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Acanthosis nigricans

Acanthosis nigricans



Acanthosis nigricans

Acanthosis nigricans



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    Acanthosis nigricans Acanthosis nigricans Presentation Transcript

    • Acanthosis nigricans Presentations and Implications
    • Case 1 - clinical background
      • 49-year-old woman
      • Obese, increased BMI, normal blood sugar, disturbed lipid profile
      • thick, scaly, erythematous verrucous plaque confined to neck
      • no other skin lesions
    • Case 2 - clinical background
      • 46-year-old man
      • Obese, increased BMI, normal lipid profile
      • History of MOD present
      • hyperpigmented, velvety plaques seen on neck and axilla
    • Case 3 - clinical background
      • 44-year-old man
      • Obese, increased BMI
      • Recent scaly, plaques seen on neck and on knuckles
    • The Macroscopic Manifestations
      • In all these patients, the skin in the creases and flexor surfaces is rougher, thicker, and darker than elsewhere.
      • These characteristics are most evident:
        • On the back and sides of the neck;
        • In the axilla, knee, knuckles and elbow creases;
        • In the groin area; And.
        • Around the waist.
    • The Microscopic Manifestations
    • The Microscopic Details
    • What Is This That We Have Been Seeing? Acanthosis nigricans
    • What Is Acanthosis Nigricans?
      • First described in 1889 by a German dermatologist, as a physical skin finding.
      • In 1976, Acanthosis nigricans was linked to hyperinsulinemia - a consequence of insulin resistance that is associated with obesity.
      • Presently suggested as a clinical marker for high blood insulin levels, suggesting insulin resistance.
      • The presence of acanthosis nigricans indicates to both the physician and the patient that there is a serious biochemical disorder that requires intervention.
    • What Is Insulin Resistance?
      • Insulin resistance is a reduction in the ability of tissue cells, mainly those in muscle, to use insulin.
      • Consequently, the pancreas works harder to produce more insulin, and hyperinsulinemia develops to maintain blood sugar levels within normal limits.
    • Insulin Resistance: A Closer Look
      • But, the body cannot use the additional insulin, and the pancreas becomes exhausted.
      • Insulin production then decreases and the person may be diagnosed with type II diabetes.
    • Insulin Resistance: Mechanisms
      • Pre receptor ( abnormal insulin or insulin antibodies)
      • Receptor ( decreased receptor number or affinity)
      • Postreceptor (abnormal signal transduction and phosphorylation)
      • Glucose transporter ( decreased GLUT 4 molecule)
    • Insulin Resistance: Manifestations Hypertension, Atherosclerosis, POS Central obesity, Acanthosis Nigricans, disturbed glucose tolerance Clinical manifestations Dyslipidaemia Glucose tolerance Biochemical abnormalities Vascular abnormalities High TG, Low HDL-C; Small, dense LDL Insulin resistance Hyperinsulinaemia Abnormal thrombolysis ED & VSC dysfunction
    • History of SYNDROME - X
      • Concept of insulin resistance is more than 50 yrs old.
      • Himsworth (in 1936 lancet) wrote about subdivision of DM into insulin sensitive and insulin insensitive.
      • In 1960 RIA measured insulin levels proved this.
      • Raevan ( Banting oration, 1988) introduced the concept of IR.
      • All manifestations of IR present together gives rise to the condition of syndrome-x.
    • Definition of Syndrome-x
      • Complex interrelationship of metabolic abnormalities such as
      HYPERINSULINAEMIA DYSLIPIDAEMIA HYPERTENSION GLUCOSE INTOLERANCE CENTRAL OBESITY associated with an increased risk of coronary artery disease in type 2 DM.
    • Insulin Resistance: Associated Conditions
      • Cardiovascular problems.
      • Hypertension.
      • Increased cholesterol and triglycerides.
      • In females, high insulin levels may increase the risk of developing Polycystic ovarian syndrome that is characterized by –.
        • amenorrhea (irregular menstrual cycles),
        • hirsutism (extreme facial hair),
        • Severe acne,
        • Enlarged ovaries, and.
        • Obesity.
    • Insulin Resistance: Pathophysiology
      • Acanthosis nigricans is caused by hyperinsulinemia.
      • Insulin resistance due to obesity underlies the hyperinsulinemia in obesity-associated acanthosis nigricans.
    • Insulin Resistance: Pathophysiology
      • Elevated fasting blood insulin levels or c-peptide levels confirm the presence of hyperinsulinemia underlying the diagnosis of atypical acanthosis nigricans;
      • At times, the high level of insulin that causes symptoms of hyperinsulinemia is often able to maintain glucose homeostasis in the face of insulin resistance.
      • Thus, the blood glucose in these patients may generally be in the normal range, though frank non-insulin dependent diabetes mellitus may be present, particularly in patients over 40.
    • Insulin Resistance: Link With Acanthosis Nigricans
      • The postulated mechanism mediating the association of insulin resistance with AN is that -
        • The resulting Hyperinsulinemia leads to binding of insulin to insulin-like growth factor receptors on keratinocytes and fibroblasts, with resultant hyperplasia of the skin.
    • Insulin Resistance: Link With Acanthosis Nigricans
      • Studies have revealed that AN is present in –
        • 21% of diabetic patients [microscopic acanthosis nigricans in type 2 diabetes,j Cutan med Surg 2001 sep-Oct;5(5):390-3 by manus RM, Gottschalk R, Alanen K, Shum DT, Grundy P]
        • 55% of obese patients [ I Packianathan, O Stevenson & N finer , Centre for obesity research, Luton and Dunstable hospital NHS trust, Luton, UK, diabetes care 1999 Oct;22(10):1655-9 ]
        • … % Of obese, non-diabetic patients
        • … % Of obese, diabetic patients
      • Studies have revealed that IR is present in more than 90% of patients with AN
    • Diagnosis of Acanthosis Nigricans
    • Diagnosis of Obesity
      • For clinical purposes, 3 diagnostic methods are used:
        • Body mass index - BMI
        • Skin fold thickness
        • Bio - impedance analysis
      • Distribution of body fat has great prognostic significance -
        • Gynaecoid pattern - fat accumulates in the lower body.
        • Android pattern - fat accumulates in the abdomen.
    • Grading of Obesity
      • Abdominal obesity is a better predictor of IR, DM, IGT
      • Abdominal obesity is suggested by a waist-to-hip ratio of
        • > 1.0 for males
        • > 0.8 for females
      • Distribution of body fat has great prognostic significance -
        • Gynaecoid pattern - fat accumulates in the lower body.
        • Android pattern - fat accumulates in the abdomen.
    • Assessment of Obesity by BMI- Modified WHO Classification of Overweight & Obesity
      • BMI = wt (kg)/ height in meters
      • CLASS BMI
      • Normal range 18.50 - 24.99
      • Grade 1 Overweight 25 - 29.99
      • Grade 2a Overweight 30 - 34.99
      • Grade 2b Overweight 35 - 39.99
      • Grade 3 Overweight 40.00
    • Assessment of Obesity By Skin Thickness
      • Instrument used: Harpenden calipers
      • Percent of body fat is calculated as described by DUMIN & WOMERSLE
      • SKIN FOLD THICKNESS: 4 sites are used
        • 2 sites for trunk - subscapsular & supra-iliac
        • 2 sites for periphery - Triceps & Thigh
    • Assessment of Obesity By Bioimpedance Analysis
      • Measures the electrical impedance of the body and computes total body water based on an in-built program.
      • Further derivation of percent body fat and lean body mass is made from total body water.
      • Body fat (%) Males Females
      • Normal 12 - 20 20 - 30
      • Borderline 21 - 25 31 - 33
      • Obese > 25 > 33
    • Therapy of Acanthosis Nigricans
    • Therapy of AN
      • Optimal treatment of cutaneous manifestations has not been defined.
      • Symptomatic treatments, include topical antibiotics, topical (or systemic) retinoids, and keratolytics.
      • Although AN is not an inflammatory disorder, superpotent topical corticosteroids can be tried for their atrophogenic effect.
      • The most effective treatment is weight loss / exercise to correct the underlying endocrinologic abnormality.
      • The cutaneous changes of acanthosis nigricans respond to reductions in blood insulin levels.