Cutaneous manifestations of Castleman disease.

BACKGROUND: Castleman disease (CD) is a lymphoproliferative B-cell disease that is diagnosed from lymphoid hyperplasia with vascular proliferation. Symptoms may include fever, night sweats, and weight loss. Cutaneous manifestations often may go unnoticed since little has been described in the literature regarding them. MATERIALS AND METHODS: A search of CD with cutaneous manifestations was performed in PUBMED, ProQuest, Ovid, Scopus, EMBASE, and Medline. All articles included patients over 18 years of age with a diagnosis of CD and cutaneous manifestations. RESULTS: A total of 68 articles were included. The most common cutaneous manifestations include paraneoplastic pemphigus and erythematous-brown plaques, papules, or nodules. Patients presenting with these manifestations should always have a thorough physical exam, and clinicians should try to identify any palpable lymph nodes. A complete workup to rule out other neoplasias needs to be performed as well. CONCLUSIONS: A better understanding of these skin manifestations of CD may help physicians promptly diagnose and reconsider the path of diagnostic tests to identify this entity.

Acanthosis nigricans in middle-age adults: A highly prevalent and specific clinical sign of insulin resistance.

BACKGROUND: Insulin resistance (IR) precedes the diagnosis of many metabolic and non-metabolic illnesses, including type 2 diabetes mellitus (T2DM). Acanthosis nigricans (AN) is a clinical sign associated with IR. However, AN prevalence and diagnostic accuracy in middle-age adults before or at the time of prediabetes/diabetes diagnosis remain uncertain. METHODS: With the aim to define AN prevalence and diagnostic accuracy, adults between 40 and 60 years of age were consecutively invited to participate in the study. Participants were categorised into one of two main groups: individuals with normoglycaemia (group 1) and hyperglycaemia (group 2 [ie, prediabetes/diabetes]). Demographic, clinical, anthropometric characteristics, homeostasis model assessment of IR, homeostatic model assessment of ß-cell function, as well as the presence of AN on the neck, axillae, elbows and knuckles were assessed. RESULTS: A total of 320 consecutive participants with a mean age of 49.3 years (59.4% women) were included. Overall, AN prevalence was 46.3%, while AN in group 1 and group 2 was 36.3% and 49.6%, respectively (P = .04). The most common affected sites in group 1 (n = 80) were the knuckles (21.2%) and the neck (17.5%), while in group 2 (n = 240), the neck (29.6%) followed by the knuckles (26.7%). The specificity and positive predictive value of AN for IR were 0.85 and 0.86 in group 1 and 0.90 and 0.96 in group 2, respectively. CONCLUSIONS: In middle-age adults, within the entire spectrum of carbohydrate tolerance, AN is highly prevalent and specific. This finding supports its assessment as a reliable and convenient clinical sign of IR. The understanding of AN behaviour through different carbohydrate tolerance strata, and its different locations, could lead to early detection of individuals at high metabolic risk or help direct a more pathophysiological treatment approach in patients with T2DM.

Acanthosis nigricans in the knuckles: An early, accessible, straightforward, and sensitive clinical tool to predict insulin resistance.

Any clinical/biochemical marker revealing obesity or diabetes before their appearance is valuable. Insulin resistance (IR) is present in both disorders many years before occurrence. Accordingly, we determined whether acanthosis nigricans (AN) in the knuckles is associated to higher insulin and homeostasis model assessment for estimated insulin resistance (HOMA-IR) index values, and assessed the influence of body-mass index (BMI) and the diagnostic performance of AN in the knuckles to detect IR. In this cross-sectional controlled study, we included men or women, 18 to 23 years old, with or without AN in the knuckles. In 149 cases with AN in the knuckles and 145 controls, fasting insulin was higher in cases (13.45 µU/mL ± 7.8 vs. 8.59 µU/mL ± 3.63, P < .001, respectively). Mean HOMA-IR index was also higher (2.86 ± 1.68 vs. 1.78 ± 0.77, P < .001). A significant increase in fasting insulin and HOMA-IR values between and within BMI groups from normal through obese category was identified in controls and cases. By multivariate regression analysis, cases with normal BMI were significantly associated to a HOMA-IR ≥2.5 (OR = 3.09, CI95% = 1.75-5.48, P = .001). A model of AN in the knuckles, normal BMI, and increased waist circumference allowed identifying 2 out of 3 cases with HOMA-IR index ≥2.5. AN in the knuckles could be addressed with two aims: as an easy, accessible, and costless diagnostic tool suggesting hyperinsulinemia secondary to IR, and, an early marker of IR even in the absence of overweight or obesity.

Skin Manifestations of Insulin Resistance: From a Biochemical Stance to a Clinical Diagnosis and Management.

Worldwide, more than 1.9 billion adults are overweight, and around 600 million people suffer from obesity. Similarly, ~382 million individuals live with diabetes, and 40-50% of the global population is labeled at "high risk" (i.e., prediabetes). The impact of these two chronic conditions relies not only on the burden of illnesses per se (i.e., associated increased morbidity and mortality), but also on their increased cost, burden of treatment, and decreased health-related quality of life. For this review a comprehensive search in several databases including PubMed (MEDLINE), Ovid EMBASE, Web of Science, and Scopus was conducted. In both diabetes and obesity, genetic, epigenetic, and environmental factors overlap and are inclusive rather than exclusive. De facto, 70-80% of the patients with obesity and virtually every patient with type 2 diabetes have insulin resistance. Insulin resistance is a well-known pathophysiologic factor in the development of type 2 diabetes, characteristically appearing years before its diagnosis. The gold standard for insulin resistance diagnosis (the euglycemic insulin clamp) is a complex, invasive, costly, and hence unfeasible test to implement in clinical practice. Likewise, laboratory measures and derived indexes [e.g., homeostasis model assessment of insulin resistance (HOMA-IR-)] are indirect, imprecise, and not highly accurate and reproducible tests. However, skin manifestations of insulin resistance (e.g., acrochordons, acanthosis nigricans, androgenetic alopecia, acne, hirsutism) offer a reliable, straightforward, and real-time way to detect insulin resistance. The objective of this review is to aid clinicians in recognizing skin manifestations of insulin resistance. Diagnosing these skin manifestations accurately may cascade positively in the patient's health by triggering an adequate metabolic evaluation, a timely treatment or referral with the ultimate objective of decreasing diabetes and obesity burden, and improving the health and the quality of care for these patients.

Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test.

Background. Multidrug-resistant tuberculosis (MDR-TB) is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction) that if not diagnosed could seriously jeopardize patients' health. Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 µg) ACTH stimulation test at baseline and at 6-12 months of follow-up after antituberculosis treatment and culture conversion. Methods. A total of 48 men or women, aged ≥18 years (HIV-negative patients diagnosed with pulmonary MDR-TB) were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 µg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment. Results. Forty-seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2%) of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3%) alternatively, using 550 nmol/L. After antituberculosis intensive phase drug-treatment and a negative mycobacterial culture (10.2 ± 3.6 months) adrenocortical function was restored in all cases. Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical dysfunction or treat insufficient stimulated cortisol levels in the setting of MDR-TB.

Ovarian and adrenal androgens and their link to high human chorionic gonadotropin levels: a prospective controlled study.

Background. Although the association between human chorionic gonadotropin (hCG) and hyperandrogenism was identified more than 40 years ago, relevant questions remain unanswered. Design and Methods. We conducted a prospective, longitudinal, and controlled study in 23 women with a diagnosis of a complete hydatidiform mole (HM). Results. All participants completed the study. Before HM evacuation mean hCG was markedly higher in the cases than in the control group (P ≤ 0.001). Free testosterone (T) and dehydroepiandrosterone sulfate (DHEA-S) were found to be higher in the cases (2.78 ± 1.24 pg/mL and 231.50 ± 127.20 µ/dL) when compared to the control group (1.50 ± 0.75 pg/mL and 133.59 ± 60.69 µ/dL) (P = 0.0001 and 0.001), respectively. There was a strong correlation between hCG and free T/total T/DHEA-S concentrations (r = 0.78; P ≤ 0.001, r = 0.74; P ≤ 0.001, and r = 0.71; P ≤ 0.001), respectively. In the cases group 48 hours after HM evacuation, hCG levels were found to be significantly lower when compared to initial levels (P = 0.001) and free T and DHEA-S declined significantly (P = 0.0002 and 0.009). Conclusion. Before uterus evacuation, hCG, free T, and DHEA-S levels were significantly higher when compared with controls finding a strong correlation between hCG and free T/DHEA-S levels. Forty-eight hours after HM treatment hCG levels declined and the difference was lost. A novel finding of our study is that in cases, besides free T, DHEA-S was also found to be significantly higher and both the ovaries and adrenal glands appear to be the sites of this androgen overproduction.