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On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.86 no.4 supl.1 Rio de Janeiro July/Aug. 2011
Use of cyclosporin in a patient with hepatitis C and pustular psoriasis*
Lislaine BommI; Carolina ZimmermannI; Roberto SoutoII; Aline BressanIII; Alexandre GrippIV
IMD, Resident in Dermatology, Pedro Ernesto University Hospital, Rio de Janeiro State University (HUPE - UERJ), Rio de Janeiro (RJ), Brazil
IIMD Dermatologist, Auxiliary in the General Outpatient Dermatology Clinic, Pedro Ernesto University Hospital, Rio de Janeiro State University (HUPE - UERJ), Rio de Janeiro (RJ), Brazil
IIIPost-graduation in Dermatology, Pedro Ernesto University Hospital, Rio de Janeiro State University (HUPE - UERJ), Rio de Janeiro (RJ), Brazil; MD Dermatologist in infirmary and immunobiology clinic, Pedro Ernesto University Hospital, Rio de Janeiro State University (HUPE - UERJ), Rio de Janeiro (RJ), Brazil
IVMaster's degree in Dermatology; Assistant Professor of Dermatology and Head of Dermatology Infirmary of the Pedro Ernesto University Hospital, Rio de Janeiro State University (HUPE - UERJ), Rio de Janeiro (RJ), Brazil
Cyclosporine has been contraindicated in patients with chronic infections such as infection with hepatitis C because of its immunosuppressive effect. Recent studies have shown however that cyclosporine suppresses viral replication and thus cannot exacerbate infection with hepatitis C when employed for treating patients with psoriasis. We present the case of a female patient with psoriasis for 30 years and hepatitis C for 20 years, with diffuse circinate lesions. Improvement in the skin condition and liver enzymes was obtained with the use of cyclosporine, with no adverse effect.
Keywords: Cyclosporine; Hepatitis C; Psoriasis
With the increased incidence and/or prevalence of infectious diseases, including infection with hepatitis C (3% of world population), it is not uncommon in clinical practice for patients to present with both psoriasis and hepatitis C, which makes treatment a challenge for the dermatologist. 1
Systemic treatment of psoriasis is performed with so-called conventional drugs such as methotrexate, cyclosporin and acitretin, as well as with immunobiological medicines. 2 The choice of medication depends on patient variables such as age, sex, co-morbidities, underlying diseases, lifestyle etc. Hepatitis C is mainly treated with a combination of interferon (which works directly against the virus and boosts immune response) with ribavirin (synthetic analogue of guanosine which acts directly on RNA and DNA viruses). 3.4
In patients with psoriasis and hepatitis C, interferon exacerbates psoriasis and the hepatotoxicity and immunosuppression caused by the majority of therapies for psoriasis treatment, which could worsen the hepatitis C infection. It is therefore contraindicated in these conditions. However, recent findings on the anti-viral effect of ciclosporin on the hepatitis C virus have opened new prospects for using it safely and effectively in patients with psoriasis and hepatitis C.
Female patient, 75 years old, diagnosed with plaque psoriasis treated with topical drugs for over 30 years, with worsening of skin lesions over previous 6 months. The lesions became more erythematous, pustular, pruritic and painful, with scaly edges. The patient (current weight 51kg) admitted to no other systemic symptoms. Dermatological examination revealed erythematous, circinate scaly edges on upper and lower limbs, the inframammary region, trunk and face (Figures 1 and 2). Past medical history of hepatitis C when clinically monitored in hepatology service 20 years previously, with worsening of liver function in the last year.
Skin biopsy and laboratory tests showed altered liver enzymes (Table 1). Cyclosporine 3mg/kg/day was started and after 8 weeks the patient showed improvement of skin lesions (Figure 3) and liver enzymes. The PASI score decreased from 27 to 9, with a serum cyclosporine value of 219 ng / ml.
Circinate pustular psoriasis or pustular ring is a localized form of pustular psoriasis manifested by outbreaks of annular lesions, with erythema and pustules on the periphery, generally located on the trunk and roots of members with no systemic manifestation. It is rare condition and typical psoriasis lesions are usually not present.
Cyclosporine is an immunosuppressive medication that can be very useful for the treatment of psoriasis. It belongs to the family of calcineurin inhibitors and acts as a prodrug since it remains inactive until it connects with its cytoplasmic receptor known as cyclophilin. 2 The cyclosporin-cyclophilin complex inhibits calcineurin phosphatase activity, leading to inhibition of T-cell function and to decreased production of IL-2 (interleukin 2). The recommended daily dose for the treatment of psoriasis is 3-5mg/kg/day. 2.3
Using cyclosporine is at present contraindicated for patients with difficult-to-control arterial hypertension, renal dysfunction and T-cell lymphoma. 3 It also involves a number of relative contraindications such as breastfeeding, the use of other immunosuppressants, migraine and in patients with chronic infections. Therefore a good clinical and laboratory evaluation of the patient is needed before using this medication. Due to the risk of nephrotoxicity, hypertension and malignancy, the use of cyclosporine should be used for a minimum length of time. 1,2,3
A patient's inability to generate an effective immune response is one factor which causes an infection to become established and maintain its chronicity, as in the case of patients with hepatitis C. This explains why cyclosporine is traditionally contraindicated in patients with chronic infections 4.
Recent studies nevertheless demonstrate that cyclosporine acts as a mechanism for suppressing the viral replication of HCV. This occurs by inhibiting the functional association of intracellular cyclophilin (a cofactor for viral replication) with the viral protein NS5B (crucial viral protein for viral replication), thus decreasing the HCV viral load and leading to improved liver function in some cases. 4.5 Studies also suggest that the HCV genotype 1b is the most sensitive to inhibition by cyclosporine given that it is dependent on the cyclophyn for replication. 6.7
Evidence also exists that the inhibitory effect of cyclosporine on HCV viral replication (by blocking cyclophyn) is independent of the immunosuppressive function of cyclosporine, which is achieved through the inhibition of calcineurin. 7.8
The use of cyclosporine in patients with psoriasis and hepatitis C improves skin condition without exacerbating hepatitis. In some cases it may even lead to improvement in liver function and viremia. 8.9 The case described above showed clinical improvement with the use of cyclosporine, as well as improvement of liver enzymes, with no adverse effects.
These recent findings of the anti-HCV effect of cyclosporine renew the prospects for considering this drug to be a good option for treating psoriasis in patients with hepatitis C. Although more studies on its safety and efficacy are called for (the literature contains only a few case reports) it can be used with caution.
1. Sociedade Brasileira de Dermatologia. Consenso Brasileiro de Psoríase 2009. 1st ed. Rio de Janeiro: Sociedade Brasileira de Dermatologia, 2009. 116 p. [ Links ]
2. Bressan AL, Souto RS, Fontenelle E, Gripp AC. Imunossupressores em Dermatologia. An Bras Dermatol. 2010;85:9-22. [ Links ]
3. Rosmarin DM, Lebwohl M, Elewski BE, Gottlieb AB, National Psoriasis Foundation. Cyclosporine and psoriasis: 2008 National Psoriasis Foudation Consensus Conference. J Am Acad Dermatol. 2010;62:838-53. [ Links ]
4. Frankel AJ, Van Voorhees AS, Hsu S, Korman NJ, Lebwohl MG, Bebo BF Jr, et al. Treatment of psoriais in patients with Hepatitis C: from Medical Board of the National Psoriasis Foudation. J Am Acad Dermatol. 2009;61:1044-55. [ Links ]
5. Imafuku S, Tashiro A, Furue M. Cyclosporin treatment of psoriasis in a patient with chronic hepatitis C. Br J Dermatol. 2007;156:1367-9. [ Links ]
6. Watashi K, Hijikata M, Hosaka M, Yamaji M, Shimotohno K. Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. Hepatology. 2003;38:1282-8. [ Links ]
7. Inoue K, Umehara T, Ruegg UT, Yasui F, Watanabe T, Yasuda H, et al. Evaluation of a cyclophilin inhibitor in hepatitis C virus-infected chimeric mice in vivo. Hepatology. 2007;45:921-928 [ Links ]
8. Yang F, Robotham JM, Nelson HB, Irsigler A, Kenworthy R, Tang H. Cyclophilin A is an essential cofactor for hepatitis C virus infection and the principal mediator of cyclosporine resistance in vitro. J Virol. 2008;82:5269-78. [ Links ]
9. Cecchi R, Bartoli L. Psoriasis and hepatitis C treated with anti-TNF alpha therapy (etanercept). Dermatol Online J. 2006;12:4. [ Links ]
Mailing address: Received on 12.02.2011. * Study undertaken at: Pedro Ernesto University Hospital, Rio de Janeiro State University (HUPE - UERJ) - Rio de Janeiro (RJ), Brazil.
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Approved by the Advisory Board and accepted for publication on 30.03.11.
Conflict of interest: None
Financial funding: None
Received on 12.02.2011.
* Study undertaken at: Pedro Ernesto University Hospital, Rio de Janeiro State University (HUPE - UERJ) - Rio de Janeiro (RJ), Brazil.