Statins in dermatology

Statins are competitive inhibitors of 3-hydroxy-3-methylyglutaryl-coenzyme A reductase and reduce low-density lipoprotein-C levels. Statins are well-tolerated drugs used for prevention of atherosclerosis and cardiovascular events. Statins possess anti-inflammatory, immunomodulatory, antioxidant, metabolic, and possible anticancer effects. Statins are reported to be effective against psoriasis, dermatitis, graft-versus-host disease, uremic pruritus, vitiligo, and hirsutism. Topical forms of statins are employed in the treatment of acne, seborrhea, rosacea, and rhinophyma. Animal studies show the beneficial effect of statins against contact dermatitis and wound healing. They have promising anti-HIV effects as well. This article succinctly reviews the various cellular and molecular effects of statins, their applications in cutaneous medicine and their side effects.     

An unusually large squamous cell carcinoma mass arising from the lower lip

Squamous cell carcinoma (SCC) of the lip is a relatively common malignancy of the head and neck region. Tumor thickness, grading, and perineural invasion are significant prognostic indicators. We report an 81-year-old, otherwise healthy woman presenting with a huge friable mass originating from her lower lip. The lesion had started as a small papule 8 years before. It later became eroded and ulcerative and transformed into a slow growing, flesh-colored mass that began interfering with her speaking and eating. Radiologic studies showed no evidence of bone involvement. The lesion was diagnosed histopathologically as squamous cell carcinoma. The patient was advised to undertake palliative treatment such as surgery or chemotherapy, but she refused any intervention.     

RETRACTED ARTICLE: Carpal tunnel syndrome in patients who are receiving long-term renal hemodialysis

Introduction The development of a carpal tunnel syndrome has become an increasingly recognized problem in patients who are treated by long-term hemodialysis. Arteriovenous fistula has been identified as one of the possible cause for the development of carpal tunnel syndrome. Materials and methods Wrists of 558 hemodialysis patients who had fistula at least 1 year served as the case group and the other intact wrists of the same patients served as the control group. Carpal tunnel syndrome was diagnosed clinically; however, 232 random patients underwent electrodiagnostic studies the day after hemodialysis. Results In 170 (30.5%) wrists with arteriovenous fistula developed carpal tunnel syndrome versus 68 (12.2%) in the contralateral wrist. Three patients had a concurrent diagnosed radial steal syndrome. In all three wrists that had radial steal syndrome developed carpal tunnel syndrome. There was a correlation, however, between the development of the carpal tunnel syndrome, and the side of the longest vascular access. Contrary to the clinical assessment, electrodiagnostic studies did not indicate any significant association between the frequency of carpal tunnel syndrome and arteriovenous fistula or its duration. Conclusion Hemodialysis patients are at considerable risk of developing carpal tunnel syndrome in the wrist with an arteriovenous fistula. Close observation and routine clinical examination is mandatory to prevent further problems.     

The Association of Dietary and Urinary Sodium With Bone Mineral Density and Risk of Osteoporosis: A Systematic Review and Meta-Analysis

Objective: Although some earlier studies have indicated an association between dietary/urinary sodium and bone mass density (BMD), bone mass content (BMC), and the risk of osteoporosis (OS), findings are still conflicting. The aim of this study was to summarize the relation of dietary/urinary sodium with BMD, BMC, and the risk of OS.

Methods: We conducted a systematic search up to April 2017 in PubMed/MEDLINE, SCOPUS, and Web of Science to find relevant studies. Articles with cross-sectional and cohort designs in which odds ratios (ORs), correlations (r), or beta coefficients were reported for the association between dietary/urinary sodium and OS, BMD, or BMC were included.

Results: Pooling 11 effect sizes with a total of 39,065 people showed that higher sodium consumption significantly increased the risk of OS (OR = 1.20; 95% confidence interval [CI], 1.02–1.41; p = 0.026), with high heterogeneity among studies (I² = 68.0%; p = 0.001). Subgroup analyses showed significantly higher risk of OS in premenopausal women (OR = 1.31; 95% CI, 1.01–1.69; p = 0.036), in participants with a mean age older than 50 years (OR = 1.15; 95% CI, 1.04–1.28; p = 0.005), in dietary sodium intake subgroup (OR = 1.45; 95% CI, 1.19–1.77; p < 0.001), and in individuals with adjustment for energy (OR = 1.77; 95% CI, 1.38–2.27; p < 0.001). The correlation coefficients showed no significant association between urinary sodium and BMD (r = ?0.46; 95% CI, ?0.74 to ?0.18; p = 0.02).

Conclusions: We found a positive association between sodium intake and the risk of OS, while no association was found with urinary sodium. Furthermore, there was no significant correlation between sodium intake and BMD. Due to high heterogeneity in this research, more studies are suggested.     

Disparities in Infant Mortality Due to Congenital Anomalies on Guam

In the 1970''s and 1980''s, there were large inter-village disparities in infant mortality due to congenital anomalies on Guam. A village-level analysis was conducted to determine if these disparities can be explained by behavioral (ie, median age of village females, village fertility ratio), structural (ie, population density, persons per household, single mother households per village, married females per village), and environmental (ie, living in a village where Agent Orange (AO) spraying was conducted) factors. Village-level data for live births and infant mortality due to congenital anomalies (1970–1989) was collected from Guam''s Office of Vital Statistics. Data on median age of village females, village fertility ratio, population density, persons per household, single mother households, and married females were obtained from the 1980 US Census. Estimates of village-level AO use were provided through personal communications, and villages were dichotomized into AO and non-AO spray areas. Village location was classified by usual residence of the mother. Linear regression was used to determine associations between infant mortality due to congenital anomalies and the behavioral, structural, and environmental factors. The association between AO spray area and infant mortality due to congenital anomalies was statistically significant under univariable (B [95%CI] = 1.88 [0.64,3.11], P = .005) and multivariable conditions (B [95%CI] = 2.02 [0.08,3.96], P = .042). These results suggest that infants born to mothers whose usual residence was in an AO spray area on Guam are at an increased risk of mortality due to congenital anomalies. Further studies using individual-level data are needed to validate these results.     

Possible molecular mechanisms to account for the involvement of tryptase in the pathogenesis of psoriasis

Tryptase has been suggested to take part in the pathophysiology of psoriasis mainly through the production of C3a by cleaving C3. However, studies using tryptase preparations of high purity do not support this notion. Therefore, although tryptase is unanimously believed to be involved in the immunopathogenesis of psoriasis, no convincing mechanism has been proposed for its role. This paper proposes several mechanisms by which this enyme may exert its role in the pathobiology of psoriasis.

Tryptase is a mitogen for epithelial cells and stimulates IL-8 production and ICAM-1 expression by these cells. It also induces the expression of mRNA for IL-1β and IL-8 and stimulates the selective release of IL-8 from endothelial cells and TNF-α, IL-1β, and IL-6 from lymphocytes and monocytes.

Besides itself being a chemoattractant for neutrophils, tryptase activates mast cells and generates kinins from kininogen, thereby playing a crucial role in leukocyte infiltration into psoriatic lesions. This enzyme also induces leukocyte infiltration partly through activating endothelial PAR-2, which contributes to leukocyte rolling, adherence and recruitment by inducing the release of endothelial platelet-activating factor.

Through activating PAR-2, tryptase could also trigger the development of Langerhans cells which play a crucial role in the pathophysiology of psoriasis.

This enzyme is a mitogen for fibroblasts, which are probably involved in the pathophysiology of psoriasis through production of insulin-like growth factor-I (IGF-I).

Tryptase is a gelatinase and also activates stromelysin-1 (MMP-3), thereby contributing to the disruption of psoriatic basement membrane and to the joint damage seen in psoriatic arthritis.

Increase of tryptase levels following trauma could also provide a mechanism for Koebner phenomenon seen in psoriasis.     

Levamisole: a safe and economical weapon against pediculosis

Twenty-eight patients with pediculosis capitis, defined as the presence of pruritus, living eggs, and/or lice in the hair, were enrolled in an uncontrolled open pilot study. The subjects were school-age girls (7-12 years old), apparently free of other diseases, and not treated for pediculosis for 4 weeks prior to this study. Family contacts were not treated for pediculosis. The mothers of the patients, who had given informed consent, were asked not to use any topical pediculocide on the girls during the drug trial. Other than the drug administered in the study, the subjects did not take any oral medicine, including cotrimoxazole and ivermectin, during the trial. Treatment consisted of 3.5 mg/kg once daily oral administration of levamisole for 10 successive days, which was given to the subjects in their school by health personnel. A 10-day course was chosen because the subjects lived in unhygienic and overcrowded conditions in a poor village where head lice infestation was hyperendemic. Therefore, two treatment courses spaced 10 days apart could not preclude new infestations from other affected persons and fomites and might have led to a false deduction of drug ineffectiveness. Substituting "N" for the grade of living nits and "L" for adult lice, three forms of response based on the meticulous examination of the entire scalp with the use of a lens with high magnification and a powerful light source were considered: (i) total responsiveness, defined as N2 = 0 and L2 = 0; (ii) partial responsiveness, defined as 0 not equal N2 < N1 and 0 not equal L2 < L1; and (iii) complete unresponsiveness, defined as N2 > or = N1 or L2 > or = L1. The detection of unhatched nits which were operculated and generally located within one-quarter of an inch of the scalp was used to indicate the presence of lice infestation and also to judge the clinical response. For those small nits whose opercula were difficult to see with a hand lens, a low power microscopic study was performed to determine whether the nits were unhatched or not. Of the 28 girls enrolled in the study, one patient refused to take the drug after 2 days of treatment. No adverse reactions were noted in any of the 28 subjects. On the 11th day, meticulous hair examination showed that 23 patients had responded to treatment (85%; 95% confidence interval (CI): 66-94%). Of these, 18 showed complete responsiveness (67%; 95% CI: 48-82%). More complete information is given in Table 1. Confidence intervals were calculated using the likelihood method. This study suggests that levamisole is effective against pediculosis with a dose of 3.5 mg/kg administered for 10 days.