PERIANAL INFECTIOUS COMPLICATIONS IN PATIENTS WITH GRANULOCYTOPENIA AND HAEMATOLOGICAL MALIGNANCIES

AIM: to study the perianal infection (PI) in patients with granulocytopaenia (GCP) and hematological malignancies (HM).

PATIENTS AND METHODS: the prospective study (2016-1018) includes 95 episodes of PI in 76 patients with HM (male/female 35/44; mean age of 35 (17-69)). 43(54.4%) of the patients were detected to develop acute leukemia (AML – 34 (43%); ALL – 9(11.4%); NHL – 17(21.5%).
The comparison of PI episodes within the GCP period (number of granulocytes less than 0.5x109/l) and without it was done.

RESULTS: PI episodes within the period of GCP were significantly much more often than those without GCP (77.9% vs 22.1%, relative risk 3.5 (95% CI: 2.4-5.2).
The biggest number of PI episodes in the setting of GCP was registered within the period of chemotherapy (ChT): in the phase of consolidation (28.4%) and induction (13.3%) of acute leukemia ChT and lymphomas’ ChT (20.3%). Anal fissures were the most frequent source of PI within GCP period (66.2% vs 19.1% without GCP, p<0.001). Inflammatory changes in perianal tissues were clinical features of PI in the setting of GCP in 89.2% of the cases: inflammatory mass in 71.6% (vs 23.8% without GCP, p<0.001), abscess in 8.1% (vs 66.7% without GCP, p<0.001).
In 10.8% of the cases of PI with GCP only perianal pain and fever were registered. No tissues change was detected with the lowest WBC count (Me 0.2 (0.1-0.5) x109/l). Bloodstream infections were detected in 15 (20.3%) episodes within the period of GCP only, of them in 6 (8.1%) cases the species matching of microorganisms in blood and in rectum was noticed.
Within the period of GCP antibacterial therapy was carried out in 98.6% of the cases: antibacterial therapy  alone was applied in 87.8% of the episodes (vs 7.2% without GCP, p<0.001); both antibacterial therapy and  surgical treatment were carried out in 10.8% (vs 61.9% without GCP, p<0.001) of the cases. Mean duration of antibiotic treatment of patients with GCP was drastically longer in the group of postoperative patients in  comparison with the group of those who had conservative treatment (25.5 vs 15.1 days, p=0.05). Antimicrobial therapy within GCP period resulted into inflammation regress in 83.1% of the cases; abscess or fistula  formation, hence surgical treatment in 13.8% of the cases; progression of infection in 3.1% of the cases. Increase of GCP duration up to 30 and more days is connected with bacteremia rate increase (12.5% vs 28%, p<0.05); combinations of PI with other infections (25% vs 52%, p<0.05); requirement of antimicrobial therapy modification (16.7% vs 40%, p<0.05).

CONCLUSION: GCP significantly raises risk of PI. PI that develops in the setting of GCP, is characterized by  abnormal, often low clinical manifestations and high risk of sepsis. Invasion of microorganisms through affected tissue seals is the basic mechanism of perianalinfection within the period of GCP. Antibacterial therapy is the prior method of PI treatment in the settings of GCP; antibacterial therapy efficiency is 83.1%. Need for surgery in the period of GCP is associated with the infectious episode and antibacterial therapy duration increase. Lengthening of GCP is a negative predictor in PI treatment.

1. Klyasova, G.A. Antimicrobial therapy. In the book: Program treatment of blood system diseases. Edited by V.G. Savchenko. Moscow: Praktika Publ.; 2012. pp. 829-853. (In Russ.)

2. Morcos B, Amarin R, Abu Sba A. et al. Contemporary management of perianal conditions in febrile neutropenic patients. Eur J Surg Oncol. 2013;39(4):404–7. doi: 10.1016/j.ejso.

3. Grewal H, Guillem JG, Quan SH, et al. Anorectal Disease in Neutropenic Leukemic Patients. Operative v s . Nonoperative Management. Dis Colon Rectum. 1994; 37:1095–1099; doi: 10.1007/BF02049810.

4. Haliloglu N, Gulpinar B, Ozkavukcu E. et al. Typical MR imaging findings of perianal infections in patients with hematologic malignancies. Eur J Radiol. 2017 Aug;93:284-288. doi: 10.1016/j.ejrad.2017.05.046.

5. Chen CY, Cheng A, Huang SY. et al. Clinical and microbiological characteristics of perianal infections in adult patients with acute leukemia. PLoS One. 2013; 8(4). doi:10.1371/journal.pone.0060624; http://www.plosone.org, http://www.pubmedcentral.gov/tocrender.fcgi?journal=440.

6. Cohen JS1, Paz IB, O'Donnell MR et al. Treatment of perianal infection following bone marrow transplantation. Dis Colon Rectum. 1996 Sep;39(9):981-5.

7. Lehrnbecher T, Marshall D, Gao C. et al. A Second Look at Anorectal Infections in Cancer Patients in a Large Cancer Institute: The Success of Early Intervention with Antibiotics and Surgery. Infection. 2002; 30(5):272–276.

8. Sullivan PS, Moreno C. A Multidisciplinary Approach to Perianal and Intra-Abdominal Infections in the Neutropenic Cancer Patient. Oncology (Williston Park). 2015 Aug;29(8):581-90.PMID: 26281844.

9. Solmaz S, Korur A, Gereklioğlu Ç, et al. Anorectal Complications During Neutropenic Period in Patients with Hematologic Diseases. Mediterr J Hematol Infect Dis. 2016 Mar 1;8(1):e2016019. doi: 10.4084/MJHID.2016.019. eCollection 2016.PMID: 26977278.

10. Loureiro RV, Borges VP, Tomğ AL et al. Anorectal complications in patients with haematological malignancies. Eur J Gastroenterol Hepatol. 2018 Jul;30(7):722-726. doi: 10.1097/MEG.0000000000001133.

11. Vanhueverzwyn R, Delannoy A, Michaux JL, et al. Anal lesions in hematologic diseases. Dis Colon Rectum. 1980;23:310-312.

12. Shtyrkova S.V., Klyasova G.A., Ntanishyan KI. et al. Perianal infection in patients with hemoblastosis: Risk factors and possibilities of prevention. Terapevticheskij arkhiv. 2016; no.7, pp.72-77. (In Russ.) DOI: 10.17116/terarkh201688772-77https://goo.gl/EPSNlD

13. Vogel JD, Johnson EK, Morris AM et al. Clinical Practice Guideline for the Management of Anorectal Abscess, Fistula-in-Ano, and Rectovaginal Fistula. Dis Colon Rectum. 2016 Dec;59(12):1117-1133. No abstract available. PMID: 27824697.

14. Shelygin Yu.A., Blagodarnyj L.A. Spravochnik po koloproktologii. [Coloproctology Handbook]. Moscow: Litterra, 2012: 596 p. (in Russ.).

15. Ommer A, Herold A, Berg E. et. al. German S3 guideline: anal abscess. Int J Colorectal Dis. 2012; 27: 831-837.

16. Chang H, Kuo MC, Tang TC, Lin TL. et al. Clinical Features and Recurrence Pattern of Perianal Abscess in Patients with Acute Myeloid Leukemia. Acta Haematologica. 2017; 138(1):10–13. doi:10.1159/000475589.

17. Okhmat VA, Klyasova GA, Parovichnikova EN, et al. Antibiotic Treatment of Febrile Neutropenia in Patients with Acute Leukemia. Clinical oncohematology. 2018; v. 11, no.1, pp. 100–9. DOI: 10.21320/2500-2139-2018-11-1-100-109/ (in Russ.).

18. Shtyrkova S.V., Karagyulyan S.R., Gemdzhian E.G., Ntanishyan K.I. Perianal infections as first presentation of hemoblastosis and aplastic anemia. Koloproktologia. 2019; v. 18, no.4(70), pp. 116-129. (in Russ.). https://doi.org/10.33878/2073-7556-2019-18-4-116-129