Acta Biomedica Scientia ACANTHOSIS NIGRICANS
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Prithhwish Kundu et al. / Acta Biomedica Scientia. 2017; 4(3): 110-115. Acta Biomedica Scientia e - ISSN - 2348 - 2168 Print ISSN - 2348 - 215X www.mcmed.us/journal/abs Review Article ACANTHOSIS NIGRICANS: AN EDIFYING REVIEW Prithwish Kundu*1, Richa Wadhawan2, Dharti Gajjar3, Mareen Suhaff4, Gaurav Solanki5 1Junior Resident, Department of Oral Medicine, Diagnosis & Radiology, Pacific Dental College and Hospital, Udaipur, Rajasthan, India. 2Reader, Department of Oral Medicine, Diagnosis & Radiology, Institute of Dental Education & Advance Studies, Gwalior, Madhya Pradesh, India. 3Senior Lecturer, Department of Oral Medicine, Diagnosis & Radiology, Narsinhbhaipatel Dental College & Hospital, Visnagar, Gujarat, India. 4Undergraduate, Institute of Dental Education & Advance Studies, Gwalior, Madhya Pradesh, India. 5Private Practitioner, Jodhpur, Rajasthan, India. ABSTRACT Acanthosis Nigricans (AN) is a skin condition characterized by hyperpigmentation and hyperkeratosis of the skin, particularly of skin fold regions, such as of the neck and groin and axillae. Various benign forms of AN have been identified in which the disorder may be inherited as a primary condition or associated with various underlying syndromes, obesity, or the use of certain medications. Keywords :- Acanthosis Nigricans, Hyperpigmentation, Obesity, Metabolic disturbances. Access this article online Home page: Quick Response code http://www.mcmed.us/journal/abs DOI: http://dx.doi.org/10.21276/abs.2017.4.3.1 Received:05.07.17 Revised:10.07.17 Accepted:13.07.17 INTRODUCTION Acanthosis Nigricans (AN) is a skin disease that is Epidemiology characterized by hyper pigmented, thick, velvety plaque Recently a high prevalence of AN has been usually occurring in the body folds. It may involve other observed which may be associated with rising prevalence of parts of the body [1]. The common sites are neck, armpit, obesity and diabetes. There is no gender predilection. popliteal fossa and groin region. It also sometimes occurs According to age, race, frequency of type, degree of obesity on the elbow, knee, knuckles and oral, gastrointestinal or and concomitant endocrinopathy, the prevalence rate varies anogenital mucosa [2-5] .The earliest changes of the face from 7% to 74%. It is commonly found in Native are usually dryness, pigmentation and roughness of the Americans. According to the American Academy of skin, which in affected area is gray-brown or black [6]. Dermatology, people of African, Caribbean, or Hispanic These usually occur symmetrically and are descent are also at an increased risk. All ethnic groups are histopathologically characterized by papillomatosis and equally at risk of acanthosis nigricans when body mass hyperkeratosis of the skin. The term AN was originally index (BMI) is well above normal. Hud et al. after proposed by Unna. The first case was described by Pollitzer conducting a research reported that AN is more and Janovsky in 1891 [7]. predominant in black women when compared to white women. The malignant variant of AN is rare. The frequency of acanthosis nigricans varies between ethnic groups [8]. Corresponding Author Prithwish Kundu Email: - [email protected] 110 | P a g e Prithhwish Kundu et al. / Acta Biomedica Scientia. 2017; 4(3): 110-115. Etiopathogenesis drugs, and as a genetic disorder[12]. Various other causes Individuals affected with AN have shown or syndromes associated with AN are given in Table 2. increased levels of insulin or an abnormal response to exogenously administered insulin. It has been demonstrated Types that insulin crosses dermoepidermal junction (DEJ) to reach According to Shwartz RA [1], acanthosis nigricans keratinocytes. Insulin regulates carbohydrate, lipid and can be classified as: Benign, Pseudo AN associated with protein metabolism and weakly promotes growth by obesity, Syndromic, Malignant, Acral, Unilateral, Drug binding to “classic” insulin receptors at low concentrations. Induced, and Mixed. However, insulin exerts more potent growth-promoting A more simplified classification had been effects through binding to insulin-like growth factor 1 proposed by Hernandez-Perez [13]. He classified AN as receptors (IGF-1Rs) that are similar in size and subunit simple AN (not related to malignancy) and paraneoplastic structure to insulin receptors at higher concentrations. This AN. Burke et al. used a scale of 0-4 based on how many stimulates proliferation of keratinocytes and fibroblasts, areas are affected to classify AN [7].This scale correlates leading to AN [9]. Apart from direct toxic effects, with fasting insulin and body mass index (BMI). Hence it is hyperinsulinemia also acts indirectly by increasing free easy to use and has a high inter-observer reliability. IGF-1 levels in circulation. The activity of IGF-1 is regulated by insulin-like growth binding proteins (IGFBPs), Clinical Features which increase IGF-1 half life, deliver IGFs to target tissues The characteristic feature of AN is dark, coarse, and regulate levels of metabolically active “free” IGF-1. thickening of the skin with a velvety texture which are IGFBP-1 and IGFBP-2 are both decreased in obese usually symmetrically distributed [14]. The initial change individuals with hyperinsulinemia, increasing plasma evident is grey-brown/black pigmentation with dryness and concentrations of free IGF-1, which promotes cell growth roughness of the skin. The affected areas are palpably and differentiation. The etiopathogenesis has been thickened and covered by small papillomatous eruptions, summarized as a flow chart in Table 1. giving it a characteristic velvety texture. With time the The fact that insulin-dependent activation of IGF- thickening increases and the skin lines are further 1Rs can facilitate AN development can be justified by the accentuated. The surface becomes mammilated and following observations: wrinkled, with the development of larger warty out growths 1. IGF receptors can be detected in cultured fibroblasts [15]. AN is usually asymptomatic, but occasionally, it can and keratinocytes. be itchy. The lesions affect back and sides of neck, axillae, 2. Insulin has been demonstrated to cross dermoepidermal groin, and ante-cubital and popliteal areas [14, 15]. Neck is junction and at high concentrations it can stimulate growth the most common site affected (99%) in children when and replication of fibroblasts. compared with axillae (73%). Face, eyelids, flexor and 3. Severity of AN in obesity correlates positively with extensor surface of elbows and knees, dorsa of joints of fasting insulin concentration. hands, umbilicus, external genitalia, inner aspects of thighs Thus, insulin may promote AN through direct and anus are also involved.With extensive involvement, activation of the IGF-1 signaling pathway[10]. The fact that lesions can be found over the areolae, conjunctiva, and lips AN is more common in areas such as neck and axillae [15]. suggests that perspiration and/or friction may be predisposing factors. For AN, other than insulin-receptor Oral Manifestations antibody, unknown autoantibodies have been implicated. Involvement of mucous membranes is relatively This could explain the effectiveness of cyclosporine in rare for AN. But oral mucous membrane may have a treating AN with autoimmune manifestations [11]. Insulin delicate velvety wrinkled appearance in affected and IGF-1 levels are affected by hepatitis C infection and individuals. There may be extensive papillomatosis of the both of them may be implicated in etiopathogenesis of lips, palate, gingiva and tongue in some cases[16]. acrochordons and AN through their proliferative and differentiating properties. Acanthosis nigricans maligna Malignant An (ANM) might be explained by elevated levels of Rarely generalized involvement can be found in transforming growth factor (TGF-α), exerting effects on AN, mostly in adults with underlying malignancy. epidermal tissue through epidermal growth factor (EGF) ‘Acanthosis nigricans maligna’ (ANM) is the term used for receptor. IGF-1, fibroblast growth factor, and melanocyte the malignant variety of AN. In most cases (70-90%), it stimulating hormone α that regulates melanocyte occurs in the course of adenocarcinomas of abdominal pigmentation and stimulates growth of keratinocytes, can organs, particularly gastric cancer followed by play a role in the pathogenesis of hyperplasia and adenocarcinoma of pancreas, ovary, kidneys, bladder, hyperpigmentation. It can occur with endocrine diseases bronchi, thyroid, bile duct, breast, and esophagus [14]. such as Cushing disease and diabetes mellitus, from tumors ANM is clinically indistinguishable from benign forms, but of the pituitary gland, underlying malignancies, certain usually the appearance is sudden and profuse. Frequently 111 | P a g e Prithhwish Kundu et al. / Acta Biomedica Scientia. 2017; 4(3): 110-115. the oral, nasal and laryngeal mucosa, esophagus and areola Dowling-Degos disease of nipple are involved. Papillomatous lesions may be seen It presents as a progressive brown black on the eyelids and conjunctiva. Leukonychia and hyperpigmentation of the flexures withsoft fibromas and hyperkeratosis of nails has also been reported. follicular hyperkeratosis [18]. Acrochordons are often found in affected areas [16]. Warning signs for malignancy in AN patients include age MANAGEMENT >40 years, not having any previous endocrine disorder or The management of AN involves multiple aspects any genetically determined disease, unexplained weight including treatment of underlying disease or tumor,