Chapter 72
Skin Manifestations of Paediatric Metabolic Syndrome
Gregor Holzer,
Beatrix Volc-Platzer,
Gregor Holzer
Department of Dermatology, Donauspital SMZ Ost, Vienna, Austria
Search for more papers by this authorBeatrix Volc-Platzer
Department of Dermatology, Donauspital SMZ Ost, Vienna, Austria
Search for more papers by this authorGregor Holzer,
Beatrix Volc-Platzer,
Gregor Holzer
Department of Dermatology, Donauspital SMZ Ost, Vienna, Austria
Search for more papers by this authorBeatrix Volc-Platzer
Department of Dermatology, Donauspital SMZ Ost, Vienna, Austria
Search for more papers by this authorBook Editor(s):Peter Hoeger,
Veronica Kinsler,
Albert Yan,
John Harper,
Arnold Oranje,
Christine Bodemer,
Margarita Larralde,
David Luk, Vibhu Mendiratta,
Diana Purvis,
Peter Hoeger
Search for more papers by this authorVeronica Kinsler
Search for more papers by this authorAlbert Yan
Search for more papers by this authorJohn Harper
Search for more papers by this authorArnold Oranje
Search for more papers by this authorChristine Bodemer
Search for more papers by this authorMargarita Larralde
Search for more papers by this authorVibhu Mendiratta
Search for more papers by this authorDiana Purvis
Search for more papers by this authorFirst published: 20 November 2019
Summary
Metabolic syndrome (MetS) has emerged as a new epidemic not only in adults but also in children and adolescents. It comprises a cluster of cardiovascular risk factors such as hypertension, visceral obesity, dyslipidaemia and altered glucose metabolism, i.e. glucose intolerance. Visceral obesity and insulin resistance (IR), together with latent inflammation, represent the core pathophysiology. Anthropomorphic and – less easy to measure and compare in young age groups – laboratory parameters are used for diagnosis. Similar to other systemic diseases, skin signs and conditions can provide diagnostic clues to the risk factors of the MetS. (Pseudo-)acanthosis nigricans, fibroma pendulans and striae distensae are significantly associated with obesity, insulin resistance and diabetes. Obesity and diabetes mellitus promote cutaneous infections, such as erysipelas and intertrigo. Skin signs due to hyperandrogenaemia such as acne vulgaris, hirsutism and androgenetic alopecia develop in young females and may be associated with obesity and/or polycystic ovary syndrome (PCOS). Hidradenitis suppurativa is associated with overweight and obesity in both genders. Psoriasis worsens in obese children and young adults, mainly due to the release of proinflammatory cytokines from fat tissue. The association between body mass index and severity of psoriasis has been demonstrated in several cohorts. The high prevalence of the MetS among psoriasis patients is already discernible among paediatric psoriasis patients, as several risk factors of the MetS can be demonstrated in this patient group. Recently, neonatal obesity has been described to be associated with an increased risk of atopic dermatitis (AD) in infancy.
References
- Alberti KG, Zimmet P, Shaw J. The metabolic syndrome – a new worldwide definition. Lancet 2005; 366 (9491): 1059–62.
- Kassi E, Pervanidou P, Kaltsas G, Chrousos G. Metabolic syndrome: definitions and controversies. BMC Medicine 2011; 9: 48.
- Sookoian S, Pirola JC. Non-alcoholic fatty liver disease and metabolic syndrome: shared-genetic basis of pathogenesis. Hepatology 2016; 64: 1417–20.
- Cui J, Chen C-H, Lo M-T et al. Shared genetic effects between hepatic steatosis and fibrosis: a prospective twin study. Hepatology 2016; 64: 1547–58.
- Li Z, Celestin J, Lockey RF. Pediatric sleep apnea syndrome: an update. J Allergy Clin Immunol Pract 2016; 4: 852–61.
- Chen W, Srinivasan SR, Elkasabany A, Berenson GS. Cardiovascular risk factors clustering features of insulin resistance syndrome (Syndrome X) in a biracial (Black-White) population of children, adolescents, and young adults: the Bogalusa Heart study. Am J Epidemiol 1999; 150: 667–74.
- Bahl D, Singh K, Sabharwal, M, Arora M. Anthropometric indices for the prediction of metabolic syndrome and its features, among children and adolescents. Ind J Sci Technol 2014; 7(8): 1066–77.
- Katzmarzyk PT. Prevalence of risk factors for metabolic syndrome in adolescents: National Health and Nutrition Examination Survey (NHANES), 2001–2006. Arch Pediatr Adolesc Med 2009; 163: 371–7.
- Laurson KR, Welk GJ, Eisenmann JC. Diagnostic performance of BMI percentiles to identify adolescents with metabolic syndrome. Pediatrics 2014; 133: e330–8.
- Ford ES, Li C. Defining the metabolic syndrome in children and adolescents: will the real definition please stand up? J Pediatr 2008; 152: 160–4.
- Weiss R. Childhood metabolic syndrome: must we define it to deal with it? Diabetes Care 2011; 34 Suppl 2: S171–6.
- International Diabetes Federation. Criteria of metabolic syndrome in children and adolescents. Available at: www.idf.org/e-library/consensus-statements.html
- Cook S, Weitzman M, Auinger P et al. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988–1994. Arch Pediatr Adolesc Med 2003; 157: 821–7.
- Owens S, Galloway R. Childhood obesity and the metabolic syndrome. Curr Atheroscler Rep 2014; 16(9): 436.
- Napolitano M, Megna M, Monfrecola G. Insulin resistance and skin diseases. Sci World J 2015: 479354.
- Cruz PD Jr, East C, Bergstresser PR. Dermal, subcutaneous, and tendon xanthomas: diagnostic markers for specific lipoprotein disorders. J Am Acad Dermatol 1988; 19(1): 95–111.
- Behm B, Schreml S, Landthaler M, BabilasSkin signs in diabetes mellitus. J Eur Acad Dermatol Venereol 2012; 26: 1203–11.
References
- Chan JC, Tong PC, Critchley JA. The insulin resistance syndrome: mechanisms of clustering of cardiovascular risk. Semin Vasc Med 2002; 2(1): 45–57.
- Weiss R, Bremer AA, Lustig RH. What is metabolic syndrome, and why are children getting it? Ann N Y Acad Sci 2013; 1281: 123–40.
- Reaven GM. Banting Lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37(12): 1595–607.
- Eckel RH, Alberti KG, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2010; 375(9710): 181–3.
- Tritos NA, Mantzoros CS. Clinical review 97: syndromes of severe insulin resistance. J Clin Endocrinol Metab 1998; 83(9): 3025–30.
- Napolitano M, Megna M, Monfrecola G. Insulin resistance and skin diseases. Sci World J 2015: 479354.
- Cruz PD Jr, Hud JA Jr. Excess insulin binding to insulin-like growth factor receptors: proposed mechanism for acanthosis nigricans. J Invest Dermatol 1992; 98: 82S–5S.
- Flier JS, Usher P, Moses AC. Monoclonal antibody to the type I insulin-like growth factor (IGF-I) receptor blocks IGF-I receptor-mediated DNA synthesis: clarification of the mitogenic mechanisms of IGF-I and insulin in human skin fibroblasts. Proc Natl Acad Sci USA 1986: 83: 664–8.
- Siddle K, Urso B, Niesler CA et al. Specificity in ligand binding and intracellular signalling by insulin and insulin-like growth factor receptors. Biochem Soc Trans 2001; 29(Pt 4): 513–25.
- Flier JS, Usher P, Moses AC. Monoclonal antibody to the type I insulin-like growth factor (IGF-I) receptor blocks IGF-I receptor-mediated DNA synthesis: clarification of the mitogenic mechanisms of IGF-I and insulin in human skin fibroblasts. Proc Natl Acad Sci USA 1986: 83: 664–8.
- Conover CA, Hintz RI, Rosenfeld RG. Comparative effects of somatomedin C and insulin on the metabolism and growth of cultured human fibroblasts. J Cell Physiol 1985; 122: 133–41.
- Thomopoulos P, Roths T. Insulin receptors in normal and transformed fibroblasts: relationship to growth and transformation. Cell 1976; 8: 417–23.
- Mirsa P, Nickoloff BJ, Morhenn VB et al. Characterization of insulin-like growth factor-1/somatomedin C receptors on human keratinocyte monolayers. J Invest Dermatol 1986; 87: 264–7.
- Verrando P, Ortonne JP. Insulin binding properties of normal and transformed human epidermal cultured keratinocytes. J Invest Dermatol 1985; 85: 328–32.
- Pugeat,M, Crave JC, Elmidani M et al. Pathophysiology of sex hormone binding globulin (SHBG): relation to insulin. J Steroid Biochem Mol Biol 1991; 40(4–6): 841–9.
- Willis D, Mason H, Gilling-Smith C, Franks S. Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries. J Clin Endocrinol Metab 1996; 81(1): 302–9.
- Yildiz, BO, Azziz R. The adrenal and polycystic ovary syndrome. Rev Endocr Metab Disord 2007; 8(4): 331–42.
- Horton R, Pasupuletti V, Antonipillai I. Androgen induction of steroid 5 alpha-reductase may be mediated via insulin-like growth factor-I. Endocrinology 1993; 133(2): 447–51.
- Melnik BC, Zouboulis CC. Potential role of FoxO1 and mTORC1 in the pathogenesis of Western diet-induced acne. Exp Dermatol 2013; 22(5): 311–15.
- Melnik BC, Schmitz G. Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris. Exp Dermatol 2009; 18(10): 833–41.
- Smith RN, Mann NJ, Braue A et al. The effect of a high-protein, low glycemic-load diet versus a conventional, high glycemic-load diet on biochemical parameters associated with acne vulgaris: a randomized, investigator-masked, controlled trial. J Am Acad Dermatol 2007; 57(2): 247–56.
- Rich-Edwards JW, Ganmaa D, Pollak M et al. Milk consumption and the prepubertal somatotropic axis. Nutr J 2007; 6: 28.
- Coimbra S, Catarino C, Santos-Silva A. The triad psoriasis-obesity-adipokine profile. J Eur Acad Dermatol Venereol 2016; 30(11): 1876–85.
- Wang YJ. Chen Y. Zhao L et al. Psoriasis is associated with increased levels of serum leptin. Br J Dermatol 2008; 158(5): 1134–5.
- Oh YJ, Lim HK, Choi JH et al. Serum leptin and adiponectin levels in Korean patients with psoriasis. J Korean Med Sci 2014; 29(5): 729–34.
- Koebnick C, Black MH, Smith N. The association of psoriasis and elevated blood lipids in overweight and obese children. J Pediatr 2011; 159(4): 577–83.
- Armstrong AW, Harskamp CT, Armstrong EJ. Psoriasis and the risk of diabetes mellitus: a systematic review and meta-analysis. JAMA Dermatol 2013; 149(1): 84–91.
- Paller AS, Mercy K, Kwasny MJ et al. Association of pediatric psoriasis severity with excess and central adiposity: an international cross-sectional study. JAMA Dermatol 2013; 149(2): 166–76.
- Becker L, Tom WL, Eshagh K et al. Excess adiposity preceding pediatric psoriasis. JAMA Dermatol 2014; 150(5): 573–4.
- Yim KM, Armstrong AW. Updates on cardiovascular comorbidities associated with psoriatic diseases: epidemiology and mechanisms. Rheumatol Int 2017; 37: 97–105.
- Boehncke WH, Buerger C, Boehncke S. Co-morbidities in psoriasis vulgaris. Hautarzt 2009; 60(2): 116–21.
References
- Kong AS, Vanderbloemen L, Skipper B et al. Acanthosis nigricans predicts the clustering of metabolic syndrome components in Hispanic elementary school-aged children. J Pediatr Endocr Met 2012; 25: 1095–102.
- Stuart CA, Pate CJ, Peters EJ. Prevalence of acanthosis nigricans in an unselected population. Am J Med 1989; 87: 269–72.
- Schwartz RA. Acanthosis nigricans. J Am Acad Dermatol 1994; 31: 1–19.
- Rogers DL. Acanthosis nigricans. Semin Dermatol 1991; 10: 161–3.
- Wolff K, Johnson RA, Saavedra AP. Acanthosis nigricans. In: Color Atlas and Synopsis of Clinical Dermatology. New York: McGraw Hill Education, 2013.
- Hirokawa M, Matsumoto M, Iizuka H. Confluent and reticulated papillomatosis: a case with concurrent acanthosis nigricans associated with obesity and insulin resistance. Dermatology 1994; 188(2): 148–51.
- Mesquita-Guimaraes J. X-linked ichthyosis. Ultrastructural study of 4 cases. Dermatology 1981; 162: 157–66.
- Guarnieri C, Guarnieri F, Cannavo SP. Terra firma-forme dermatosis. Int J Dermatol 2008; 47: 482–4.
- Browning J, Rosen T. Terra firma-forme dermatosis revisited. Dermatol Online J 2005; 11: 15.
- Pinder VAE, Eriyagama S, Saracino A, Moosa Y. Terra firma-forme dermatosis: another cause of reticulate pigmentation. Clin Exp Dermatol 2012; 37: 446–7.
- Curth HO. Benign type of acanthosis nigricans. Arch Dermatol 1936; 34: 353–66.
- Curth HO. Acanthosis nigricans. Birth Defects Orig Artic Ser 1971; 7(8): 31–9.
- Curth HO, Hilberg AW, Machacek GF et al. The site and histology of the cancer associated with acanthosis nigricans. Cancer 1962; 15: 433–9.
- Higgins SP, Freemark, M, Prose NS. Acanthosis nigricans: a practical approach to evaluation and management. Dermatol Online J 2008; 14(9): 2.
- 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: 739–45.
- Berk DR, Spector EB, Bayliss SJ. Familial acanthosis nigricans due to K650T FGFR3 mutation. JAMA Dermatol 2007; 143: 1153–6.
- Napolitano M, Megna M, Monfrecola G. Insulin resistance and skin diseases. Sci World J 2015: 479354.
- Schilling WH, Crook MA. Cutaneous stigmata associated with insulin resistance and increased cardiovascular risk. Int J Dermatol 2014; 53: 1062–9.
- Cruz PD Jr, Hud JA Jr. Excess insulin binding to insulin-like growth factor receptors: proposed mechanism for acanthosis nigricans. J Invest Dermatol 1992; 98: 82S–85S.
- Thomopoulos P, Roths T. Insulin receptors in normal and transformed fibroblasts: relationship to growth and transformation. Cell 1976; 8: 417–23.
- Mirsa P, Nickoloff BJ, Morhenn VB et al. Characterization of insulin-like growth factor-1/somatomedin C receptors on human keratinocyte monolayers. J Invest Dermatol 1986; 87: 264–7.
- Verrando P, Ortonne JP. Insulin binding properties of normal and transformed human epidermal cultured keratinocytes. J Invest Dermatol 1985; 85: 328–32.
- Dassanayake AS, Kasturiratne A, Niriella MA et al. Prevalence of acanthosis nigricans in an urban population in Sri Lanka and its utility to detect metabolic syndrome. BMC Res Notes 2011; 4: 25.
- Litonjua P, Pinero-Pilona A, Aviles-Santa L et al. Prevalence of acanthosis nigricans in newly-diagnosed type 2 diabetes. Endocr Pract 2004; 10: 101–6.
- Brickman WJ, Huang J, Silverman BL et al. Acanthosis nigricans identifies youth at high risk for metabolic abnormalities. J Pediatr 2010; 156: 87–92.
- Stuart CA, Gilkison CR, Smith MM et al. Acanthosis nigricans as a risk factor for non-insulin dependent diabetes mellitus. Clin Pediatr 1998; 37: 73–9.
- Orfanos CE, Adler YD, Zouboulis CC.The SAHA syndrome. Horm Res 2000; 54: 251–8.
- Schmidt TH, Khanijow K, Cedars MI et al. Cutaneous findings and systemic associations in women with polycystic ovary syndrome. JAMA Dermatol 2016; 152: 391–8.
- Bellot-Rojas P, Posadas-Sanchez R, Caracas-Portilla N et al. Comparison of metformin versus rosiglitazone in patients with Acanthosis nigricans: a pilot study. J Drugs Dermatol 2006; 5: 884–9.
- Tankova T, Koev D, Dakovska L, Kirilov G. Therapeutic approach in insulin resistance with acanthosis nigricans. Int J Clin Pract 2002; 56: 578–81.
- Berger BJ, Gross PR. Another use for tretinoin-pseudoacanthosis nigricans. Arch Dermatol 1973; 108: 133–4.
- Darmstadt GL, Yokel BK, Horn TD. Treatment of acanthosis nigricans with tretinoin. Arch Dermatol 1991; 127: 1139–40.
- Blobstein SH. Topical therapy with tretinoin and ammonium lactate for acanthosis nigricans for acanthosis nigricans associated with obesity. Cutis 2003; 71: 33–4.
- Katz RA. Treatment of acanthosis nigricans with oral isotretinoin. Arch Dermatol 1980; 116: 110–11.
- Ozdemir M, Toy H, Mevlitoglu I, Demirkesen C. Generalized idiopathic acanthosis nigricans treated with acitretin. J Dermatol Treat 2006; 17: 54–6.
- Walling HW, Messingham M, Myers LM et al. Improvement of acanthosis nigricans on isotretinoin and metformin. J Drugs Dermatol 2003; 2: 677–81.
- Kuzuya H, Matsuura N, Sakamoto M et al. Trial of insulin-like growth factor I therapy for patients with extreme insulin resistance syndromes. Diabetes 1993; 42: 696–705.
- Downs AM, Kennedy CT. Somatotrophin-induced acanthosis nigricans. Br J Dermatol 1999; 141: 390–1.
- Böhm M, Luger TA, Metze D. Treatment of mixed-type acanthosis nigricans with topical calcipotriol. Br J Dermatol 1998; 139: 932–4.
- Lee HW, Chang SE, Lee MW et al. Hyperkeratosis of the nipple associated with acanthosis nigricans: treatment with topical calcipotriol. J Am Acad Dermatol 2005; 52: 529–30.
- Rosenbach A, Ram R. Treatment of acanthosis nigricans of the axillae using a long-pulsed (5-msec) alexandrite laser. Dermatol Surg 2004; 30: 1158–60.
- Chobanian AV, Bakris GL, Black HR et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: 2560–72.
- Knowler WC, Barrett-Connor E, Fowler SE et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393–403.
References
- Al-Himdani S, Ud-Din S, Gilmore S, Bayat A. Striae distensae: a comprehensive review and evidence-based evaluation of prophylaxis and treatment. Br J Dermatol 2014; 170 (3): 527–47.
- Muzaffar F1, Hussain I, Haroon TS Physiologic skin changes during pregnancy: a study of 140 cases Int J Dermatol 1998; 37(6): 429–31.
- Ammar NM, Rao B, Schwartz RA, Janniger CK Adolescent striae Cutis 2000; 65(2): 69–70.
- Thomas RGR, Liston WA. Clinical associations of striae gravidarum. J Obstet Gynaecol 2004; 24: 270–1.
- Di Lernia V, Bonci A, Cattania M et al. Striae distensae (rubrae) in monozygotic twins. Pediatr Dermatol 2001; 18: 261–2.
- McKusick VA. Transverse striae distensae in the lumbar area in father and two sons. Birth Defects Orig Artic Ser 1971; 58: 169–76.
- Pinkus H, Keech MK, Mehregan AH. Histopathology of striae distensae, with special reference to striae and wound healing in the Marfan syndrome. J Invest Dermatol 1966; 46: 283–92.
- Davey CM. Factors associated with the occurrence of striae gravidarum. J Obstet Gynaecol Br Commonw 1972; 79: 1113–14.
- Hermanns JF, Pierard GE. High-resolution epiluminescence colorimetry of striae distensae. J Eur Acad Dermatol Venereol 2006; 20: 282–7.
- Elsaie ML, Baumann LS, Elsaaiee LT. Striae distensae (stretch marks) and different modalities of therapy: an update. Dermatol Surg 2009; 35: 563–73.
- Kang S. Topical tretinoin therapy for management of early striae. J Am Acad Dermatol 1998; 39: S90–2.
- Mallol J, Belda MA, Costa D et al. Prophylaxis of striae gravidarum with a topical formulation. A double blind trial. Int J Cosmet Sci 1991; 13: 51–7.
- Watson RE, Parry EJ, Humphries JD et al. Fibrillin microfibrils are reduced in skin exhibiting striae distensae. Br J Dermatol 1998; 138: 931–7.
- Davey CM. Factors associated with the occurrence of striae gravidarum. J Obstet Gynaecol Br Commonw 1972; 79: 1113–14.
- Atwal GS, Manku LK, Griffiths CE, Polson DW. Striae gravidarum in primiparae. Br J Dermatol 2006; 155(5): 965–9.
- Pierard-Franchimont C, Hermanns JF, Hermanns-Le T et al. Striae distensae in darker skin types: the influence of melanocyte mechanobiology. J Cosmet Dermatol 2005; 4: 174–8.
- Kang S, Kim KJ, Griffiths CE et al. Topical tretinoin (retinoic acid) improves early stretch marks. Arch Dermatol 1996; 132: 519–26.
- Elson ML. Treatment of striae distensae with topical tretinoin. J Dermatol Surg Oncol 1990; 16: 267–70.
- Ash K, Lord J, Zukowski M et al. Comparison of topical therapy for striae alba (20% glycolic acid/0.05% tretinoin versus 20% glycolic acid/10% L-ascorbic acid. Dermatol Surg 1998; 24: 849–56.
References
- Napolitano M, Megna M, Monfrecola G. Insulin resistance and skin diseases. ScientificWorldJournal 2015: 479354.
- Sudy E, Urbina F, Maliqueo M, et al. Screening of glucose/insulin metabolic alterations in men with multiple skin tags on the neck. J Dtsch Dermatol Ges 2008; 6: 852–6.
- Rasi A, Soltani-Arabshahi R, Shabazi N. Skin tags as a cutaneous marker for impaired carbohydrate metabolism: a case control study. Int J Dermatol 2007; 46: 1155–9.
References
- Bergman R, Kasif Y, Aviram M et al. Normolipidemic xanthelasma palpebrarum: lipid composition, cholesterol metabolism in monocyte-derived macrophages, and plasma lipid peroxidation. Acta Derm Venereol 1996; 76: 107–110.
- Segal P, Insull W Jr, Chambless LE et al. The association of dyslipoproteinemia with corneal arcus and xanthelasma. The Lipid Research Clinics Program Prevalence Study. Circulation 1986; 73: I108–18.
- Ribera M, Pinto X, Argimon JM et al. Lipid metabolism and apolipoprotein E phenotypes in patients with xanthelasma. Am J Med 1995; 99: 485–90.
- Schilling WH, Crook MA. Cutaneous stigmata associated with insulin resistance and increased cardiovascular risk. Int J Dermatol 2014; 53: 1062–9.
- Cruz PD Jr, East C, Bergstresser PR. Dermal, subcutaneous, and tendon xanthomas: diagnostic markers for specific lipoprotein disorders. J Am Acad Dermatol;1988; 19(1): 95–111.
- Hachem SB, Mooradian AD. Familial dyslipidaemias: an overview of genetics, pathophysiology and management. Drugs;2006; 66(15): 1949–69.
- Bito T, Kawakami C, Shimajiri S et al. Generalized eruptive xanthoma with prominent deposition of naked chylomicrons: evidence for chylomicrons as the origin of urate-like crystals. J Cutan Pathol 2010; 37: 1161–7.
- Naik S. Eruptive xanthomas. Dermatol Online J 2001; 7: 11.
- Renner R, Teuwen I, Harth W et al. Eruptive xanthomas with hypertriglyceridaemia. Hautarzt 2008; 59: 995–9.
References
- Behm B, Schreml S, Landthaler M, BabilasSkin signs in diabetes mellitus. J Eur Acad Dermatol 2012; 26: 1203–11.
- Genoni G, Prodam F, Marolda A et al. Obesity and infection: two sides of one coin. Eur J Pediatr 2014; 173(1): 25–32.
- Romano G, Moretti G, di Benedetto A et al. Skin lesions in diabetes mellitus: prevalence and clinical correlations. Diabetes Res Clin Pract 1998; 39(2): 101–6.
- de Macedo GM, Nunes S, Barreto T. Skin disorders in diabetes mellitus: an epidemiology and physiopathology review. Diabetol Metab Syndr 2016; 8(1): 63.
- Wolff K, Johnson RA, Saavedra AP. Color Atlas and Synopsis of Clinical Dermatology. New York: McGraw Hill Education, 2013.
- Yosipovitch G, de Vore A, Dawn A. Skin surface pH in intertriginous areas in NIDDM patients. Possible correlation to candidal intertrigo. Diabetes Care 1993; 16(4): 560–3.
- Chang SJ, Hsu SC, Tien KJ et al. Metabolic syndrome associated with toenail onychomycosis in Taiwanese with diabetes mellitus. Int J Dermatol 2008; 47(5): 467–72.
- Hamilton EJ, Martin N, Makepeace A et al. Incidence and predictors of hospitalization for bacterial infection in community-based patients with type 2 diabetes: the fremantle diabetes study. PLoS One 2013; 8(3): e60502.
- Goh T, Goh LG, Ang CH, Wong CH. Early diagnosis of necrotizing fasciitis. Br J Surg 2014; 101(1): e119–25.
- Pearson-Stuttard J, Blundell S, Harris T et al. Diabetes and infection: assessing the association with glycaemic control in population-based studies. Lancet Diabetes Endocrinol 2016; 4(2): 148–58.
- Morgan AJ, Schwartz RA. Diabetic dermopathy: a subtle sign with grave implications. J Am Acad Dermatol 2008; 58: 447–51.
- Sibbald RG, Landolt SJ, Toth D. Skin and diabetes. Endocrinol Metab Clin North Am 1996; 25: 463–72.
- Valle Jimenez M, Estepa RM, Camacho RM et al. Endothelial dysfunction is related to insulin resistance and inflammatory biomarker levels in obese prepubertal children. Eur J Endocrinol 2007; 156(4): 497–502.
- Shemer A, Bergman R, Linn S et al. Diabetic dermopathy and internal complications in diabetes mellitus. Int J Dermatol 1998; 37: 113–15.
- Jelinek JE. Cutaneous manifestations of diabetes mellitus. Int J Dermatol 1994; 33(9): 605–17.
- Bernstein JE, Medenica M, Soltani K et al. Bullous eruption of diabetes mellitus. Arch Dermatol 1979; 115: 324–5.
- Hwang JH, Cho KH, Park KC et al. A case of congenital scleredema. Clin Exp Dermatol 1998; 23(3): 139–40.
- Rho YW, Suhr KB, Lee JH, Park JK. A clinical observation of scleredema adultorum and its relationship to diabetes. J Dermatol 1998; 25(2): 103–7.
- Huntley AC. Finger pebbles: a common finding in diabetes mellitus. J Am Acad Dermatol 1986; 14: 612–17.
- Guarnieri C, Guarnieri F, Borgia F et al. Finger pebbles in a diabetic patient: Huntley's papules. Int J Dermatol 2005; 44: 755–6.
- Hollister DS, Brodell RT. ‘Finger pebbles’. A dermatologic sign of diabetes mellitus. Postgrad Med 2000; 107: 209–10.
- Martinon-Torres F, Martinon-Sanchez JM, Martinon-Sanchez F. Localized granuloma annulare in children. A review of 42 cases. Eur J Pediatr 1999; 158(10): 866.
- Friedman-Birnbaum R, Haim S, Gideone O, Barzilai A. Histocompatibility antigens in granuloma annulare. Comparative study of the genetics of the generalized and localized types. Br J Dermatol 1978; 98(4): 425–8.
- Felner EI, Steinberg JB, Weinberg AG. Subcutaneous granuloma annulare: a review of 47 cases. Pediatrics 1997; 100(6): 965–7.
- Cyr PR. Diagnosis and management of granuloma annulare. Am Fam Physician 2006; 74(10): 1729–34.
- Plotner AN, Mutasim DF. Successful treatment of disseminated granuloma annulare with methotrexate. Br J Dermatol 2010; 163(5): 1123–4.
- De Silva BD, Schofield OM, Walker JD. The prevalence of necrobiosis lipoidica in children with type 1 diabetes. Br J Dermatol 1999; 141(3): 593–4.
- Reid SD, Ladizinski B, Lee K et al. Update on necrobiosis lipoidica: a review of etiology, diagnosis, and treatment options. J Am Acad Dermatol 2013; 69: 783–91.
- Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum histopathologic study of 98 cases. Arch Dermatol 1966; 94: 1–10.
- O'Toole EA, Kennedy U, Nolan JJ et al. Necrobiosis lipoidica: only a minority of patients have diabetes mellitus. Br J Dermatol 1999; 140: 283–6.
- Davison JE, Davies A, Moss C et al. Links between granuloma annulare, necrobiosis lipoidica diabeticorum and childhood diabetes: a matter of time? Pediatr Dermatol 2010; 27(2): 178–81.
References
- Kurzen H, Kurokawa I, Jemec G et al. What causes hidradenitis suppurativa? Exp Dermatol 2008; 17(5): 455–6; discussion 457–72.
- Sellheyer K, Krahl D. ‘Hidradenitis suppurativa’ is acne inversa! An appeal to (finally) abandon a misnomer. Int J Dermatol 2005; 44(7): 535–40.
- Scheinfeld N. Hidradenitis suppurativa in prepubescent and pubescent children. Clin Dermatol 2015; 33(3): 316–19.
- Mengesha YM, Holcombe TC, Hansen RC. Prepubertal hidradenitis suppurativa: two case reports and review of the literature. Pediatr Dermatol 1999; 16(4): 292–6.
- Palmer RA, Keefe M. Early-onset hidradenitis suppurativa. Clin Exp Dermatol 2001; 26(6): 501–3.
- Deckers IE, van der Zee H, Boer J, Prens E. Correlation of early-onset hidradenitis suppurativa with stronger genetic susceptibility and more widespread involvement. J Am Acad Dermatol 2015; 72(3): 485–8.
- Liy-Wong C, Pope E, Lara-Corrales I. Hidradenitis suppurativa in the pediatric population. J Am Acad Dermatol 2015; 73 (5 Suppl 1): S36–41.
- Lewis F, Messenger AG, Wales JK. Hidradenitis suppurativa as a presenting feature of premature adrenarche. Br J Dermatol 1993; 129(4): 447–8.
- Harrison BJ, Read GF, Hughes LE. Endocrine basis for the clinical presentation of hidradenitis suppurativa. Br J Surg 1988; 75(10): 972–5.
- Miller IM, Ellervik C, Vinding G et al. Association of metabolic syndrome and hidradenitis suppurativa. JAMA Dermatol 2014; 150(12): 1273–80.
- Canoui-Poitrine F, Revuz J, Wolkenstein P et al. Clinical characteristics of a series of 302 French patients with hidradenitis suppurativa, with an analysis of factors associated with disease severity. J Am Acad Dermatol 2009; 61(1): 51–7.
- Kromann CB, Ibler K, Kristiansen V, Jemec G. The influence of body weight on the prevalence and severity of hidradenitis suppurativa. Acta Derm Venereol 2014; 94(5): 553–7.
- Karagiannidis I, Nikolakis G, Zouboulis CC. Endocrinologic aspects of hidradenitis suppurativa. Dermatol Clin 2016; 34(1): 45–9.
- Coimbra S, Catarino C, Santos-Silva A. The triad psoriasis-obesity-adipokine profile. J Eur Acad Dermatol Venereol 2016; 30(11): 1876–85.
- Sabat R, Chanwangpong A, Schneider-Burrus S, et al. Increased prevalence of metabolic syndrome in patients with acne inversa. PLoS One 2012; 7(2): e31810.
- Gold DA, Reeder V, Mahan M, Hamzavi I. The prevalence of metabolic syndrome in patients with hidradenitis suppurativa. J Am Acad Dermatol 2014; 70(4): 699–703.
- Verdolini R, Clayton N, Smith A, et al. Metformin for the treatment of hidradenitis suppurativa: a little help along the way. J Eur Acad Dermatol Venereol 2013; 27(9): 1101–8.
References
- Franks S. Polycystic ovary syndrome in adolescents. Int J Obes 2008; 32(7): 103541.
- Azziz R, Woods K, Reyna R et al. The prevalence and features of the polycystic ovary syndrome in anunselected population. J Clin Endocrinol Metab 2004; 89(6): 2745–9.
- Mehrabian F, Khani B, Kelishadi R, Ghanbari E. The prevalence of polycystic ovary syndrome in Iranian women based ondifferent diagnostic criteria. Endokrynol Pol 2011; 62(3): 238–42.
- Christensen SB, Black M, Smith N et al. Prevalence of polycystic ovary syndrome in adolescents. Fertil Steril 2013; 100(2): 470–7.
- Dokras A, Bochner M, Hollinrake E et al. Screening women with polycystic ovary syndrome for metabolic syndrome. Obstet Gynecol 2005; 106(1): 131–7.
- Leibel NI, Baumann E, Kocherginsky M, Rosenfield R. Relationship of adolescent polycystic ovary syndrome to parental metabolicsyndrome. J Clin Endocrinol Metab 2006; 91(4): 1275–83.
- Coviello AD, Legro RS, Dunaif A. Adolescent girls with polycystic ovary syndrome have an increased risk of the metabolic syndrome associated with increasing androgen levels independent of obesity and insulin resistance. J Clin Endocrinol Metab 2006; 91(2): 492–7.
- Nelson,VL, Kin K, Rosenfield R et al. The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. J Clin Endocrinol Metab 2001; 86(12): 5925–33.
- Rosenfield RL. Polycystic ovary syndrome and insulin-resistant hyperinsulinemia. J Am Acad Dermatol 2001; 45(3 Suppl): S95–104.
- Pugeat, M, Crave J, Elmidani M et al. Pathophysiology of sex hormone binding globulin (SHBG): relation to insulin. J Steroid Biochem Mol Biol 1991; 40(4–6): 841–9.
- Yildiz BO, Azziz R. The adrenal and polycystic ovary syndrome. Rev Endocr Metab Disord 2007; 8(4): 331–42.
- McCartney CR, Prendergast K, Chhabra S et al. The association of obesity and hyperandrogenemia during thepubertal transition in girls: obesity as a potential factor in the genesis of postpubertal hyperandrogenism. J Clin Endocrinol Metab 2006; 91(5): 1714–22.
- Anderson AD, Solorzano CM, McCartney CR. Childhood obesity and its impact on the development of adolescent PCOS. Semin Reprod Med 2014; 32(3): 202–13.
- Hoeger K. Obesity and weight loss in polycystic ovary syndrome. Obstet Gynecol Clin North Am 2001; 28(1): 85–97, vi–vii.
- Azziz R, Carmina E, Dewailly D et al. Positions statement: criteria for defining polycystic ovary syndrome as apredominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006; 91(11): 4237–45.
- Witchel SF, Oberfield S, Rosenfield R et al. The diagnosis of polycystic ovary syndrome during adolescence. Horm Res Paediatr 2015; 1 Apr (epub ahead of print).
- Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81(1): 19–25.
- Wild RA, Carmina E, Diamanti-Kandarakis E et al. Assessment of cardiovascular risk and prevention of cardiovascular diseasein women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab 2010; 95(5): 2038–49.
- Hudecova M, Jan H, Christian B, Poromaa-Inger S. Long-term reproductive and metabolic consequences of PCOS. Curr Diabetes Rev 2012; 8(6): 444–51.
- Giudice LC. Endometrium in PCOS: implantation and predisposition to endocrine CA. Best Pract Res Clin Endocrinol Metab 2006; 20(2): 235–44.
- Ehrmann DA. Metabolic dysfunction in PCOS: relationship to obstructive sleep apnea. Steroids 2012; 77(4): 290–4.
- Hossain N, Stepanova M, Afendy A et al. Non-alcoholic steatohepatitis (NASH) in patients with polycystic ovariansyndrome (PCOS). Scand J Gastroenterol 2011; 46(4): 479–84.
- Barry JA, Kuczmierczyk A, Hardiman P. Anxiety and depression in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod 2011; 26(9): 2442–51.
- Lucky AW. Hormonal correlates of acne and hirsutism. Am J Med 1995; 98(1A):89S94S.
- Spritzer PM, Motta A. Adolescence and polycystic ovary syndrome: current concepts on diagnosis and treatment. Int J Clin Pract 2015; 69(11): 1236–46.
- Conway GS, Honour J, Jacobs H. Heterogeneity of the polycystic ovary syndrome: clinical, endocrine and ultrasound features in 556 patients. Clin Endocrinol 1989; 30(4): 459–70.
- Archer JS, Chang R. Hirsutism and acne in polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 2004; 18(5): 737–54.
- Falsetti L, Gambera A, Platto C, Legrenzi L. Management of hirsutism. Am J Clin Dermatol 2000; 1(2): 89–99.
- Lowenstein EJ. Diagnosis and management of the dermatologic manifestations of thepolycystic ovary syndrome. Dermatol Ther 2006; 19(4): 210–23.
- Housman E, Reynolds RV. Polycystic ovary syndrome: a review for dermatologists: Part I. Diagnosis and manifestations. J Am Acad Dermatol 2014; 71(5): 847.
- Rosenfield RL. The diagnosis of polycystic ovary syndrome in adolescents. Pediatrics 2015; 136(6): 1154–65.
- Falsetti L, Gambera A, Andrico S, Sartori E. Acne and hirsutism in polycystic ovary syndrome: clinical, endocrine-metabolic and ultrasonographic differences. Gynecol Endocrinol 2002; 16(4): 275–84.
- Schmidt TH, Khanijow K, Cedars M et al. Cutaneous findings and systemic associations in women with polycystic ovary syndrome. JAMA Dermatol 2016; 152(4): 391–8.
- Carmina E, Rosato F, Janni A et al. Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism. J Clin Endocrinol Metab 2006; 91(1): 2–6.
- Dunaif A, Green G, Phelps R et al. Acanthosis nigricans, insulin action, and hyperandrogenism: clinical, histological, and biochemical findings. J Clin Endocrinol Metab 1991; 73(3): 590–5.
- Orfanos CE, Adler Y, Zouboulis C. The SAHA syndrome. Horm Res 2000; 54(5–6): 251–8.
- Dalamaga, M, Papadavid E, Basios G et al. Ovarian SAHA syndrome is associated with a more insulin-resistant profile and represents an independent risk factor for glucose abnormalities in women with polycystic ovary syndrome: a prospective controlled study. J Am Acad Dermatol 2013; 69(6): 922–30.
- Elmer KB, George R. HAIR-AN syndrome: a multisystem challenge. Am Fam Physician 2001; 63(12): 2385–90.
- Tsikouras P, Spyros L, Manav B et al. Features of polycystic ovary syndrome in adolescence. J Med Life 2015; 8(3): 291–6.
- Glueck CJ, Goldenberg N, Pranikoff J et al. Effects of metformin-diet intervention before and throughout pregnancy on obstetric and neonatal outcomes in patients with polycystic ovary syndrome. Curr Med Res Opin 2013; 29(1): 55–62.
- Buzney E, Sheu J, Buzney C, Reynolds R. Polycystic ovary syndrome: a review for dermatologists: Part II. Treatment. J Am Acad Dermatol 2014; 71(5): 859.
- Geller DH, Pacaud D, Gordon C et al. State of the art review: emerging therapies: the use of insulin sensitizers in the treatment of adolescents with polycystic ovary syndrome (PCOS). Int J Pediatr Endocrinol 2011; 2011: 9.
References
- Boccardi D, Menni S, La Vecchia C et al. Overweight and childhood psoriasis. Br J Dermatol 2009; 161: 484–6.
- Ozden MG, Tekin NS, Gürer MA et al. Environmental risk factors in pediatric psoriasis: a multicenter case-control study. Pediatr Dermatol 2011; 28(3): 306–12.
- Koebnick C, Black MH, Smith N et al. The association of psoriasis and and elevated blood lipids in overweight and obese children. J Pediatr 2011; 159(4): 577–83.
- Au S-C, Goldminz AM, Loo DS et al. Association between pediatric psoriasis and the metabolic syndrome. J Am Acad Dermatol 2012; 66(6): 1012–13.
- de Ferranti SD, Gauvreau K, Ludwig DS et al. Prevalence of the metabolic syndrome in American adolescents: findings from the third National Health and Nutrition Examination Survey. Circulation 2004; 110: 2494–7.
- Paller AS, Mercy K, Kwasny MJ et al. Association of pediatric psoriasis severity with excess and central adiposity. JAMA Dermatol 2013; 149(2): 166–77.
- Augustin M, Glaeske G, Radtke MA et al. Epidemiology and comorbidity of psoriasis in children. Br J Dermatol 2010; 162(3): 633–6.
- Shipman AR, Millington GW. Obesity and the skin. Br J Dermatol 2011; 165: 743–50.
- Avram MM, Avram AS, James WD. Subcutaneous fat in normal and diseased states: 1. Introduction. J Am Acad Dermatol 2005; 56: 663–70.
- Lu Y, Chen H, Nikamo P et al. Association of cardiovascular and metabolic disease genes with psoriasis. J Invest Dermatol 2013; 133(3): 836–9.
- Nestle F, Kaplan D, Barker J. Psoriasis. N Engl J Med 2009; 361: 496–509.
- Shlyankevich J, Mehta N, Krueger J et al. Accumulating evidence for the association and shared pathogenic mechanisms between psoriasis and cardiovascular-related co-morbidities. Am J Med 2014; 127: 1148–53.
- Bergboer JGM, Ostveen AM, de Jager MEA et al. Paediatric-onset psoriasis is associated with ERAP1 and IL23R loci, LCE3C_LCE3B deletion and HLA-C*06 . Br J Dermatol 2012; 167: 922–5.
- Herron MD, Hinckley M, Hoffman MS et al. Impact of obesity and smoking on psoriasis: presentation and management. Arch Dermatol 2005; 141(12): 1527–34.
- Beck L, Tom WL, Eshagh K et al. Excess adiposity preceding pediatric psoriasis. JAMA Dermatol 2014; 150(5): 573–4.
- Lee A, Smith SD, Hong E et al. Association between pediatric psoriasis and waist-to-height ratio in the absence of obesity: a multicenter Australian study. JAMA Dermatol 2016; 152: 1314–19.
- Burden-Teh E, Thomas KS, Ratib S et al. The epidemiology of childhood psoriasis: a scoping review. Br J Dermatol 2016; 174: 1242–57.
- Bronckers IMGJ, Paller AS, van Geel MJ et al. Psoriasis in children and adolescents: diagnosis, management and comorbidities. Pediatr Drugs 2015; 17: 373–84.
- Mahé E, Maccari F, Beauchet A et al. Childhood-onset psoriasis: association with future cardiovascular and metabolic comorbidities. Br J Dermatol 2013; 169: 889–95.
References
- Silverberg JI, Kleiman E, Lev-Tov H et al. Association between obesity and atopic dermatitis in childhood: a case-control study. J Allergy Clin Immunol 2011; 127(5): 1180–6.
- Zhang A, Silverberg JI. Association of atopic dermatitis with being overweight and obese: a systematic review and metaanalysis. J Am Acad Dermatol 2015; 72(4): 606–16.
- Silverberg JI, Becker L, Kwasny M et al. Central obesity and high blood pressure in pediatric patients with atopic dermatitis. JAMA Dermatol 2015; 151(2): 144–52.
- Silverberg JI, Greenland P. Eczema and cardiovascular risk factors in 2 US adult population studies. J Allergy Clin Immunol 2015; 135(3): 721–8.
- Yamanaka K, Mizutani H. ‘Inflammatory skin march’: IL-1-mediated skin inflammation, atopic dermatitis, and psoriasis to cardiovascular events. J Allergy Clin Immunol 2015; 136(3): 823–4.
