Immunosuppressive Treatment of ANCA Vasculitis May Increase Patients’ Risk of Late-onset Pneumonia

Immunosuppressive Treatment of ANCA Vasculitis May Increase Patients’ Risk of Late-onset Pneumonia

Patients with ANCA-associated vasculitis using an immunosuppressive therapy may be at risk of late-onset pneumonia caused by opportunistic Pneumocystis jirovecii infection, a new study suggests.

The study, “Late-onset Pneumocystis jirovecii pneumonia (PJP) in patients with ANCA-associated vasculitis,” was published in the journal Clinical Rheumatology.

ANCA-associated vasculitis, or AAV, is characterized by chronic inflammation of small- to medium-sized vessels, triggered by an autoimmune response against the cells that line blood vessels.

Therapies that dampen the immune system’s response — called immunosuppressive therapies — are effective in improving patient outcomes. However, patients using them also are known to be at higher risk of life-threatening infections, including infections with the opportunistic fungi Pneumocystis jirovecii.

Researchers in the U.K. aimed to characterize the time between AAV diagnosis and the onset of pneumonia caused by P. jirovecii, and to identify potential risk factors linking the two.

Using data from the Aberdeen Royal Infirmary, they identified 16 AAV patients who were infected with P. jirovecii during a follow-up of 10 years (11% of the dataset’s total AAV population). As controls, researchers included 114 AAV patients with no signs of infection.

Most infected patients were being treated with cyclophosphamide, an oral immunosuppressive, and prednisolone as steroid therapy. During the induction treatment for AAV, 14 patients were also  treated to prevent P. jirovecii infection.

While most AAV patients who acquire such infections do so during the induction period — in the first six months after being diagnosed — most patients (80%) in this study acquired P. jirovecii infection after six months or post-induction. In six cases, patients’ immunosuppressive treatment was also increased within the three months that preceded the fungal infection.

Researchers also found that all patients had abnormally low levels of lymphocytes, a type of white blood cell, before a P. jirovecii infection, suggesting this is a risk factor for such infection in AAV patients.

Renal involvement and use of oral cyclophosphamide were also more common in AAV patients who acquired an infection. However, additional analysis linked only the absence of renal symptoms at diagnosis to a lower risk of infection.

Overall, the findings support that P. jirovecii infection can happen after the induction phase in AAV patients, especially in cases of escalating immunosuppression.

Extending P. jirovecii treatment may be useful, especially for patients who require more extensive immunosuppressive therapies and have signs of lymphopenia (low lymphocyte levels), the researchers concluded.

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