Skin Rash During HCV Therapy/Pictures

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Skin Rash During Chronic Hepatitis C Therapy
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Chandra Veluru, MD, Dileep Atluri, MD, Rajagopal Chadalavada, MD, Elke Burns, RN, and Kevin D. Mullen, MD
Division of Gastroenterology, MetroHealth Medical Center, Case Western University, Cleveland, Ohio
Corresponding author.


Address correspondence to: Dr. Chandra Veluru, Division of Gastroenterology, MetroHealth Medical Center, Case Western University, Cleveland, OH 44109; E-mail:
cveluru@metrohealth.org
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References
Hepatitis C virus (HCV) infection remains a significant clinical and public health challenge, with approximately 4.1 million individuals infected in the United States.1 The World Health Organization estimates that 3–4 million individuals are infected each year worldwide, with a global 170 million chronic HCV carriers at risk of developing liver cirrhosis and/or liver cancer. Various types of skin rash have been reported due to HCV infection, as well as anti-HCV treatment. Some skin rashes improve with anti-HCV treatment, whereas others worsen, necessitating the discontinuation of the treatment and the initiation of therapy targeted toward the rash itself. We describe 3 cases that illustrate the therapeutic dilemmas that can arise when a patient develops a skin rash during treatment with pegylated interferon alfa-2a with ribavirin.
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Case #1
A 47-year-old Hispanic woman presented with a 2-day history of inflammatory skin lesions on her arms and legs. Her medical history was remarkable only for HCV infection, and she was on Week 1 of therapy with pegylated interferon alfa-2a (180 μg once a week) and ribavirin (1,200 mg daily). The patient developed pruritic, confluent, papular erythematous eruptions with occasional vesicles over her arms and legs away from the peginterferon injection site (Figures 1 and 2). She had no history of dermatologic disease or atopy.

Figure 1
Confluent erythematous rash on the lower extremity of the patient described in case #1.
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Figure 2
Erythematous rash with vesicles on the upper arm of the patient described in case #1.
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The patient had genotype 1 HCV infection, with a viral load of 1,240,000 IU/mL prior to the initiation of anti-HCV therapy. Laboratory examination at the time of the development of the skin rash showed a decrease in white blood cell count (3,200/μL), red blood cell count (442 × 106 μL), hemoglobin (14 g/dL), and platelets (49,000/μL), as well as elevations in aspartate aminotransferase (70 IU/L) and alanine aminotransferase levels (44 IU/L).

Due to severe discomfort from the rash, ribavirin was discontinued with the intention to resume therapy once the rash resolved. By Day 4, the patient reported significant improvement of the skin lesions, and ribavirin therapy (1,200 mg daily) was resumed. The patient tolerated the therapy without reappearance of the rash (Figures 3 and 4).

Figure 3
 


Resolution of the rash shown in Figure 1 after discontinuation of ribavirin.

Figure 4
 

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Resolution of the rash shown in Figure 2 after discontinuation of ribavirin.
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Case #2
A 43-year-old white woman presented with a 4-day history of inflammatory skin lesions on her face, neck, arms, and legs. Her medical history was remarkable only for HCV infection, and she was on Week 3 of therapy with pegylated interferon alfa-2a (180 μg once a week) and ribavirin (1,200 mg daily). The eruptions were limited to the pegylated interferon alfa-2a injection sites after the initial 2 treatments. However, after Week 3, the patient developed pruritic, confluent, papular erythematous eruptions with occasional vesicles on her face, neck, arms, and legs away from the injection sites.
The patient had genotype 1 HCV infection, with a viral load of 1,500,000 IU/mL prior to the initiation of anti-HCV therapy. Laboratory examination at the time of the development of the skin rash showed a decrease in white blood cell count (1,700/μL), red blood cell count (370 × 106 μL), hemoglobin (12 g/dL), and platelets (76,000/μL), as well as elevations in aspartate aminotransferase (61 IU/L) and alanine aminotransferase levels (38 IU/L).

We recommended the use of moisturizing lotion and steroid topical cream (1% hydrocortisone) to the affected areas and continued anti-HCV therapy. The patient reported mild improvement in the skin lesions. We subsequently started the patient on oral antihistamine (diphenhydramine 25 mg every 6 hours), which relieved her symptoms at the time. However, at Week 8 of anti-HCV therapy, she noticed the worsening of her skin lesions and pruritis.

Due to the severity of the rash, ribavirin was discontinued with the intention to resume therapy once the rash was reasonably controlled. By Day 5, the patient reported significant improvement of the skin lesions, and we recommended the resumption of ribavirin. The patient tolerated the therapy without reappearance of the rash.
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Case #3
A 51-year-old woman presented with a 2-day history of inflammatory skin lesions on her arms and legs. Her medical history was remarkable only for HCV infection, and she was on Week 2 of therapy with pegylated interferon alfa-2a (180 μg once a week) and ribavirin (1,200 mg daily). The first week of anti-HCV therapy was uneventful, but the patient subsequently developed pruritic, confluent, papular erythematous eruptions with occasional vesicles over her abdomen, arms, and legs away from the injection sites.

The patient had genotype 1 HCV infection, with a viral load of 239,000 IU/mL prior to the initiation of anti-HCV therapy. Laboratory examination at the time of the development of the skin rash showed a decrease in white blood cell count (2,300/μL), red blood cell count (465 × 106 μL), hemoglobin (14.4 g/dL), and platelets (71,000/μL), as well as elevations in aspartate aminotransferase (175 IU/L) and alanine aminotransferase levels (190 IU/L).
Due to severe discomfort from the rash, ribavirin was discontinued. By Day 4, the patient reported significant improvement of the skin lesions, and we recommended the resumption of ribavirin. The patient tolerated the therapy without reappearance of the rash.
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Discussion
Various types of dermatologic manifestations have been reported due to HCV infection and during anti-HCV therapy. The incidence of skin lesions during anti-HCV therapy is 24–28%, according to randomized controlled clinical trials.2-4 Fried5 reported that injection-site reactions occurred in approximately 60% of cases. In the cases discussed above, skin lesions developed away from interferon injection sites. Interestingly, the rash improved with the discontinuation of ribavirin for several days, and none of the patients experienced a recurrence of the rash after rechallenging the ribavirin therapy.The exact mechanism of ribavirin-induced skin rash during the early stage of anti-HCV therapy is unknown. Skin reactions that occur during the early course of anti-HCV therapy may be due to histamine-like side effects from ribavirin. Ribavirin has been found to cause itching, nasal stuffiness, recurrent bronchitis, and asthmalike symptoms.

These histamine-like side effects occur in 10–20% of patients and are usually mild to moderate in severity. Stryjek-Kaminska and colleagues6 have reported photoallergic skin reactions from ribavirin. However, in our case series, some of the patients developed skin lesions in areas not exposed to the sun, and none of the patients experienced a recurrence of lesions after reintroducing ribavirin.Skin lesions may vary in severity from localized rash to diffuse skin involvement. Depending upon the severity of the rash, we recommend topical therapies, starting with moisturizing lotions or steroid skin cream (eg, 1% hydrocortisone or triamcinolone). Oral antihistamines may be helpful if topical therapies do not relieve symptoms. If skin lesions worsen despite the measures discussed above, we recommend discontinuing ribavirin until the rash resolves and then reintroducing ribavirin.

The development of diffuse skin lesions during the early course of anti-HCV therapy has been reported in Europe7,8 and Asia9 but not in the United States to our knowledge. This paper may be the first reported case series in the United States. We think that these skin lesions are common in early anti-HCV therapy and are underreported in the United States. In their case series, Dereure and colleagues7 found nonspecific skin biopsies with a dermal, mainly perivascular, mononuclear infiltrate. They also noted that skin testing was poorly informative and not predictive of relapse. In all previously reported cases from other continents, it was unclear whether interferon or ribavirin was the contributing factor for the rash. In our case series, it is clear that discontinuing ribavirin for several days (less than a week) was sufficient to recover from the rash, and none of our patients required discontinuing pegylated interferon alfa-2a.
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Summary
Our 3 cases show that skin rash during early anti-HCV treatment away from interferon injection sites is due to ribavirin. Depending upon the severity of the rash, we recommend topical therapies, starting with moisturizing lotions or steroid skin cream (eg, 1% hydrocortisone or triamcinolone). Oral antihistamines may be helpful if topical therapies do not relieve symptoms. If skin lesions worsen despite the measures discussed above, we recommend discontinuing ribavirin until the rash resolves and then reintroducing the drug. Skin testing and histology are often not initially necessary.We acknowledge the consent and cooperation of the patients discussed in the case series.
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References

1. Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705–714. [PubMed]
2. McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998;339:1485–1492. [PubMed]
3. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet. 2001;358:958–965. [PubMed]
4. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–982. [PubMed]
5. Fried MW. Side effects of therapy of hepatitis C and their management. Hepatology. 2002;36:S237–S244. [PubMed]
6. Stryjek-Kaminska D, Ochsendorf F, Röder C, Wolter M, Zeuzem S. Photoallergic skin reaction to ribavirin. Am J Gastroenterol. 1999;94:1686–1688. [PubMed]
7. Dereure O, Raison-Peyron N, Larrey D, Blanc F, Guilhou JJ. Diffuse inflammatory lesions in patients treated with interferon alfa and ribavirin for hepatitis C: a series of 20 patients. Br J Dermatol. 2002;147:1142–1146. [PubMed]
8. Savk E, Uslu G, Karaoğlu AO, Sendur N, Karaman G. Diffuse cutaneous eruption due to interferon alfa and ribavirin treatment of chronic hepatitis C. J Eur Acad Dermatol Venereol. 2005;19:396–398. [PubMed]
9. Hashimoto Y, Kanto H, Itoh M. Adverse skin reactions due to pegylated interferon alpha 2b plus ribavirin combination therapy in a patient with chronic hepatitis C. Virus. J Dermatol. 2007;34:577–582.

1 comments:

  1. I was treated for HCV in the beginning of 2002. I was on therapy for 6 months. 1 shot per week with with pegylated interferon alfa-2a and ribavirin. I started experiencing skin lesions that were extremely itchy about 6 months prior to this. The site of the skin rash started at my feet and eventually worked its way up the front of both my legs (shins). I completed the therapy at the end of 2002. The rash disappeared completely from my left leg and both feet. For the first eight years after treatment, I have tested non-detectable for HCV. I have been told I only need to be tested every 5 years now. My right leg still has some of this rash and its worse when I sweat or during the winter when my skin is overly dry. I have also noticed that if I do not shave my legs at least every 2 days the rash will become worse and itch alot more. the perscription creams/steroids never helped. The only thing that has worked is applying lotion (olay quench) and making sure I shave on a daily basis. Not sure if this is related to having HCV but I never had any skin problems prior to this nor have I had any other skin conditions. Psoriasis and exzema have been ruled out. Can anyone tell me if the rash is actually caused from HCV and not the treatment?

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