Is slow nail growth a risk factor for onychomycosis?

This study was carried out to determine whether slow nail growth is a predisposing factor for onychomycosis or if onychomycosis results in slow nail growth. Forty-nine patients with unilateral onychomycosis of the great toenail were enrolled and classified in two groups according to the size of affected area, i.e. more than half or less than half of the toenail. The growth rates of affected and unaffected great toenails of all patients were measured. Before a normal appearance was reached, the growth rates of affected great toenails, when the affected area occupied more than half of total nail plate, was slower than that of the unaffected great toenails. After a normal appearance was achieved, there were no differences in growth rates between affected and unaffected great toenails. Therefore, this study of patients with unilateral toenail onychomycosis did not support the hypothesis that slow nail growth rate is a predisposing factor for onychomycosis.     

Is first trimester exposure to the combination of antiretroviral therapy and folate antagonists a risk factor for congenital abnormalities?

OBJECTIVES: To assess use of antiretroviral therapy (ART) by HIV positive pregnant women in London since 1994 and the risk of congenital abnormalities associated with multidrug exposure during the first trimester of pregnancy. METHODS: Retrospective multicentre study of medical, obstetric, and paediatric notes of all mother-infant pairs, where the mother was known to be HIV infected before delivery, using a standardised proforma. RESULTS: In this study of 195 mother-infant pairs, use of ART during any stage of pregnancy increased from 33.3% in 1994 to 92.5% in 1999 (p=0.01, trend). First trimester exposure increased from 0% in 1994 to 27.5% in 1999 (p=0.00045, trend). Congenital malformations were observed in nine infants (4.6%). Compared with infants not exposed to ART or folate antagonists during the first trimester (n=148), exposure to both ART and folate antagonists during the first trimester (n=13) was associated with an increased risk of congenital abnormalities (4% v 23.1%; OR 7.10, 95% CI 1.5, 34.2). No malformations were observed in the 34 children exposed to either ART or folate antagonists alone during the first trimester. CONCLUSION: An increasing number of HIV infected women conceived while on ART. Although there is no evidence of teratogenicity caused by ART if given alone during the first trimester, exposure to the combination of ART and folate antagonists was associated with a significantly higher risk of congenital abnormalities in this cohort.     

Is primary melanoma ulceration a factor of good response to adoptive immunotherapy?

Background Primary melanoma ulceration is a factor of poor prognosis at the local and regional stage. The physiopathological mechanisms which explain its prognostic impact are still little known. However, two recent studies suggest that it could be a predictive factor of good response to a non‐specific immunotherapy (interferon‐alpha) and to an active immunotherapy (vaccine). Objective The aim of this study was to determine whether ulceration could be a factor of good prognosis in the context of an adoptive immunotherapy with tumour infiltrating lymphocytes (TIL) in stage III regional lymph node metastatic melanoma (sixth American Joint Committee on Cancer staging system) and whether it was associated with an improvement in the effectiveness of this treatment compared with the control group. Methods We have included all the patients treated in open prospective randomized TIL vs. control protocols in our unit from 1997 to 2009. Clinical data were derived retrospectively from patient files. Statistical analysis was performed using log‐rank tests, Cox models and tests for interaction. Results A total of 144 patients were included. In the group of 80 patients treated with TIL, primary melanoma ulceration remained a pejorative factor for relapse‐free and overall survival in univariate and multivariate analysis. The presence of ulceration did not change the effectiveness of TIL treatment in comparison with the control group with regards to relapse‐free and overall survival. Conclusion Our study demonstrates that primary melanoma ulceration does not have any impact on the response to TIL adoptive immunotherapy and thus does not confirm its positive prognostic value suggested by two other immunotherapy approaches.     

Should we consider hypohidrotic ectodermal dysplasia as a possible risk factor for malignant melanoma?

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a rare multisystem disorder that typically affects hair, teeth, nails, and sweat glands in combination with abnormalities of ectodermal originated tissues. OBJECTIVE: To raise the issue of whether heightened awareness is required in the follow-up of pigmented lesions in patients with HED. METHODS/RESULTS: Two patients with HED are reported. The first had a history of two malignant melanomas, whereas the second presented with a novel malignant melanoma. CONCLUSION: Although a prospective epidemiologic study to determine the incidence of malignant melanoma in patients with HED is virtually impossible and the probable pathogenesis warrants further investigation, these two case reports, in conjunction with other recent reports associating other ectodermal dysplasias with malignant melanoma, suggest that heightened awareness might be prudent in the follow-up of pigmented lesions in patients with HED.     

Basal cell carcinoma of the foot. Is the pedoscope a risk factor?

Basal cell carcinomas of the foot are absolutely rare. We describe the case of a 72-year-old female patient who developed a multicentric superficial BCC present on the lateral edge of the right foot. The patient remembers the regular control of the fit of footwear by an X-ray apparatus, the so-called shoe fluoroscope (=Pedoskop in Germany). Probably this may be a hardly estimated risk factor in the genesis of BCC of the foot.     

Prematurity: is it a risk factor for striae distensae?

Background Although the causes of striae distensae (SD) remain to be elucidated, the condition is known to relate to changes in the structures that provide the skin with its tensile strength and elasticity. Objective This study was conducted to evaluate whether premature birth is a risk factor for SD. Methods A total of 15,475 parous women ranging in age from 18‐45 years were interviewed between January 2007 and June 2009. After exclusion criteria were applied, a total of 1336 women were included in the study. Group 1 consisted of 1231 women of reproductive age who had been born at term. Group 2 included 105 women of reproductive age who had been born prematurely. The main outcome measure was the prevalence of SD. Results The overall prevalence of SD was 34.6% (462/1336). Mild SD was significantly more common (P < 0.01) in women who had been born prematurely (49.5%) than in women who had been born at term (31.8%). A multivariate analysis using backward stepwise logistic regression analysis identified that height, weight, gravidity, parity and abortion were found to be significantly associated with SD. Conclusions Striae distensae was significantly more common in women who had been born prematurely than in women who had been born at term.     

Is sentinel lymph node biopsy of therapeutic relevance for melanoma?

INTRODUCTION: It is still unclear whether sentinel lymph node biopsy (SLNB) has an effect on the survival or recurrence-free survival of patients. It would be necessary to compare patients with SLNB (or with selective lymph node dissection in the case of positive SLNB) and patients without SLNB who received only a close clinical and sonographic follow-up. To date, no results from prospective, randomized studies of SLNB are available. MATERIAL AND METHODS: Patients with SLNB (n = 283) and patients in clinical stage I and II with close follow-up examinations only (n = 3,514) were studied retrospectively in this investigation with regard to prognostic factors established in the literature: sex, age, tumor thickness, histological tumor type, ulceration and localization. RESULTS: Multivariate analysis did not show an independent significant advantage with regard to survival when SLNB had been performed (p = 0.37). Compared with patients in clinical stage I and II with close follow-up only (n = 2,617),patients in stage I and II with negative SLNB (n = 238) had no significantly lower melanoma-related mortality (p =0.36) but significantly fewer recurrences in the regional lymph node area (p = 0.0015). With regard to survival without distant metastases and disease-specific survival, patients with positive SLNB (n = 33) did not significantly benefit by comparison with patients who developed lymph node metastasis identified clinically or sonographically later during follow-up examinations (n = 246; p =0.89 and p = 0.38, respectively). CONCLUSION: In the relatively short follow-up period after SLNB, patients for whom SLNB had been performed did not have - on the whole - a prognostic advantage over patients who were subject only to close follow-up monitoring. Patients for whom subclinical lymph node metastases had been removed as the result of a positive SLNB did not have a better prognosis than patients without SLNB who had developed lymph node metastases within the follow-up period [corrected]     

Is there a role for systemic targeted therapy after surgical treatment for metastases of renal cell carcinoma?

Metastatic renal cell carcinoma (mRCC) is a challenging disease. Despite the new targeted therapies, complete remissions occur only in 1%-3% of the cases, and the most effective first-line treatment drugs have reached a ceiling in overall survival (ranging from 9 to 49 mo). Metastasectomy remains to be the only curative option in most patients with mRCC. Prognostic nomograms have been recently published, so we have tools to classify patients in risk groups, allowing us to detect the cases with the higher risk of recurrence after metastasectomy. Although sparse, there is some evidence of effectiveness of neoadjuvant targeted therapy before metastasectomy; but with an increase in surgical complications due to the effects of these new drugs in tissue healing. We have aimed to answer the question: Is there a role for systemic targeted therapy after surgical treatment for metastases of renal cell carcinoma? We have made a search in Pubmed database. As far as we know, evidence is low and it’s based in case reports and small series of patients treated with adjuvant drugs after neoadjuvant therapy plus metastasectomy in cases of partial response to initial systemic treatment. Despite the limitations and high risk of bias, promising results and cases with long-term survival with this approach have been described. Two ongoing clinical trials may answer the question that concerns us.     

Is there still a role for UV therapy in itch treatment?

Itching is a frequent and greatly distressing symptom related to many skin and systemic diseases. New insights into the pathophysiology of itchy skin and potentially involved mediators have increased the interest in and development of new treatments that specifically act on targets involved in the transmission and perception of itching. Phototherapy has long been known and used as an effective treatment for various kinds of chronic itching. However, despite its well‐known beneficial effects, the mechanisms behind the antipruritic effect of phototherapy are less well‐known. In addition, phototherapy requires the use of expensive equipment in dermatology offices, patients must undergo repeated treatments and no large, randomized, controlled trials have yet supported the antipruritic effect of UV. Therefore, phototherapy is rarely recommended as a treatment method for chronic pruritic diseases or only used as a last recourse. However, the wide range of pruritic conditions that can be successfully treated with phototherapy, together with its low acute side effects, extremely low frequency of interactions with other medications, possibilities to combine phototherapy with other treatment modalities and the fact that patients of almost all ages—from childhood to old age, including women during pregnancy or lactation—can be treated make UV therapy advantageous over other treatments of chronic pruritus. Thus, despite the development of new targeted therapies against pruritus, UV therapy is neither outdated nor the ‘last recourse’, but should be considered early on in the treatment of chronic pruritus.     

Is there truly a risk of lymphoma from biologic therapies?

The treatment of psoriasis has undergone a revolution with the advent of biologic therapies, including infliximab, etanercept, adalimumab, efalizumab, and alefacept. Biologics are generally safe and well tolerated. However, there has been concern over the risk of lymphoma with use of these agents because of their immunosuppressive properties. This review summarizes the current evidence in regards to lymphoma risk with biologic therapy obtained from case reports and case series, observational studies, clinical trials, and meta-analyses. The majority of data for T-cell inhibitors comes from case reports and relatively small, short-term clinical trials. In addition to published case reports and case series, TNF-α inhibitors have also been studied extensively in large cohort studies and meta-analyses of clinical trials derived primarily from the rheumatoid arthritis population. Current data are neither sufficient to completely rule out an increased risk of lymphoma associated with biologics, nor to firmly establish a causal relationship between biologics and lymphoma. Short- to intermediate-term treatment with biologics (e.g., up to 4 years) appears to be very safe with respect to lymphoma risk, especially with TNF-α inhibitors in which their potential risks appear to be well defined. Continued vigilance is warranted; however, in the appropriate patient, the risk-to-benefit profile of psoriasis treatment with respect to lymphoma risk appears highly favorable.     

Signalling and chemosensitivity assays in melanoma: is mutated status a prerequisite for targeted therapy?

Selection for targeted therapies in melanoma is currently based on the search for mutations in selected genes. We aimed at evaluating the interest of signalling and chemosensitivity studies in addition to genotyping for assessing the best suitable treatment in an individual patient. We extracted genomic DNA and melanoma cells from tumor tissue of a skin metastasis of a 17-year-old woman with stage IV melanoma progressing despite three successive lines of treatment. Despite the absence of mutation in BRAF, NRAS cKIT, the MAPK pathway was activated and a significant response to sorafenib, a mitogen-activated protein kinase (MAPK)/RAF inhibitor, was found in signalling and chemosensitivity assays. A treatment combining sorafenib and dacarbazine produced a partial response for 9 months, with marked necrosis in some lesions. Chemosensitivity assays and signalling pathway studies could be of great value in addition to genotyping for assessing the most appropriate treatment in melanoma.