Lviv clinical bulletin 2013, 3(3): 18-30

https://doi.org/10.25040/lkv2013.03.018

Visual Signs of Chronic Diffuse Liver Diseases: the Stigma of Skin, its Appendages and Mucous Membranes

Posted onAuthorAdminЗалишити коментар / Leave a comment

M. Abrahamovych, O. Abrahamovych, O. Fayura

Danylo Halytsky Lviv National Medical University

Introduction. The condition of the skin has always been a reflection of the state of the internal organs, in particular, organs of the gastrointestinal system, liver. Most skin symptoms are not specific to the hepatobiliary system, and therefore can be observed in other diseases. However, often the presence of skin stigma and patient complaints can be very helpful in verifying the diagnosis. According to the results of research in the world, palmar erythema occurs in 23.0%, telangiectasias (vascular “spiders”) – in 33.0%, and the triad of symptoms – palmar erythema, telangiectasias and white nails – in 21.0% of the patients with the liver cirrhosis. Despite all the importance, the topic is not sufficiently covered in the medical literature.

Aim. Comprehensively describe stigmata of the skin, its appendages and mucous membranes in patients with chronic digguse liver diseases (CDLD).

Materials and methods. The results of complex clinical-laboratory and instrumental examination of 2 007 patients with CDLD that were treated during the period of 2005-2013 in the Lviv Regional Hepatologic Center, which was created on the basis of the Department of Internal Medicine N 1 of the Danylo Halytsky Lviv National Medical University and the Gastroenterological Department of the Lviv Regional Clinical Hospital are presented. Among these patients there were 1 508 men (75.1%) and 499 women (24.9%) at the age of 47.9 ± 0.2 years. Before the start of treatment in a hospital, they were examined (according to the order of the Ministry of Health of Ukraine N 271 dated 13.06.05 “On Approval of Protocols of the Providing of Medical Care on the Specialty “Gastroenterology”), on the basis of the results of which the clinical diagnoses were set.

Results. Skin changes are often the first predictors of CDLD. For example, a combination of pigmentation, jaundice and xanotomy confirms the diagnosis of primary liver biliary cirrhosis. In the vast majority of patients with chronic liver diseases there are pathogenetically syntropical co- and polistigmata of the skin, which are of great diagnostic value. They allow an experienced doctor to suspect or to set the diagnosis before the special comprehensive examination and to determine the tactics of treatment. The most widespread  disorders  found in the cirrhotic patients were  dyschromia,  in  particular,  jaundice,  spider  nevi,  palmar  erythema,  «cardinal»   tongue, «paper-money» skin, «caput medusae», «lacquer» nails.

Conclusions. Chronic diffuse liver diseases are mainly accompanied by the pathogenic syntropic skin, its appendages and mucous membranes lesions, which are of important diagnostic value and help the experienced physician suspect or set the diagnose before a special comprehensive examination, choose the treatment tactics before the getting the results of this examination.

References

  1. Vorozhbit OB. The Problem of Extrahepatic Lesions in Chronic Hepatitis C. Practical Medicine. 2003; 3: 97-101. (Ukrainian).
  2. Okorokov A. Diagnosis of the Diseases of Internal Organs. Moscow: Medical L-re, 2003; 5. pp. 171-238. (Russian).
  3. d’Ovidio R, Sgarra C, Conserva A, Angelotti UF, Erriquez R, Foti C. Alterated integrin expression in lichen planopilaris. Head Face Med. 2007;3:11. https://doi.org/10.1186/1746-160X-3-11
  4. Kemp EH, Gavalas NG, Gawkrodger DJ, Weetman AP. Autoantibody responses to melanocytes in the depigmenting skin disease vitiligo. Autoimmun Rev. 2007;6:138-142. https://doi.org/10.1016/j.autrev.2006.09.010
  5. Banyai AL. There is more than surface appearance to skin spiders. Chest. 1971;60:48. https://doi.org/10.1378/chest.60.1.48
  6. Beau JHS. Note sur certains caracteres de semeiologie retrospective presentes par les ongles. Arch Generales Med. 1846;10:447-458.
  7. Bernstein JE, Swift R. Relief of intractable pruritus with naloxone. Arch Dermatol. 1979;115:1366-1367. https://doi.org/10.1001/archderm.1979.04010110058029
  8. Bertini G, Rubaltelli FF. Non-invasive bilirubinometry in neonatal jaundice. Semin Neonatol. 2002;7:129-133. https://doi.org/10.1053/siny.2002.0100
  9. Peyrot I, Boulinguez S, Sparsa A, Le Meur Y, Bonnetblanc JM, Bedane C. Bier’s white spots associated with scleroderma renal crisis. Clin Exp Dermatol. 2007;32(2):165-167. https://doi.org/10.1111/j.1365-2230.2006.02298.x
  10. Pham TH, Kaushik S, Lin BP, Jones DB. Case report: acanthosis nigricans in association with primary biliary cirrhosis: resolution after liver transplantation. J Gastroenterol Hepatol. 1996;11(11):1021-1023. https://doi.org/10.1111/j.1440-1746.1996.tb00025.x
  11. Chastain MA. The glucagonoma syndrome: a review of its features and discussion of new perspectives. Acad Dermatol. 1990;23:850-854.
  12. Kumar N, Aggarwal SR, Anand BS. Comparison of truncal hair distribution in alcoholic liver disease and alcohol-related chronic pancreatitis. J Gastroenterol Hepatol. 2001;16(8):855-856. https://doi.org/10.1046/j.1440-1746.2001.02528.x
  13. Carbone M, Arduino PG, Carrozzo M, Gandolfo S, Argiolas MR, Bertolusso G et al. Course of oral lichen planus: a retrospective study of 808 northern Italian patients. Oral Dis. 2009;15(3):235-243. https://doi.org/10.1111/j.1601-0825.2009.01516.x
  14. Cox NH, Coulson IH. Systemic diseases and the skin. Burns T, Breathnach S, Griffith C, editors. Rook’s Textbook of Dermatology. 8th ed. Singapore: Wiley Blackwell, 2010. p. 1-113. https://doi.org/10.1002/9781444317633.ch62
  15. Crosti A, Gianotti F. Eruptive dermatosis of probable viral origin situated on the acra. Dermatologica (in French). 1957;115(5):671-677. https://doi.org/10.1159/000256031
  16. Kaul V, Friedenberg FK, Braitman LE, Anis U, Zaeri N, Fazili J et al. Development and validation of a model to diagnose cirrhosis in patients with hepatitis C. Am J Gastroenterol. 2002;97(10):2623-2628. https://doi.org/10.1111/j.1572-0241.2002.06040.x
  17. Dickson E, Fleming C, Ludwig J. Primary biliary cirrhosis. Popper H, Schaffner F, editors. Progress in Liver Diseases. New York: Grune and Stratton, 1978. 487 p.
  18. El Darouti M, Abu el Ela M. Necrolytic acral erythema: a cutaneous marker of hepatitis C. Int J Dermatol. 1996;35:252-256. https://doi.org/10.1111/j.1365-4362.1996.tb02997.x
  19. Gandelman G, Aronow WS, Weiss MB. Resolving hyperlipidemia after liver transplantation in a patient with primary sclerosing cholangitis. Am J Ther. 2006;13:171-174. https://doi.org/10.1097/00045391-200603000-00014
  20. Guillevin L, Mahr A, Callard P, Godmer P, Pagnoux C, Leray E et al. Hepatitis B virus-associated polyarteritis nodosa: clinical characteristics, outcome, and impact of treatment in 115 patients. Medicine (Baltimore). 2005;84(5):313-322. https://doi.org/10.1097/01.md.0000180792.80212.5e
  21. Chuang TY, Stitle L, Brashear R, Lewis C. Hepatitis C virus and lichen planus: a case-control study of 340 patients. J Am Acad Dermatol. 1999;41(5 Pt 1):787-789. https://doi.org/10.1016/S0190-9622(99)70025-3
  22. Soufir N, Descamps V, Crickx B, Thibault V, Cosnes A, Bécherel PA et al. Hepatitis C virus infection in cutaneous polyarteritis nodosa: a retrospective study of 16 cases. Arch Dermatol. 1999;135(8):1001-1002. https://doi.org/10.1001/archderm.135.8.1001
  23. Anand AC, Mukherjee D, Rao KS, Seth AK. Hepatopulmonary syndrome: prevalence and clinical profile. Indian J Gastroenterol. 2001;20(1):24-27.
  24. Holzberg M, Walker HK. Terry’s nails: revised definition and new correlations. Lancet. 1984;1:896-899. https://doi.org/10.1016/S0140-6736(84)91351-5
  25. Neri S, Raciti C, D’Angelo G, Ierna D, Bruno CM. Hyde’s prurigo nodularis and chronic HCV hepatitis. J Hepatol. 1998;28(1):161-164. https://doi.org/10.1016/S0168-8278(98)80216-X
  26. Allocca M, Crosignani A, Gritti A, Ghilardi G, Gobatti D, Caruso D et al. Hypercholesterolaemia is not associated with early atherosclerotic lesions in primary biliary cirrhosis. Gut. 2006;55(12):1795-1800. https://doi.org/10.1136/gut.2005.079814
  27. Ibbotson SH. Disseminated superficial porokeratosis: what is the association with ultraviolet radiation? Clin Exp Dermatol. 1996;21:48-50. https://doi.org/10.1046/j.1365-2230.1996.d01-177.x
  28. Dasgupta R, Saha I, Pal S, Bhattacharyya A, Sa G, Nag TC et al. Immunosuppression, hepatotoxicity and depression of antioxidant status by arecoline in albino mice. Toxicology. 2006;227(1-2):94-104. https://doi.org/10.1016/j.tox.2006.07.016
  29. Fornasa CV, Farini R, Fava G, Peserico A, Naccarato R. Incidence of skin changes during active chronic hepatitis and liver cirrhosis. Comparison with normal controls. Minerva Med. 1979;70(40):2741-2746.
  30. Simsek H, Savas C, Akkiz H, Telatar H. Interferon-induced vitiligo in a patient with chronic viral hepatitis C infection. Dermatology. 1996;193(1):65-66. https://doi.org/10.1159/000246208
  31. Johnston GA, Graham Brown RAC. The skin and disorders of the alimentary tract, the hepatobiliary system, kidney, and cardiopulmonary system. Fitzpatrick’s Dermatology in General Medicine. 7th ed. Wolff K, Goldsmith LA, Katz SI et al. New York: Mcgraw Hill, 2008. p. 1445-1460.
  32. Barton JC, Rao SV, Pereira NM, Gelbart T, Beutler E, Rivers CA et al. Juvenile hemochromatosis in the southeastern United States: a report of seven cases in two kinships. Blood Cells Mol Dis. 2002;29(1):104-115. https://doi.org/10.1006/bcmd.2002.0545
  33. Matsumoto M, Ohki K, Nagai I, Oshibuchi T. Lung traction causes an increase in plasma prostacyclin concentration and decrease in mean arterial blood pressure. Anesth Analg. 1992;75:773-776. https://doi.org/10.1213/00000539-199211000-00021
  34. Kremer AE, Martens JJ, Kulik W, Ruëff F, Kuiper EM, van Buuren HR et al. Lysophosphatidic acid is a potential mediator of cholestatic pruritus. Gastroenterology. 2010;139(3):1008-1018. https://doi.org/10.1053/j.gastro.2010.05.009
  35. Barton JC, McDonnell SM, Adams PC, Brissot P, Powell LW, Edwards CQ et al. Management of hemochromatosis. Hemochromatosis Management Working Group. Ann Intern Med. 1998;129(11):932-939. https://doi.org/10.7326/0003-4819-129-11_Part_2-199812011-00003
  36. Lançoni G, Ravinal RC, Costa RS, Roselino AM. Mast cells and transforming growth factor-beta expression: a possible relationship in the development of porphyria cutanea tarda skin lesions. Int J Dermatol. 2008;47:575-581. https://doi.org/10.1111/j.1365-4632.2008.03607.x
  37. Mela M, Mancuso A, Burroughs AK. Review article: pruritus in cholestatic and other liver diseases. Aliment Pharmacol Ther. 2003;17:857-870. https://doi.org/10.1046/j.1365-2036.2003.01458.x
  38. Gaspari R, Avolio AW, Zileri Dal Verme L, Agnes S, Proietti R, Castagneto M et al. Molecular adsorbent recirculating system in liver transplantation: safety and efficacy. Transplant Proc. 2006;38:3544-3551. https://doi.org/10.1016/j.transproceed.2006.10.032
  39. Muehrcke RC. The finger-nails in chronic hypoalbuminaemia; a new physical sign. Br Med J. 1956;1:1327-1328. https://doi.org/10.1136/bmj.1.4979.1327
  40. Khanna VJ, Shieh S, Benjamin J, Somach S, Zaim MT, Dorner W et al. Necrolytic acral erythema associated with hepatitis C: effective treatment with interferon alfa and zinc. Arch Dermatol. 2000;136(6):755-757. https://doi.org/10.1001/archderm.136.6.755
  41. Oji V, Traupe H. Ichthyoses: differential diagnosis and molecular genetics. Eur J Dermatol. 2006;16:349-359.
  42. Otto AI, Horvath I, Feldmann J. Multiple firm, painless erythematous papules with a yellowish hue. Arch Dermatol. 2005;141:1595-1600. https://doi.org/10.1001/archderm.141.12.1595-d
  43. Park BS, Moon SE, Kim JA. Disseminated superficial porokeratosis in a patient with chronic liver disease. J Dermatol. 1997;24:485-487. https://doi.org/10.1111/j.1346-8138.1997.tb02826.x
  44. Smith AG, Shuster S, Bomford A, Williams R. Plasma immunoreactive beta-melanocyte-stimulating hormone in chronic liver disease and fulminant hepatic failure. J Invest Dermatol. 1978;70:326-327. https://doi.org/10.1111/1523-1747.ep12543496
  45. Waalen J, Felitti V, Gelbart T, Ho NJ, Beutler E. Prevalence of hemochromatosis-related symptoms among individuals with mutations in the HFE gene. Mayo Clin Proc. 2002;77:522-530. https://doi.org/10.4065/77.6.522
  46. Brown MA, George CR, Dunstan CR, Kalowski S, Corrigan AB. Prurigo nodularis and aluminium overload in maintenance haemodialysis. Lancet. 1992;340(8810):48. https://doi.org/10.1016/0140-6736(92)92458-R
  47. Pechère M, Krischer J, Rosay A, Hirschel B, Saurat JH. Red fingers syndrome in patients with HIV and hepatitis C infection. Lancet. 1996;348(9021):196-197. https://doi.org/10.1016/S0140-6736(05)66142-9
  48. Li CP, Lee FY, Hwang SJ, Chang FY, Lin HC, Lu RH et al. Role of substance P in the pathogenesis of spider angiomas in patients with nonalcoholic liver cirrhosis. Am J Gastroenterol. 1999;94(2):502-507. https://doi.org/10.1111/j.1572-0241.1999.883_l.x
  49. Sadick NS, Niedt GW. A study of estrogen and progesterone receptors in spider telangiectasias of the lower extremities. J Dermatol Surg Oncol. 1990;16(7):620-623. https://doi.org/10.1111/j.1524-4725.1990.tb00090.x
  50. Satapathy SK, Bernstein D. Dermatologic disorders and the liver. Clin Liver Dis. 2011;15:165-182. https://doi.org/10.1016/j.cld.2010.09.001
  51. Satoh T, Yokozeki H, Nishioka K. Vascular spiders and paper money skin improved by hemodialysis. Dermatology. 2002;205:73-74. https://doi.org/10.1159/000063136
  52. Serrao R, Zirwas M, English JC. Palmar erythema. Am J Clin Dermatol. 2007;8:347-356. https://doi.org/10.2165/00128071-200708060-00004
  53. Morioka D, Togo S, Kumamoto T, Takeda K, Matsuo K, Inayama Y et al. Six consecutive cases of successful adult ABO-incompatible living donor liver transplantation: a proposal for grading the severity of antibody-mediated rejection. Transplantation. 2008;85(2):171-178. https://doi.org/10.1097/TP.0b013e31815e9672
  54. Li CP, Lee FY, Hwang SJ, Chang FY, Lin HC, Lu RH et al. Spider angiomas in patients with liver cirrhosis: role of alcoholism and impaired liver function. Scand J Gastroenterol. 1999;34(5):520-523. https://doi.org/10.1080/003655299750026272
  55. Stander S, Luger T, Metze D. Treatment of prurigo nodularis with topical capsaicin. J Am Acad Dermatol. 2001;44:471-478. https://doi.org/10.1067/mjd.2001.110059
  56. Stulberg DL, Clark N, Tovey D. Common hyperpigmentation disorders in adults: Part I. Diagnostic approach, cafe au lait macules, diffuse hyperpigmentation, sun exposure, and phototoxic reactions. Am Fam Physician. 2003;68:1955-1960.
  57. Kono T, Kobayashi H, Ishii M, Nishiguchi S, Taniguchi S. Synchronous development of disseminated superficial porokeratosis and hepatitis C virus-related hepatocellular carcinoma. J Am Acad Dermatol. 2000;43(5 Pt 2):966-968. https://doi.org/10.1067/mjd.2000.103265
  58. Terry R. White nails in hepatic cirrhosis. Lancet. 1954;266(6815):756-759. https://doi.org/10.1016/S0140-6736(54)92717-8
  59. Finn SM, Rowland M, Lawlor F, Kinsella W, Chan L, Byrne O et al. The significance of cutaneous spider naevi in children. Arch Dis Child. 2006;91(7):604-605. https://doi.org/10.1136/adc.2005.086512
  60. Tomasiewicz K, Modrzewska R, Semczuk G. Vitiligo associated with pegylated interferon and ribavirin treatment of patients with chronic hepatitis C: a case report. Adv Ther. 2006;23:139-142. https://doi.org/10.1007/BF02850354
  61. Montero JL, Pozo JC, Barrera P, Fraga E, Costán G, Domínguez JL et al. Treatment of refractory cholestatic pruritus with molecular adsorbent recirculating system (MARS). Transplant Proc. 2006;38(8):2511-2513. https://doi.org/10.1016/j.transproceed.2006.08.052
  62. Trepo C, Guillevin L. Polyarteritis nodosa and extrahepatic manifestations of HBV infection: the case against autoimmune intervention in pathogenesis. J Autoimmun. 2001;16:269-274. https://doi.org/10.1006/jaut.2000.0502
  63. Tsuji T. Experimental hemosiderosis: relationship between skin pigmentation and hemosiderin. Acta Derm Venereol. 1980;60:109-114.
  64. Vassilopoulos D, Calabrese LH. Extrahepatic immunological complications of hepatitis C virus infection. AIDS. 2005;19(3 Suppl):123-127. https://doi.org/10.1097/01.aids.0000192080.56808.38
  65. Wang H, Yosipovitch G. New insights into the pathophysiology and treatment of chronic itch in patients with end stage renal disease, chronic liver disease and lymphoma. Int J Dermatol. 2010;49:1-11. https://doi.org/10.1111/j.1365-4632.2009.04249.x