Dalekos G N, Christodoulou D, Kistis K G, Zervou E K, Hatzis J, Tsianos E V
Department of Internal Medicine, Medical School, University of Ioannina, Greece.
Eur J Gastroenterol Hepatol. 1998 Nov;10(11):933-9. doi: 10.1097/00042737-199811000-00006.
Alpha-interferon therapy may occasionally account for immune-mediated phenomena. This study was conducted in an attempt to investigate the incidence of the development of immune-mediated dermatological diseases during alpha-interferon therapy in patients with chronic viral hepatitis. The latter has not been evaluated prospectively, whereas most of the previous studies examined small numbers of interferon treated patients or consisted of case reports.
A prospective case-control study.
A tertiary referral centre.
One hundred and twenty consecutive patients with chronic viral hepatitis (67 with hepatitis B, 45 with hepatitis C, six with both hepatitis viruses, and two with delta hepatitis) were evaluated during a course of alpha-interferon therapy. In addition, 120 consecutive patients with chronic liver diseases (disease control group), who had never received alpha-interferon therapy, were evaluated during the period of the study (at least for 12 months).
Recombinant alpha-interferon at a dose of 4.5 or 5 million units subcutaneously (s.c.) three times per week for 6 to 12 months was administered to patients with hepatitis B. The patients with chronic hepatitis C were treated with 3 million units s.c. three times per week for 12 to 18 months. The patients with chronic hepatitis B and C infections received 4.5 million units for 6 months, and then 3 million units for an additional 6 to 12 months. Finally, the patients with chronic delta hepatitis received 5 million units for 1 year or more.
To assess prospectively the incidence of these dermatological disorders during alpha-interferon therapy and to estimate if there is any relationship between their development and the clinical, laboratory or other characteristics of the patients with chronic hepatitis.
Three to 6 months after the initiation of alpha-interferon three patients with chronic viral hepatitis (two with hepatitis C and one with hepatitis B) developed lichen planus, whereas one patient with hepatitis C developed relapsing aphthous stomatitis. The development of these disorders was significantly associated only with the presence of antinuclear antibodies before the initiation of alpha-interferon (P=0.000000). None of the patients from the disease control group had such a manifestation during the follow-up. Lichen planus resolved after the end of therapy in all of them. In contrast, therapy was discontinued in the patient who developed aphthous stomatitis, owing to the painful lesions.
This study demonstrated that alpha-interferon may rarely (3.3%) induce immune-mediated dermatological disorders, especially lichen planus. The development of these disorders may reflect a subclinical or covert autoimmune background of patients, as suggested by the presence, although in low titres, of antinuclear antibodies. However, when lichen planus developed, it was mild, did not require the discontinuation of therapy and resolved after alpha-interferon administration had ceased.
α干扰素治疗偶尔可引发免疫介导现象。本研究旨在调查慢性病毒性肝炎患者接受α干扰素治疗期间免疫介导性皮肤病的发生率。此前尚未对其进行前瞻性评估，而大多数既往研究纳入的接受干扰素治疗的患者数量较少或仅为病例报告。
前瞻性病例对照研究。
三级转诊中心。
120例连续的慢性病毒性肝炎患者（67例乙型肝炎患者、45例丙型肝炎患者、6例同时感染两种肝炎病毒的患者以及2例丁型肝炎患者）在接受α干扰素治疗期间接受评估。此外，120例连续的慢性肝病患者（疾病对照组），他们从未接受过α干扰素治疗，在研究期间（至少12个月）接受评估。
乙型肝炎患者皮下注射重组α干扰素，剂量为450万或500万单位，每周3次，持续6至12个月。慢性丙型肝炎患者接受皮下注射300万单位，每周3次，持续12至18个月。慢性乙型和丙型肝炎感染患者先接受450万单位治疗6个月，然后再接受300万单位治疗6至12个月。最后，慢性丁型肝炎患者接受500万单位治疗1年或更长时间。
前瞻性评估α干扰素治疗期间这些皮肤病的发生率，并评估其发生与慢性肝炎患者的临床、实验室或其他特征之间是否存在关联。
开始使用α干扰素3至6个月后，3例慢性病毒性肝炎患者（2例丙型肝炎患者和1例乙型肝炎患者）出现扁平苔藓，而1例丙型肝炎患者出现复发性阿弗他口炎。这些疾病的发生仅与开始使用α干扰素前存在抗核抗体显著相关（P = 0.000000）。疾病对照组的所有患者在随访期间均未出现此类表现。所有扁平苔藓患者在治疗结束后均痊愈。相比之下，出现阿弗他口炎的患者因疼痛性病变而停止治疗。
本研究表明，α干扰素可能很少（3.3%）诱发免疫介导性皮肤病，尤其是扁平苔藓。这些疾病的发生可能反映了患者潜在的亚临床或隐匿性自身免疫背景，尽管抗核抗体滴度较低，但仍可提示这一点。然而，当出现扁平苔藓时，病情较轻，无需停止治疗，且在停止使用α干扰素后即可痊愈。
