Consider PCP prophylaxis in immunosuppressed patients

January 31, 2013

Since pneumocystis pneumonia (PCP) can occur in patients taking immunosuppressive medications for a variety of indications, one physician suggests considering PCP prophylaxis for these patients.

Dr. Kalaaji

Rochester, Minn. - Since Pneumocystis pneumonia (PCP) can occur in patients taking immunosuppressive medications for a variety of indications, one physician suggests considering PCP prophylaxis for these patients.

“In dermatology,” says Amer N. Kalaaji, M.D., “we encounter many patients whom we start on immunosuppressive medications such as prednisone. But how often do we consider prophylaxing them for PCP?” Dr. Kalaaji is an associate professor of dermatology and chair, division of dermatopathology and cutaneous immunopathology, Mayo Clinic, Rochester, Minn.

“Many dermatologists tend not to start these patients on PCP prophylaxis because the medications used for this purpose can also cause severe drug reactions and Stevens-Johnson syndrome,” says Dr. Kalaaji. “Most of us think of PCP occurring in patients with HIV, which it does. But it can also occur in patients without HIV who are on immunosuppressive medications that we use in dermatology. Therefore, we need to at least consider PCP prophylaxis.”

PCP up close

Formerly called Pneumocystis carinii, Pneumocystis jiroveci is a unicellular fungus that can be found in the lungs of healthy individuals. However, says Dr. Kalaaji, “Disease occurs when either cellular or humoral immunity is defective.”

In HIV-infected patients, PCP has a mortality rate of 10 to 20 percent, versus 30 to 60 percent in patients without HIV, he says. “It can occur in patients on immunosuppressive medications, those with primary immune deficiencies, and those with hematologic or non-hematologic malignancies,” he says, adding that based on the rheumatology, infectious disease, and pulmonary literature, risk factors for PCP include oral prednisone in doses as low as 16 mg daily for eight weeks or longer (Yale SH, Limper AH. Mayo Clin Proc 1996;71:5-13).

Other potential risk factors include the presence of pulmonary interstitial fibrosis, reduced CD4 lymphocyte counts, leukopenia, lymphopenia, and hypoalbuminemia,” Dr. Kalaaji says.

Two studies

Dr. Kalaaji and co-author Jacqueline L. Gerhart, M.D., retrospectively studied 334 patients who had undergone long-term immunosuppression for connective tissue disease or immunobullous disease. “When we looked back at those patients, a total of seven, or 2.1 percent, were diagnosed with PCP,” Dr. Kalaaji says. “None of those seven patients had received PCP prophylaxis (Gerhart JL, Kalaaji AN. J Am Acad Dermatol. 2010 Jun;62(6):957-61).”

Moreover, “All seven of these patients had comorbidities such as bladder cancer, renal transplantation or pulmonary disease,” Dr. Kalaaji adds. “Additionally, five of these patients developed PCP within three months of starting immunosuppressive therapy, and of these five, three died within one month of PCP diagnosis. Prednisone doses among the seven patients ranged from 15 mg daily to 60 mg daily.

“The development of PCP does not require high doses of prednisone, and comorbidities seem to increase the risk for PCP,” he says. Furthermore, “The 43 percent mortality rate for PCP is consistent with rates found in the literature regarding PCP mortality in non-HIV patients, which ranged from 30 to 60 percent.  However, this was a retrospective study, and it was limited to patients with connective tissue disease or immunobullous disease who had also developed pneumonia.”

Dr. Kalaaji and colleague Julia S. Lehman, M.D., addressed some of these limitations in a subsequent second study. “Unlike the first study, the objective was to determine retrospectively the frequency of PCP in dermatology patients treated with systemic immunosuppressive medications for at least one month for any dermatologic diagnosis,” Dr. Kalaaji says.

“We also wanted to characterize risk factors for the development of PCP; describe dermatologists’ and other specialists’ prophylaxis prescribing habits; and assess the frequency of PCP-related adverse events,” he adds. “The reason most dermatologists shy away from PCP prophylaxis is that we worry about the serious drug reactions patients can get with the PCP prophylaxis medications that are used - namely, trimethoprim sulfamethoxazole (TMP-SMX).”

In the second retrospective study, among 198 patients who met study criteria, “The frequency of developing PCP was quite low. Only one patient (0.5 percent) developed PCP (Lehman JS, Kalaaji AN. J Am Acad Dermatol. 2010 Nov;63(5):815-23). When we excluded those patients who had received prophylaxis, the frequency increased slightly to 0.7 percent,” Dr. Kalaaji says.

“Although adverse events were not that frequent or serious in this second study, due to the low frequency of PCP development among the study population (0.5 to 0.7 percent), we could not conclude that PCP prophylaxis is needed in every patient on immunosuppressive medication,” he says. “Rather, the decision to prophylax or not should be done on a case-by-case basis, taking into consideration a patient’s risk factors.”

Risk factors

Risk factors for the development of PCP identified in the medical literature include prednisone doses of at least 16 mg daily for longer than eight weeks; treatment with cyclophosphamide; the presence of Wegener’s granulomatosis; low CD4 lymphocyte counts; pulmonary disease (especially interstitial pulmonary fibrosis); hypoalbuminemia; hematologic and non-hematologic malignancies; primary immune deficiencies; and advanced age, Dr. Kalaaji says.

“Dermatologists in our department were only prophylaxing in 3.1 percent of cases analyzed in this second study. In contrast, pulmonary specialists in the study prophylaxed 71.4 percent of patients, and primary care physicians prophylaxed 15.4 percent of their patients,” he says.

Overall, “The take-home message is that PCP does occur in dermatology patients receiving immunosuppressive medications, albeit at a low frequency: 2.1 percent in the first retrospective study and 0.5 to 0.7 percent in the second,” Dr. Kalaaji says.

Although such low frequencies do not warrant PCP prophylaxis in every patient, “PCP’s high mortality rate of 30 to 60 percent in immunosuppressed patients necessitates that it should be considered in every patient on immunosuppressive medications, and initiated for those who have PCP risk factors,” he says.

“If a decision to prophylax for PCP is made, the prophylaxis medication most often used is TMP-SMX at a dose of one double-strength tablet by mouth daily,” he says. “Alternatively, if patients have allergies or other problems with TMP-SMX, dapsone 100 mg daily by mouth has been used successfully for PCP prophylaxis.

“A third alternative is inhaled pentamidine, 300 mg once monthly,” Dr. Kalaaji says. Additionally, Mepron (atovaquone, GlaxoSmithKline) 1,500 mg daily by mouth can be used, but it’s expensive and less often utilized, he explains.

“We also need to monitor our patients who are on immunosuppressive medications closely for the development of PCP, and if they develop symptoms or signs suspicious for PCP, they must be evaluated promptly and appropriately,” Dr. Kalaaji says.

Disclosures: Dr. Kalaaji receives royalties from an immunobullous disease atlas that he wrote.