Abstract
The skin is the largest and most visible organ in the body and can give diagnostic clues of systemic illness. These clues often become obscured through the normal aging process. The purpose of this review is to give an overview of the normal skin changes seen with aging and then discuss new findings with regards to cutaneous signs of systemic disease in the elderly. We performed a literature search on cutaneous manifestations of internal disease and limited our search to articles published within the last 5 years. We then narrowed down the articles on conditions that primarily affect the adults over the age of 65; conditions commonly seen in the elderly as well as new findings which we felt were of great significance. Ultimately, we hope to update the reader on new cutaneous diagnostic tools of internal disease.
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Kirkwood TB. Understanding the odd science of aging. Cell. 2005;120(4):437–47.
Hjelmborg VJ, Iachine I, Skytthe A, Vaupel JW, McGue M, Koskenvuo M, et al. Genetic influence on human lifespan and longevity. Hum Genet. 2006;119(3):312–21.
Vaziri H, Benchimol S. From telomere loss to p53 induction and activation of a DNA-damage pathway at senescence: the telomere loss/DNA damage model of cell aging. Exp Gerontol. 1996;31:295–301.
Davis T et al. Prevention of accelerated cell aging in the Werner syndrome. Ann N Y Acad Sci. 2006;1067:243–7.
Manju K, Muralikrishna B, Parnaik VK. Expression of disease-causing lamin A mutants impairs the formation of DNA repair foci. J Cell Sci. 2006;119:2704–14.
De la Fuente M, Hernanz A, Vallejo MC. The immune system in the oxidative stress conditions of aging and hypertension: Favorable effects of antioxidants and physical exercise. Antioxid Redox Signal. 2005;7:1356–66.
Sela BA. Dermatological manifestations of smoking. Harefuah. 2002;141(8):736–40.
Wulf HC et al. Skin aging and natural photoprotection. Micron. 2004;35:185–91.
Roskos KV et al. Pharmacodynamic measurements of methyl nicotinate percutaneous absorption: The effect of aging on microcirculation. Br J Dermatol. 1990;122:165–71.
Tezuka T et al. Terminal differentiation of facial epidermis of the aged: Immunohistochemical studies. Dermatology. 1994;188:21–4.
Plowden J et al. Innate immunity in aging: Impact on macrophage function. Aging Cell. 2004;3:161–7.
MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985;76:1536–8.
Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006;81:353–73.
Tsuchida Y. The effect of aging and arteriosclerosis on human skin blood flow. J Dermatol Sci. 1993;5:175–81.
Ryan T. The ageing of the blood supply and the lymphatic drainage of the skin. Micron. 2004;35:161–71.
Gerstein AD et al. Wound healing and aging. Dermatol Clin. 1993;11:749–57.
Longo C, Casari A, Beretti F, Cesinaro A, Pellacani.G. Skin aging: In vivo microscopic assessment of epidermal and dermal shcanges by means of confocal microscopy. Jaad Online October, 2011.
Armstrong BK, Kricker A. Epidemiology of sun exposure and skin cancer. Cancer Surv. 1996;26:133–53.
Matterne U, Apgelbacher CJ, Vogelgsang L, Loerbroks A, Weisshar E. Incindence and determinants of chronic pruritis: a population-based cohort study. Acta Derm Venereol. 2013;93:532–7.
Stander S et al. Clinical classification of itch: A position paper of the International Forum for the study of Itch. Acta Derm Venereol. 2007;87(4):291–4.
Shelley WB, Arthur RP. The neurohistology and neurophysiology of the itch sensation in man. AMA Arch Derm. 1957;76(3):296–323.
Schmelz M et al. Specific C-receptors for itch in human skin. J Neurosci. 1997;17(20):8003–8.
Berger T, Steinhoff M. Pruritus in elderly patients-eruptions of senescence. Semin Cutaneous Med Surg. 2011;30:113–7.
Fleicher A. Pruritus in the elderly: managment by senior dermatologists. JAAD. 1993;28:603–9.
Pisoni RL et al. Pruritus in haemodialysis patients: international results from the dialysis outcomes and practice patterns study (DOPPS). Nephrol Dial Transplant. 2006;21(12):3495–505.
Teoh YL.et al Pruritus in the elderly and its impact on quality of life. Jaad April 2012 Poster Reference number 5327.
Fett N et al. Five-year malignancy incidence in patients with chronic pruritus: a population-based cohort study aimed at limiting unnecessary screening practices. JAAD. 2014;70(4):651–8. Patients with chronic pruritus are often extensively worked up for malignancy which drives up health care costs. This paper concludes patient with chronic pruritus without skin findings and no other signs or symptoms of malignancy should not undergo broad screening.
Yosipovitch G. Chronic pruritus: a paraneoplastic sign. Dermatol Ther. 2010;23(6):590–6.
Sigurdsson V, Steegmans PH, van Vloten WA. The incidence of erythroderma: a survey among all dermatologists in the Netherlands. J Am Acad Dermatol. 2001;45(5):675–8.
Rym BM et al. Erythroderma in adults: a report of 80 cases. Int J Dermatol. 2005;44(9):731–5.
Sigurdsson V et al. Idiopathic erythroderma: a follow-up study of 28 patients. Dermatology. 1997;194(2):98–101.
Shuster S. High-output cardiac failure from skin disease. Lancet. 1963;1(7295):1338–40.
Sehgal VN, Srivastava G. Exfoliative dermatitis. A prospective study of 80 patients. Dermatologica. 1986;173(6):278–84.
Protopsaltis et al. Breast cancer presenting as paraneoplastic erythroderma: An extremelty rare case. Cae Reports in Medicine Vol 2014, Article ID 351065.
Gudi VS et al. Annual incidence and mortality of bullous pemphigoid in the Grampian region of north-east Scotland. Br J Dermatol. 2005;153(2):424.
Cram DL, Fukuyama K. Immunohistochemistry of ultraviolet-induced pemphigus and pemphigoid lesions. Arch Dermatol. 1972;106(6):819.
Jedlickova H et al. Bullous pemphigoid and internal diseases – A case-control study. Eur J Dermatol. 2010;20(1):96.
Brick K et al. A population-based study of the association between bullous pemphigoid and neurologic disorder. JAAD. 2014;71(6):1191–7. BP is the most common bullous disease in the elderly so knowing of the association with neulogic disorders can assist the physician in their screening practices.
Stinco G, Codutti R, Scarbolo M, Valent F, Patrone P. A retrospective epidemiological study on the association of bullous pemphigoid and neurological diseases. Acta Derm Venereol. 2005;85:136–9.
Cordel N, Chosidow O, Hellot MF, Delaporte E, Lok C, Vaillant L, et al. Neurological disorders in patients with bullous pemphigoid. Dermatology. 2007;215:187–91.
Foureur N, Mignot S, Senet P, Verpillat P, Picard-Dahan C, Crickx B. Correlation between the presence of type-2 anti-pemphigoid antibodies and dementia in elderly subjects with no clinical signs of pemphigoid. Ann Dermatol Venereol. 2006;133:439–43.
Seppanen A, Autio-Hermalinen H, Alafuzoff I, Sarkioja T, Veijola J, Jurskainem T, et al. Collagen XVII is expressed in human CNS neurons. Matrix BIol. 2006;25:185–8.
Seppeanen A, Suuronen T, Hofmann SC, Majamaa K, Alafuzoff I. Distribution of collagen XVII in the human brain. Brain Res. 2007;158:50–6.
Curth HO. Skin lesions and internal carcinoma. Cancer of the skin. Biol Diagn Manag. 1976;2:1308–41.
Cohen PR, Kurzrock R. Mucocutaneous paraneoplastic syndromes. Semin Oncol. 1997;24–3:334–59.
Pelosof LC, Gerber DE. Paraneoplastic syndromes: an approach to diagnosis and treatment. Mayo Clin Proc. 2010;85–9:838–54.
Poole S. Fenske, NA. Cutaneous markers of internal malignancy: I. Malignant involvement of the skin and the genodermatoses. JAAD. 1993;28(1):1–13.
Anhalt GJ, Kim SC, Stanley JR, et al. Paraneoplastic pemphigus: An autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med. 1990;323(25):1729–35.
Anhalt GJ. Paraneoplastic pemphigus. J Investig Dermatol Symp Proc. 2004;9(1):29–33.
Camisa C, Helm TN. Paraneoplastic pemphigus is a distinct neoplasia-induced autoimmune disease. Arch Dermatol. 1993;129:883–6.
Anhalt GJ. Paraneoplastic pemphigus. Adv Dermatol. 1997;12:77–96.
Boyce S, Harper J. Paraneoplastic dermatoses. Dermatol Clin. 2002;20(3):523–32.
Gissi DB, Bernardi A, D’Andrea M, Montebugnoli L. Paraneoplastic pemphigus presenting with a single oral lesion. BMJ Case Rep 2013; pii: bcr2012007771.
Nousari HC, Deterding R, Wojtczack H, Aho S, Uitto J, Hashimoto T, et al. The mechanism of respiratory failure in paraneoplastic pemphigus. N Engl J Med. 1999;340:1406.
Winkler DT, Strnad P, Meier ML, Roten S, Went P, Lyrer P, et al. Myasthenia gravis, paraneoplastic pemphigus and thymoma, a rare triade. J Neurol. 2007;254(11):1601–3.
Chorzelski T, Hashimoto T, Maciejewska B, Amagai M, Anhalt GJ, Jablonska S. Paraneoplastic pemphigus associated with Castleman tumor, myasthenia gravis and bronchiolitis obliterans. J Am Acad Dermatol. 1999;41(3 Pt 1):393–400.
Wang R, Li J, Wang M, Hao H, Chen X, Li R, Zhu X. Prevalence of myasthenia gravis and associated autoantibodies in paraneoplastic pemphigus and their correlations with symptoms and prognosis. Br J Dermatol. 2014; doi: 10.1111/bjd.13525 Epub ahead of print This study suggests an association between paraneoplastic pemphigus and myasthenia gravis that has not previously been clearly established. Recognition of this association may be helpful in the recognition and management of paraneoplastic pemphigus.
Joly P, Richard C, Gilbert D, Courville P, et al. Sensitivity and specificity of clinical, histologic, and immunologic features in the diagnosis of paraneoplastic pemphigus. J Am Acad Dermatol. 2000;43:619–26.
Lehman VT, Barrick BJ, Pittelkow MR, Peller PJ, Camilleri MJ, Lehman JS. Diagnostic imaging in paraneoplastic autoimmune multiorgan syndrome: retrospective single site study and literature review of 225 patients. Int J Dermatol. 2014 Jul 29. doi: 10.1111/ijd.12603. [Epub ahead of print].
Rodot S, Botcazou V, Lacour JP, et al. Paraneoplastic pemphigus: review of the literature, apropos of a case associated with chronic lymphoid leukemia. Rev Med Interne. 1995;16(12):938–43.
Leger S, Picard D, Ingen-Housz-Oro S, Arnault JP, Aubin F, Carsuzaa F, et al. Prognostic factors of paraneoplastic pemphigus. Arch Derm. 2012;148(10):1165–72.
Mutasim DF, Pelc NJ, Anhalt GJ. Paraneoplastic pemphigus. Dermatol Clin. 1993;11(3):473–81.
U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2011 Incidence and Mortality Web-based Report. Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute. 2014.
Hong MK, Kong J, Namdarian B, Longano A, Grummet J, Hovens CM, et al. Paraneoplastic syndromes in prostate cancer. Nat Rev Urol. 2010;7(12):681–92.
Matzkin H, Braf Z. Paraneoplastic syndromes associated with prostatic carcinoma. J Urol. 1987;138:1129–33.
Subramonian K, Sundaram SK, MacDonald Hull SP. Carcinoma of the prostate associated with dermatomyositis. BJU Int. 2000;86:401–2.
Obasi OE, Garg SK. Bazex paraneoplastic acrokeratosis in prostate carcinoma. Br J Dermatol. 1987;117:647–51.
Da Rosa AC, Pinto GM, Bortoluzzi JS, Duquia RP, de Almeida Jr HL. Three simultaneous paraneoplastic manifestations (ichthyosis acquisita, Bazex syndrome, and Leser-Trelat sign) with prostate adenocarcinoma. J Am Acad Dermatol. 2009;61:538–40.
Momm F, Pflieger D, Lutterbach J. Paraneoplastic erythroderma in a prostate cancer patient. Strahlenther Onkol. 2002;178:393–5.
McCourt C, Feighery C, McIntyre G, Walsh M, Hoey S. Eruptive nevi in prostate cancer: is this a paraneoplastic phenomenon? Int J Dermatol. 2013;52(2):212–3.
Lookingbill DP, Spangler N, Helm KF. Cutaneous metastases in patients with metastatic carcinoma: a retrospective study of 4020 patients. JAAD. 1993;29:228–36.
Rolz-Cruz G, Kim CC. Tumor invasion of the skin. Dermatol Clin. 2008;26:89–102.
Krathen RA, Orengo IF, Rosen T. Cutaneous metastasis: a meta-analysis of data. South Med J. 2003;96(2):164–7.
Wong CY, Helm MA, Helm TN, Zeitouni N. Patterns of skin metastases: a review of 25 years’ experience at a single cancer center. Int J Dermatol. 2014;53(1):56–60. An important component to the early recognition of cutaneous metastasis is an understanding of which primary cancers are most frequently involved. This article provides an update of these frequencies. A better understanding of this will help to guide history, physical examinations, and work-up in patients suspected to have cutaneous metastasis.
Blecher K, Friedman A. A biopsy diagnosis? clinical clues and patterns to help distinguish cutaneous metastases: part I of II. J Drugs Dermatol. 2011;10(6):678–82.
Saeed S, Keehn CA, Morgan MB. Cutaneous metastasis: a clinical, pathological, and immunohistochemical appraisal. J Cutan Pathol. 2004;31(6):419.
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Brandon Markus declares that he has no conflict of interest.
Benjamin M. Perry declares that he has no conflict of interest.
William Lear declares that he has no conflict of interest.
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Markus, B., Perry, B.M. & Lear, W. Skin Manifestations of Internal Disease in Older Adults. Curr Geri Rep 4, 257–264 (2015). https://doi.org/10.1007/s13670-015-0135-8
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DOI: https://doi.org/10.1007/s13670-015-0135-8