RECURRENT LYMPHOPENIA CAUSED BY RIFAMYCINS

Abstract

Introduction We present an unusual finding of lymphopenia, possibly caused by rifamycins in a patient with recurrent pulmonary Mycobacterium avium complex (MAC) infection. Serial follow-up of patient's absolute lymphocyte count (ALC) during his three courses of antimicrobial therapy for pulmonary MAC infection. Panel A shows patient's absolute lymphocyte count (ALC) in relation to the three treatment courses he received for his MAC infection. Panel B, C, and D show details of the antibiotic agents he used, in relation to his ALC trend during his first, second and third treatment courses respectively. Case Description A 71-year-old HIV-negative man with history of bronchiectasis and recurrent pulmonary MAC infection was evaluated in our clinic for an unexplained lymphopenia. He was receiving rifabutin, ethambutol and azithromycin for his third pulmonary MAC infection (quinolone-resistant) but continued to have malaise, fever and a productive cough. His absolute lymphocyte count (ALC) was 250 cells/μL (1000-4800 cells/μL). Lymphocyte subsets revealed a CD4+T-cell count of 63 cells/μL (730-2250 cells/μL), CD8+T-cell count of 86 cells/μL (250-1240 cells/μL), and CD19+B-cell count of 75 cells/μL (160-390 cells/μL). Immunoglobulin levels were normal. He had protective antibody titers to diphtheria, and tetanus. Antibody titers to 20 out of 23 pneumococcal serotypes were considered protective. We found that his lymphopenia was intermittent and closely associated with the use of rifamycins. We therefore discontinued rifabutin and started clofazamine. Within one month his pulmonary symptoms improved, and his ALC returned to normal (1170 cells/μL). Repeat lymphocyte subsets analysis showed an improvement of his CD4+ and CD8+T cell counts (251 cells/μl, and 219 cells/μL respectively). Discussion The intermittent nature of lymphopenia, late age at onset, and preserved protective vaccine titers favored a secondary cause for lymphopenia in our patient. The close association of his lymphopenia with rifamycins use implicated these medications as a likely culprit. The observed lymphopenia was severe and possibly contributed to his lingering pulmonary symptoms. Recognizing this potential side effect is important as lymphopenia can worsen MAC infection. We present an unusual finding of lymphopenia, possibly caused by rifamycins in a patient with recurrent pulmonary Mycobacterium avium complex (MAC) infection. Serial follow-up of patient's absolute lymphocyte count (ALC) during his three courses of antimicrobial therapy for pulmonary MAC infection. Panel A shows patient's absolute lymphocyte count (ALC) in relation to the three treatment courses he received for his MAC infection. Panel B, C, and D show details of the antibiotic agents he used, in relation to his ALC trend during his first, second and third treatment courses respectively. A 71-year-old HIV-negative man with history of bronchiectasis and recurrent pulmonary MAC infection was evaluated in our clinic for an unexplained lymphopenia. He was receiving rifabutin, ethambutol and azithromycin for his third pulmonary MAC infection (quinolone-resistant) but continued to have malaise, fever and a productive cough. His absolute lymphocyte count (ALC) was 250 cells/μL (1000-4800 cells/μL). Lymphocyte subsets revealed a CD4+T-cell count of 63 cells/μL (730-2250 cells/μL), CD8+T-cell count of 86 cells/μL (250-1240 cells/μL), and CD19+B-cell count of 75 cells/μL (160-390 cells/μL). Immunoglobulin levels were normal. He had protective antibody titers to diphtheria, and tetanus. Antibody titers to 20 out of 23 pneumococcal serotypes were considered protective. We found that his lymphopenia was intermittent and closely associated with the use of rifamycins. We therefore discontinued rifabutin and started clofazamine. Within one month his pulmonary symptoms improved, and his ALC returned to normal (1170 cells/μL). Repeat lymphocyte subsets analysis showed an improvement of his CD4+ and CD8+T cell counts (251 cells/μl, and 219 cells/μL respectively). The intermittent nature of lymphopenia, late age at onset, and preserved protective vaccine titers favored a secondary cause for lymphopenia in our patient. The close association of his lymphopenia with rifamycins use implicated these medications as a likely culprit. The observed lymphopenia was severe and possibly contributed to his lingering pulmonary symptoms. Recognizing this potential side effect is important as lymphopenia can worsen MAC infection.