The patient was known to have dermatomyositis with minor muscle and skin involvement but a rapidly progressive pulmonary fibrosis for which he was taking moderate doses of prednisone and oral cyclophosphamide.He was admitted with a severe deterioration in pulmonary status and was shortly admitted to ICU and subsequently intubated. Bronchoscopy quickly confirmed a diagnosis of Pneumocystis and the young patient was able recover after a short but intense battle. Such is not always the case. The acute onset and rapidly progressive disease is the norm for this group, unlike the HIV population, but the outcome is not always this good. In fact,reports of up to 65% mortality in ICU admitted patients have been published. This case sent me scurrying off to review pneumocystis prophylaxis, something that I haven't really felt compelled to do since the nasty days of my residency when the first AIDS cases arrived on the floors and pneumocystis lurked everywhere.
Fortunately, just weeks ago there was a review on pneumocystis prophylaxis in the Mayo Clinic Proceedings. This was a meta-analysis of studies involving prophylaxis in non-HIV immunosuppressed patients. Among the studies pulled was a Mayo article from 1996. In that study they reviewed all cases of PCP in non-HIV patients over a six year period. They found 116 cases with a breakdown that showed highest risk among hematological cancers, followed by transplant patients and finally inflammatory diseases, including several rheumatological patients. This included five patients with temporal arteritis, three with RA and only two Wegeners patients. I suspect the low numbers in Wegeners is because prophylaxis was already fairly common among these patients. Their conclusion was that the patients who required prednisone of >16mg/d for longer than 8 weeks were at risk.
The meta-analysis itself also came up with some interesting numbers. Their discussion centered around the risk and benefit of PCP prophylaxis. They showed that the risk of adverse effects of Septra prohylaxis was small, 1 in 32 patients, and that the risk of serious side effects, such as Stevens-Johnson or marrow aplasia,was in the order of 7-8/100,000. They calculated that any diagnosis carrying a risk of contracting PCP of >3.5% was worth prophylaxing. This would include Wegeners patients but not the other inflammatory diseases. In no study, however, did I find any specific reference to cyclophosphamide, azothiaprine, mycophenolate mofetil or any other agents used in the rheumatological arena.
When I asked an infectious disease friend of mine about the matter, I was informed that the HIV patient population receives prophylaxis when the CD4 count falls below 200, and that this probably holds for our population as well. I looked into this and found two studies in Chest from 2000 and another from 2005. Both studies concluded that low CD4 levels were highly correlated with PCP infection, in all non-HIV diseases. In the first study, 91% of patients with PCP had a CD4 count of less than 300.
Overall then PCP prophylaxis would appear to be waranted in all treated Wegeners patients, and possibly all patients receiving prolonged high dose corticosteroids. This would include the majority of temporal arteritis patients as well as many sick lupus and vasculitis patients.This certainly isn't my practice at the moment. There is still insufficient evidence concerning the use of immunosuppressors, except in the case of methotrexate in RA where there appears to be little risk. CD4 counts may help us out here, if these preliminary studies should be replicated. It may well be that we can institute prophylaxis at the onset of treatment and reassess once disease activity has been controlled, based on the CD4 count.