Acute invasive fungal sinusitis in immunocompromised children

To the Editor,

We read with interest the article by Rodriguez RC et al. entitled, “Acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases”. They report two pediatric cases with confirmed acute invasive fungal rhinosinusitis (AIFS). In the two cases, one with acute myeloid leukemia (AML) and the other with idiopathic bone marrow aplasia, Fusarium sp. was detected by histopathological and microbiological analyses. Both received antifungal treatment and surgery. The one with AML recovered, while the one with aplasia died due to septic shock.¹

Morbidity and mortality due to invasive fungal infections (IFIs) remain high in immunocompromised children such as children with cancer and bone marrow aplasia. Mortality due to IFIs have been reported to be as high as 18%², ³, ⁴; therefore, early and precise diagnosis and treatment are crucial. IFI can occur as pulmonary disease, sinusitis, hepatosplenic infection, infection in the central nervous system and other sites.², ³, ⁴, ⁵, ⁶, ⁷, ⁸ AIFS is characterized by fungal invasion of the nasal or paranasal cavity which may affect adjacent organs, such as the orbits and intracranial structures.², ³, ⁴, ⁵, ⁸, ⁹, ¹⁰ The most commonly identified fungi in AIFS are Aspergillus and Zygomycetes (Rhizopus, Mucor, Rhizomucor).⁴, ⁵, ⁸, ⁹, ¹⁰ Fusarium spp. may cause AIFS also, they usually occur in immunocompromised children, are usually invasive, the upper respiratory tract is the main entrance route.⁹, ¹⁰, ¹¹

We have reported an 8-year-old boy with acute lymphoblastic leukemia (ALL), who developed AIFS, in whom Mucor was identified as the pathogen.⁵ He was hospitalized with febrile neutropenia during the delayed intensification chemotherapy treatment. Despite the use of Intravenous (iv) cefepime. At 48 h, fever continued and the patient began to report mild pain in the left orbita. Magnetic resonance imaging (MRI) revealed lesions consistent with infection in the sphenoidal, mastoid, and ethmoid sinuses extruding the left periorbital area. Considering a fungal infection, iv voriconazole was initiated, and after a day, high fever persisted and a periorbital swelling was observed. Liposomal amphotericin B was added to antifungal therapy because we could not rule out a mucormycosis infection. After five days, fever continued and MRI revealed signs of progressive infection and periorbital abscess formation. Surgical drainage was performed and an absorbable gelatin sponge containing liposomal amphotericin B was inserted locally. Fever subsided in 24 h. No pathogen was detected in cultures. Mucormycosis was diagnosed by pathology on the surgical drainage material. Chemotherapy was initiated again. Liposomal amphotericin B was continued during delayed intensification and the first month of ALL maintenance treatment for a total of 2.5 months. Treatment was continued with oral posaconazole during the ALL maintenance treatment and was given for a total of six months. The patient has remained in remission for ALL and free of fungal infection for a total of four years from diagnosis.⁵

The incidence of invasive fungal diseases (IFD) in children with leukemia is reported to be 9-10%, and the mortality reported as high as 21-48%.², ³, ⁴, ⁶ One of the children reported by Rodriguez et al. also had leukemia.¹

The diagnosis of AIFS is challenging and fever is often the only presenting symptom. Other signs and symptoms may be very slight due to the reduced local inflammatory response capacity, which is a consequence of neutropenia. The complications of sinoorbital fungal infections may lead to bone erosion, orbital invasion, brain abscess, meningitis, hematogenous spread and death.², ⁴, ⁶, ⁸, ⁹, ¹⁰ Our case also had mild pain in the orbital area, the ophtalmologic and otolaryngologic examination was normal. The high degree of suspicion led us the prompt diagnosis. There was no clinical or radiological improvement despite specific systemic antifungal treatment in five days. However fever subsided significantly within 24 h after surgery; suggesting the importance of surgery in these cases.⁵ There was no sequelae on long term follow-up as well.

Fungal infections, including AIFS should be in the differential diagnosis in infections in immunocompromised children, according to clinical and radiological findings. A high degree of suspicion and prompt systemic empirical antifungal therapy, as well as surgical debridement, are crucial to prevent morbidity and mortality of these patients.

• DOI of original article: https://doi.org/10.1016/j.htct.2020.08.016.

References

• ¹
  Rodrigues LC, Guimaraes AF, de Oliveira IS, de Sousa PH,Romanelli RM, Kakehasi FM, et al. Acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases. Hematol Transfus Cell Ther. 2020, http://dx.doi.org/10.1016/j.htct.2020.08.016.S2531-1379(20)31283-31289 .
  » http://dx.doi.org/10.1016/j.htct.2020.08.016.S2531-1379(20)31283-31289
• ²
  Kebudi R, Kızılocak H. Febrile neutropenia in children with cancer: approach to diagnosis and treatment. Curr Pediatr Rev. 2018;14:204-9.
• ³
  Sung L. Invasive fungal infections in children with cancer. J Pediatr. 2010;156:68-73.
• ⁴
  Lehrnbecher T, Phillips R, Alexander S, Alvaro F, Carlesse F, Fisher B, et al. Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation. J Clin Oncol. 2012;30:4427-38.
• ⁵
  Kebudi R, Kızılocak H, Hafız G, Erturan Z. Successful outcome of mucormycosis in a child with acute lymphoblastic leukemia. Turk Pediatri Ars. 2020;55:207-9, http://dx.doi.org/10.14744/TurkPediatriArs.2019.12129
  » http://dx.doi.org/10.14744/TurkPediatriArs.2019.12129
• ⁶
  Celkan T, Kizilocak H, Evim M, Meral Güneş A, Özbek NY, Yarali N, et al. Hepatosplenic fungal infections in children with leukemia-risk factors and outcome: a multicentric study. J Pediatr Hematol Oncol. 2019;41:256-60, http://dx.doi.org/10.1097/MPH.0000000000001431
  » http://dx.doi.org/10.1097/MPH.0000000000001431
• ⁷
  Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017;102:433-44.
• ⁸
  Saffioti C, Mesini A, Bandettini R, Castagnola E. Diagnosis of invasive fungal disease in children: a narrative review. Expert Rev Anti Infect Ther. 2019;17:895-909.
• ⁹
  Yakirevitch A, Barg AA, Bedrin L, Primov-Fever A, Wolf M, Migirov L. Acute invasive fungal rhinosinusitis in children with hematologic malignancies: outcome of surgical treatment. Pediatr Hematol Oncol. 2015;32:568-75.
• ¹⁰
  Arnoni MV, Paula CR, Auler ME, Simões CC, Nakano S, Szeszs MW, et al. Infections caused by Fusarium species in pediatric cancer patients and review of published literature. Mycopathologia. 2018;183:941-9.
• ¹¹
  Tacyildiz N, Yavuz G, Unal E, Gözdasoğlu S, Ertem M, Aysev D. Fungal infection from Fusarium spp. in children with refractory hematologic malignancies. Med Pediatr Oncol. 1999;33:596-7, http://dx.doi.org/10.1002/(sici)1096-1911x(199912)33:6<596::aid-mpo17>3.0.co;2-i
  » http://dx.doi.org/10.1002/(sici)1096-1911x(199912)33:6<596::aid-mpo17>3.0.co;2-i

Publication Dates

• Publication in this collection
  21 Mar 2022
• Date of issue
  Jan-Mar 2022

History

• Received
  06 Jan 2021
• Published
  20 Mar 2021