Frequency of Oral Mucositis and Local Virus Reactivation in Herpes Simplex Virus Seropositive Children with Myelosuppressive Therapy

Abstract

Background: Oral mucositis (OM) is a common chemo- and radiotherapy adverse effect in oncological pediatric patients. Herpes simplex virus (HSV) infection can cause a severe clinical course. We hypothesize, that HSV seropositivity is a risk factor for local HSV-1 reactivation and increased frequency of OM in patients with myelosuppressive therapies.

Patients and Method: We evaluated the prevalence of seropositivity of HSV-1 between June 2011 and April 2014 in patients with potential oncological disease and correlated it to the frequency of OM and local viral reactivation in OM under myelosuppressive therapy.

Results: The overall rate of HSV-seropositivity in our cohort was 22%. 48 patients underwent myelosuppressive therapy. Of these, 7 were HSV-1 IgG positive and 41 negative. All patients with OM under myelosuppressive therapy and positive local swab for viral HSV (l-PCR) were HSV-1 IgG positive before the start of therapy (100%). The absolute risk for OM in HSV-1 IgG positive patients was increased by 58.5% (95%CI: 20.0  − 72.2%) corresponding to a relative risk (RR) of 2.4 (95%CI: 1.7–3.5, P=0.009). The multivariable adjusted OR to suffer 2 or more OM episodes in HSV-1 IgG positivity was 8.8 (95%CI: 1.5–95.8, P=0.014).

Discussion and Conclusion: In HSV-1 IgG positive patients half of the OM episode showed HSV reactivation, and the risk for multiple OM episodes was increased. These patients should be investigated for HSV-infection in every OM episode. Prophylactic and preemptive therapeutic measures should be discussed early, but prospective data on HSV prophylaxis and preemptive treatment is required.

Zusammenfassung

Hintergrund: Orale Mucositis (OM) ist eine bekannte Komplikation bei pädiatrisch-onkologischen Patienten unter Chemo- und Radiotherapie. Herpes simplex Virus (HSV)-Infektionen können zu schwerwiegenden klinischen Verläufen führen. HSV-1 seropositive Patienten scheinen unter myelosuppressiver Therapie ein erhöhtes Risiko für lokale HSV-1 Reaktivierung während OM Episoden zu haben und leiden häufiger an OM Episoden im Vergleich zu HSV-1 seronegativen Patienten.

Patienten und Methode: Wir haben die HSV-1 Prävalenz von Patienten mit potentiell onkologischer Erkrankung zwischen Juni 2011 und April 2014 ermittelt und in Korrelation zu OM-Frequenz und lokaler Virusreaktivierung in OM-Episoden unter myelosuppressiver Therapie gestellt.

Ergebnisse: Die Rate der seropositiven Patienten in unserer Kohorte war 22%. Alle Patienten mit OM unter myelosuppressiver Therapie und lokal positivem HSV-Abstrich (1-PCR) waren vor Beginn der Therapie HSV-1 IgG positiv (100%). Das absolute Risiko einer OM in HSV-1 IgG positiven Patienten betrug 58% (95%CI: 20.0–72.2%), entsprechend einem relativen Risiko (RR) von 2.4 (95% CI: 1.7–3.5, P=0.009). Die Multivariabel-angepasste OR im Falle von HSV-1 Seropositivität an 2 oder mehr OM zu leiden, betrug 8.8 (95% CI: 1.5–95.8, P=0.014).

Diskussion und Schlussfolgerung: In HSV-1 IgG positiven Patienten konnten in der Hälfte aller OM Episode eine HSV-Reaktivierung beobachtet werden. Das Risiko von multiplen OM Episoden war in dieser Patientengruppe erhöht. Diese Patienten sollten in jeder OM Episode bezüglich HSV-Infektion abgeklärt werden. Prophylaktische und präemptive Therapiemassnahmen sollten frühzeitig in Betracht gezogen werden; prospektive Studien bezüglich prophylaktischer und präemptiver Therapie sind erforderlich.

Key words

hsv-seroprevalence - hsv-reactivation - oral mucositis - myelosuppressive therapy - hsv-1 - children

Schlüsselwörter

hsv-Seroprävalenz - hsv-Reaktivierung - orale mucositis - myelosuppressive therapie - hsv-1 - kinder

• References

• 1 Bradley H, Markowitz LE, Gibson T et al. Seroprevalence of herpes simplex virus types 1 and 2-United States, 1999-2010. J Infect Dis 2014; 209: 325-333
• 2 Carrega G, Castagnola E, Canessa A et al. Herpes simplex virus and oral mucositis in children with cancer. Support Care Cancer 1994; 2: 266-269
• 3 Da Cruz Campos M, Campos C, Aarestrup F et al. Oral mucositis in cancer treatment: Natural history, prevention and treatment. Molecular and clinical oncology 2014; 2: 337-340
• 4 Djuric M, Jankovic L, Jovanovic T et al. Prevalence of oral herpes simplex virus reactivation in cancer patients: a comparison of different techniques of viral detection. J Oral Pathol Med 2009; 38: 167-173
• 5 Elting LS, Bodey GP, Keefe BH. Septicemia and shock syndrome due to viridans streptococci: a case control study of predisposing factors. Clin Infect Dis 1992; 14: 1201-1207
• 6 Greenberg MS, Friedman H, Cohen SG et al. A comparative study of herpes simplex infections in renal transplants and leukemic patients. J Infect Dis 1987; 156: 280-2807
• 7 Holzinger D, Kühn J, Ehlert K et al. HSV-1 viremia as a potential cause of febrile neutropenia in an immunocompromised child. J Pediatr Hematol Oncol 2010; 32: e19-e21
• 8 Kramer MA, Uitenbroek DG, Ujcic-Voortman JK et al. Ethnic differences in HSV1 and HSV2 seroprevalence in Amsterdam, the Netherlands. Euro Surveill 2008; 13
• 9 Laubereau B, Zwahlen M, Neuenschwander B et al. Herpes simplex virus type 1 and 2 in Switzerland. Schweiz Med Wochenschr 2000; 130: 143-150
• 10 Lauten M, Güttel C, Härtel C et al. Herpes simplex virus reactivation and disease during treatment for childhood acute lymphoblastic leukemia. Klin Padiatr 2013; 225: 1-2
• 11 Pebody RG, Andrews N, Brown D et al. The seroepidemiology of herpes simplex virus type 1 and 2 in Europe 2. Sex Transm Infect 2004; 80: 185-191
• 12 Pico J, Avila-Garavito A, Naccache P. Mucositis: Its occurrence, consequences, and treatment in the oncology setting. The oncologist 1998; 3: 446-451
• 13 Sauerbrei A, Schmitt S, Scheper T et al. Seroprevalence of herpes simplex virus type 1 and 2 in Thuringia, Germany, 1999–2006. Euro Surveill 2011; 16
• 14 Sonis S, Clark J. Prevention and management of oral mucositis induced by antineoplastic therapy. Oncology 1991; 5: 11-18