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Keywords:

  • Interferon;
  • hepatitis;
  • abscess

Abstract

  1. Top of page
  2. Abstract
  3. Case 1
  4. Case 2
  5. Case 3
  6. References

Abscess formation at the injection site is an unusual infectious complication of interferon-α (IFN-α) treatment of chronic hepatitis C virus (HCV) infection, but remote abscess formation during IFN-α therapy is very rare. In the present communication, we report three cases of remote abscess formation detected among 68 patients with chronic viral hepatitis treated with IFN-α, and review the pertinent English literature. We believe that, as fever and constitutional symptoms are common side effects of IFN-α treatment, a high index of suspicion is indicated to exclude abscess formation in cases of unexplained fever during IFN-α therapy.

The interferons comprise a family of related proteins of four main groups: α, β, Ω, and γ. Naturally occurring interferon-α (IFN-α) consists of a family of at least 23 predominantly non-glycosylated proteins of molecular masses between 17 000 and 22 000 Da. Therapeutic preparations consist either of a mixture of interferon species derived from virus-stimulated Namalwa cells (Wellferon), or recombinant DNA-produced single-component IFN-α species (Intron A, Roferon A). IFN-α has been widely used in the treatment of chronic hepatitis B and C [1,2]. It binds to specific cell receptors and produces immunomodulatory, antiviral and antifibrotic activity, resulting in an overall beneficial effect in patients with chronic hepatitis B and C virus infection [3]. The major side effects of IFN-α include an influenza-like syndrome, fever, fatigue, muscle aches, weight loss, psychological effects, and hematologic abnormalities. Unusual or severe side effects include seizures, autoimmune manifestations, thyroid dysfunction, skin rashes, and renal or cardiac disease [4]. Several isolated reports have recently suggested that IFN-α treatment may be associated with several immunosuppressive effects [5,6]. Major side effects of IFN-α therapy include serious bacterial infections. Abscess formation at the infection site is an unusual infectious complication [7–9], but remote abscess formation during IFN-α therapy is very rare and hardly reported [10–13]. In the present communication, we report three cases of remote abscess formation detected among 68 patients with chronic viral hepatitis treated with IFN-α, and review the pertinent English literature. All the patients attended the Infectious Diseases Clinics of Patras University Hospital, a 600-bed tertiary hospital in southwestern Greece.

Case 1

  1. Top of page
  2. Abstract
  3. Case 1
  4. Case 2
  5. Case 3
  6. References

A 42-year-old Caucasian male had been followed for anti-Hbe-positive, hepatitis B virus (HBV) DNA-positive chronic hepatitis B without evidence of cirrhosis as confirmed by liver biopsy. His past medical history was unremarkable. He was treated with subcutaneous IFN-α2a (Roferon, Hofman-La Roche, Basel, Switzerland) 4.5 MU three times weekly. The patient complained of mild myalgia and fatigue, which spontaneously resolved after the second week of treatment. Two months after IFN-α initiation, the patient developed high fever, leukocytosis, and angina. IFN-α was discontinued, and amoxicillin–clavulanate 625 mg orally every 8 h was prescribed, with no response. Re-evaluation two days later revealed a peritonsilar abscess. Surgical drainage was carried out, and the symptoms resolved. No microorganism was detected on blood culture and drainage fluid culture. One month later, IFN-α treatment was restarted with the same regimen. The patient completed 12 months of treatment uneventfully. The response of chronic hepatitis was complete. During the six-year follow-up, the patient was in good health.

Case 2

  1. Top of page
  2. Abstract
  3. Case 1
  4. Case 2
  5. Case 3
  6. References

A 26-year-old Caucasian male had been followed for HbeAg-positive, HBV DNA-positive chronic hepatitis B without evidence of cirrhosis as confirmed by liver biopsy. His past medical history was unremarkable. He was treated with subcutaneous IFN-α2a (Roferon, Hoffman-La Roche) 4.5 MU three times weekly. During the third month of treatment, the patient developed a perianal abscess which was surgically incised and drained, resulting in resolution of symptoms. The results of laboratory evaluation revealed mildly elevated liver function tests, but otherwise were within normal limits. IFN-α treatment was discontinued for a ten-day period during the infection, and restarted with the same schedule. Two months later, a perianal abscess, followed by low-grade fever, developed again. Laboratory evaluation and colonoscopy did not reveal significant findings. IFN-α treatment was discontinued, and surgical drainage was carried out, with prompt resolution of symptoms. Blood culture and culture of pus revealed no pathogen. IFN-α treatment was reinstituted after two months, with the same regimen, and continued uneventfully for six months. The dose was then increased to 9 MU three times weekly for six months because of a lack of response. No other infectious complications were recorded during treatment. The patient failed to respond to IFN-α therapy, and lamivudine therapy was subsequently given. The patient has been in good health during a five-year follow-up.

Case 3

  1. Top of page
  2. Abstract
  3. Case 1
  4. Case 2
  5. Case 3
  6. References

A 48-year-old Caucasian male had been followed for post-transfusion HCV RNA-positive chronic hepatitis C without evidence of cirrhosis as confirmed by liver biopsy. His past medical history was unremarkable except for blood transfusions 10 years ago because of a motor vehicle accident. Subcutaneous IFN-α2b (Intron, Schering-Plough Corp, Kenilworth, NJ, USA) 5 MU three times weekly was started. Forty days after treatment was started, the patient developed acute pain, tenderness, swelling and erythema over the right axilla associated with low-grade fever and leukocytosis with left shift differentiation. The patient denied trauma, use of antiperspirants, or history of hidradenitis. A diagnosis of suppurative lymphadenitis was made, and IFN-α was discontinued and replaced with antibiotics (amoxicillin–clavulanate 625 mg every 8 h orally for one week), without clinical response. Excision and drainage was carried out, with prompt resolution of signs and symptoms. Blood culture was negative, while culture of the pus yielded Staphylococcus aureus. Three weeks later, IFN-α treatment was restarted, and continued for a 12-month period. No further infections were recorded. The patient was doing well during a 4-year follow-up, and his HCV RNA was repeatedly negative.

Although infectious complications are among the major side effects of chronic interferon therapy, abscess formation away from the site of infection is rarely listed. A Medline search covering the period 1966–2002 revealed only four similar cases in addition to ours, three of them in leukemia or cancer patients, and only one in a patient with chronic hepatitis C. Abscess locations in these cases were epidural, splenic, gluteal, and hepatic. In three of them, the patients were severely immunosuppressed (advanced lung carcinoma, hairy cell leukemia), and in one, abscess formation may represent overlapping toxicity with interleukin-2. In five of eight cases, the outcome was favorable with combined medical and surgical treatment; in one case (case 2), the infection recurred within two months of IFN-α readministration, although relapse is not an unusual feature of perianal abscess. In one case, the patient died from the infection, despite the absence of severe immunosuppression (the patient had chronic hepatitis C and liver abscess). The characteristics of our patients are shown in Table 1.

Table 1.  Clinical characteristics of three cases of remote abscess formation during IFN-α therapy
 Case 1Case 2Case 3
  1. M, male; F, female; CHB, chronic hepatitis B; CHC, chronic hepatitis C; MU, million units; TWI, three times weekly; SC, subcutaneously.

Age/sex42M26M48M
Underlying conditionsCHBCHBCHC
Abscess locationPeritonsilarPerianalSuppurative lymphadenitis
Duration of IFN-α treatment before abscess formation60 days90 days40 days
Type of IFN-αα2aα2aα2b
Dose of IFN-α/route4.5 MU TIW/SC4.5 MU TIW/SC5 MU TIW/SC
Other immunosuppressive agentsNoneNoneNone
OutcomeCuredCuredCured

We did a case–control study comparing our cases with a series of chronic HBV or HCV patients attending the Infectious Diseases Clinics and not treated with IFN-α. We detected three cases of remote abscess formation among 68 IFN-α-treated patients with chronic HBV or HCV infection, while no such cases were found among 132 HBV-positive or HCV-positive chronic healthy carriers, characterized by a negative HBV DNA or HCV RNA assay. We also found no such cases among 39 patients with chronic hepatitis B treated with oral lamivudin. By performing a chi-square test, we found that remote abscesses were statistically more frequent in patients receiving IFN-α therapy (P < 0.01). Our cases revealed some unique features. The patients had no underlying diseases other than chronic hepatitis without cirrhosis, there was no local port of entry of the bacteria, and the dose of interferon was lower than in the other reported cases. The white blood cells, including neutrophils, were not decreased as a result of IFN-α treatment. We believe that impairment of systemic or local defense mechanisms triggered by IFN-α administration and subsequent seeding from circulating bacteria may explain the formation of the abscess.

In conclusion, IFN-α may rarely be associated with remote abscess formation during therapy. Fever and constitutional symptoms are common side effects of IFN-α treatment. Therefore, a high index of suspicion is indicated to exclude abscess formation in cases of unexplained fever during IFN-α therapy.

References

  1. Top of page
  2. Abstract
  3. Case 1
  4. Case 2
  5. Case 3
  6. References
  • 1
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