Implications of a Clinically Ignored Site of Acanthosis Nigricans: The Knuckles

 

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Abstract

Background: The clinical epidemiology of acanthosis nigricans (AN) has not been entirely studied. Most studies mention only its prevalence taking any “typical site” as a whole. These studies were carried out at different ages, races, anthropometries, and skin phototypes without analyzing the comparative clinical connotation of different sites. Furthermore, it has never been explored as a potential early expression of insulin resistance before it becomes clinically evident. The objective was to determine the prevalence and body distribution of AN in easy-access sites to physical examination in a Latin American youth population and its clinical implications as an early marker for obesity.

Design and Patients: We conducted a prospective, cross-sectional, observational study in 703 randomly selected students. Participants’ mean age was 19.1±1.68 years. Overweight and obesity occurred in 23.6% and 6.8%, respectively. 3 observers blindly assessed neck, axillae, elbow and knuckles.

Results: AN was identified in any of the examined sites in 47.8% of the participants. Its prevalence increased from 41% to 86% from normal to obese anthropometric categories. AN occurred in 1–4 sites in 23.1%, 10.8%, 6.9% and 7.1% of cases, respectively. The knuckles was the site with the highest prevalence of AN as an overall group (31.3%) and in the normal (24.9%) and overweight body mass index (46.4%) categories and there was a higher prevalence in the cases above the median in the normal body mass index category. In the obese group, AN was slightly more common in the neck but all sites had a very similar high prevalence.

Conclusion: AN occurs with a high prevalence in Latin American youths, and its prevalence is much higher in a “non-classical” and ignored location where it is very easy to detect during physical examination: the knuckles. It may also occur earlier in this location in the evolution to obesity. The presence of AN in the knuckles in any patient, even if they have a normal body mass index, might indicate the likelihood of an early clinical manifestation of insulin resistance and metabolic consequences.

• References

• 1 American Diabetes Association . Economic costs of diabetes in the US. in 2012. Diabetes Care 2013; 36: 1033-1046
  CrossrefPubMedGoogle Scholar
• 2 Hernández-Ávila M, Gutiérrez JP, Reynoso-Soberón N. Diabetes mellitus en México. El estado de la epidemia. Salud Pública Mex 2013; 55 (Suppl. 02) S129-S136
  PubMedGoogle Scholar
• 3 Lau DC, Shen GX. Cardiovascular complications of diabetes. Can J Diabetes 2013; 37: 279-281
  CrossrefPubMedGoogle Scholar
• 4 Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607
  CrossrefPubMedGoogle Scholar
• 5 Vinner RM, Segal TY, Lichtarowicz-Krynska E et al. Prevalence of the insulin resistance syndrome in obesity. Arch Dis Child 2005; 90: 10-14
  CrossrefPubMedGoogle Scholar
• 6 Adiels M, Taskinen M-R, Boren J. Fatty liver, insulin resistance, and dyslipidemia. Curr Diabetes Rep 2008; 8: 60-64
  CrossrefPubMedGoogle Scholar
• 7 Andersen DK. Diabetes and cancer: placing the association in perspective. Curr Opin Endocrinol Diabetes Obes 2013; 20: 81-86
  CrossrefPubMedGoogle Scholar
• 8 Jung KY, Cho SY, Kim HJ et al. Nonalcoholic steatohepatitis associated with metabolic syndrome: relationship to insulin resistance and liver histology. J Clin Gastroenterol 2014; Epub ahead of print
  PubMedGoogle Scholar
• 9 Schwartz RA. Acanthosis nigricans. J Am Acad Dermatol 1994; 31: 1-19
  CrossrefPubMedGoogle Scholar
• 10 Pollitzer S. Acanthosis nigricans. A symptom of a disorder of the abdominal sympathetic. Jour A M A 1909; LIII: 1369-1373
  PubMedGoogle Scholar
• 11 Kahn CR, Flier JS, Bar RS et al. The syndromes of insulin resistance and acanthosis nigricans: insulin-receptor disorders in man. N Engl J Med 1976; 294: 739-745
  CrossrefPubMedGoogle Scholar
• 12 Hermanns-Lê T, Scheen A, Piérard GE. Acanthosis nigricans associated with insulin resistance: pathophysiology and management. Am J Clin Dermatol 2004; 5: 199-203
  CrossrefPubMedGoogle Scholar
• 13 Aswani R, Lochow A, Dementieva Y et al. Acanthosis nigricans as a clinical marker to detect insulin resistance in Caucasian children from West Virginia. Clinical Pediatrics 2011; 50: 1057-1061
  CrossrefPubMedGoogle Scholar
• 14 Brockow K, Steinkraus V, Rinninger F et al. Acanthosis nigricans: a marker for hyperinsulinemia. Pediatric Dermatology 1995; 12: 323-326
  CrossrefPubMedGoogle Scholar
• 15 Hermanns-Lê t Hermanns JF, Piérard GE. Juvenile acanthosis nigricans and insulin resistance. Pediatric Dermatology 2002; 19: 12-14
  CrossrefPubMedGoogle Scholar
• 16 Stuart CA, Pate CJ, Peters EJ. Prevalence of acanthosis nigricans in an unselected population. Am J Med 1989; 87: 269-272
  CrossrefPubMedGoogle Scholar
• 17 Burke JP, Hale DE, Hazuda HP et al. A quantitative scale of acanthosis nigricans. Diabetes Care 1999; 22: 1655-1659
  CrossrefPubMedGoogle Scholar
• 18 Brickman WJ, Huang J, Silverman BL et al. Acanthosis nigricans identifies youth at high risk for metabolic abnormalities. J Pediatr 2010; 156: 87-92
  CrossrefPubMedGoogle Scholar
• 19 Kluczynik CE, Mariz LS, Souza LC et al. Acanthosis nigricans and insulin resistance in overweight children and adolescents. An Bras Dermatol 2012; 87: 531-537
  CrossrefPubMedGoogle Scholar
• 20 Stuart CA, Smith MM, Gilkison CR et al. Acanthosis nigricans among Native Americans: an indicator of high diabetes risk. Am J Public Health 1994; 84: 1839-1842
  CrossrefPubMedGoogle Scholar
• 21 Mukhtar Q, Cleverley G, Voorhees RE et al. Prevalence of acanthosis nigricans and its association with hyperinsulinemia in New Mexico adolescents. J Adolesc Health 2001; 28: 372-376
  CrossrefPubMedGoogle Scholar
• 22 Yamazaki H, Ito S, Yoshida H. Acanthosis nigricans is a reliable cutaneous marker of insulin resistance in obese Japanese children. Pediatr Int. 2003; 45: 701-705
  CrossrefPubMedGoogle Scholar
• 23 Kong AS, Williams RL, Smith M et al. RIOS Net Clinicians. Acanthosis nigricans and diabetes risk factors: prevalence in young persons seen in southwestern US primary care practices. Ann Fam Med. 2007; 5: 202-208
  CrossrefPubMedGoogle Scholar
• 24 Lopez-Alvarenga JC, García-Hidalgo L, Landa-Anell MV et al. Influence of skin color on the diagnostic utility of clinical acanthosis nigricans to predict insulin resistance in obese patients. Arch Med Res 2006; 37: 744-748
  CrossrefPubMedGoogle Scholar
• 25 Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol 1988; 124: 869-871
  CrossrefPubMedGoogle Scholar
• 26 Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults – The Evidence Report . National Institutes of Health. Obes Res 1998; 6 (Suppl. 02) 51S-209S
  CrossrefPubMedGoogle Scholar
• 27 Gregg EW, Li Y, Wang J et al. Changes in Diabetes-Related Complications in the United States, 1990–2010. N Engl J Med 2014; 370: 1514-1523
  CrossrefPubMedGoogle Scholar
• 28 Rizzo M, Tyndall EK, Frontoni S et al. Rapid and easy assessment of insulin resistance contributes to early detection of polycystic ovary syndrome. J Endocrinol Invest 2013; 36: 527-530
  PubMedGoogle Scholar
• 29 González-González JG, Mancillas-Adame LG, Fernández-Reyes M et al. Androgenetic alopecia and insulin resistance in young men. Clinical Endocrinol 2009; 71: 494-499
  CrossrefPubMedGoogle Scholar
• 30 Pan JJ, Qu HQ, Rentfro A et al. Prevalence of Metabolic Syndrome and Risks of Abnormal Serum Alanine Aminotransferase in Hispanics: A Population-Based Study. PLoS ONE 2011; 6: e21515
  CrossrefPubMedGoogle Scholar
• 31 Barquera S, Campos-Nonato I, Hernández-Barrera L et al. Prevalencia de obesidad en adultos mexicanos, ENSANUT 2012. Salud Pública Mex 2013; 55 (Suppl. 02) S151-S160
  PubMedGoogle Scholar
• 32 López-Alvarenga JC, Montesinos-Cabrera RA, Velázquez-Alva C et al. Short stature is related to high body fat composition despite body mass index in a Mexican population. Arch Med Res 2003; 34: 137-140
  CrossrefPubMedGoogle Scholar
• 33 Ryan AS, Roche AF, Kuczmarski RJ. Weight, stature, and body mass index data for Mexican Americans from the third national health and nutrition examination survey (NHANES III, 1988-1994). Am J Hum Biol 1999; 11: 673-686
  CrossrefPubMedGoogle Scholar
• 34 Guran T, Turan S, Akcay T et al. Significance of acanthosis nigricans in childhood obesity. J Paediatr Child Health 2008; 44: 338-341
  CrossrefPubMedGoogle Scholar
• 35 Nguyen TT, Keil MF, Russell DL et al. Relation of acanthosis nigricans to hyperinsulinemia and insulin sensitivity in overweight African American and white children. J Pediatr 2001; 138: 474-480
  CrossrefPubMedGoogle Scholar
• 36 Hardin DS. Screening for type 2 diabetes in children with acanthosis nigricans. Diabetes Educ 2006; 32: 547-552
  CrossrefPubMedGoogle Scholar
• 37 Hirschler V, Aranda C, Oneto A et al. Is acanthosis nigricans a marker of insulin resistance in obese children?. Diabetes Care 2002; 25: 2353
  PubMedGoogle Scholar
• 38 Pinheiro AC, Rojas P, Carrasco F et al. Acanthosis nigricans as an indicator of insulin resistance in Chilean adult population. Nutr Hosp 2011; 26: 940-944
  PubMedGoogle Scholar
• 39 Wasniewska M, Arrigo T, Crisafulli G et al. Recovery of acanthosis nigricans under prolonged metformin treatment in an adolescent with normal weight. J Endocrinol Invest 2009; 32: 939-940
  CrossrefPubMedGoogle Scholar
• 40 Ghosh S, Roychowdhury B, Mukhopadhyay S et al. Clearance of acanthosis nigricans associated with insulinoma following surgical resection. QJM 2008; 101: 899-900
  CrossrefPubMedGoogle Scholar
• 41 International Diabetes Federation . IDF Diabetes Atlas. 6^th edn. Brussels, Belgium: International Diabetes Federation; 2013. http://www.idf.org/diabetesatlas
  Google Scholar
• 42 Lai JJ, Chang P, Lai KP et al. The Role of Androgen and Androgen Receptor in the Skin- Related Disorders. Arch Dermatol Res 2012; 304: 499-510
  CrossrefPubMedGoogle Scholar
• 43 DeFronzo RA, Ferranini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991; 14: 173-194
  CrossrefPubMedGoogle Scholar