Overview of Hepatitis C and Skin

DERMATOLOGYNURSING Overview of Hepatitis C and Skin Connie M. Chung Julia R. Nunley Hepatitis C (HCV) is the most common cause of chronic liver disease and hepatocellular carcinoma, as well as the leading indication for liver transplantation in the Western world. For many patients, cutaneous manifestations may be the only, the earliest, or the most apparent sign of the underlying infection. The dermatologic manifestations of HCV infection are reviewed. Objectives This educational activity is designed for nurses and other health care providers who care for and educate patients regarding hepatitis C and the skin. For those wishing to obtain continuing nursing education credit, an evaluation follows. After studying the information presented in this article, the nurse will be able to: 1. Describe the incidence, epidemiology, and pathogenesis of hepatitis C. 2. List the extrahepatic dermatologic manifestations of hepatitis C. 3. Discuss treatment-associated disorders related to hepatitis C. H Connie M. Chung, MD, PhD, is Chief Resident, Dermatology, Virginia Commonwealth University Medical Center, Richmond, VA. Julia R. Nunley, MD, is Program Director, and Associate Professor, Department of Dermatology, Virginia Commonwealth University Medical Center, Richmond, VA. This article and the CE answer/ evaluation form are also available online at www.dermatologynursing.net epatitis C (HCV) affects nearly 170 million people worldwide and between 3 and 4 million Americans; 3% and 1.8% of the respective populations (Boyer et al., 2002; Pawlotsky, 2004; Pearlman, 2004). It is the most common cause of chronic liver disease and hepatocellular carcinoma, as well as the leading indication for liver transplantation in the Western world. There will be an estimated 35,000 new cases this year and the number of diagnosed cases is expected to quadruple between the years of 1990 to 2020 (Kim, 2002). Approximately 85% of those infected will develop chronic disease, 20% of whom will progress to cirrhosis over the ensuing 20 to 30 years (Pawlotsky, 2004). Once cirrhosis occurs, hepatocellular carcinoma develops at a rate of about 2% per year (Pearlman, 2004). Currently HCV accounts for 8,000 to 12,000 deaths per year in the United States, which is expected to triple by the year 2020 (Davis, Albright, Cook, & Rosenberg, 2003). Fortunately, treatment is cost effective and timely intervention may halt the natural progression of the disease and save lives (Davis et al., 2003). To do this, however, individuals with HCV infection must first be identified. For many patients, cutaneous manifestations may be the only, the earliest, or the most apparent sign of the underlying infection. Therefore, it is important to understand the dermatologic manifestations of HCV infection. Epidemiology Hepatitis C virus, an RNA virus belonging to the Flaviviridae family, was first identified in 1989 as the primary cause of “non-A, non-B hepatitis” (Choo et al., 1989). With the only known natural host being humans, HCV is transmitted primarily through direct contact with infected blood or blood products (Pawlotsky, 2004). Exposure to tainted blood exists in a variety of Note: The authors reported no actual or potential conflict of interest in relation to this continuing nursing education article. DERMATOLOGY NURSING/October 2006/Vol. 18/No. 5 425 DERMATOLOGYNURSING contexts including intravenous drug use, blood transfusion (before 1992), solid organ transplantation from an infected donor, occupational exposure, tattoos, snorting cocaine through shared straws, high-risk sexual behavior, and maternal-infant transmission (Boyer et al., 2002). In the United States, the most common risk factor is intravenous drug use (Pearlman, 2004). Sexual transmission rates are very low; however, sexual promiscuity, co-infection with human immunodeficiency virus, or coinfection with herpes simplex type2 increases the likelihood of sexual transmission (Pearlman, 2004; Poynard, Yuen, Ratziu, & Lai, 2003). There are six distinct genotypes of HCV and multiple subtypes. Most of the clinical consequences of the different genotypes are identical although their response to therapy is dissimilar. Genotype 1 is the most common in the United States and is unfortunately the least responsive to therapy; genotypes 2 and 3 are much more amenable to therapy (Boyer et al., 2002; Lauer & Walker, 2001). The current standard treatment regimen is the combination of pegylated interferon and ribavirin (Boyer et al., 2002). Overall, about 60% of individuals who adequately complete this course of therapy successfully eradicate the virus and attain a sustained viral response (SVR); these individuals are essentially cured (Russo, Zacks, & Fried, 2003). However, the actual SVR rate for genotype 1 is closer to 55% whereas that of genotypes 2 and 3 is nearly 80% to 90% (Boyer et al., 2002). Studies have shown that liver histology and function improve and remain stable in those who obtain an SVR and the risk of developing hepatocellular carcinoma becomes almost zero (Tanikawa, 2004; Teoh & Farrell, 2004). Recent data suggest that even non-responders may have some benefit to therapy as well (Fargion, Valenti, 2004). Fracanzani, & Table 1. Cutaneous Manifestations of HCV Well-Accepted Manifestations • Pruritus • Mixed cryoglobulinemia • Necrolytic acral erythema Frequently Associated Conditions • Porphyria cutanea tarda • Lichen planus • Polyarteritis nodosa Case Reports or Reports of Series • Psoriasis • Vitiligo • Dermatomyositis • Erythema multiforme • Erythema nodosum • Bechet’s • Pyoderma gangrenosum Pathogenesis HCV is both hepatotrophic and lymphotropic, but does not appear to be a cytopathic virus (Lauer & Walker, 2001; Pawlotsky, 2004; Poynard et al., 2003). Even though the exact mechanism(s) through which HCV causes disease is unknown, most of its consequences appear to be immunologically mediated (Heydtmann, Shields, McCaughan, & Adamas, 2001; Poynard et al., 2003). Studies suggest that the host’s immunologic response to HCV is an alteration in CD4+ and CD8+ T-cell responses and B-cell stimulation with proliferation, clonal expansion, and excessive production of autoantibodies (Dammacco, Sansonno, Piccoli, Tucci, & Racanelli, 2001; Pawlotsky, 2004). These changes are self-preserving, as they allow the virus to go unchecked and multiply freely. In addition, many of the cutaneous and extracutaneous complications of HCV can be attributed to these immunologic modifications. 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. 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). Mixed cryoglobulinemia. 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). 426 DERMATOLOGY NURSING/October 2006/Vol. 18/No. 5 DERMATOLOGYNURSING Figure 1. Hyperkeratotic dome-shaped papules with central excoriations are the characteristic features of prurigo nodules as seen on this patient’s thigh. Figure 2. Non-blanching erythematous papules are the notable findings of these palpable purpura characteristic for the vasculitis associated with MC. Figure 3. Erosions, crust, and blisters are evident on the hands of this patient with PCT. Figure 4. The polygonal purple papules of LP are evident on the forearms of this patient with HCV. 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 clini- cal 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 (Dam- DERMATOLOGY NURSING/October 2006/Vol. 18/No. 5 427 DERMATOLOGYNURSING macco et al., 2001; Mayo, 2002). Necrolytic acral erythema. 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. 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. 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, & MorenoOtoro, 2003). How HCV induces 428 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. 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). Polyarteritis nodosa. 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 disorders. 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). Treatment-Associated Disorders Pegylated interferon-alpha with ribavirin is the standard of care for treating chronic HCV infection. Interferon causes cutaneous reactions in about 10% of patients DERMATOLOGY NURSING/October 2006/Vol. 18/No. 5 DERMATOLOGYNURSING (Stafford-Fox & Guindon, 2000). Most of these are nonspecific eczematous and lichenoid reactions (Sookoian et al., 1999); however, interferon also has been associated with the development of psoriasis, vitiligo, and sarcoidosis (Hurst & Mauro, 2005; Simsek, Savas, Akkiz, & Telatar, 1996). Although rare, ribavirin can trigger a photosensitivity reaction to ultraviolet B light (Dereure, Raison-Peyron, Larrey, Blanc, & Guilhou, 2002). Combination therapy increases the incidence of cutaneous reactions to 30%. Again, most are nonspecific reactions and are rarely cause for cessation of therapy. Conclusion Hepatitis C is reaching epidemic proportions and is a significant cause of morbidity worldwide. Timely intervention can stabilize the disease and positively impact morbidity and mortality. This underscores the importance of detecting individuals infected with HCV. Since dermatologic manifestations may be the only and most apparent sign of chronic HCV, it is salient that health care professionals be aware of these dermatologic manifestations. References Antinori, S., Esposito, R., Aliprandi, C., & Tadini, G. (1991). Erythema multiforme and hepatitis C. Lancet, 337, 428. Areias, J., Velho, G.C., Cerqueira, R., Barbedo, C., Amaral, B., Sanches, M., et al. (1996). Lichen planus and chronic hepatitis C: Exacerbation of the lichen under interferon-alpha 2a therapy. European Journal of Gastroenterology and Hepatology, 8, 825-828. Boyer, J.L., Chang, E.B., Collyar, D.E., Deleve, L.D., Feinberg, J., Judge, T.A., et al. (2002). National institutes of health consensus development conference statement: Management of hepatitis C: 2002 - June 10-12, 2002. Hepatology, 36, S3-S20. Brouet, J.C., Clauvel, J.P., Klein, M., & Seligmann, M. (1974). Biologic and clinical significance of cryoglobulins: A report of 86 cases. American Journal of Medicine, 57, 775-788. Carson, C.W., Conn, D.L., Czaja, A.J., Wright, T.L., & Brecher, M.E. (1993). Frequency and significance of antibodies to hepatitis C in polyarteritis nodosa. The Journal of Rheumatology, 20, 304-309. Choo, Q., Kuo, G., Weiner, A.J., Overby, L.R., Bradley, D.W., & Houghton, M. (1989). Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science, 224, 359-362. Chuang, T.-Y., Stitle, L., Brashear, R., & Lewis, C. (1999). Hepatitis C virus and lichen planus: A case-control study of 340 patients. Journal of the American Academy of Dermatology, 41, 787-789. Cordel, N., Chosidow, O., & Frances, C. (2000). Cutaneous disorders associated with hepatitis C virus infection. Annals of Medicine Internal, 151, 46-52. Cosserat, J., Cacoub, P., & Bletry, O. (1996). Immunologic disorders of C virus chronic hepatitis. Nephrology, Dialysis, Transplantation, 11, 31-35. Dammacco, F., Sansonno, D., Piccoli, C., Tucci, F.A., & Racanelli, V. (2001). The cryoglobulins: An overview. European Journal of Clinical Investigation, 31, 628-638. Davis, G.L., Albright, J.E., Cook, S.F., & Rosenberg, D.M. (2003). Projecting future complications of chronic hepatitis C in the United States. Liver Transplantation, 9, 331-338. Dereure, O., Raison-Peyron, N., Larrey, D., Blanc, F., & Guilhou, J.-J. (2002). Diffuse inflammatory lesions in patients treated with interferon alpha and ribavirin for hepatitis C: A series of 20 patients. British Journal of Dermatology, 147, 1142-1146. Domingo, P., Ris, J., Martinez, E., & Asas, R. (1990). Erythema nodosum and hepatitis C. Lancet, 336(8727), 1377. Fargion, S., Fracanzani, A.L., & Valenti, L. (2004). Treatment choices for people infected with HCV. Journal of Antimicrobial Chemotherapy, 53, 708-712. Feiner, H.D. (1983). Relationship of tissue deposits of cryoglobulin to clinical features of mixed cryoglobulinemia. Human Pathology, 14, 710-715. Fisher, D.A., & Wright, T. (1994). Pruritus as a symptom of hepatitis C. Journal of the American Academy of Dermatology, 30, 629-632. Fitzpatrick, T.B., Johnson, R.A., Wolff, K., & Suurmond, D. (2001). Color atlas and synopsis of clinical dermatology: Common and serious diseases (4th ed.). New York: McGraw-Hill. Gerlach, J.T., Diepolder, H.M., & Zachoral, R. (2003). Acute hepatitis C: High rate of both spontaneous and treatment- induced viral clearance. Gastroenterology, 125, 80-88. Gisbert, J.P., Garcia-Buey, L., Pajares, J.M., & Moreno-Otero, R. (2003). Prevalence of hepatitis C virus infection in porphyria cutanea tarda: Systemic review and meta-analysis. Journal of Hepatology, 39, 620-627. Hadziyannis, S.J. (1998). Skin diseases associated with hepatitis C virus infection. Journal of the European Academy of Dermatology and Venerology, 10, 12-21. Hannon, C.W., & Swerlick, R.A. (2003). Vasculitis. In J.L. Bolognia, J.L. Jorizzo, & R.P. Rapini (Eds.), Dermatology (pp. 381-402). Philadelphia: Elsevier. Heydtmann, M., Shields, P., McCaughan, G., & Adamas, D. (2001). Cytokines and chemokines in the immune response to hepatitis C infection. Current Opinion in Infectious Disease, 14, 279-287. Hivnor, C.M., Yan, A.C., Junkins-Hopkins, J.M., & Honig, P.J. (2004). Necrolytic acral erythema: Response to combination therapy with interferon and ribavirin. Journal of the American Academy of Dermatology, 50, S121-124. Hurst, E., & Mauro, T. (2005). Sarcoidosis associated with pegylated interferon alpha and ribavirin treatment for chronic hepatitis C. Archives of Dermatology, 141, 865-868. Kanazawa, K., Yaoita, H., Murata, K., & Okamoto, H. (1995). Association of prurigo with hepatitis C virus infection. Archives of Dermatology, 131, 825853. Kanazawa, K., Yaoita, H., Tsuda, F., & Okamoto, H. (1996). Hepatitis C virus infection in patients with urticaria. Journal of the American Academy of Dermatology, 35, 195-198. Karlsberg, P.L., Lee, W.M., Casey, D.L., Cockerell, C.J., & Cruz, P.C. (1995). Cutaneous vasculitis and rheumatoid factor positivity as presenting signs of hepatitis C virus-induced mixed cryoglobulinemia. Archives of Dermatology, 131, 1119-1123. Khanna, V.J., Shieh, S., Benjamin, J., Somach, S., TarifZaim, M., Dorner Jr., W., et al. (2000). Necrolytic acral erythema associated with hepatitis C. Archives of Dermatology, 136, 755-757. Kim, W.R. (2002). The burden of hepatitis C in the United States. Hepatology, 36, S30-S34. Lauer, G.M., & Walker, B.D. (2001). Hepatitis C virus infection. New England Journal of Medicine, 345, 41-52. Mayo, M.J. (2002). Extrahepatic manifestation of Hepatitis C infection. The American Journal of the Medical Sciences, 325, 135-148. DERMATOLOGY NURSING/October 2006/Vol. 18/No. 5 429 DERMATOLOGYNURSING Meltzer, M., & Franklin, E. (1966). Cryoglobulinemia: A study of twentynine patients. I. IgG and IgM cryoglobulins and factors affecting cryoprecipitability. American Journal of Medicine, 40, 828-836. Mertens, J.C., Ronday, H.K., Masclee, A.A.M., & Breedveld, F.C. (1997). Rheumatic manifestations of hepatitis C virus infection. Netherlands Journal of Medicine, 51, 225-227. Murphy, G.M. (2003). Porphyria. In J.L. Bolognia, J.L. Jorizzo, & R.P. Rapini (Eds.), Dermatology (pp. 679-689). Philadelphia: Elsevier. Nagao, Y., Sata, M., Ide, T., Suzuki, H., Tanikawa, K., Itoh, K., et al. (1996). Development and exacerbation of oral lichen planus during and after interferon therapy for hepatitis C. European Journal of Clinical Investigation, 26, 11711174. Pawlotsky, J.-M. (2004). Pathophysiology of hepatitis C virus infection and related liver disease. Trends in Microbiology, 12, 96-102. Pawlotsky, J.-M., Dhumeaux, D., & Bagot, M. (1995). Hepatitis C virus in derma- tology. Archives of Dermatology, 131, 1185-1193. Pearlman, B.L. (2004). Hepatitis C infection: A clinical review. Southern Medical Journal, 97, 365-373. Poynard, T., Yuen, M.-F., Ratziu, V., & Lai, C.L. (2003). Viral hepatitis C. Lancet, 362, 2095-2100. Russo, M.W., Zacks, S.L., & Fried, M.W. (2003). Management of newly diagnosed hepatitis C virus infection. Cleveland Clinic Journal of Medicine, 70, S14-20. Sanchez-Perez, J., Castro, M.D., Buezo, G.F., Fernandez-Herrera, J., Borque, M.J., & Garcia-Diez, A. (1996). Lichen planus and hepatitis C virus: Prevalence and clinical presentation of patients with lichen planus and hepatitis C virus infection. British Journal of Dermatology, 134, 715-719. Schwaber, M.J., & Zlotogorski, A. (1997). Dermatologic manifestations of hepatitis C infection. International Journal of Dermatology, 36, 251-254. Shiohara, T., & Kano, Y. (2003). Lichen planus and lichenoid dermatoses. In J.L. Bolognia, J.L. Jorizzo, & R.P. Rapini (Eds.), Dermatology (pp. 175-198). Philadelphia: Elsevier. Simsek, H., Savas, C., Akkiz, H., & Telatar, H. (1996). Interferon-induced vitiligo in a patient with chronic viral hepatitis C infection. Dermatology, 193, 65-66. Sookoian, S., Neglia, V., Castano, G., Frider, B., Kien, M.C., & Chohuela, E. (1999). High prevalence of cutaneous reactions to interferon alpha plus ribavirin combination therapy in patients with chronic hepatitis C virus. Archives of Dermatology, 135, 1000. Stafford-Fox, V., & Guindon, K.M. (2000). Cutaneous reactions associated with alpha interferon therapy. Clinical Journal of Oncology Nursing, 4, 164-168. Tanikawa, K. (2004). Pathogenesis and treatment of hepatitis C virus-related liver diseases. Hepatobiliary and Pancreatic Diseases International, 3, 17-20. Teoh, N.C., & Farrell, G.C. (2004). Management of chronic hepatitis C virus infection: A new era of disease control. Internal Medicine Journal, 34, 324-337. Concerned about the treatment of Psoriasis and Psoriatic Arthritis during pregnancy? The Autoimmune Diseases in Pregnancy Research Study may help provide more answers. The purpose of the research study is to prospectively evaluate the risks to the fetus from autoimmune diseases and the medications used to treat these diseases during pregnancy. Who can enroll? Pregnant women who have a diagnoses of Psoriasis and/or Psoriatic Arthritis with or without the use of medications. For more information about medication use in pregnancy or to enroll in the study call toll-free… (877) 311-8971 www.otispregnancy.org/autoimmune 430 DERMATOLOGY NURSING/October 2006/Vol. 18/No. 5