Recognizing and treating cutaneous signs of liver disease

ALCOHOLIC CIRRHOSIS AND THE SKIN

The cutaneous changes associated with alcoholic cirrhosis are more widely recognized than those due to other forms of liver dysfunction. In the United States, approximately 3 million people have alcoholic cirrhosis, the second-leading reason for liver transplantation.^49,50

As the body’s main site of alcohol metabolism, the liver is the organ most affected by excessive alcohol intake, which can lead to end-stage liver disease secondary to alcoholic cirrhosis.^41,51 The characteristic feature of cirrhosis is advanced fibrous scarring of parenchymal tissue and the formation of regenerative nodules with increased resistance to blood flow throughout the organ.^41,52 The insufficient blood flow damages vital structures in the liver and compromises liver function. For example, liver cirrhosis leads to defective hepatic synthesis of clotting factors and results in bleeding disorders.

Cutaneous lesions often accompany alcoholic cirrhosis and have been detected in up to 43% of people with chronic alcoholism.⁵³ Skin changes in alcoholic cirrhosis can be of great diagnostic value. The combined prevalence of spider angiomas, palmar erythema, and Dupuytren contracture in alcoholic cirrhosis was found to be 72%. Paper-money skin and Dupuytren contracture are more distinct lesions for alcoholic cirrhosis.³¹ Recognizing these skin changes contributes to the diagnosis and staging of liver cirrhosis.^51,52

Dupuytren contracture

Dupuytren contracture is characterized by progressive fibrosis and thickening of tendons in the palmar fascia, the connective tissue that lies beneath the skin of the palms.⁵⁴ Over time, as fibrotic involvement expands across the fascia, rampant stiffness of the joints ensues, sometimes to a point where the fingers cannot fully flex or extend.⁵⁴

Although the exact cause of Dupuytren contracture is unknown, it appears to be associated with excess alcohol consumption and can be found in patients with alcoholic cirrhosis.^54,55 These patients often present with painless stiffness of the fingers, curling of fingers, and loss of motion in involved fingers.⁵⁴ Surgery in the form of limited fasciectomy has been curative in such patients.⁵⁴

Disseminated superficial porokeratosis

Porokeratosis is a keratinization disorder of clonal origin that presents as a linear configuration of white scaly papules that coalesce into plaques throughout the body.⁵⁶ Although it most commonly afflicts fair-skinned people, patients with alcoholic cirrhosis have a much greater susceptibility than the general population.^57,58

A recent study⁵⁸ documented that the lesions completely resolved when liver function improved, thus underlining the relationship between the two conditions. Since immunosuppression has been linked to eruption of the lesion, the fact that both humoral and cell-mediated immune responses are impaired in alcoholic liver disease provides another dimension to the association between porokeratosis and alcoholic cirrhosis.⁵⁸

These lesions can transform into squamous cell carcinoma.⁵⁹ The risk of widespread metastases in squamous cell carcinoma highlights the importance of dermatologic consultation in such patients.⁵⁹

HEPATITIS C AND THE SKIN

Extrahepatic manifestations have been documented in up to 74% of people with hepatitis C virus infection.⁶⁰ In addition to parasthesias, arthralgias, and myalgias, hepatitis C has a significant association with porphyria cutanea tarda, lichen planus, vitiligo, sialadenitis, urticarial vasculitis, corneal ulcers, xerosis, pruritus, and prurigo nodularis.^60–64 Although the primary causative agents of sialadenitis are bacteria, viruses such as hepatitis C have been implicated as a cause of chronic sialadenitis with associated xerostomia.⁶⁵

Patients with hepatitis C being treated with interferons also present with cutaneous manifestations such as hyperkeratosis and vasculitis.⁶³

Porphyria cutanea tarda

Porphyria cutanea tarda is the most common of the porphyrias, disorders distinguished by deficiencies or defects in one or more of the enzymes responsible for hepatic production of heme.⁶⁶ If these enzymes are impaired, heme precursors such as porphyrins accumulate.⁶⁶

Porphyria cutanea tarda results from a deficiency of the hepatic enzyme uroporphyrin decarboxylase. In the absence of this enzyme, shortwave visible light activates uroporphyrin deposited in the skin, resulting in a photochemical reaction that generates reactive oxygen species that lead to the characteristic skin blistering.

Although porphyria cutanea tarda is associated with liver disease in general, recent studies confirm that patients with hepatitis C are at particularly high risk.⁶⁷ Those with the disorder often present with skin photosensitivity. ⁶⁸ Many develop blisters on sun-exposed skin, including the dorsal aspects of the hands and forearms and on the neck and face. Chronic porphyria cutanea tarda can lead to scarring, alopecia, and skin ulceration.⁶⁹ As the blisters heal, keratin-filled milial cysts may develop in the areas of ulceration.

The condition is also commonly associated with melasma-like hyperpigmentation and hypertrichosis in sun-exposed areas of the head and neck. People of Northern European ancestry may be more at risk than the general population because of a presumed genetic susceptibility.⁷⁰

Treatment. Because many patients with porphyria cutanea tarda have iron overload, they need to restrict foods rich in iron and to avoid alcohol.^71,72 Severe cases may necessitate iron removal via phlebotomy or antimalarial therapy. Patients with porphyria cutanea tarda induced by hepatitis C should have their bodily iron stores depleted before starting antiviral therapy.⁶⁰