Acanthosis Nigricans

AUTHORS: Alexander K.C. Leung, MD and C. Pion Kao, MD CITATION: Leung AKC, Kao CP. Acanthosis nigricans. Consultant Pediatr. 2004;3(5):241-243. doi:10.25270/cfp.2004.10.00001   HISTORY A 9-year-old Chinese girl with thickening and hyperpigmentation of the skin over the nape and axillae. Hyperpigmentation noted 2 years ago; 6 months earlier, the skin became thickened and velvety. No positive findings on review of systems. No family history of diabetes mellitus or any similar skin disorder. PHYSICAL EXAMINATION Skin over the nape and axillae hyperpigmented, thickened, velvety. Height, 137 cm (50th percentile); weight, 47 kg (2 kg above the 97th percentile). Remainder of examination results, normal.   WHAT'S YOUR DIAGNOSIS? (Answer and discussion on next page.) , ANSWER: ACANTHOSIS NIGRICANS In 1889, Pollitzer and Janovsky simultaneously described a skin disorder that Unna named acanthosis nigricans (acantho, from Greek meaning “thorn,” and nigricans, from Latin meaning “becoming black”).1,2 Acanthosis nigricans is characterized by hyperpigmentation and velvety thickening of the skin. INCIDENCE In one survey of 1412 children in an unselected population, 7.1% had acanthosis nigricans.3 Its prevalence was 5.7% at 11 years of age, 9.3% at 12 years, 6.6% at 13 years, 7.1% at 14 years, 7.8% at 15 years, and 6.5% at 16 years. The disease tends to be more common in dark-skinned persons.3 There is no sex predilection.3 PATHOGENESIS The exact pathogenesis is not known. It has been postulated that the condition is likely the result of stimulation of insulin-like growth factor receptors on keratinocytes or fibroblasts, thereby leading to increased proliferation and growth of epidermal cells. ETIOLOGY Childhood acanthosis nigricans is most commonly caused by obesity.4 When associated with obesity, acanthosis nigricans is usually weight-dependent; the condition regresses with weight reduction.2 Endocrinopathies, such as insulin resistance, diabetes mellitus, polycystic ovary disease, ovarian hyperthecosis, pineal hyperplasia or pinealoma, acromegaly, hypothyroidism, Addison disease, and Cushing disease, have been associated with the development of acanthosis nigricans.5,6 There are 2 clinical types of insulin resistance: •Type A is seen in girls and young women with hyperandrogenic features.2 •Type B occurs in older women with autoimmune disorders, including autoantibodies to the insulin receptor. With either type of insulin resistance, there is a compensatory hyperinsulinism.6,7 This may eventually lead to non–insulin-dependent (type 2) diabetes mellitus when the pancreatic beta cells become exhausted.8 Acanthosis nigricans may be induced by systemic corticosteroids, estrogens (such as diethylstilbestrol), oral contraceptives, nicotinic acid, and fusidic acid.2 Acanthosis nigricans may also be inherited as an autosomal dominant trait with variable penetrance.9 Hereditary acanthosis nigricans may present at birth or during childhood. Acanthosis nigricans has been reported to be associated with many different syndromes. These include the Hirschowitz syndrome, Lawrence-Seip syndrome, Bloom syndrome, Rud syndrome, and Rabson-Mendenhall syndrome.2,8 Acanthosis nigricans may also be a manifestation of an internal malignancy—notably adenocarcinoma of the GI tract.7 Malignant acanthosis nigricans is characterized by a sudden onset and rapid progression of the lesion.2 Malignant acanthosis nigricans occurs mainly in adults. Its occurrence in children is extremely rare, but it has been described.8 Acanthosis nigricans may also be idiopathic. HISTOLOGY Acanthosis nigricans is characterized by epidermal papillomatosis and hyperkeratosis. The local darkening of the skin is the result of increased thickness and an increased keratin content of the superficial epithelium.3,10 CLINICAL MANIFESTATIONS The classic lesion consists of dark, velvety thickening of the skin.2 Although the lesion can occur anywhere on the body, the most common sites of involvement are the nape and sides of the neck (Figure), the axillae, flexural areas, and the groin. The lesion typically presents in a symmetric fashion. The first cutaneous change is hyperpigmentation. Parents often complain that the child’s skin is dirty and that the “dirt” cannot be removed despite all of their efforts. Figure. Hyperpigmentation involving the neck developed in this 8-year-old obese girl. The affected area resembled unwashed skin. Many cases of acanthosis nigricans are associated with heat and friction in the flexural folds. This girl had worn a uniform to school—a jumper and blouse with a collar—for 6 months. The condition cleared spontaneously once school ended and she no longer wore her collared blouse. (Courtesy of Robert P. Blereau, MD)   TREATMENT Treatment of acanthosis nigricans should be directed at the underlying cause if possible. This may consist of weight reduction, discontinuation of causative drugs, treatment of underlying endocrinopathy, or removal of an underlying malignancy.2,8,11 For patients with idiopathic acanthosis nigricans and for those whose underlying cause is not amenable to treatment (eg, syndromal acanthosis nigricans), emollients, topical keratolytics, topical or systemic retinoids, and dietary fish oil supplementation may provide some improvement. Dr Leung is clinical associate professor of pediatrics at the University of Calgary and pediatric consultant at the Alberta Children’s Hospital. Dr Kao is clinical assistant professor of pediatrics at the University of Calgary and pediatric consultant at the Alberta Children’s Hospital.   REFERENCES: 1. Skiljevic DS, Nikolic MM, Jakovljevic A, Dobrosavljevic DD. Generalized acanthosis nigricans in early childhood. Pediatr Dermatol. 2001;18:213-216. 2. Schwartz RA. Acanthosis nigricans. J Am Acad Dermatol. 1994;31:1-19. 3. Stuart CA, Pate CJ, Peters EJ. Prevalence of acanthosis nigricans in an unselected population. Am J Med. 1989;87:269-272. 4. Hermanns-Le T, Hermanns JF, Pierard GE. Juvenile acanthosis nigricans and insulin resistance. Pediatr Dermatol. 2002;19:12-14. 5. Lestringant GG, Bener A, Frossard P, Townsend A. Association of acanthosis nigricans with risk of diabetes mellitus and hormonal disturbances in females. Int J Gynaecol Obstet. 2000;71:267-269. 6. Stuart CA, Gilkison CR, Smith MM, et al. Acanthosis nigricans as a risk factor for non-insulin dependent diabetes mellitus. Clin Pediatr (Phila). 1998;37:73-79. 7. Brockow K, Steinkraus V, Rinninger F, et al. Acanthosis nigricans: a marker for hyperinsulinemia. Pediatr Dermatol. 1995;12:323-326. 8. Schwartz RA, Janniger CK. Childhood acanthosis nigricans. Cutis. 1995;55: 337-341. 9. Dhar S, Dawn G, Kanwar AJ, Nada R. Familial acanthosis nigricans. Int J  Dermatol. 1996;35:126-127. 10. Stuart CA, Driscoll MS, Lundquist KF, et al. Acanthosis nigricans. J Basic Clin Physiol Pharmacol. 1998;9:407-418. 11. Uyttendaele H, Koss T, Bagheri B, et al. Generalized acanthosis nigricans in an otherwise healthy young child. Pediatr Dermatol. 2003;20:254-256.