Immune Reconstitution Illness

I was consulted on a patient with lymphoma, who developed a lobar pneumonia-an infection that affected about 1/5 of his lung tissue. His immune system had been weakened by the lymphoma, and chemotherapy, but his bone marrow was recovering, and his white blood cell count was improving. He was treated with antibiotics, and was slowly improving. His hematologist found that his blood levels of IgG were very low-a common finding in lymphoma. He wanted to treat the patient with intravenous immune globulin, but the patient refused, because he is a Jehovah’s witness (a religion that proscribes transfusion of any human cells, products, or tissues, including IVIG). His team really wanted to help him get better, so they asked if he would accept treatment with filgrastim, a molecule that stimulates neutrophil production. Since this did not come from another human, he accepted. Two days later his lungs became inflamed, filled with water, and he had to be placed on a ventilator.
What happened?
Most of the clinical signs and symptoms of infections are due to the inflammatory response to the infection. When his neutrophil count increased suddenly and massively, neutrophils attacked his infected lungs. There are other examples of this that are well described. The most well known occurs in patients with AIDS. When patients with advanced AIDS are treated with antiretroviral therapy, a few will develop immune reconstitution illness-a reaction to organisms that were already present, but not clinically apparent because there was no inflammatory response to them. Zidovudine, (AZT) was the first drug we had to treat HIV infection, in 1988. It was a pretty weak antiretroviral, but in a small number of patients, after it was started, an immune reconstitution illness was observed. They developed local soft tissue abscesses with mycobacterium avium complex, a bacterium that usually affects the bloodstream and liver, and is manifested mostly by fever. In these cases, immune function improved somewhat, and attempted to localize the bacteria in a soft tissue abscess. In the early 1990s, when this occurred, the number of cases was small, and little was made of the observations. Later, when we developed really potent antiretroviral therapies, immune reconstitution inflammatory syndrome (IRIS) was seen in many cases, and became scientifically accepted.
Leukemia patients sometimes will have fevers when their white blood cell counts are low, but no identifiable iinfection source. When their bone marrow recovers from chemotherapy, candidal abscesses appear in the liver. The candida (fungus) was there all along, but we could only “see” it when their neutrophils responded to it with inflammation.
So, did my patient have an immune reconstitution illness? Maybe-it is hard to say in a single case, but it seems plausible.
The follow-up? The patient recovered, the ventilator was removed, and he was discharged from the hospital.