D e r m a t o l o g i c D i s o rde r s a n d th e L i v e r

Sanjaya K. Satapathy,
KEYWORDS  Cirrhosis  Chronic liver disease  Hepatitis  Dermatologic disorder
MD, DM
a

, David Bernstein,

MD, AGAF

b,c,

*

Dermatologic manifestations are one of the most common extrahepatic manifestations and often provide the first clues of the underlying liver disease. An understanding of these various manifestations and their underlying disorder will better prepare nondermatologists for these diagnostic challenges and appropriate care can be instituted in a timely manner. This review focuses on the dermatologic manifestations of liver diseases in general and of various infectious, autoimmune, metabolic, hereditary, developmental, and neoplastic liver disorders. In addition, hepatotoxicity of the dermatologic drugs is reviewed.

LIVER DISEASE AND THE SKIN

Manifestations of the liver and skin disorders are inter-related in various ways. For a better understanding of the pathophysiologic process involved in this inter-relation, they are divided into the following five categories: 1. 2. 3. 4. 5. Dermatologic manifestations of liver cirrhosis. Systemic diseases affecting both liver and the skin Primary skin disorders affecting the liver Dermatologic manifestations of specific liver diseases Drugs used by dermatologists causing hepatotoxicity.

Long Island Jewish Medical Center at Albert Einstein College of Medicine, North Shore-Long Island Jewish Health system, 270-05 76th Avenue, New Hyde Park, NY 11040, USA b Digestive Disease Institute, Department of Medicine, North Shore University Hospital and Long Island Jewish Medical Center, North Shore University Hospital, 300 Community Drive, Manhasset, NY 11030, USA c Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA * Corresponding author. Digestive Disease Institute, Department of Medicine, North Shore University Hospital and Long Island Jewish Medical Center, North Shore University Hospital, 300 Community Drive, Manhasset, NY 11030. E-mail address: dbernste@nshs.edu Clin Liver Dis 15 (2011) 165–182 doi:10.1016/j.cld.2010.09.001 1089-3261/11/$ – see front matter Ó 2011 Elsevier Inc. All rights reserved. liver.theclinics.com

a

1 Abnormal serum estradiol levels1 and regional differences in the peripheral circulation of patients with cirrhosis have been attributed as causes. gestational syphilis.2 Palmar erythema can occur in conditions unrelated to liver disease. gemfibrozil. V of the neck. thyrotoxicosis. Approximately 33% of patients with cirrhosis have spider angiomas. have been reported to cause palmar erythema. and albuterol (salbutamol).1 Spider nevi Spider nevi. It is usually detectable when the serum level of bilirubin exceeds 2 mg/dL (34 mmol/L). Elevation of both unconjugated and conjugated bilirubin occurs in patients with hepatocellular disease due to impaired canalicular excretion or biliary obstruction. 1. Young age. or liver palms. in pregnant women. central body with symmetrically radiating thin branches. and basic fibroblast growth factor have been attributed as significant independent predictors of spider nevi in cirrhotic patients. or spider angiomas. cholestyramine. and human T-lymphotropic virus 1–associated myelopathy. and upper part of the trunk above the nipple line and arms). the central vessel being an arteriole. 1). Spider nevi occur in healthy people.3 Many factors have been associated with the pathogenesis of spider nevi in patients with cirrhosis. rheumatoid arthritis. resembling spider’s legs. It is the most obvious sign of liver disease and is best seen in the conjunctivae. such as pregnancy. are telangiectases consisting of a central arteriole with superficially radiating small vessels (Fig. Twenty-three percent of patients with cirrhosis. and are mainly observed in the superior vena cava distribution area (ie. is a nonspecific red discoloration of the palms and fingertips of the hands. . Palmar erythema Palmar erythema. topiramate. or in women using hormonal contraception. manifest palmar erythema. They are characterized by a vascular. especially at puberty.4 The presence of spider nevi is accompanied by an increased serum estradiol/free testosterone ratio in male Fig. elevated plasma vascular endothelial growth factor.1 Drugs. from varying causes. such as amiodarone.166 Satapathy & Bernstein Dermatologic Manifestations of Liver Cirrhosis Jaundice Jaundice (icterus) is the clinical manifestation of hyperbilirubinemia and presents as yellow discoloration of the skin and mucous membranes. diabetes mellitus. Spider nevi. in the face.

and central nervous system. primary biliary cirrhosis (PBC) in 2.1%). Spider nevi can be successfully treated with laser therapy for cosmetic reasons.8%) in patients with juvenile SLE compared with adult patients (1. whereas secondary ¨ Sjogren syndrome describes the former in association with rheumatoid arthritis. cardiovascular system. and autoimmune hepatitis in 2.12 Harvey and colleagues11 reported hepatomegaly in 35% of patients but without any evidence of impairment of liver function.7%. viral chronic hepatitis or cirrhosis (4. Other clinical features include Raynaud phenomenon. achlorhydria (from atrophic gastritis).” Previous studies have shown that12.5 People who have significant hepatic impairment cannot detoxify estrogen from the blood. immunologically mediated disease classically involves the skin. congestive heart failure. nodular regenerative hyperplasia in 6.3%) has been reported. splenomegaly. The spider angiomas associated with liver disease may resolve when liver function improves or when a liver transplant is performed. Holzberg postulated that these vascular changes were related to the premature aging of the nail bed. such as systemic lupus erythematosus (SLE).8 biopsies of nail beds that were performed on several patients showed dilated vasculature in the dermis of the distal band.6 White nails (Terry nails) Terry nails is a physical finding in which fingernails and/or toenails appear white with a characteristic ground glass appearance with a dark band at the tip and the absence of a lunula. affect both the skin and the liver. and drug-induced hepatitis or cholangitis (2. In a study conducted by Holzberg and Walker. psoriasis.7%). however.7–10 The pathogenesis of these nail changes is unclear but is thought to be due to a decrease in vascularity and an increase in connective tissue within the nail bed. chronic renal failure. Histologically. The dermatologic manifestations range from dryness (sicca) and its complications to vasculitis. Seven percent of patients with ¨ Sjogren syndrome have evidence of liver disease—either subclinical (2%) or .7 Although aging is a common cause of Terry nails.Dermatologic Disorders and the Liver 167 cirrhotic patients. sarcoidosis. and leukopenia. A higher prevalence of autoimmune liver disease (9.1%. especially in younger patients. Abnormalities of liver function are not included in the diagnostic criteria of SLE.7%. alopecia. Primary Sjogren syndrome consists of the association of keratoconjunctivitis sicca. Patients with SLE. the most common findings were fatty infiltration and “atrophy and necrosis of the central hepatic cells. A large pathologic series14 of 73 patients with SLE showed hepatic arteritis in 15. and cirrhosis are all systemic diseases that are associated with Terry nails. Systemic Disorders Affecting Both Liver and the Skin Many of the systemic diseases. it is important for physicians to consider other disease entities that can lead to this abnormal nail appearance.8%. Systemic lupus erythematosus SLE is a chronic. Other causes of liver disease included fatty liver (73%). Terry nails are associated with several diseases and advancing age. have a 25% to 50% chance of developing abnormal liver tests. including autoimmune and rheumatoid-related disorders.13 advanced liver disease is not usually seen in SLE patients. An increase in number or size of spider nevi may suggest progressive liver damage. xerostomia.11. kidneys. resulting in high levels of estrogen.7–10 Type 2 diabetes mellitus. which resulted in the abnormal appearance of the nail. and swelling of the salivary glands.15 Sjogren syndrome ¨ ¨ Sjogren syndrome is a chronic autoimmune disorder that can be classified as primary ¨ or secondary. and lichen planus (LP) (Table 1).

however. which are distinguished by the extent of skin thickening: limited and diffuse cutaneous scleroderma The CREST (calcinosis cutis.16 Positive titers for AMA are usually accompanied by histopathologic abnormalities consistent with PBC. Raynaud phenomenon. kidneys. and telangiectasia) syndrome is a form of limited scleroderma that is associated with anticentromere antibodies. Scleroderma is classified into two major subsets. with limited cutaneous involvement. lungs.18. small blood vessel vasculopathy.18 . The disorder is characterized by three features: tissue fibrosis.16 Ninety-two percent of patients with a positive AMA have liver involvement with features similar to stage I PBC. heart. esophageal dysfunction. Two population-based studies showed association of PBC with systemic sclerosis.17 Scleroderma Scleroderma (systemic sclerosis) is a chronic systemic disease that targets the skin.168 Satapathy & Bernstein Table 1 Associated hepatic manifestations of systemic and primary skin diseases Systemic/Primary Skin Disease SLE Hepatic Manifestations Hepatic arteritis PBC Nodular regenerative hyperplacia Autoimmune hepatitis Fatty liver Cirrhosis PBC Hepatitis C PBC (with systemic sclerosis) Chronic intrahepatic cholestatis Micronodular billiary cirrhosis Budd-Chiari syndrome NAFLD Risk for methotrexate-induced cirrhosis Mild liver chemistry abnormality to fulminant hepatic failure Nonspecific liver chemistry abnormality PBC PSC Drug-induced hepatitis (with Dapson) Cholestasis Venooclusive disease Cirrhosis Hepatic metastasis from melanoma and basal cell carcinoma (rare) Hepatic lymphoma with cutaneous T-cell lymphoma ¨ Sjogren syndrome Scleroderma Sarcoidosis Psoriasis DHS and toxic epidermal necrolysis Dermatitis herpetiformis Mastocytosis Malignant dermatologic disorders asymptomatic (5%)—manifested by elevated liver enzyme levels and positive test results for anti-mitochondrial antibody (AMA). and an autoimmune response associated with specific autoantibodies. even in the presence of normal liver enzyme levels. sclerodactyly.19 Such an association of PBC has not been confirmed. gastrointestinal tract. An association ¨ of hepatitis C and Sjogren syndrome has been suggested as well. and musculoskeletal system.

abnormal keratinocyte differentiation. and activated CD41 and CD81 T-cell infiltrates in the dermis and epidermis. heart.Dermatologic Disorders and the Liver 169 Sarcoidosis Sarcoidosis is a multisystem disease characterized by noncaseating granulomas in the affected organs. and subsequent thrombosis. chronic intrahepatic cholestasis. periportal fibrosis. and the liver is not spared from its brunt. venous stasis. or a clinical chameleon. abdominal pain. Sarcoidosis of the skin may have an extremely heterogeneous clinical presentation and is capable of imitating a variety of diseases.29. in dermatology it is often called The Great Imitator. Previous studies on hepatotoxicity after long-term methotrexate therapy in patients with PsA found that the risk of developing cirrhosis may be as high as 25%.33. Methotrexate is the most widely used drug in the treatment of psoriasis. and in nearly one-third of all cases the skin lesions are associated with an inflammatory joint disease known as psoriatic arthritis (PsA). angiogenesis with vasodilatation. causing narrowing of venous vessels.21 Approximately 50% to 79% of livers are involved by biopsy and 67% to 70% by autopsy. a detailed review of which is beyond the scope of this review and is described elsewhere. nervous system. or obstruction of the extrahepatic bile ducts by granulomatous hepatic hilar lymph nodes. they do not develop encephalopathy after portasystemic shunts. and fever25 Hepatomegaly is found in approximately 21% to 50% of the patients.27 Other vascular complications include portal vein thrombosis because of stasis from obliteration of small portal veins33 and Budd-Chiari syndrome because of extrinsic compression of hepatic veins by sarcoid granulomas. and joints.30 Jaundice is rare26 and may be due to intrahepatic cholestasis. including skin. respectively.38 The risk of serious liver disease among patients with rheumatoid arthritis who receive low-dose methotrexate has been reported to be less than 1 per 1000 cases after 5 years of treatment. consequently.20. Alkaline phosphatase is more reliable than g-glutamyl transpeptidase in predicting liver involvement.26–28 Abnormal liver chemistries are found in only 35% of patients. Psoriasis Psoriasis is a chronic inflammatory skin disease that affects 1% to 3% of the general population. and micronodular biliary cirrhosis.32 Progressive liver disease due sarcoidosis may lead to the development of portal hypertension.31 Hyperglobulinemia is common.33 Because such patients have little hepatic dysfunction. These various manifestations are summarized in Table 1. the histologic abnormalities include noncaseating granulomas. progressive diminution in the number of interlobular bile ducts.20 The clinical morphology of cutaneous sarcoidosis may vary within a wide range.35 Severe liver dysfunction and jaundice are uncommon.34 Development of cirrhosis is not a prerequisite of portal hypertension.39 Due to the cost and morbidity associated with liver biopsy and the relatively low incidence of serious methotrexate-induced liver toxicity.21–24 Patients with sarcoidosis are infrequently symptomatic due to liver disease and may present with pruritus.30 Liver involvement may occur without lung involvement in up to 26% of the patients. hemolysis. It is characterized by epidermal hyperproliferation.37 The clinical presentation is highly variable in terms of lesion localization and severity. Hepatotoxicity of the drugs used in the treatment for psoriasis is a major concern for hepatologists. the British Association of Dermatologists has questioned the appropriateness . In sarcoidosis. Many cutaneous lesions can mimic sarcoidosis of the skin either clinically or/and pathologically.36 Primary Skin Disorders Affecting the Liver Many primary skin disorders have a variety of systemic manifestations. hepatocellular dysfunction.

where it is closely associated with obesity (overall and abdominal). and laboratory abnormalities. as reported by Shear and Spielberg. Drug-induced hypersensitivity and toxic epidermal necrolysis The incidence of drug-induced hypersensitivity (DHS) and toxic epidermal necrolysis is unclear because of their variable presentations.50 Liver tests improve in these patients as does the small . especially when potentially hepatotoxic drug therapy is considered.45 Angioedema (especially facial or periorbital swelling) may be a sign of a systemic and potentially severe life-threatening reaction.44 Recent studies have linked psoriasis to nonalcoholic fatty liver disease (NAFLD).49 Previous studies have shown abnormalities of bilirubin or elevated liver enzyme levels in 17% of the patients in a series of 60 cases of DHS. diverse clinical features.49 Overall prevalence is estimated at between 10 and 39 cases per 100.49 Erythematous papulovesicular lesions are characteristically distributed symmetrically on extensor body surfaces and on the buttocks and back. carbamazepine. Stevens-Johnson syndrome. Rarely. metabolic syndrome. and in some cases pharyngitis. generalized follicular pustules or more severe skin reactions.42 etenercept. lymphadenopathy. and patients have a gluten-sensitive enteropathy that is histologically apparent but generally asymptomatic.47 Silver sulfadiazine is not usually recommended in cases of toxic epidermal necrolysis because it has been reported to cause leukopenia and sulfonamides are associated with severe cutaneous adverse reactions. or toxic epidermal necrolysis. mainly between the ages of 20 and 55. Hepatic disease occurs more often in patients with celiac disease than in those with DH (approximately 45% compared with 17%) and is thought to be related to the degree of gut mucosal damage. The organ involvement can vary from mild elevations in liver enzymes to marked abnormalities in function tests with hepatomegaly and fulminant hepatic necrosis.46 Laboratory features of the syndrome are leukocytosis with eosinophilia and atypical lymphocytosis.170 Satapathy & Bernstein of routine liver biopsy. and PsA and more likely to cause severe liver fibrosis (compared with nonpsoriasis NAFLD). but some investigators recommend the use of prednisone at a dosage of 1 to 2 mg/kg per day if symptoms are severe.000 annually. The incidence of these severe skin reactions as part of anticonvulsant-induced hypersensitivity syndrome was found as high as 9% among 53 patients with anticonvulsant-induced hypersensitivity syndrome induced by phenytoin.40 Other safety concerns in regard to the hepatoxicity are related to therapy with infliximab. The efficacy of corticosteroids is debatable.40 Routine work-up for NAFLD may thus be warranted in patients with psoriasis.or high-grade fever followed by development of a cutaneous eruption. The authors reported that NAFLD is highly prevalent among psoriasis patients. Treatment is primarily symptomatic and hospitalization is required in life-threatening situations. The reaction usually begins with low.48 Dermatitis herpetiformis Dermatitis herpetiformis (DH) is an intensely pruritic. which is greater in celiac disease than in DH. such as exfoliative dermatitis.43 and vitamin A. may occur. or phenobarbital. The liver is the most frequently involved internal organ in DHS and the rate is reported to be 34% to 94%. DHS starts within the first 2 to 8 weeks after initial drug exposure. Granular deposits of IgA (normally involved in immunoprotection of the body’s mucosal surfaces. chronic blistering disease that often appears suddenly. The incidence of liver chemistry abnormalities was higher (19%) in those on a normal diet than those on a gluten-free diet (9%). The skin rash is most commonly an exanthema with or without pruritus.41. especially the respiratory and gastrointestinal tracts) at the dermoepidermal junction are the immunologic marker of this disease. and is more common in men than women.

the host response to mast cell mediators.Dermatologic Disorders and the Liver 171 bowel when a gluten-free diet is adhered to.63 Studies have shown that the degree of hepatomegaly varies with the type of systemic mastocytosis and that the degree of alkaline phosphatase elevation correlates with liver size. gastrointestinal tract. anorectal canal. hepatic metastases have been described.60 Gastrointestinal and liver involvement is common in systemic mastocytosis. fibrosis. and. mainly as a consequence of immunosuppressant treatment.63 The most common liver test abnormalities is an elevated alkaline phosphatase. Reports of autoantibody abnormalities in PSC and the known association of a-gliadin and antiendomysial antibodies in DH suggest a possible underlying immune mechanism. or the presence of an underlying non–mast cell hematologic process. liver. rarely.63. seven patients (16%) had biopsy-documented hepatic lymphoma.62. and sclerosing cholangitis. portal hypertension.56 Dapsone hypersensitivity syndrome typically presents with a triad of fever. and parotid gland.65 Reported liver biopsy findings include the following: (1) bridging fibrosis.63 Manifestations of liver involvement include hepatomegaly (48%). skin eruption.52 and primary sclerosing cholangitis (PSC). PBC51. respectively. and other systems) involvement.59.70 Basal cell carcinoma is a malignant but slow-growing tumor and is locally invasive. (3) inflammatory cell infiltrates in the portal tracts and lobules. Skin cancers have been reported to be high as 40% in liver transplant .64 Four published case report series describe the cholestatic liver manifestations of systemic mastocytosis. Clinical manifestations of systemic mastocytosis vary depending on the mast cell burden in different tissues.63 Abdominal pain and diarrhea are the two most common gastrointestinal symptoms. (5) cholestasis.72 Another uncommon yet important entity is the cutaneous T-cell ´ lymphomas (mycosis fungoides and Sezary syndrome). autoimmune cholangitis.61. occurring several weeks to as late as 6 months after the initial administration of the drug. rarely extending beyond basal layer. (2) cirrhosis. although a variety of other factors are involved.66–69 From these series. genital tract. (4) venoocclusive disease.54 Both DH and PSC are strongly associated with certain HLA types. Uncommonly.58 The exact cause has not been elucidated. Primary hepatic malignant melanoma is exceedingly rare. occurring in 51% and 43% of patients. Malignant dermatologic disorders and the liver Malignant melanoma occurs most frequently in skin but also in many organs and tissues of the body. Dapsone used in treating DH may increase bilirubin (indirect) because of drug-induced hemolytic anemia but can also directly cause liver function test abnormalities in isolation or as part of the dapsone syndrome. and internal organ (lung. but the only prospective study reports an 80% prevalence.53.55. three distinct histologic patterns of cholestatic livers manifesting systemic mastocytosis have emerged—intrahepatic cholestasis. Mastocytosis Mastocytosis is characterized by an excessive number of apparently normal mast cells in the skin and in various tissues. DHS could be fatal. Liver transplant recipients are at increased risk of developing cancer.57 If not promptly identified and treated. accessory nasal cavity. and ascites (5%–50%). including the retina.61–65 The prevalence of gastrointestinal symptoms is estimated to be 51% (range 14%–85%).71. and mast cell infiltrate. In Huberman and colleagues’73 ´ series of 43 patients with cutaneous T-cell lymphomas (mycosis fungoides and Sezary syndrome). Clinicians and pathologists need to have a high index of clinical suspicion for systemic mastocytosis in proper clinical context with multisystemic symptoms and signs to avoid its attendant morbidity and mortality. liver impairment in DH may be caused by either of two autoimmune disorders. neurologic.

78 amoebiasis.172 Satapathy & Bernstein recipients and are the most frequently encountered cancer. although rarely involvement could be direct through transcutaneous extension/fistulization of hepatic infections.74–76 The most common skin cancer type was nonmelanoma skin cancer. Most of the dermatologic manifestations described in HBV infections are Table 2 Dermatologic manifestations associated with specific liver diseases Liver Disease Autoimmune liver disease (mostly with PBC) Associated Dermatologic Conditions Xanthomatous lesions Melanosis LP Scleroderma CREST Xanthomas LP MC PCT Sicca syndrome Anecdotal observations Psoriasis PAN Behcet syndrome ¸ Leukocytoclastic reactions Myositis/dermatomyositis Chronic urticaria Chronic pruritus Kaposi’s pseudosarcoma Vitiligo Mooren corneal ulcer Acral necrolytic erythema Papular eruption Gianotti-Crosti syndrome Erythema nodosum LP Lecocytoclastic vasculitis PAN MC Dermatomyositis-like syndrome Pyoderma gangreonosum PCT Skin neoplacia Dermatomyositis Cutaneous metastasis Hereditary and developmental disorder Hepatitis C infection Hepatitis B infection Hepatic neoplasm . with a higher frequency of basal cell cancer than melanoma.77 Cutaneous Manifestations of Specific Liver Diseases Direct extension from infective hepatic lesions The skin is mostly involved indirectly in infectious liver diseases.80 Dermatologic manifestations of hepatitis B virus infection Hepatitis B virus (HBV) infection can produce or induce various dermatologic manifestations (Table 2). Skin cancer education should be integrated into the care of transplant patients as part of their numerous visits to the transplant clinic to reduce their risk of skin cancer.79 and hydatid cysts. such as actinomycosis.

113 . characterized by hepatitis B e (HBe) antigenemia and high HBV replication.94 Approximately 7% to 8% of acute HBV infection patients develop PAN. such as erythema nodosum. mucous membranes. are common in HBV and hepatitis C virus (HCV) infections.83 Gianotti-Crosti syndrome. possibly involving HBeAg. however. it is not an antineutrophil cytoplasmic antibody–mediated vasculitis. nails. Response to interferonbased regimen has been documented. the most important are summarized in Table 2. circulating HBV-related Ags distinct from HBeAg could be involved. It is now well established that approximately 80% of MC is secondary to HCV infection. facilitates seroconversion. particularly in the skin and kidney.93 Manifestations. screening patients with oral LP for antibodies to HCV needs consideration.99 Antiviral treatment of CHC is the therapy of first choice for all patients with MC complicating hepatitis C infection.100 Evidence of HCV RNA has been found with high frequency in organs affected in cryoglobulinemia. ulcerations.89 dermatomyositis-like syndrome. the investigators concluded that LP patients have significantly higher risk than controls of being HCV seropositive. still undefined. PAN.82 some recurrent papular eruptions. and fatigue. 2). Acral necrolytic erythema is a papulosquamous and sometimes vesiculobullous eruption bearing clinical and histologic similarity to other necrolytic erythemas.97 Dermatologic manifestations of hepatitis C virus infection Among the many cutaneous manifestations associated with chronic hepatitis C (CHC). myalgias. and nutritional deficiency syndromes. The majority of the HBV/PAN cases are associated with wild-type HBV infection. including PBC and chronic active hepatitis or cirrhosis of unknown origin.90 pyoderma gangrenosum.86 leukocytoclastic vasculitis. MC. supporting the concept that lesions could result from the deposit of viral antigen-antibody (Ag/Ab) complexes soluble in Ag excess.101. pseudoglucagonoma.106–108 In a recent metanalysis including 33 studies comparing the seroprevalence of HCV in LP patients and six reporting the prevalence of LP in patients with HCV infection. This therapy surpasses the conventional treatment of PAN (which consists of corticosteroids and cyclophosphamide). and hair (Fig. erythema nodosum. and plasma exchanges. livido reticularis. The first-line treatment for HBV-associated PAN is shortterm steroid therapy.96 These observations have been challenged.88 mixed cryoglobulinemia (MC). An increased prevalence of chronic liver diseases has been reported in patients with LP.99 Patients with essential mixed cryoglobulinemia (EMC) display palpable purpura in the legs (which is worse distally and inferiorly). urticaria. and prevents the development of long-term hepatic complications of chronic HBV infection.109 In view of that possible association.84 LP.81 These disorders include serum sickness–like prodrome. This may suggest that other.95 Although HBV-associated PAN shares the characteristics of classic PAN.91 porphyria cutanea tarda (PCT).98.110–113 Chronic lesions are hyperkeratotic plaques with erosions and peripheral erythema preferring the acral parts of the legs. antiviral agents. such as necrolytic migratory erythema.92 and increased susceptibility to skin neoplasia.85.99 LP is an idiopathic inflammatory disease with characteristic clinical and pathologic features affecting the skin. cutis marmorata. other investigations have failed to document this finding. because cases of PAN have been reported in patients with precore mutations.102 Many studies have confirmed a significant association of LP with HCV101–105.109 A similar relationship of having LP was found among HCV patients in the same study. LP. symmetric polyarthritis.87 polyarteritis nodosa (PAN).Dermatologic Disorders and the Liver 173 immune complex–related illnesses.

PCT. PCT. LP. especially the cholestatic autoimmune liver diseases like PBC.117 Dermatologic manifestations commonly associated with PBC are xanthomatous lesions and melanosis. dermatologic lesions are the presenting signs and symptoms. The initial management of PCT should continue to be vigorous iron removal. Hypertrophic lesions are often chronic. bullae. In 38. purple color. hereditary hemochromatosis with PCT has two implications: all patients with PCT should be screened for HCV infection with measurement of antibodies against HCV. Papulosquamous skin lesions. and milia on the dorsal side of right hand. 3. They are often characterized by the six Ps: pruritus. papules. and CHC (see Table 1). residual pigmentation and scarring can occur when the lesions eventually clear. (A) LP. planar. nonspecific skin lesions typically seen in patients with advanced liver disease can also be found. (B) LP. and plaques. 2. patients who are HCV positive should be considered for treatment of HCV infection with interferonbased therapies. Various case reports exist in the literature Fig.115 After this has been accomplished. . Considering the proved association between EMC. all patients with these disorders should be tested for HCV. 3).7% of the patients with PBC. polygonal shape. and all should undergo HFE gene mutational analysis to look for either of the two mutations (C282Y or the H63D) that have been linked with iron overload.114 The frequent association of both CHC infection and HLA-linked. are associated with many skin manifestations.174 Satapathy & Bernstein Fig. CHC is also a risk factor for PCT (Fig. Erosive erythematous patches. and all cases of CHC should be investigated for the presence of these disorders. to the point of mild iron deficiency.117 At the late stages. Images depict some of the cardinal features.116 Autoimmune liver diseases Autoimmune liver diseases.

acral creases (striate palmar and plantar xanthomas).5%). and (5) posterior embryotoxon.7%). improve after liver transplantation.130 leiomyosarcoma.124 Hepatic neoplasm Hepatocellular carcinoma (HCC) rarely involves the skin. A close monitoring of the liver function tests during the initial phase of therapy . fine-needle aspiration. (3) cardiovascular abnormalities. reddish-blue. or as a result of seeding after percutaneous invasive procedures. helixes. or HBV. such us congenital rubella. shoulders. and widespread xanthomata.131 and sarcomatoid carcinoma. mostly because of the tumor’s hypervascularity. isotretinoin. especially in patients with chronic or recently diagnosed liver disease. dapsone. Primary hepatic cancers may rarely be associated with a PCT-like picture. chloroquine. inguinal areas. such as percutaneous ethanol injection.128 Previous investigators128 have observed that lesions may clinically resemble a pyogenic granuloma (also known as granuloma telangiectaticum). dermatitis-urticaria (15.120.121 and CREST syndrome. hydroxychloroquine. pruritus.125. renal disturbances. (2) peculiar facies. itraconazole. cyclophosphamide.127 A case of dermatomyosistis after HCC in a patient with hepatitis B has been described. mycophenolate mofetil. popliteal fossae. Hepatotoxicity secondary to methotrexate and dapsone is discussed previously. gluteal areas.129 Cutaneous metastases of hepatic tumors.128 They may be necrotic or purulent and may exhibit massive bleeding when ulcerated or traumatized. painless. and the occurrence of cutaneous metastasis as the disease may be seen in 1% to 5% of cases.Dermatologic Disorders and the Liver 175 describing a more frequent association of PBC with LP. methotrexate. cyclosporine.123 Cutaneous manifestations include jaundice.132 or as a complication of hepatic intraarterial chemotherapy133 or cutaneous seeding after fine-needle biopsy of liver metastases134 have been reported.4%). Cutaneous HCC should be considered in the context of a fast-growing nodule on the head. and hypercholesterolemia. and fluconazole. and disturbances of pigmentation (12. The drugs commonly used in dermatology that present a significant risk of direct hepatic toxicity include azathioprine.135 Hepatotoxicity of Dermatologic Drugs Hepatic toxicity may occasionally occur as a result of systemic drugs prescribed by dermatologists. a hematologic route. some of the following can be observed: growth retardation. Cutaneous HCC lesions may be solitary or multiple and are usually firm. neoplastic lesions (18. the lymphatics.122 In a series 49 cases.125–127 Cutaneous metastasis may occur through local invasion. Xanthelasma and tuberous xanthomas are also present. and percutaneous microwave coagulation therapy. Xanthomas (29%) are caused by chronic cholestasis and severe hypercholesterolemia and are seen on the extensor surfaces of the fingers.4%). including cholestasis. (4) vertebral arch defects. such as epithelioid hemangioendothelioma. and high-pitched voice. where they are usually confluent.136 Other uncommon causes include chlorambucil. occurs less frequently and has a worse prognosis than the syndromic type. cytomegalovirus. or chest. Less frequently. pruritus.118. and elbows and knees. Hereditary and developmental liver disease Alagille syndrome Alagille syndrome (arteriohepatic dysplasia)123 is a genetic disorder with autosomal dominant transmission (chromosome 20p). Koulentaki and colleagues117 reported fungal skin infections (31. mental retardation. and nodular lesions of 1 to 5 cm without ulceration. The syndromic type is characterized by five main features: (1) chronic cholestasis.119 scleroderma. and acitretin. nape. bone abnormalities. Many aspects of the syndrome. A nonsyndromic type associated with a1-antitrypsin deficiency and viral infections.

et al. Matsumoto T. J Pediatr Surg 1995. Johnson GC. Lancet 1984. et al. Regional differences in peripheral circulation between upper and lower extremity in patients with cirrhosis. Scheepers JH.95:669–76.33: 291–437. Crowson CS. Serrao R. Li CP. 13. Systemic lupus erythematosus: review of the literature and clinical analysis of 138 cases. English JC.9:2832–5. Quaba AA. Shulman LE. Nabai H. 10. Spider angiomas in patients with liver cirrhosis: role of alcoholism and impaired liver function. Poterucha JJ. J Postgrad Med 2002. 6. 2. 8. Apparent hepatic dysfunction in lupus erythematosus. many of the systemic diseases. Lancet 1954.266:757–9. Arch Intern Med 1955.32:977–81. Palmar erythema. especially autoimmune and related disorders.35: 2159–64. Kobayashi S. Spider angiomas in patients with liver cirrhosis: role of vascular endothelial growth factor and basic fibroblast growth factor. Tumulty PA. Zimmerman HJ. The liver in collagen diseases: pathologic study of 160 cases with particular reference to hepatic arteritis. . REFERENCES 1. Khasnis A.30:101–4. World J Gastroenterol 2003. Walker HK. Zirwas M.000/mm3 in the presence of fulminant DHS. Lee FY. Shimizu H. J Rheumatol 2008. Kollerup G. SUMMARY In conclusion. Terry R. have common involvement of skin and the liver. 5.25:883–9. Scand J Gastroenterol 1999. et al. Terry’s nails: revised definition and new correlations. Concomitant CBC values are pivotal to the diagnosis of this subset of hepatic toxicity. recognition of these associations is of utmost importance in diagnosing these conditions early so as to initiate timely interventions with a curative intention.136 Patients receiving dapsone. Medicine 1954. Okumura H. and adenopathy) in patients who have DHS. Gokula RM. Lee FY. 9. 7. 4. 11.1:896–9. et al. et al.61:31–2. and minocycline should be encouraged to report these signs and symptoms promptly. Cutis 1998. et al. 3. 14.136 In addition to dapsone. Holzberg M. Kofman S. Jensen LB. Chowdhary VR. Scand J Gastroenterol 1990. Treatment of nevi aranei with the pulsed tunable dye laser at 585 nm. Harvey AM.48:307–9. Hwang SJ. It is common for the absolute eosinophil count to exceed 1000/mm3 and rarely reaches levels higher than 10.176 Satapathy & Bernstein is of paramount importance in to order to detect hepatotoxicities in a timely fashion. fatigue. These manifestations may be liver specific and sometimes reflect the severity of the liver diseases. Nail changes before and after heart transplantation: personal observation by a physician. Katsuta Y. Nail abnormalities in nondermatologic patients: prevalence and possible role as diagnostic aids. et al. Am J Clin Dermatol 2007. 12. Spider nevus. Also. pharyngitis. Jemec GB.8: 347–56. J Am Acad Dermatol 1995. azathioprine and minocycline are associated with DHS. Hwang SJ. A characteristic morbilliform or erythrodermic cutaneous eruption is present concomitantly with symptoms resembling infectious mononucleosis (fever. Thus.34:520–3. Liver involvement in systemic lupus erythematosus: case review of 40 patients. White nails in hepatic cirrhosis. patients with liver disorders have a wide array of cutaneous manifestations. Aramaki T. Li CP. azathioprine.

et al.56:173–7. PBC autoantibodies. Course of asymptomatic liver involvement in sarcoidosis: role of therapy in selected cases.19:725–49. . et al. Sharma OP. 25. Liver 2000. et al.1:131–43. Bethlem NM. et al. J Rheumatol 2009. Zimmerman HJ. 20. Molina PL. autoimmune hepatitis and nodular regenerative hyperplasia of the liver.26:554–60. Ann Intern Med 1954. Cutaneous sarcoidosis: the great imitator: etiopathogenesis. 30. Fritzler MJ. including twenty-two autopsies. Klatskin G.46:1171–3.90:612–22. 23. et al. Assassi S. 26. et al. Clark M. 34.278:439–44. Br J Rheumatol 1998. Radiology 1995. Ricker W.20:366–73. Johns CJ.338:745–8. 22. Clinical features and serum antinuclear antibodies in 230 danish patients with systemic sclerosis. J Clin Pathol 1949. Irving KS. Nolan JP. Br J Rheumatol 1994. Lebacq EG. Barbatis C. et al. Park JH. Boitnott JK. Ishak KG. Moutsopoulos HM. Rudzki C.7:375–82. Rosenberg JC. Sarcoidosis Vasc Diffuse Lung Dis 1997. et al. Value of liver biopsy in sarcoidosis. morphology.36:2250–6. Medicine 1970.108:831–4. Modawi SB. LP-X test in sarcoidosis patients with liver involvement: comparison with other liver function tests. 27. Cervera R. Ann Intern Med 1964.14: 73–6. 29. 33. Sarcoidosis: a clinicopathologic review of three hundred cases. including autopsy findings and review of the evidence for sarcoid involvement of the liver as found in the literature. differential diagnosis. Sarcoidosis: report of ten autopsy cases in Japan. and hepatic parameter abnormalities in a large population of systemic sclerosis patients. Am J Med 1975. Hepatic granulomas: review of 73 patients from one hospital and survey of the literature. Irani SK. 37:39–45. Vatti R. Branson JH. Hercules H. 17. Garcia-Carrasco M. Am J Clin Dermatol 2006. Dobbins WO 3rd. Arnett FC. Moreno-Merlo F. The fever of sarcoidosis. Wanless IR. Hepatitis C virus infection in primary sjogren’s syndrome: prevalence and significance in a series of 90 patients. 28.49: 375–95. Sarcoidosis and chronic hepatic disease: a clinical and pathologic study of 20 patients. Tahir H. A comparison of autoimmune liver disease in juvenile and adult populations with systemic lupus erythematosus—a retrospective review of cases. Portal hypertension complicating hepatic sarcoidosis. Sen D. 24. Hepatology 1997. Iwai K. Surgery 1971. Primary biliary cirrhosis (PBC). 32. 31. Jacobsen S. The role of granulomatous phlebitis and thrombosis in the pathogenesis of cirrhosis and portal hypertension in sarcoidosis. 16. Rheumatology (Oxford) 2007. Zakaria N. 21. Eur J Gastroenterol Hepatol 2006. Tchernev G.61:455–61. Ann N Y Acad Sci 1976. and clinical management.Dermatologic Disorders and the Liver 177 15. Halberg P. Skopouli FN. Ann Rheum Dis 1997. primary biliary cirrhosis. Heller F. Ullman S. Am Rev Respir Dis 1964. Arch Pathol Lab Med 1984. 19. Liver involvement in primary sjogren’s syndrome.195:757–62. Maddrey WC. Chronic intrahepatic cholestasis of sarcoidosis. Ramos M. Warshauer DM. 18. Shimamatsu K. Natural history of hepatic sarcoidosis and its response to treatment. Sarcoidosis—hepatic involvement: presentation of a case with fatal liver involvement. Hamman SM. J Clin Gastroenterol 1979.40:111–45.59:373–87. Nodular sarcoidosis of the liver and spleen: analysis of 32 cases. Oka H. Kennedy PT.69:294–9.18:721–6.

Holt AP. Dermatologica 1985. Goodwin RM. J Dermatolog Treat 1997. 63:531–44. Carbamazepine-induced acute liver failure as part of the DRESS syndrome. Kosseifi SG.34: 421–2. Cowley G. Arch Dermatol 1978. Nollevaux MC. Degott C. Barker JN. Hepatic sarcoidosis with portal hypertension.18:363–5. Valla D.36:329–35.81:71–5. et al. 54. Gabrielsen TO.26:182–6. Walton S. Baccano G. Abnormal liver function tests induced by dapsone in a patient with dermatitis herpetiformis and primary sclerosing cholangitis. et al. Germano V.82:1826–32. et al. 48. Hepatic injury in dermatitis herpetiformis. Ann Rheum Dis 2005.61:165–8.114:947. Clin Exp Dermatol 1987. Pessegueiro-Miranda H. Primary biliary cirrhosis in a diabetic male with dermatitis herpetiformis. et al. 39. Goldin R. QJM 1987. Autoimmune hepatitis associated with infliximab in a patient with palmoplantar pustular psoriaisis. Use of silver sulfadiazine in Stevens-Johnson syndrome. Lewis HM. Dermatitis herpetiformis. A report of seven cases with a review of the literature.178 Satapathy & Bernstein 35. et al. Hall RP 3rd. Bansky G. Clin Exp Dermatol 2009. 52. et al. Current management of psoriasis. et al. et al. 57. The Dapsone hypersensitivity syndrome revisited: a potentially fatal multisystem disorder with prominent hepatopulmonary manifestations. Ann Pharmacother 1994. Dapsone: modes of action. Maibach H. J Occup Med Toxicol 2006.59:988–91. Wojnarowska F. Autoimmune hepatitis associated with infliximab in a patient with psoriatic arthritis.64:1519–20. Sheehan-Dare R. Int J Clin Pract 2005. 42. Am J Gastroenterol 1986. Guiot Y. Br J Dermatol 1996. J Clin Invest 1988. 44.99:873–81. 38. 36. . Fry L. Horsmans Y. Walton C. Fairhurst DA. Griffiths CE. Pfaltz M. Gawkrodger DJ.8:27–55. Dreyer NA. 56. 50. Leonard JN. Dermatitis herpetiformis and primary sclerosing cholangitis. Rincon-Aznar B.38:478–85.1:9. Walker AM. Acta Derm Venereol 1981. 37. J Invest Dermatol 1992. Naibitt DJ. 45. Pathogenesis and clinical features of psoriasis.35:2286–7. Roenigk HH Jr. Hypervitaminosis A-induced liver fibrosis: stellate cell activation and daily dose consumption. Arthritis Rheum 1993. 55. Guha B. toxicity and possible strategies for increasing patient tolerance. 43. Methotrexate in psoriasis: consensus conference.28:736. Levell NJ.12:46–7. on behalf of the therapy guidelines and audit subcommittee of the British association of dermatologists. Stone SP.129:507. Syn WK. Dapsone-induced jaundice. Budd-chiari syndrome in sarcoidosis. Lancet 2007. 49. Clin Exp Dermatol 1993. Fremia ML. Leak AM. Picchianti Diamanti A. 40. J Rheumatol 2008.14:172–3. 41. Spielberg SP. Primary biliary cirrhosis associated with celiac disease and dermatitis herpetiformis. Funch D. Liver Int 2006. 47. et al. 51. Chopra S. Auerbach R. Br J Dermatol 1993.170:31–4. Br J Dermatol 1999. Kirby B.370:263–71.134:1109–12. Determinants of serious liver disease among patients receiving low-dose methotrexate for rheumatoid arthritis. 53. Keaveney A. J Am Acad Dermatol 1998. Shear NH. Russi EW. Anticonvulsant hypersensitivity syndrome: in vitro assessment of risk. 46. Hoel PS. Coleman MD. et al. Systemic corticosteroids in the phenytoin hypersensitivity syndrome. Nassour DN. Hepatotoxicity associated with etanercept in psoriatic arthritis. Brophy D.

Mastocytosis: pathology. Liver Transpl 2008. Bernal Bellido C. Sahel J. Baron TH. Geller AC. Huberman MS.14:579–623. ¨ 74. Horny HP.109:1677–81. 70.22:1163–70. Boudreaux DJ. Scand J Infect Dis 2004. et al. Pirro N. Systemic mastocytosis: a rare cause of noncirrhotic portal hypertension simulating autoimmune cholangitis— report of four cases. Barrera Pulido L. et al.93:106–8. Am J Clin Oncol 2007. Yam LT.92:1197–200. 65. Chan CH. 63.89:ECR35. Matthews MJ. Am J Gastroenterol 1998. 61. Thomas JE. Eren S. Systemic mastocytosis. Millard LG. 59. Extrahepatic manifestations of chronic viral hepatitis. 62. ´ 75. Nakamoto S. Pyrsopoulos NT. Suto H. 18:190–1. Caner I. J Eur Acad Dermatol Venereol 2007. Bernhard JD. Kyriakou D. and current options for therapy. Gastrointestinal dysfunction in systemic mastocytosis.41:2447–9. Fong TL. 73. Pukkala E. Prog Transplant 2008. Campbell M. Sperr WR. Akin C. Tallon Aguilar L. Risk of malignant neoplasms after liver transplantation: a population-based study. Am J Med 1986. 64.45:1683–8. Causes and predisposing factors of de novo tumors in our series of liver transplant recipients. Curr Gastroenterol Rep 2001. Gastroenterol Clin Biol 2005. Kouroumalis E. Skin cancer education in transplant recipients. genetics. Feuerstein I. Transplant Proc 2009. et al. Transplant Proc 2009. Safyan EL. 67.95:657–67. Kaiserling E. Lancet 1997.30:661–3. Cancer 1980. . Mast cell cholangiopathy: another cause of sclerosing cholangitis. Gomez de la Camara A. Gastroenterology 1995. et al. Leuk Lymphoma 2005. Hockerstedt K. Gastrointestinal abnormalities and involvement in systemic mastocytosis. Gold JF. Furuta M. 72.21:262–3. Valent P. 77. Marbello L. Radiat Med 1995.3:71–8. et al. Mican JM. Jensen RT. Nosari A. Koehler RE. 81. Gore A. et al. Affleck AG.63:532–8. 80.18:232–41. et al. Haematologica 2004. Aberg F. A childhood case of primary hepatic actinomycosis presenting with cutaneous fistula. Anghilieri M. Malignancy after liver transplantation: cumulative risk for development.349:1379–85. Buyukavci M. Konsolas J. et al. Hepatic involvement in the cutaneous T-cell lymphomas: results of percutaneous biopsy and peritoneoscopy. Swerdlow SH. Veerabagu MP. Cutaneous amoebiasis due to liver abscess. Metcalfe DD. MRI of malignant melanoma of liver. Annu Rev Med 2004. Gastroenterology 1988. et al. ´ ´ ´ ´ 76. Giant primary basal cell carcinoma with fatal hepatic metastases. Jimenez Romero C. et al. et al. Rupard EJ.36:62–3. Golkar L. 66. Reddy KR. Liver findings in generalized mastocytosis. Hepatic involvement in mastocytosis: clinicopathologic correlations in 41 cases. 68. Cancer 1989. et al. Intrahepatic cholestasis due to systemic mastocytosis: a case report and review of literature. Hepatology 1995. di Bisceglie AM. Rodgers WH. et al. Cent Afr J Med 1972. Akin C.29:748–9.Dermatologic Disorders and the Liver 179 58. Cherner JA. Hepatic involvement in systemic mast cell disease. Mastocytosis. Bunn PA Jr. 78. Marques Medina E. Bastid C. Am J Gastroenterol 1997. Dubois A.14:1428–36. Cutaneous fistulation of a liver hydatid cyst. 71. 79.13:143–5. Basal cell carcinoma with hepatic metastases. et al. et al. Jensen RT.80:819–26.55:19–32. 60.46:35–48. Hematol Oncol Clin North Am 2000. 69. Aggressive systemic mastocytosis mimicking sclerosing cholangitis.41:2453–4. A clinicopathologic study. A prospective study. Li CY.

BMJ 1990. 91. Buezo GF. The etiology and pathophysiology of mixed cryoglobulinemia secondary to hepatitis C virus infection. Kaufman L.9:602–3.137:561–4. 103.116:577–89. Polyarteritis nodosa and extrahepatic manifestations of HBV infection: the case against autoimmune intervention in pathogenesis. 89.32:97–103. Gower RG. J Autoimmun 2001. Pouget F. Am J Med 1978. 95. 97. et al.62:222–8. 86. Callard P. Pittsley RA.19:111–29. De Castro M. Stransky J. The clinical course of viral hepatitis. Tsai CC. A multicentre case-control study. Maggiore G. A retrospective survey. Kohler PF. Br J Dermatol 1996.16:31–4. Arrieta JJ. et al. Chevrant-Breton J. 100. Arch Dermatol 1994. et al. 98. Franklin EC. Levo Y. Sanchez-Perez J. Weiss TD. Cryoglobulinemia—a clinical and laboratory study. Rongioletti F. J Am Acad Dermatol 1987. N Engl J Med 1977.74:238–53. Pyoderma gangrenosum (phagedenic pyoderma). Cas Lek Cesk 1998. Rebora A. Jubert C. et al. Martinez MI. 101. Association between hepatitis B virus and essential mixed cryoglobulinemia. Cheng GS. Millikan LE. Trepo C.84:313–22. et al. Lichen planus and hepatitis C virusrelated chronic active hepatitis. 87.300:227–30.71:109–14. 99. Mahr A. . Hepatology 2000. Malina L. Acute hepatitis B simulating dermatomyositis. Meltzer M.134:715–9. Baldassare AR. Cohen P. Havlıckova M. Erythema nodosum and hepatitis B infection. Small vessel vasculitis and HBsAg. 83.9:1–21. Medicine 1995. Guillevin L. Wu MM. Sausker WF. Lowosky MS.130:73–6. Parsons ME.180 Satapathy & Bernstein 82. 88. Detection of hepatitis C virus replication by in situ hybridization in epithelial cells of anti-hepatitis C virus-positive patients with and without oral lichen planus. Logeais B. Lichen planus and hepatitis C virus: prevalence and clinical presentation of patients with lichen planus and hepatitis C virus infection. Chronic hepatic porphyria and hepatitis B and C virus infections. Lichen planus and liver diseases. and impact of treatment in 115 patients. outcome. et al. Lhote F. Casqueiro M. Clin Gastroenterol 1980. 85. ´ ´ ´ ´ 92. Polyarteritis nodosa related to hepatitis B virus. Kassab HJ. Hsueh YM. Small vessel vasculitis caused by hepatitis B virus immune complexes. Mixed cryoglobulinemia in chronic hepatitis C infection.35(2):77–81. Medicine 1994. 84. Grifeo S. Multiple risk factors associated with arsenic-induced skin cancer: effects of chronic liver disease and malnutritional status. Hepatitis B virus–associated polyarteritis nodosa: clinical characteristics. A prospective study with long-term observation of 41 patients. Marzani M.239:959. Guillevin L.64:269–73. Medicine (Baltimore) 2005. Elias K. Dermatologic disorders associated with viral hepatitis infections. Skin lesions in viral hepatitis: histologic and immunofluorescent findings. Russo GG. Shearn MA. Int J Dermatol 1996. et al. 94. Ann Dermatol Venereol 1989. J Am Acad Dermatol 1983. Lichen planus and chronic active hepatitis. et al. Lopez-Malpica F. J Allergy Clin Immunol 1978. Pawlotsky J-M. et al.16:269–74. Guillevin L. Cryoglobulins with rheumatoid factor activity. Gorevic PD. Gruppo italiano studi epidemiologici in dermatologia (GISED). Levey JM. et al. et al.73:53–67. Br J Cancer 1995. 102.40:837–56. Agnello V. A clinicopathologic analysis of 10 cases and review of recent literature. 90. JAMA 1978. Semin Immunopathol 1997. Peculiar papular skin lesions occurring in hepatitis B carriers. 93.296:1501–4. Rodriguez-Inigo E.64:52–6. Bjornsson B. Pibouin M. Acta Derm Venereol 1984. 96. Sanchez JL. Am J Med 1966. et al. II. Banner B.

Gagetta M.1:258–9. Insulin resistance and lichen planus in patients with HCV-infectious liver diseases. El Darouti M. Lichen planus and hepatitis C virus infection. Rossi V. J Am Acad Dermatol 2004.Dermatologic Disorders and the Liver 181 104. Ciocca M.16:601–12. 126. Miller DJ. Stitle L. Acta Derm Venereol 1999. Thompson RP. et al. 112. Powell FC. Monforte NG. Ramonet M.41:787–9. Necrolytic acral erythema: a cutaneous marker of viral hepatitis C (report). J Gastroenterol Hepatol 2008. Shieh S.51:214. 14:328. J Pediatr Gastroenterol Nutr 2010.23:850–4. Benjamin J.106:699–703. 123. ´ ´ ´ 106.27: 1661–9. Powell FC. Schwarz KB. 118. Murray-Lyon IM. Cutaneous metastasis of occult hepatocellular carcinoma: a case report. Hepatology 1998. 125. Tucker SC. Nagao Y. J Eur Acad Dermatol Venereol 2003. Hepatitis C virus infection and lichen planus: a systematic review with meta-analysis. Bonkovsky HL. 119. Stefanidou M. Scleroderma and primary biliary cirrhosis. Junkins-Hopkins JM. Conde E. Chuang TY. Primary biliary cirrhosis and the CREST syndrome: a report of 22 cases. 116. 109. Br J Dermatol 1982.21: 1–30. Schroeter AL. Hadzic N. Carrozzo M. The glucagonoma syndrome: a review of its features and discussion of new perspectives. Dupin N.22:11–4. Gimenez-Garcıa R. Abu El Ela M. Int J Dermatol 1996. Necrolytic acral erythema: response to combination therapy with interferon and ribavirin. Dermatological manifestations in primary biliary cirrhosis patients: a case control study. Br J Dermatol 1982. Sata M.  124. .60:1046–9. Lichen planus. et al. J Am Acad Dermatol 1989. 110. Lodi G. Alagille syndrome: cutaneous manifestations in 38 children. Khanna VJ. 108.44:159–82. Amador A. Alagille syndrome and liver transplantation. 114. 122. Am J Gastroenterol 2006. Kawasaki K. 120. Ioannidou D.107:616. Alberti N. 121. and HFE gene mutations in North America. primary biliary cirrhosis and penicillamine. Lunel F. Oral Dis 2010.79:378–9. Ann Rheum Dis 2001. 117. Pimstone N. Porphyria cutanea tarda. Hepatitis C virus and lichen planus: a case-control study of 340 patients.50:11–5.23:580–5. Mehta S. Cutaneous metastasis from hepatocellular carcinoma as the first clinical sign. de Agustin P. Chastain MA. Ansell ID.50:S121–4. Chosidow O.133:1052–3. Hivnor CM. et al. Coulson IH. Acta Cytol 2007. et al.62:75–82. Graham-Brown RA. Necrolytic acral erythema associated with hepatitis C: effective treatment with interferon alfa and zinc. Bejarano N. 113. Perez-Castrillon JL. Pediatr Dermatol 2005. QJM 1987. Brashear R. Bonkovsky HL. Rheumatic disorders and primary biliary cirrhosis: an appraisal of 170 Italian patients. Garcia MA. Sarkany I. et al. 111. Yan AC. Arch Dermatol 2000. et al.136(6):755–7. Kamath BM. Dickson ER. 101:541–6.35:252–6. 105. Oral lichen planus and hepatitis C virus infection: a fortuitous association? Arch Dermatol 1997. Lichen planus and primary biliary cirrhosis. Nutritional deficiency and the skin. Pellicano R. Koulentaki M.17:291–5. J Am Acad Dermatol 2001. Rogers RS. Sherlock S. Lichen planus is not associated with hepatitis C virus infection in patients from North West England. et al. BMJ 1970. et al. et al. Dickson ER. 107. Hepatitis C: a review and update. J Hepatobiliary Pancreat Surg 2007. Poh-Fitzpatrick M. Acad Dermatol 1990. Marasini B. 115. J Am Acad Dermatol 1999. et al. et al. hepatitis C.

Pequignot R. et al. Vignon-Pennamen MD. Ann Dermatol Venereol 1989. Br J Dermatol 2003. Lee SJ. 129. McGrath FP. Sarcomatoid carcinoma of the liver with skin and pleural metastases. et al. Hepatocellular carcinoma in porphyria cutanea tarda: frequency and factors related to its occurrence. Siersema PD. Kubota Y.148:1069–71. O’Hagan S. Okusaka T. ten Kate FJ. Cutaneous metastases of hepatic epithelioid hemangioendothelioma. et al. Liver 1992. Iitoyo M. Remlinger K.43:130–1. Janssen F. 136. et al. et al. Mulder PG. Prognosis of hepatocellular carcinoma patients with extrahepatic metastases. . Varroud-Vial C. Hepatic leiomyosarcoma revealed by cutaneous metastasis.24:78.29:595–9. Clin Radiol 1991. 135. Okada S. Thevenot T. Gibney RG. Rheumatol Int 2009.25:195–205.12:56–61. Ishii H. Kee SJ.44:251. 133. Gastroenterol Clin Biol 1999. 128. Clin Exp Dermatol 1999. et al.23:991–2. vi–ii. Permal S. Cutaneous metastasis as a complication of hepatic intra-arterial chemotherapy. Dermatol Clin 2007. Ulster Med J 1997. Cutaneous metastasis from hepatocellular carcinoma resembling pyogenic granuloma. Cutaneous seeding following fine needle biopsy of colonic liver metastases. 131. Hepatogastroenterology 1997. Koga T. 132. Kim TJ. Koshiyama T.182 Satapathy & Bernstein 127. et al. Nakayama J. Suggested guidelines for patient monitoring: hepatic and hematologic toxicity attributable to systemic dermatologic drugs. Nishie W. 134. Wolverton SE.66:136–7.116: 864–6. Dermatomyositis associated with hepatitis B virusrelated hepatocellular carcinoma. Rowley VA. 130. Diamond T.

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