Glucocorticoids and the skin

Glucocorticoids are the most effective anti -inflammatory agents currently available, but a variety of adverse effects limit their clinical usefulness. This work explores further two facets of the interaction between glucocorticoids and the skin, with the aim of identifying means of reducing glucocorticoid toxicity.(a) Metabolism of glucocorticoids by skin: Human skin is active in the terminal metabolism of cortisol to cortisone, but the biological implications of this process in skin are uncertain. Because there are technical difficulties in dealing with human skin, an animal model, the nude mouse, has been evaluated for its suitability to the study of the metabolism of corticosterone to 11B- dehydrocorticosterone (the homologous reaction in rodents of cortisol to cortisone conversion in man); a process mediated by 1 l ß- hydroxysteroid dehydrogenase. The skin of the nude mouse has previously been shown to be appropriate for pharmacokinetic and phannacodynamic studies of glucocorticoids. In this model, skin 11B- hydroxysteroid dehydrogenase had an apparent Km for corticosterone of 37 p.M. Skin 11B- hydroxysteroid dehydrogenase was up- regulated, in -vivo, by active glucocorticoids and was NADP dependent. By comparison, kidney 1 Iß- hydroxysteroid dehydrogenasé had a higher apparent Km (120 μM) for corticosterone, used NAD and NADP with equal facility and was not regulated in- vivo by glucocorticoids. These data suggest that the skin may possess an isoform distinct from that of the kidney. Immunohistochemical studies demonstrated that 11ß -hydroxysteroid dehydrogenase was most abundant in the epidermis. In- vitro, this enzyme was markedly inhibited by glycyrrhetinic acid, the active principle in liquorice. Using the classic bioassay of glucocorticoid activity (skin vasoconstrictor assay), it was found that co- application of glycyrrhetinic acid and hydrocortisone resulted in potentiation of skin vasoconstrictor activity of hydrocortisone. This suggests that inhibition of hydrocortisone metabolism might explain the long recognised but poorly understood anti - inflammatory action of liquorice and its congeners and may represent a novel means of targeting glucocorticoid therapy.(b) Skin vasoconstrictor response (blanching) to topical glucocorticoids: Glucocorticoids applied topically to human skin produce vasoconstriction in dermal vessels, the degree of which correlates closely with the potency and clinically efficacy of these compounds. Although previous workers had noted heterogeneity in blanching responses to glucocorticoids, this was never systematically studied. In qualitative studies, it was shown that skin blanching was inducible by RU- 28362, a specific glucocorticoid receptor (type II) agonist and blocked by RU- 38486, a glucocorticoid antagonist. Moreover, aldosterone (type I receptor agonist) failed to produce blanching. In addition blanching was observed in an individual with clinical and biochemical features of aldosterone receptor deficiency. These data therefore suggest that blanching is a glucocorticoid specific phenomenon mediated via the classical glucocorticoid receptor. To test whether skin vasoconstrictor response might reflect glucocorticoid sensitivity, blanching responses was tested in a clinical model of glucocorticoid resistance. In patients with glucocorticoid resistant asthma, skin responsiveness was also found to be diminished. Responsiveness was also somewhat diminished in a cohort of asthmatics on long term prednisolone. Skin vasoconstrictor responsiveness might therefore reflect systemic sensitivity to glucocorticoids and previous glucocorticoid use might reduce skin responsiveness. When tested against other parameter indicating systemic glucocorticoid effects, acute systemic glucocorticoid exposure over 10 days did not affect skin responsiveness. It is possible that resistance to the anti -inflammatory effects of glucocorticoids might accrue from long term exposure and it might therefore be possible to use the skin vasoconstrictor assay a marker for glucocorticoid sensitivity - a novel purpose for this long used assay

Acute pneumonitis secondary to subcutaneous silicone injection

Following silicone injection, end organ toxicity can occur. To our knowledge this report documents the first case of silicone embolization in the Caribbean and serves to highlight an emergent danger associated with its illicit use for cosmetic purposes in this region

Does insulin resistance co-exist with glucocorticoid resistance in the metabolic syndrome? Studies comparing skin sensitivity to glucocorticoids in individuals with and without acanthosis nigricans

<p>Abstract</p> <p>Background</p> <p>The metabolic syndrome is associated with increased risk for both diabetes and coronary artery disease, which insulin resistance alone does not satisfactorily explain. We propose an additional and complementary underlying mechanism of glucocorticoid resistance.</p> <p>Results</p> <p>Using acanthosis nigricans (AN) and skin vasoconstrictor (SVC) response to topically applied beclomethasone dipropionate as markers of insulin and glucocorticoid resistance, respectively, we compared anthropometric, biochemical, pro-inflammatory markers and the SVC response in subjects with AN in two studies: STUDY 1 was used to compare subjects with AN (Grade 4, n = 32), with those without AN (n = 68) while STUDY 2 compared these responses among a cross-section of diabetic patients (n = 109) with varying grades of AN (grade 0, n = 30; grade 1, n = 24; grade 2, n = 18; grade 3, n = 25; grade 4, n = 12).</p> <p>Findings</p> <p>In both studies there was an inverse relationship between AN Grade 4 and the SVC response, (P < 0.001). In STUDY 1, AN Grade 4 was associated with age, waist circumference, BMI, fasting blood glucose, plasma lipids and hs-CRP (P < 0.05). SVC was an independent predictor of CRP and those with combined AN and a negative SVC response, CRP levels were highest. In Study 2 when the SVC response in subjects with type 2 diabetes mellitus with varying degrees of AN was studied, it showed that for any degree of AN, the SVC response is more likely to be negative and was independent of gender and ethnicity.</p> <p>Conclusion</p> <p>An absent SVC response represents a new biomarker for the metabolic syndrome and the exaggerated inflammatory response, which characterizes the metabolic syndrome, may be an outcome of deficient glucocorticoid action in vascular tissue.</p

Bariatric Surgery in the Caribbean: Is It Safe in a Low-Volume, Third World Setting?

Bariatric surgery is a well-recognized modality of management of obesity. In addition to obesity, it effectively controls diabetes mellitus, and hypertension. It has been recommended that bariatric surgery should be done in “designated centers” of excellence where there is a high volume of case turnover. Caribbean nations are not spared from the global spread of the obesity epidemic; however, not many patients get the benefits of bariatric surgery. This study aimed to establish that bariatric surgery could be safely and efficiently undertaken in a low-volume center outside the “designated centers” with comparable patient outcomes even in a third world setting. Though “patient numbers” generally imply better outcome, in an environment where these numbers cannot be achieved, patients should not be denied the access to surgery once good outcomes are achieved

Prevalence of self-reported diabetes, hypertension and heart disease in individuals seeking State funding in Trinidad and Tobago, West Indies

AbstractObjectiveDiabetes, hypertension and heart disease inflict a heavy health burden on the Caribbean Republic of Trinidad and Tobago. This study assessed the prevalence of self- reported diabetes, hypertension and heart disease in lower socioeconomically placed individuals accessing welfare grants.MethodData collected between July 2008 and June 2009 were analyzed from 14,793 responses. The survey sought information on education, average monthly income, health, housing, and household facilities.ResultsSelf-reported disease prevalence was 19.5% (95% CI: 18.9–20.2) for diabetes mellitus; 30.2% (95% CI: 29.5–30.9) for hypertension; and 8.2% (95% CI: 7.7–8.6) for cardiac disease. Diabetes and cardiac disease had equivalent gender frequency; hypertension was more prevalent in women (p<.001). Disease prevalence was highest in Indo-Trinidadians, married and divorced subjects, non-Christians and increased with age. Those with primary education alone were at greatest risk.ConclusionTrinidad and Tobago have a high prevalence of hypertension, diabetes and heart disease. Hypertension showed gender specificity in women. Prevalence was highest in Indo-Trinidadians, increased with age, and primary education alone was a risk factor. Interventions to arrest the high prevalence of chronic non-communicable diseases to promote wellness are needed in Trinidad and Tobago

The National Eye Survey of Trinidad and Tobago (NESTT): Rationale, objectives and methodology

Purpose: This paper describes the rationale, study design and procedures of the National Eye Survey of Trinidad and Tobago (NESTT). The main objective of this survey is to obtain prevalence estimates of vision impairment and blindness for planning and policy development. Methods: A population-based, cross-sectional survey was undertaken using random multistage cluster sampling, with probability-proportionate-to-size methods. Eligible participants aged 5 years and older were sampled from the non-institutional population in each of 120 cluster segments. Presenting distance and near visual acuity were screened in their communities. People aged 40 years and older, and selected younger people, were invited for comprehensive clinic assessment. The interview included information on potential risk factors for vision loss, associated costs and quality of life. The examination included measurement of anthropometrics, blood glucose, refraction, ocular biometry, corneal hysteresis, and detailed assessment of the anterior and posterior segments, with photography and optical coherence tomography imaging. Adult participants were invited to donate saliva samples for DNA extraction and storage. Results: The fieldwork was conducted over 13 months in 2013–2014. A representative sample of 10,651 individuals in 3410 households within 120 cluster segments identified 9913 people who were eligible for recruitment. Conclusion: The study methodology was robust and adequate to provide the first population-based estimates of the prevalence and causes of visual impairment and blindness in Trinidad and Tobago. Information was also gathered on risk factors, costs and quality of life associated with vision loss, and on normal ocular parameters for the population aged 40 years and older

Prominent Bilateral Hand Tremor in Hashimoto's Encephalopathy: A Video Demonstration

Background: Hashimoto's encephalopathy often presents with neuropsychiatric manifestations including seizures and movement disorders. Case Report: We describe a patient who presented with bilateral hand tremor and mild cognitive defects that fulfilled the criteria for a diagnosis of Hashimoto's encephalopathy. There was a rapid response to glucocorticoid therapy with relapse following treatment withdrawal. Discussion: Recently published clinical criteria for the diagnosis of Hashimoto's encephalopathy include seizures, myoclonus, hallucinations, or stroke-like episodes but do not include tremor. Our case had mild cognitive dysfunction and a coarse tremor as the predominant clinical features, which probably represent mild disease.</p

A case of spuriously high CK-MB: Contemplate beyond cardiac

Creatine kinase-MB (CK-MB) is a widely tested enzyme in cardiac disease and thus has important clinical implications. We relate the scenario of a young patient presenting with chest pain whose CK-MB levels remained inordinately elevated despite a normal total CK level, resolution of symptoms and exclusion of coronary artery disease. Further analysis by electrophoresis revealed the presence of a rare molecular variant of creatine kinase: macro-CK type 1. While this may be a benign finding, there are sparse data demonstrating an association with non-cardiac pathologies such as malignancy, endocrinopathies, connective tissue and autoimmune diseases. Thus, after further exclusion of these associated conditions, the patient was reassured on the likely benign nature of macro-CK in this case