Extrahepatic Manifestations
Only about one-third of patients with acute HCV have symptoms, which may include fatigue, anorexia, and myalgias (Pearlman, 2004). Interestingly, these patients are more likely to clear the virus (Gerlach, Diepolder, & Zachoral, 2003). However, chronic HCV is associated with extrahepatic manifestations in up to 38% of patients and are, most commonly, rheumatologic (19%) or cutaneous (17%) (Pearlman, 2004). Although the literature is chock full with reports associating HCV with a myriad of cutaneous effects, many have yet to be verified. The disorders discussed herein are currently well accepted and frequently associated with cutaneous manifestations of chronic HCV (see Table 1 ).
Pruritus is a presenting symptom in 20% of patients and is associated with nonspecific lesions such as prurigo nodules (see Figure 1) and excoriations (Kanazawa, Yaoita, Murata, & Okamoto, 1995). Although the pathogenesis is uncertain, a portion of the hepatocyte cell membrane in association with a non-bile pruritogen may be causative, acting as an opioid agonist (Fisher & Wright, 1994). However, subclinical cholestasis may also be a contributing factor (Cordel, Chosidow, & Frances, 2000). Treatment options include topical antipruritics, systemic antihistamines, rifampin, naloxone or naltrexone, and ultraviolet B phototherapy (Schwaber & Zlotogorski, 1997).
Hyperkeratotic dome-shaped papules with central excoriations are the characteristic features of prurigo nodules as seen on this patient's thigh.
Mixed cryoglobulinemia (MC) is unequivocally associated with HCV. Cryoglobulins are monoclonal or polyclonal immunoglobulins that reversibly precipitate at low temperatures; cryoglobulinemia occurs when these proteins are present in the circulation. There are three types of cryoglobulinemia (Brouet, Clauvel, Klein, & Seligmann, 1974). Type I is monoclonal and is associated with lymphoproliferative diseases. Types II and III are mixed and polyclonal and are more commonly associated with autoimmune disorders, viral infections, and chronic liver disease. HCV accounts for up to 90% of cases of MC and MC are found in approximately 54% of patients with HCV, although it is not always symptomatic (Cosserat, Cacoub, & Bletry, 1996; Karlsberg, Lee, Casey, Cockerell, & Cruz, 1995; Mertens, Ronday, Masclee, & Breedveld, 1997). The clinical manifestations of MC are due to deposition of immune complexes within the vascular bed (Feiner, 1983). The classic triad of the cryoglobulinemic syndrome consists of purpura, arthralgias, and weakness (Meltzer & Franklin, 1966); however, glomerulonephritis, peripheral neuropathy, and generalized vasculitis are other common complications (Dammacco et al., 2001). Palpable purpura (see Figure 2) is the most common clinical finding, occurring in 90% of cases (Dammacco et al., 2001). Purpura typically occur in intermittent crops on the lower extremities and last between 3 and 10 days (Hannon & Swerlick, 2003). Other skin lesions associated with MC include livedo reticularis, ischemic ulcers, acrocyanosis, and hemorrhagic bullae (Schwaber & Zlotogorski, 1997). Clinical resolution has been described with treatment of interferon-alpha alone or in combination with ribavirin (Dammacco et al., 2001; Mayo, 2002).
Non-blanching erythematous papules are the notable findings of these palpable purpura characteristic for the vasculitis associated with MC.
Necrolytic acral erythema is a rare, but pathognomonic, manifestation of HCV; all cases to date are associated with HCV (Hivnor, Yan, Junkins-Hopkins, & Honig, 2004; Khanna et al., 2000). Patients develop annular, hyperkeratotic, and violaceous plaques with raised scaly borders, although some lesions may be vesiculobullous. Lesions are acral in distribution. The pathogenesis of the disorder is unknown and the response to treatment is highly variable. Suggested treatments include amino acid and zinc supplementation, interferon-alpha, and ribavirin.
Porphyria cutanea tarda (PCT) is a photosensitivity disorder due to a decrease in functional uropophryinogen decarboxylase (UROD) and an increase in circulating porphyrins. Patients develop skin fragility and blisters in sun-exposed areas, most commonly on the dorsal hands (see Figure 3) and face. Lesions may become hemorrhagic and subsequently heal with scarring and milia formation. Over time, hyperpigmentation, hypertrichosis, and sclerodermoid changes can develop.
Erosions, crust, and blisters are evident on the hands of this patient with PCT.
There are two types of PCT: familial is associated with UROD deficiency in both the hepatocyte and erythrocyte, whereas the sporadic or acquired form is associated with hepatocyte UROD deficiency only. Acquired PCT is more common and is associated with hepatic dysfunction of multiple causes including chronic persistent hepatitis and cirrhosis.
The association between HCV and PCT is variable, ranging from 4% to 90%, depending upon the geographic prevalence of HCV (Hadziyannis, 1998). PCT, however, is observed in only 5% of patients with HCV (Gisbert, Garcia-Buey, Pajares, & Moreno-Otoro, 2003). How HCV induces PCT is not known. HCV probably triggers PCT in genetically/metabolically predisposed individuals (Cordel et al., 2000; Mayo, 2002). Co-morbid factors such as alcohol use, estrogen therapy, iron overload, and/or a genetic defect for hemochromatosis are required for expression of PCT (Pawlotsky, Dhumeaux, & Bagot, 1995). Interferon-alpha may improve symptoms of PCT (Mayo, 2002). However, the mainstay of treatment remains phlebotomy and absolute avoidance of alcohol and other triggers. Low-dose hydroxychloroquine (200 mg twice weekly) may be useful in HCV-infected patients, but must be used cautiously as to not flare the disease (Murphy, 2003).
Lichen planus (LP) is an inflammatory disease of the skin and mucous membranes. It is characterized by pruritic, purple, polygonal, papules with an overlying reticulate pattern of white lines called Wickman's striae (see Figure 4) (Fitzpatrick, Johnson, Wolff, & Suurmond, 2001; Shiohara & Kano, 2003). LP most commonly occurs on the flexor surfaces of the wrists and forearms, dorsal hands, the anterior aspect of the lower legs, the presacral area, and the neck. Oral and genital mucosal involvement is also common. Oral lesions arise most commonly on the buccal mucosa and appear as white lacey papules, though they may become erosive. Up to 35% of patients with LP have chronic liver disease (Mayo, 2002). Between 4% and 60% of cases of LP are associated with HCV, depending upon the prevalence of HCV in the geographic area surveyed (Chuang, Stitle, Brashear, & Lewis, 1999). Oral LP is possibly more frequently associated with HCV (Sanchez-Perez et al., 1996); however, the association between LP and HCV is not firmly established because of the geographic variability (Hadziyannis, 1998). Standard therapies for LP include topical corticosteroids or immunomodulators, systemic retinoids such as acitretin, and phototherapy (Shiohara & Kano, 2003). Treatment with interferon-alpha may improve, worsen, and even trigger LP (Areias et al., 1996; Hadziyannis, 1998; Nagao et al., 1996).
The polygonal purple papules of LP are evident on the forearms of this patient with HCV.
Polyarteritis nodosa (PAN) is a multisystem necrotizing vasculitis of medium and small-size vessels (Hannon & Swerlick, 2003). Cutaneous lesions are observed in 25% to 60% of patients with systemic PAN and include purpura (23%), segmentary edema (22%), and nodules (13%) (Cordel et al., 2000). Livedo reticularis and ulceration can also be seen. Cutaneous lesions are frequently located in dependent sites predominantly on the lower extremities below the knee. PAN is most commonly associated with hepatitis B and 10% to 50% of the patients with PAN have hepatitis B surface antigen (Pawlotsky et al., 1995). Hepatitis C occurs less frequently. Several studies have shown a prevalence ranging from 5% to 20% (Cordel et al., 2000; Pawlotsky et al., 1995). Data suggest that PAN related to HCV may have a more benign course (Carson, Conn, Czaja, Wright, & Brecher, 1993).
Other dermatologic manifestations associated with HCV are anecdotal. Isolated cases include urticaria, erythema nodosum, erythema multiforme, malakoplakia, pyoderma gangrenosum, dermatomyositis, and psoriasis (Antinori, Esposito, Aliprandi, & Tadini, 1991; Cordel et al., 2000; Domingo, Ris, Martinez, & Asas, 1990; Kanazawa, Yaoita, Tsuda, & Okamoto, 1996).
Dermatology Nursing. 2006;18(5):425-430. © 2006 Jannetti Publications, Inc.
Cite this: Overview of Hepatitis C and Skin - Medscape - Oct 01, 2006.
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