Inpatients With 'Unexplained' Leukocytosis

Unexplained or persistent leukocytosis is an increasing common cause of consultation to infectious disease physicians. Patients appear to be in a state of continued inflammation recently described as the persistent inflammation-immunosuppression and catabolism syndrome (PICS). Hospital course of such patients is frequently prolonged and associated with extensive use of empiric broad-spectrum antibiotics. We wished to determine the associated clinical features and outcome of such patients in anticipation of future specific diagnostic and therapeutic approaches to this syndrome.

We reviewed all infectious disease consultations from July 1, 2017, to March 31, 2018, for reason for consultation. Of those whose primary reason was "leukocytosis" or "bandemia," each chart was assessed for demographics, reason for admission, hospital day of consultation, peak white blood cell count, infections and possible microbiological colonization, antibiotic use, and outcome.

A total of 29 patients were identified, constituting 4.5% of consults during the study period. Cause of admission was sepsis in 7, major trauma 6, cerebrovascular accident 5, major elective surgery 4, ischemic leg 3, and 1 each lung mass, acute myocardial infarction, interstitial lung disease, and angioblastic lymphoma. Peak total leukocyte count (WBC) was 26.4K ± 8.8 on mean day 9.6 ± 5.5 days of hospitalization. Mean duration of leukocytosis greater than 11K was 14.5 ± 10.6 days. Peak percentage early myelocytic ("band") leukocytes was 18.4 ± 13.8 and was of higher than 5% for a duration of 4.5 ± 5.6 days. Total eosinophilia count >500 was observed in 15 patients (range 500-2800) median hospital day 12. All patients received multiple and prolonged courses of broad-spectrum combination empiric antibiotics without apparent benefit either in terms of leukocytosis, signs of sepsis if present, or change in cultures, although those 7 with confirmed sepsis at admission tended to have shorter duration of leukocytosis and hospital course, whereas patients with trauma manifested greatest "bandemia." Most patients became colonized with resistant opportunistic organisms, the most significant being Clostridium difficile enteritis in 6 patients. Hospitalization was prolonged, and most common disposition was to nursing home or rehabilitation (11 patients, mean day of discharge 21.6 ± 16.8) and home (8 patients, day 16.0 ± 9.3). Three patients died at mean hospital day 35.7 ± 29.7.

Except for 1 person with pelvic abscess post-cystectomy, patients appeared to have extensive tissue damage rather than active infection driving the leukocytosis. Patients appeared to meet clinical criteria for PICS that was substantiated by development of eosinophilia. Future studies should include direct measurements of the CD33CD11b+ myeloid suppressor cells, and the relative contribution of damage-associated molecular patterns (DAMPS) compared with pathogen-associated molecular patterns (PAMPS) such as endotoxin and other microbial products. More prudent and effective use of antibiotics could be possible.