Dysfunction in the body’s second largest organ, the liver, often yields changes in the body’s largest organ, the skin. If we can recognize these manifestations early, we are better able to promptly diagnose and treat the underlying liver disease, as well as the skin lesions.
The liver has many jobs: synthesizing proteins such as clotting factors, complements, and albumin; neutralizing toxins; and metabolizing lipids and carbohydrates. Insults to the liver can compromise any of these functions, affecting visceral organs, joints, gastrointestinal tissues, and the skin. Dermatologic signs of specific liver diseases include alopecia and vitiligo associated with autoimmune hepatitis, and xanthelasma in chronic cholestatic liver disease.
This article reviews the important cutaneous manifestations of specific liver diseases. We focus first on skin conditions that may represent liver disease, and then we discuss several major liver diseases and their typical cutaneous manifestations.
JAUNDICE AND HYPERBILIRUBINEMIA
Establishing whether the excess bilirubin is conjugated or unconjugated gives a clue as to whether the cause is prehepatic, intrahepatic, or posthepatic.3–8 One of the liver’s main functions is to conjugate bilirubin into a secretable form. Prehepatic causes of jaundice include hemolysis and ineffective erythropoiesis, both of which lead to higher levels of circulating unconjugated bilirubin.4 Intrahepatic causes of jaundice can lead to both unconjugated and conjugated hyperbilirubinemia.4,8 Posthepatic causes such as bile duct obstruction primarily result in conjugated hyperbilirubinemia.4
PRURITUS AND PRURIGO NODULARIS
Pruritus can be multifactorial or the result of a specific dermatologic or systemic condition.9 A thorough history and physical examination are warranted to rule out hepatic or systemic causes of itching.10
The liver neutralizes toxins and filters bile salts. If its function is impaired, these materials can accumulate in the body, and deposition in the skin causes irritation and itching.11,12 In cholestatic liver disorders such as primary sclerosing cholangitis and obstructive gallstone disease, pruritus tends to be generalized, but worse on the hands and feet.13
Although the severity of pruritus is not directly associated with the level of bile salts and toxic substances, lowering bile salt levels can mitigate symptoms.11
Treatment. Pruritus due to liver disease is particularly resistant to therapy.
In a strategy described by Mela et al for managing pruritus in chronic liver disease,14 the initial treatment is the anion exchange resin cholestyramine (Questran) at a starting dose of 4 g/day, gradually increased to 24 g/day in two doses at mealtimes.
If the pruritus does not respond adequately to cholestyramine or the patient cannot tolerate the drug, then the antituberculosis drug rifampin (Rifadin) can be tried. Rifampin promotes metabolism of endogenous pruritogens and has been effective against cholestatic pruritus when started at 150 mg/day and increased up to 600 mg/day, depending on the clinical response.14
Third-line drug therapies include opioid antagonists such as naltrexone (ReVia) and nalmefene (Revex).14,15
Plasmapheresis can be considered if drug therapy fails.16 Experimental therapies include albumin dialysis using the molecular adsorbent recirculating system (a form of artificial liver support), antioxidant treatment, and bright-light therapy.15 Liver transplantation, when appropriate, also resolves cholestatic pruritus.14
Prurigo nodularis, distinguished by firm, crusty nodules, is associated with viral infections (eg, hepatitis C, human immunodeficiency virus), bacterial infections, and kidney dysfunction.17,18 The lesions are intensely pruritic and often lead to persistent scratching, excoriation, and, ultimately, diffuse scarring.19
Treatment. Although the exact cause of prurigo nodularis is not known and no cure exists, corticosteroid or antihistamine ointments control the symptoms in most patients with hepatitis.19 Low doses of thalidomide (Thalomid), a tumor necrosis factor antagonist, have also been used safely and effectively.18,19