

S-100, an acidic calcium-binding protein, is present within cells of neuroendocrine origin. Its value in the immunohistochemical diagnosis of tumours of melanocytic origin is well established. More recently, a potential role has been proposed for the serum concentration of this protein as a marker of metastatic melanoma disease activity. In the present study, the concentration of serum S-100 protein was measured in 97 patients with histologically proven malignant melanoma who were attending a dermatology and/or oncology department for the follow-up of their disease. Serum S-100 was also measured in 48 control subjects without malignant melanoma. The clinical stage of the patients was classified according to the criteria of the American Joint Committee on Cancer into stages I-IV. The median (range) serum S-100 protein concentration was significantly higher in stage I (0.11 (0.1-0.21) microgram/L, P < 0.001), stage II (0.11 (0.05-0.22) microgram/L, P < 0.001), stage III (0.24 (0.07-0.41) microgram/L, P < 0.0001) and stage IV (0.39 (0.06-15.0) microgram/L, P < 0.0001) compared with the control group (0.1 (0.05-0.15) microgram/L). At a threshold value of 0.2 microgram/L, the sensitivity and specificity for detection of advanced disease were 82% and 91%, respectively. Thus serum S-100 protein may be a valuable prognostic marker for malignant melanoma and for monitoring therapy. Serum S-100 protein concentration was also compared with the Breslow thickness of the tumours. There was a significant correlation between these variables (n = 72, rs = 0.32, P < 0.01). Combining a serum S-100 threshold value of > 0.22 microgram/L and a Breslow thickness of > 4 mm improved the sensitivity and specificity for the presence of secondary spread to 91% and 95%, respectively. Therefore, a combination of both baseline serum S-100 protein and Breslow thickness may provide a better indication of the prognosis at diagnosis.

Expression of E-cadherin in human epidermal non-melanoma cutaneous tumours.

E-cadherin is a calcium-sensitive, cell-to-cell, adhesion molecule that is expressed widely in normal human epithelial tissue. Abnormal expression has been described in colorectal, breast and nasopharyngeal squamous cell carcinomas, where loss of E-cadherin is associated with an increased metastatic potential. We have examined, by standard immunohistochemical techniques using the monoclonal antibody HECD-1 (E-cadherin monoclonal antibody), the distribution of E-cadherin in normal human skin and in non-melanoma neoplastic lesions. In the normal epidermis, E-cadherin was strongly expressed on the surface of keratinocytes and specialized epithelial structures. Staining was absent from the lower pole of basal keratinocytes in contact with the basement membrane. Weak cytoplasmic staining was also noted in basal keratinocytes. No reactivity was demonstrated in dermal structures. The assessment of cutaneous tumours demonstrated an altered pattern of staining in most cases. Cell surface expression was reduced in 28 of 30 cases of basal cell carcinomas (BCC). Twenty showed an additional feature of positive staining on the dermal aspect of peripheral cells of tumour lobules. In squamous cell carcinomas (SCC) (n = 16), surface expression was attenuated in eight and absent in a further four. Strong surface expression, similar to normal skin was seen in all examples of Bowen's disease (n = 6), viral wart (n = 3), seborrhoeic keratosis (n = 3) and actinic keratosis (n = 4). This study demonstrates that, in BCC and SCC, but not in premalignant lesions, cell-surface expression of E-cadherin is reduced, consistent with the observation that the loss of E-cadherin is associated with tumour invasion.

Confluent and reticulate papillomatosis of Gougerot and Carteaud clearing with minocycline.

Confluent and reticulate papillomatosis is a rare disorder producing sharply circumscribed hyperpigmented ichthyosiform scaling lesions in a seborrhoeic distribution. Its exact aetiology is unknown and its response to therapy is poor. This case is unusual in responding to minocycline having failed with the more conventional approaches.

Prevalence of von Recklinghausen neurofibromatosis in Dunedin, New Zealand.

A point prevalence study of von Recklinghausen neurofibromatosis (NF-1) was undertaken in greater Dunedin, New Zealand, having a base population of 113,700. A total of 52 individuals with NF-1 were identified, for a crude prevalence estimate of 45.7 per 100,000 (95% confidence interval 31.6-59.8 per 100,000) or 1 in 2,190 and an age-standardized prevalence of 48.5 per 100,000 (95% confidence interval 34.7-62.4 per 100,000) or 1 in 2,062. This is the highest prevalence estimate reported to date. This is presumed most likely to be due to a small population effect. The prevalence of NF correlated with age, being greatest among those aged 20-29 years and relatively low among those 60 or more years of age.