case report

Peginterferon alfa related psoriasis in a patient with acute hepatitis C and review of the literature 11 3

Summary The Interferon (IFN) which is the standard treatment for Hepatitis C, may cause a lot of side effects including dermatological anomalies. This paper pres-ents a psoriasis case which occurred in relation with the treatment of acute hepatitis C (AHC) with peginterferon alfa (peg-IFN-α). A 60-year-old male patient came to the hospital with symptoms of high liver enzymes. The patient with history of a recent operation showed anti-HCV (+), HCVRNA 3.5  million  IU/mL and HCV geno-type 1b in the tests. Without any other etiological fac-tors found in the patient, we started a treatment of peg-IFNα-2b with the diagnosis of AHC. After 3 weeks, psori-atic plaques were observed in various parts of the body. Antiviral treatment of the patient was concluded within 6 months. His psoriasis treatment initially commenced with local agents followed by phototherapy. Permanent viral response was seen in the patient and his lesions recovered rapidly after the antipsoriatic and antiviral treatment. Psoriasis and other autoimmune diseases should be considered even though they are encountered rarely,and the patients should be informed of the pos-sible risks before planning treatment with peg-IFN-α.

Keywords Psoriasis · Peginterferon alfa · Hepatitis C

PEG Interferon alpha assoziierte Psoriasis bei einem Patienten mit akuter Hepatitis Cund Übersicht über die entsprechende Literatur

Zusammenfassung Interferon (IFN), das Standard-Therapeutikum für Hepatitis C, kann zahlreiche Neben-wirkungen, inklusive dermatologischer Anomalien, hervorrufen. Die vorliegende Arbeit berichtet über einen Patienten mit Psoriasis, die im Zusammenhang mit einer PEG Interferon alpha (peg-IFNα) Behandlung einer akuten Hepatitis C (AHC) auftrat: Ein 60 Jahre al-ter Mann, der vor kurzem eine Operation hatte, kam in das Spital wegen hoher Leberenzyme. Die Tests ergaben positive anti-HCV, HCV RNA 3,5 Millionen IU/ml und HCV Genotyp 1b. Nach Ausschluss anderer ätiologischer Faktoren begannen wir unter Annahme der Diagnose einer AHC mit einer Behandlung mit peg-IFNα 2b. Drei Wochen nach Beginn der Therapie wurden an verschie-denen Körperstellen psoriatische Plaques sichtbar. Die antivirale Therapie wurde nach insgesamt 6 Monaten Therapie beendet. Die Therapie der Psoriasis bestand zunächst aus lokal aufgetragenen Wirkstoffen und dann aus Phototherapie. Der Patient zeigte ein permanentes virales Ansprechen. Die Läsionen erholten sich nach der anti-psoriatischen und antiviralen Therapie rasch. Pso-riasis und andere autoimmune Erkrankungen sollten bei der Planung einer Therapie mit Peg-IFNα immer in Betracht gezogen worden, obwohl sie nur selten auftre-ten. Die Patienten sollten über dieses mögliche Risiko noch vor Beginn der Therapie informiert werden.

Schlüsselwörter Psoriasis · PEG Interferon alpha · Hepatitis C

Wiener klinische WochenschriftThe Central European Journal of Medicine

Wien Klin WochenschrDOI 10.1007/s00508-013-0408-1

Peginterferon alfa related psoriasis in a patient with acute hepatitis C and review of the literatureMuhammed Sait Dag · Zeynel Abidin Öztürk · Nimet Yılmaz · Hakan Çam · Abdurrahman Kadayıfçı

Z. A. Öztürk, MD, Specialist ()Faculty of Medicine, Department of Internal Medicine, Division of Geriatric Medicine, Gaziantep University, 27100 Sahinbey, Gaziantep, Turkeye-mail: zaodr79@yahoo.com

M. S. Dag, MD, Specialist · N. Yılmaz, MD, Specialist · H. Çam, MD, Specialist · Prof. A. KadayıfçıFaculty of Medicine, Department of Internal Medicine, Division of Gastroenterology, Gaziantep University, 27100 Sahinbey, Gaziantep, Turkey

Received: 23 April 2013 / Accepted: 16 July 2013© Springer-Verlag Wien 2013

2 Peginterferon alfa related psoriasis in a patient with acute hepatitis C and review of the literature

case report

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Introduction

Generally, asymptomatic progressing acute hepati-tis C (AHC) may cause complications like cirrhosis and hepatocellular carcinoma by becoming highly chronic if untreated [1]. Because of its antiviral and immune mod-ulator characteristics, peginterferon alfa (peg-IFN-α) is the standard treatment option for chronic hepatitis C (CHC) [2]. However, interferons (IFN) cause significant side effects on various organs and systems. They may cause side effects such as psoriasis, eczema, alopecia, lupus, lichenoid eruptions, and pigment changes on the dermatological system [3]. The immunomodulatory effects of the IFNs may cause a worsening in the course of an autoimmune disease such as psoriasis or make a latent autoimmune disease become evident [4–6]. Pso-riasis is a disease whose causes are not precisely known and it leads to significant visual and psychological mor-bidity with the lesions it creates [7]. In this paper, a pso-riasis case due to the peg-IFNα-2b treatment of a patient with AHC who did not have a history of dermatological illness has been presented and related literature has been reviewed.

Case report

A 60-year-old male patient came to the hospital with symptoms of high liver enzymes and fatigue. The patient did not show any history of chronic sickness and der-matological diseases. The case history revealed that the patient had undergone a blood transfusion approxi-mately 3 months ago during an orthopedic surgery. No pathology has been detected in the physical examina-tion. His laboratory results were as follows: aspartate aminotransferase 450 U/L (5–34), alanine aminotransfer-ase 335 U/7 L (3–55), total bilirubin 0.8 mg/dL, alkaline

phosphatase 120  U/L, gamma-glutamyl transferase 17, prothrombin time 13 s, and whole blood count was nor-mal. The anti-HCV (+) patient had HCV genotype 1b and his HCVRNA level was determined as 3.5 million IU/mL. No pathology was diagnosed in the upper abdomen USG and other etiological factors were not taken into con-sideration for the patient. The patient was considered to have AHC and a treatment of peg-IFNα-2b with a dose of 1.5 µg/week [PegIntron, MSD] was started. During 3rd week of the treatment, a few maculopapular plaques in millimetric sizes were observed in the abdomen region. After the 3rd month, these plaques had spread to the face,scalp, arms, torso and legs, and their diameters increased in size (Fig. 1). The patient has received consul-tation from the dermatological department and changes in accordance with psoriasis have been detected in the histological examination of the skin lesions. No family history, drug or another infectious etiological factor was found in the patient who was diagnosed with second-ary developing psoriasis in peg-IFN-α treatment and the patient was further subjected to local steroid treatment. The interferon treatment was carried out for 6 months in spite of the patient’s request of discontinuing it. Dur-ing the 3rd and 6th month of the antiviral treatment HCVRNA became (−) and liver enzymes showed nor-mal values. Psoriasis treatment continued locally, how-ever, upon not receiving enough response, narrow band ultraviolet B (UVB) phototherapy was carried out three times a week. There was significant regression in lesions after antiviral treatment was carried out for 9 months and phototherapy for 3 months.

Discussion

Hepatitis C is a significant viral cause of hepatitis influ-encing approximately 170 million people worldwide.

Fig. 1 Extended psoriatic lesions on various parts of the body in a patient with acute hepatitis C

case report

Peginterferon alfa related psoriasis in a patient with acute hepatitis C and review of the literature 31 3

About 80 % of the AHC cases become chronic, hence it is extremely important to diagnose and start the treatment at an early stage [1]. The IFN’s are used individually in AHC, and in KHC, in combination with ribavirin [2].

Pegylation of IFN-α with polyethylene glycol results in peg-IFN-α and its plasma half-life extends immu-nogenicity and antigenicity; the side effects decrease and patient compliance increases [8]. As the immunity decreases with pegylation, the peg-IFN-α usage worsens the secondary autoimmune sickness or makes a latent autoimmune disease become evident [4–6, 9]. Here, a latent psoriasis case in relation with peg-IFNα-2b treat-ment becomes evident even though neither the patient nor his family had a previous history of dermatological illness.

Psoriasis is an autoimmune, inflammatory, chronic, and a T-cell mediated disease whose causes are not known. However, genetic and environmental factors play a crucial part in its occurrence. In case of the IFN’s worsening an accompanying psoriasis or making the dis-ease evident, their Th1 lymphocyte stimulation and their effect of increasing cGMP in the cyclic adenosine mono-phosphate/cyclic guanosine monophosphate (cGMO) balance which plays an important role in psoriasis pathogenesis are put forward to be the possible mecha-nisms [10, 11]. Withdrawal of the psoriatic lesions after the completion or cessation of IFN treatment supports these theories [5, 6, 12, 13]. In this case, rapid recovery was acquired through the antipsoriasis treatments given, especially after completion of the IFN treatment.

It is obvious that the immune system activating IFN’s affect the course of an autoimmune sickness such as psoriasis in a negative manner [5, 6, 9, 14]. However, the course of the treatment is not clear in case of psoriasis and hepatitis C combination where the only treatment option is IFN. Recovery was observed in a patient with both, serious psoriasis and hepatitis C with the treatment of synchronized etanercept, peg-IFN-α and ribavirin [15]. In another case, Mederacke et al. reported that per-manent viral response was acquired with the same treat-ment while a worsening in the psoriasis was seen [14]. No recovery was observed in case of illness with synchro-nized peg-IFN-α and UVB treatment for chronic hepatitis B [9]. However, there were cases that the IFN treatment was given up as psoriasis and other autoimmune sick-ness had worsened during the peg-IFN-α treatment. The antiviral treatment was continued on request of the patient and rapid recovery has been achieved after the completion of peg-IFN-α treatment in addition to the antipsoriatic treatments. Upon evaluation of the overall information, the patients were informed of the possible risks and the treatment was personalized by taking the patient’s opinion. In case the IFN treatment continues, the patients should be followed up closely.

Emergence of a latent psoriasis can occur in the 1st weeks of the IFN treatment as well as years later after the completion the treatment [9, 12, 13]. In this case, psoriatic plaques started developing in the 3rd week of the treatment and we believe that personal genetic and

immunological structures are the most influencing fac-tors rather than the structure of IFN and its dosage in regards to why there is so much difference in the periods between the cases.

Topical steroids, D3 vitamin analogues, salicylic acid, and various photo-therapies can be sufficient in the treatment of mild and limited psoriasis, whereas sys-temic treatments such as oral retinoids, methotrexate, cyclosporin, and biological agents are required for severe diseases [7, 9]. As we did not receive a good response initially, phototherapy was considered. Despite of the widespread psoriasis, regression of the lesions has been achieved with phototherapy without the need of a sys-temic treatment.

Psoriasis and other autoimmune diseases should be considered even though they are encountered rarely when planning a treatment with Peg-IFN-α for acute or chronic hepatitis C and the patients should be informed of the possible risks before the treatment.

Conflict of interestAll co-authors have read and approved the final version of the manuscript. All co-authors are aware of the jour-nal’s conflict-of-interest policy; to the best of our knowl-edge, none of the co-authors has any direct or indirect conflicts of interest, financial or otherwise, relating to the subject of our report.

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