Absence of Human Herpesvirus 8 in Sarcoidosis and Crohn Disease Granulomas

Sarcoidosis and Crohn disease are chronic granulomatous conditions of unknown pathogenesis that affect multiple organ systems. A common mechanism has been proposed but never proved. Recently, it has been suggested that human herpesvirus 8 (HHV-8) might play a role in the pathogenesis of sarcoidosis based on polymerase chain reaction studies showing HHV-8 in a high proportion of affected tissues.¹ We used polymerase chain reaction studies to amplify a 233–base pair fragment of HHV-8 DNA in archived specimens of tissues from patients with sarcoidosis and Crohn disease who had never been treated with corticosteroids or immunomodulator agents to determine if HHV-8 might be present in these tissues.

Archived tissue specimens from the skin of 8 patients with sarcoidosis and from the small bowel of 7 patients with Crohn disease were selected on the basis of clinical history and histopathologic findings, including the presence of granulomas. Three Kaposi sarcoma specimens and 1 primary effusion lymphoma specimen were selected as positive control tissues, and negative controls included cutaneous squamous cell carcinomas and reexcisions of normal skin from patients with dysplastic nevi.

Two pathologists (J.W.P. and M.H.S.) independently confirmed the histopathologic diagnoses. We performed tissue preparation, polymerase chain reaction, and gel fractionation on all specimens according to the method described by Gaffey et al.² We used 50 amplification cycles. Human herpesvirus 8 DNA was not detected in affected tissues of patients with either sarcoidosis or Crohn disease. We detected HHV-8 DNA in the control samples of Kaposi sarcoma and primary effusion lymphoma but not in samples of squamous cell carcinoma or normal skin (Figure). We successfully amplified β-globulin in the Crohn disease and sarcoidosis specimens, which indicates that these specimens contained amplifiable DNA and lacked polymerase chain reaction inhibitors.

Human herpesvirus 8 is a novel member of the γ-herpesvirus subfamily that has been implicated in the pathogenesis of Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman disease.¹ The mechanism of HHV-8 in the induction and perpetuation of disease is not well understood; however, HHV-8 genetic homologues to human oncogenes and intercellular regulatory molecules may play a role in the pathogenesis of diseases related to the virus.

Although the cause of these granulomatous disorders has not yet been determined, it has been suspected that sarcoidosis and Crohn disease might share a common etiology based on clinical and pathologic similarities. Histologically, the 2 disorders can be virtually indistinguishable. Both diseases share common aberrations in the immune system, including altered numbers and responsiveness of T cells and dysregulation of various cytokines. Elevated serum levels of angiotensin converting enzyme are observed in the acute phase of both conditions.³

Our results argue against HHV-8 as an etiologic factor in sarcoidosis and Crohn disease. This supports findings of other investigators who have been unable to link HHV-8 infection with sarcoidosis.^{4 - 5} Although Di Alberti et al¹ did detect HHV-8 in archived sarcoidosis tissues using a polymerase chain reaction method similar to ours, the reasons for the discrepancy are not entirely clear. In future investigations, confirmation by in situ hybridization or control for regional prevalence of HHV-8 may be helpful.

Correspondence: Dr Patterson, Department of Pathology, University of Virginia, PO Box 800214, Charlottesville, VA 22908 (jwp9e@virginia.edu).

Financial Disclosure: None.