High levels of CMV reactivation seen in patients taking immunosuppressants

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High levels of CMV reactivation seen in patients taking immunosuppressants

Janis

Aug 16, 2004

Tokyo, Japan - Patients with connective-tissue diseases (CTD) who are taking

immunosuppressants are at unexpectedly high risk for reactivation of latent

cytomegalovirus (CMV) infection, a new study, published in the July 2004

issue of the Journal of Rheumatology, suggests [1]. Lead author Dr Takehiko

Mori (Keio University School of Medicine, Tokyo, Japan) tells rheumawire

that patients should be tested for CMV seropositivity before starting

immunosuppressive therapy and that seropositive patients should be monitored

for reactivation during treatment by using plasma polymerase chain reaction

(PCR) or a CMV antigenemia assay.

" Serological tests (IgG-EIA, etc) are not suitable for immunosuppressed

patients, " Mori points out.

CMV reactivation seen in many patients, with 1 fatality

The question of CMV reactivation has been addressed previously but not in a

conclusive way. Mori and colleagues used real-time PCR to measure CMV DNA in

peripheral blood lymphocytes (PBLs) and plasma of 18 CMV-seropositive

patients with connective-tissue diseases who were being treated with

immunosuppressants.

The investigators found detectable CMV DNA, a sign of reactivated CMV

infection, in the peripheral blood cells of 7 patients (41%) and in the

plasma of 5 (29%). All patients with CMV DNA in the plasma also had CMV DNA

in PBLs. Of the 18 patients, 12 had been tested with real-time PCR before

initiation of immunosuppressant therapy, and none had CMV DNA in PBLs.

During the study period, 1 patient . . . developed disseminated CMV

disease, including CMV pneumonitis and subsequent thrombotic

thrombocytopenic purpura, which, despite ganciclovir administration, was

fatal.

" During the study period, 1 patient with the highest copy numbers of CMV DNA

in both PBL and plasma developed disseminated CMV disease, including CMV

pneumonitis and subsequent thrombotic thrombocytopenic purpura, which,

despite ganciclovir administration, was fatal, " Mori reports.

CMV, CTD might be mutually reinforcing

Of the patients, 12 had systemic lupus erythematosus (SLE), either alone or

combined with other CTDs such as systemic sclerosis, dermatomyositis,

polymyositis, and/or rheumatoid arthritis. One patient each had

dermatomyositis, microscopic polyangiitis, rheumatoid vasculitis, and

cutaneous polyarteritis nodosa. One patient had both rheumatoid arthritis

and microscopic polyangiitis. Treatment regimens were primarily prednisolone

plus cyclosporine A or intravenous cyclophosphamide.

" Although it has been shown that infectious disease is one of the major

causes of life-threatening complications in patients with inflammatory CTD,

CMV disease in these patients has been considered rare, " the researchers

note. " Using a PCR technique, we observed a high incidence of CMV

reactivation in patients with inflammatory CTD. "

" We found that patients with inflammatory CT diseases who are being treated

with immunosuppressive therapy are at high risk for reactivation of CMV.

However, it is important to remember that reactivation and CMV-associated

disease are different, " Mori says. " In some patients on severely

immunosuppressive regimens, CMV diseases may follow the reactivation. "

Mori also points out that CMV has been reported to affect the course of

inflammatory CTD by triggering disease exacerbations or flares. This raises

the possibility that treatment to suppress CMV reactivation in particularly

high-risk patients (such as those on very intensive immunosuppressive

regimens or infected with human immunodeficiency virus) might also reduce

activity of the connective-tissue disease.

" At present, the incidence of CMV diseases in patients with rheumatoid

disease is not elucidated but probably not high. Therefore, at present, it

not considered routinely necessary for these patients to receive

prophylactic CMV therapy (such as ganciclovir), " Mori says.