- Email: [email protected]
Liver Palms (Palmar Erythema)
PHYSICAL FINDINGS Thomas J. Marrie, MD, Section Editor
Liver Palms (Palmar Erythema) Amit Nautiyal, MD,a Kapil B. Chopra, MD, AGAFb a
Department of Medicine, University of Wisconsin, Madison, Wis; bDepartment of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh, Pa.
CASE PRESENTATION A 48-year-old white woman presented with worsening fatigue, diffuse arthralgias, joint swelling, malaise, and icterus. In view of ongoing joint pains sparing the distal interphalangeal joints, early morning stiffness, strong family history of rheumatoid arthritis, positive rheumatoid factor, and a positive anti-cyclic citrullinated peptide antibody, she was recently diagnosed with rheumatoid arthritis. She had noticed a change in the color of her palms for about a year (Figure). She had no visible plantar erythema. There was no palpable hepatosplenomegaly, caput medusae, or ascites, with complete absence of other cutaneous signs of liver disease. Her liver function tests revealed hyperbilirubinemia, with a total bilirubin of 4.1 mg/dL, and elevated serum transaminases, with an alanine transaminase of 500 units/L and aspartate transaminase of 799 units/L. Her autoantibody profile revealed a positive antinuclear antibody with a titer of (1:640), with a positive anti-smooth muscle antibody titer (1:320), raising the concern for autoimmune hepatitis. She underwent a liver biopsy, which revealed moderately active hepatitis, predominantly acute, with features suggestive of transition to chronicity with bridging necrosis and early fibrosis.
DISCUSSION Palmar erythema is an often-overlooked physical finding. Although physicians have looked for cutaneous signs of liver disease for more than a century, it was Niederau et al1 who found an interesting association on univariate analysis of a strong correlation between cutaneous signs and degree of liver fibrosis. Palmar erythema, most commonly consisting of a symmetric, nonpainful, nonpruritic, slightly warm, Funding: None. Conflict of Interest: None. Authorship: We verify that both authors had access to the data and a role in writing the manuscript. Requests for reprints should be addressed to Amit Nautiyal, MD, Department of Medicine, University of Wisconsin, 600 Highland Avenue, Madison, WI 53792. E-mail address: [email protected]
0002-9343/$ -see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2009.09.025
nonscaling erythema, most frequently involves the thenar and hypothenar eminences of the palmar surface.2 Erythema is pronounced in the palms due to presence of a higher density of arteriovenous shunts.3 Microscopic evaluation of patients with palmar erythema has demonstrated increased dilatation of capillaries and superficial arterial and venous plexi in the palm compared with patients without palmar erythema.4 In a Japanese study of 50 patients with nonalcoholic liver cirrhosis, hepatic decompensation was associated with increased serum estradiol, free estradiol, estradiol/testosterone, and free estradiol/testosterone levels; an increased free estradiol/free testosterone level was observed in patients with palmar erythema, gynecomastia, and vascular spiders.5 Other suggested causative factors include disordered hepatic metabolism of bradykinin and other vasoactive substances.6 Frequently, palmar erythema has been documented in diseases associated with liver cirrhosis, including alcoholic liver disease, Wilson disease, hemochromatosis, hepatitis B virus infection, and hepatitis C virus infection.7-10 A study of 100 individuals with hepatitis C infection documented palmar erythema to be present in 24% of patients.9 Several studies have shown that there are increased free estrogen levels in individuals with several of the conditions known to cause palmar erythema, including hepatobiliary disease,11 thyrotoxicosis,12 rheumatoid arthritis,13 and pregnancy.14 Noble et al14 reported its association as a paraneoplastic manifestation in ⬎15% of individuals with both metastatic and primary brain neoplasms along with metastatic cancers of both the cecum and the tongue. The variety of possible associated factors means that evaluation of a patient presenting with palmar erythema can be a challenging task. Clinicians should evaluate patients carefully with a comprehensive history and physical examination. The history of illness should include specific inquiries about the nature of the onset of palmar erythema, previous episodes, and other systemic or cutaneous symptoms/ signs. A complete list of current medications also should be elicited from the patient. If the patient is female, pregnancy status should be determined. Other areas to be probed in-
Nautiyal and Chopra
Figure
Liver Palms (Palmar Erythema)
Palmar erythema.
clude a family history of palmar erythema, a history of liver disease, alcoholism, rheumatic/autoimmune disease, endocrine abnormalities, nutritional deficiency infection, neoplasm, and potential toxin exposure.15
References 1. Niederau C, Lange S, Fruhauf M, Thiel A. Cutaneous signs of liver disease: value for prognosis of severe fibrosis and cirrhosis. Liver Int. 2008;28:659-666. Epub 2008 Feb 26. 2. Perera GA. A note on palmar erythema (so-called liver palms). JAMA. 1942;119:1417-1418.
597 3. Bean W. Acquired palmar erythema and cutaneous vascular ‘spiders’. Am Heart J. 1943;25:463-477. 4. Walsh EN, Becker SW. Erythema palmare and naevus-araneus-like telangiectases. Arch Derm Syphilol. 1941;44:616-630. 5. Maruyama Y, Adachi Y, Aoki N, et al. Mechanism of feminization in male patients with non-alcoholic liver cirrhosis: role of sex hormonebinding globulin. Gastroenterol Jpn. 1991;26:435-439. 6. Fitzpatrick T, Arndt K, Clark W, et al. Dermatology in General Medicine. New York: McGraw-Hill; 1971. 7. Crawford D, Powell L, Halliday J. Factor’s influencing disease expression in hemochromatosis. Ann Rev Nutr. 1996;16:139-160. 8. Massarrat S, Fallahazad V, Kamalian N. Clinical, biochemical and imaging-verified regression of hepatitis B-induced cirrhosis. Liver Int. 2004;24:105-109. 9. Cribier B, Samain F, Vetter D, et al. Systematic cutaneous examination in hepatitis C virus infected patients. Acta Derm Venereol. 1998;78: 355-357. 10. Clayton PT. Diagnosis of inherited disorders of liver metabolism. J Inherit Metab Dis. 2003;26(2-3):135-146. 11. Bean WB. A note on the development of cutaneous arterial ‘spiders’ and palmar erythema in persons with liver disease and their development following the administration of estrogens. Am J Med Sci. 1942; 204:251-252. 12. Chopra IJ, Abraham GE, Chopra U, et al. Alterations in circulating estradiol-17 in male patients with Graves’ disease. N Engl J Med. 1972;286:124-129. 13. Bland JH, O’Brien R, Bouchard RE. Palmar erythema and spider angiomata in rheumatoid arthritis. Ann Intern Med. 1958;48:10261031. 14. Noble JP, Boisnic S, Branchet-Gumila MC, Poisson M. Palmar erythema: cutaneous marker of neoplasms Dermatology. 2002;204:209213. 15. Serrao R, Zirwas M, English JC. Palmar erythema. Am J Clin Dermatol. 2007;8:347-356.
Liver Palms (Palmar Erythema) Amit Nautiyal, MD,a Kapil B. Chopra, MD, AGAFb a
Department of Medicine, University of Wisconsin, Madison, Wis; bDepartment of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh, Pa.
CASE PRESENTATION A 48-year-old white woman presented with worsening fatigue, diffuse arthralgias, joint swelling, malaise, and icterus. In view of ongoing joint pains sparing the distal interphalangeal joints, early morning stiffness, strong family history of rheumatoid arthritis, positive rheumatoid factor, and a positive anti-cyclic citrullinated peptide antibody, she was recently diagnosed with rheumatoid arthritis. She had noticed a change in the color of her palms for about a year (Figure). She had no visible plantar erythema. There was no palpable hepatosplenomegaly, caput medusae, or ascites, with complete absence of other cutaneous signs of liver disease. Her liver function tests revealed hyperbilirubinemia, with a total bilirubin of 4.1 mg/dL, and elevated serum transaminases, with an alanine transaminase of 500 units/L and aspartate transaminase of 799 units/L. Her autoantibody profile revealed a positive antinuclear antibody with a titer of (1:640), with a positive anti-smooth muscle antibody titer (1:320), raising the concern for autoimmune hepatitis. She underwent a liver biopsy, which revealed moderately active hepatitis, predominantly acute, with features suggestive of transition to chronicity with bridging necrosis and early fibrosis.
DISCUSSION Palmar erythema is an often-overlooked physical finding. Although physicians have looked for cutaneous signs of liver disease for more than a century, it was Niederau et al1 who found an interesting association on univariate analysis of a strong correlation between cutaneous signs and degree of liver fibrosis. Palmar erythema, most commonly consisting of a symmetric, nonpainful, nonpruritic, slightly warm, Funding: None. Conflict of Interest: None. Authorship: We verify that both authors had access to the data and a role in writing the manuscript. Requests for reprints should be addressed to Amit Nautiyal, MD, Department of Medicine, University of Wisconsin, 600 Highland Avenue, Madison, WI 53792. E-mail address: [email protected]
0002-9343/$ -see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2009.09.025
nonscaling erythema, most frequently involves the thenar and hypothenar eminences of the palmar surface.2 Erythema is pronounced in the palms due to presence of a higher density of arteriovenous shunts.3 Microscopic evaluation of patients with palmar erythema has demonstrated increased dilatation of capillaries and superficial arterial and venous plexi in the palm compared with patients without palmar erythema.4 In a Japanese study of 50 patients with nonalcoholic liver cirrhosis, hepatic decompensation was associated with increased serum estradiol, free estradiol, estradiol/testosterone, and free estradiol/testosterone levels; an increased free estradiol/free testosterone level was observed in patients with palmar erythema, gynecomastia, and vascular spiders.5 Other suggested causative factors include disordered hepatic metabolism of bradykinin and other vasoactive substances.6 Frequently, palmar erythema has been documented in diseases associated with liver cirrhosis, including alcoholic liver disease, Wilson disease, hemochromatosis, hepatitis B virus infection, and hepatitis C virus infection.7-10 A study of 100 individuals with hepatitis C infection documented palmar erythema to be present in 24% of patients.9 Several studies have shown that there are increased free estrogen levels in individuals with several of the conditions known to cause palmar erythema, including hepatobiliary disease,11 thyrotoxicosis,12 rheumatoid arthritis,13 and pregnancy.14 Noble et al14 reported its association as a paraneoplastic manifestation in ⬎15% of individuals with both metastatic and primary brain neoplasms along with metastatic cancers of both the cecum and the tongue. The variety of possible associated factors means that evaluation of a patient presenting with palmar erythema can be a challenging task. Clinicians should evaluate patients carefully with a comprehensive history and physical examination. The history of illness should include specific inquiries about the nature of the onset of palmar erythema, previous episodes, and other systemic or cutaneous symptoms/ signs. A complete list of current medications also should be elicited from the patient. If the patient is female, pregnancy status should be determined. Other areas to be probed in-
Nautiyal and Chopra
Figure
Liver Palms (Palmar Erythema)
Palmar erythema.
clude a family history of palmar erythema, a history of liver disease, alcoholism, rheumatic/autoimmune disease, endocrine abnormalities, nutritional deficiency infection, neoplasm, and potential toxin exposure.15
References 1. Niederau C, Lange S, Fruhauf M, Thiel A. Cutaneous signs of liver disease: value for prognosis of severe fibrosis and cirrhosis. Liver Int. 2008;28:659-666. Epub 2008 Feb 26. 2. Perera GA. A note on palmar erythema (so-called liver palms). JAMA. 1942;119:1417-1418.
597 3. Bean W. Acquired palmar erythema and cutaneous vascular ‘spiders’. Am Heart J. 1943;25:463-477. 4. Walsh EN, Becker SW. Erythema palmare and naevus-araneus-like telangiectases. Arch Derm Syphilol. 1941;44:616-630. 5. Maruyama Y, Adachi Y, Aoki N, et al. Mechanism of feminization in male patients with non-alcoholic liver cirrhosis: role of sex hormonebinding globulin. Gastroenterol Jpn. 1991;26:435-439. 6. Fitzpatrick T, Arndt K, Clark W, et al. Dermatology in General Medicine. New York: McGraw-Hill; 1971. 7. Crawford D, Powell L, Halliday J. Factor’s influencing disease expression in hemochromatosis. Ann Rev Nutr. 1996;16:139-160. 8. Massarrat S, Fallahazad V, Kamalian N. Clinical, biochemical and imaging-verified regression of hepatitis B-induced cirrhosis. Liver Int. 2004;24:105-109. 9. Cribier B, Samain F, Vetter D, et al. Systematic cutaneous examination in hepatitis C virus infected patients. Acta Derm Venereol. 1998;78: 355-357. 10. Clayton PT. Diagnosis of inherited disorders of liver metabolism. J Inherit Metab Dis. 2003;26(2-3):135-146. 11. Bean WB. A note on the development of cutaneous arterial ‘spiders’ and palmar erythema in persons with liver disease and their development following the administration of estrogens. Am J Med Sci. 1942; 204:251-252. 12. Chopra IJ, Abraham GE, Chopra U, et al. Alterations in circulating estradiol-17 in male patients with Graves’ disease. N Engl J Med. 1972;286:124-129. 13. Bland JH, O’Brien R, Bouchard RE. Palmar erythema and spider angiomata in rheumatoid arthritis. Ann Intern Med. 1958;48:10261031. 14. Noble JP, Boisnic S, Branchet-Gumila MC, Poisson M. Palmar erythema: cutaneous marker of neoplasms Dermatology. 2002;204:209213. 15. Serrao R, Zirwas M, English JC. Palmar erythema. Am J Clin Dermatol. 2007;8:347-356.