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Resolution of invasive fungal sinusitis in two pediatric patients with acute lymphoblastic leukemia
International Journal of Pediatric Otorhinolaryngology Extra (2006) 1, 123—127
www.elsevier.com/locate/ijporl
CASE REPORT
Resolution of invasive fungal sinusitis in two pediatric patients with acute lymphoblastic leukemia Kristin Egan *, Elizabeth Robbins, Peggy Weintrub, Cynthia Chin, Kristina Rosbe University of California San Francisco, Department of Otolaryngology, 400 Parnassus Ave. Suite A730, San Francisco, 94143 CA, United States Received 4 January 2006; received in revised form 10 February 2006; accepted 10 February 2006
KEYWORDS Mucormycosis; Acute lymphoblastic leukemia; Immunocompromised; Invasive fungal sinusitis
Summary Two cases of invasive fungal sinusitis are presented which occurred in immunocompromised pediatric patients and were successfully resolved. The management of these cases can provide important recommendations in regards to identification and interventions, both medical and surgical, as well as the timing of treatment. # 2006 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Case reports
Invasive fungal sinusitis is an important concern among the immunocompromised pediatric population. The significant morbidity and mortality associated with this condition and the rapidity of its progression make diagnosis and prompt treatment crucial. We present case reports of pediatric patients recently diagnosed with acute lymphoblastic leukemia that were successfully treated for invasive fungal sinusitis. We also reviewed the current literature to provide the most up to date treatment guidelines for invasive fungal sinusitis in the immunocompromised patient population.
2.1. Patient one
* Corresponding author. Tel.: +1 415 566 6728. E-mail address: [email protected] (K. Egan).
A 9-year-old Caucasian male recently diagnosed with acute lymphoblastic leukemia (ALL) was admitted to the hospital after being presented with increasing pain and swelling at the medial aspect of the left eye over the course of 1 week. He also had a fever of low grade persisting for 3 days prior to admission and received a dose of intravenous (i.v.) ceftriaxone 2 days prior to admission for this. The patient had been receiving induction chemotherapy consisting of daily dexamethasone at 6 mg/m2, weekly vincristine, and a single dose of pegaspargase starting 1 month prior to admission. Symptoms of sinusitis, primarily eye pain with facial pain and pressure, developed at about day 22 of a 28-day induction period. The
1871-4048/$ — see front matter # 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pedex.2006.02.002
124
Fig. 1 Non-enhanced axial (A) and coronal (B) CT scan through the orbits demonstrates opacification of the maxillary and ethmoid sinuses bilaterally. Intrinsic high density within the thickened sinus mucosa and retained sinus secretions are characteristic for fungal infection. There is destruction of the left middle turbinate and extension of disease into the left lacrimal fossa with abscess formation and subperisoteal extension.
patient was never neutropenic at any point during induction chemotherapy or during consolidation chemotherapy. His lowest absolute neutrophil count (ANC) was 740 thirteen days prior to admission. On admission, his ANC was 2320 (Figs. 1—3). The chief complaint was eye pain and initial examination revealed the patient to be afebrile with no gross distortion of vision. There was tenderness and edema over the left lateral nasal bridge with mild erythema and no scleral injection or proptosis. The patient was empirically started on i.v. nafcillin, zosyn, and tobramycin. A computed tomography scan (CT) of the sinuses done on admission revealed an edematous left lacrimal gland, with a small rim enhancing fluid collection along the left
K. Egan et al. lacrimal fossa extending through the ethmoid sinus on the left. An MRI was done which showed mucosal thickening of the ethmoid and maxillary sinuses with a mild postseptal enhancement along the left lamina papyracea, likely representing a subperiosteal enhancement. There was no evidence for frank abscess. There was no evidence for cavernous sinus or intraconal extension of the disease. The patient was taken to the operating room for a bone marrow biopsy and a maxillary sinus aspirate was performed which grew mucormycosis. Liposomal amphotericin (10 mg/kg/day) was begun and a CT performed 2 days later revealed interval worsening of sinus opacification and of the subperiosteal abnormal soft tissue in the postseptal medial left orbit. His exam remained unchanged with left eye pain and edema over the nasal bridge. The low attenuation area within the left anterior ethmoid, left nasal mucosa, and left maxillary sinus was felt to be concerning for abscess-like collection. There remained no evidence for intraconal, cavernous sinus, or intracranial extension of disease and no evidence for bony erosion. The patient was then taken back to the operating room for a more definitive procedure given the results of the sinus aspirate and CT scans. The patient subsequently underwent endoscopic bilateral total ethmoidectomies, bilateral maxillary antrostomies and during the operation, it was noted that the left middle turbinate appeared necrotic and it was therefore removed and sent for pathology. Bilateral procedures were done to examine the right sinus cavities for evidence of disease. Thickened mucosa was noted in the ethmoids bilaterally along with bilateral maxillary polypoid mucosa. Pathology of the samples taken during the operative procedure revealed mucormycosis infiltrating respiratory mucosa bilaterally. On the left middle turbinate, it was noted that the mucormycosis was infiltrating underlying bone. A KOH showed rare non-septate hyphae consistent with Mucor. The patient was continued on amphotericin and remained afebrile. The postoperative course demonstrated a resolution of the pain and edema over the left lateral nasal bridge with stable vision and no pain on movement of extraocular muscles. The patient remained hospitalized to undergo treatment with i.v. antifungal, antibiotic, and chemotherapeutic medications. On hospital day 18, the patient was scheduled for a second look in the operating room due to the difficulty of evaluating him at the bedside. Repeated endoscopic visualization revealed no evidence of necrotic tissue. Given the previous positive cultures, a small amount of tissue adjacent to the attachment of the middle turbinate near the maxillary sinus in addition to debris in the left maxillary sinus was removed and sent for pathology. These specimens
Resolution of invasive fungal sinusitis in two pediatric patients
125
Fig. 2 Coronal (A) and axial (B) T2 sequences of the sinuses demonstrate low T2 signal intensity characteristic of fungal infection within the bilateral ethmoid sinuses, with left lacrimal fossa abscess and subperiosteal extension. There is an associated enhancement on the postgadolinium T1 images.
revealed no fungal hyphae. The patient continued to do well throughout the remainder of his hospital course and was discharged home on hospital day 23 to begin the interim maintenance phase of his chemotherapy protocol. Throughout the hospitalization, methotrexate therapy was continued, though two doses of mercaptopurine were held the day of the endoscopic sinus procedures. The mercaptopurine was resumed on postoperative day 2 without incident. A bone marrow biopsy was performed at the onset of this hospitalization as scheduled to assess response to the chemotherapeutic agents and revealed remission with blasts <5%. Approximately 1 month after discharge, concern about Patient one’s rising creatinine (from 0.4 mg/dL to 1.2 mg/dL, three times baseline) was raised and his amphotericin dose was held. After a week, his creatinine dropped to about 1½ times baseline (0.6 mg/dL). Amphotericin was then restarted on a Monday—Wednesday—Friday schedule for a duration of 4 weeks (so a total of 10 weeks of amphotericin from his last negative surgery). At the completion of amphotericin, the patient was taken back to the operating room for endoscopic examination and biopsies which were all negative for mucormycosis. Three months after his initial presentation, the patient was admitted to the hospital for edema of the skin overlying the frontal sinuses and was taken to the operating room for endoscopic examination and cultures which were again negative for mucormycosis.
2.2. Patient two An 18-year-old Hispanic male with a history of pre Bcell acute lymphoblastic leukemia undergoing che-
motherapy consisting of vincristine (1.5 mg/m2), adriamycin, and dexamethasone presented with shaking chills and right sided retro-orbital pain and headache with a temperature of 1028 and an ANC of 160. The patient had a past medical history significant for aspergilloma of the left thigh during induction therapy. Approximately 8 months prior to admission, he was hospitalized for fever and neutropenia and taken to the operating room for a CaldwellLuc right maxillary antrostomy and anterior ethmoidectomy during which biopsy specimens were taken which revealed no evidence of fungal elements. An MRI done on hospital day 2 revealed abnormal soft tissue development within the right maxillary sinus with hypointense T2 signal and partial opacification of the right anterior ethmoid sinus with areas of decreased T2 signal concerning for fungal sinusitis. He was empirically begun on voriconazole. He underwent bedside nasal biopsies which showed fungal elements with branching septate hyphae. The fungal culture grew rare Rhizopus species and the morphology of the pathological specimens was consistent with this. Therefore, on hospital day 3, the patient was taken to the operating room where he underwent endoscopic right maxillary antrostomy and total ethmoidectomy. During the procedure, a large black mass was observed in the right sinonasal cavity which was removed along with cultures sent from the operating room which revealed Rhizopus species. At this point, his antifungal coverage was switched to liposomal amphotericin since Rhizopus is not sensitive to voriconazole. The patient underwent an MRI on postoperative day 5 which when compared with the preoperative
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Fig. 3 Coronal (A) and axial (B) T2 sequences through the sinuses 8 months later demonstrate postsurgical changes of a right maxillary antrostomy. New soft tissue within the right maxillary sinus which is T2 hypointense and enhances on postgadolinium T1 coronal (C) and axial (D) sequences is characteristic for fungal sinus disease. This obstructs the right osteomeatal unit and extends into the right pterygopalatine foramen.
MRI was interpreted as unchanged but with areas that were consistent with chronic sinusitis and calcifications. No intracranial or orbital, skull base or cavernous sinus extension was visualized. The chemotherapeutic regimen for this patient was put on hold during his hospitalization and on postoperative day 10, he received a modified regimen that was consistent with what he would have received at the end of delayed intensification treatment consisting of vincristine (1.5 mg/m2, total 2 mg) and pegaspargase (2500 mg/m2, total 3700 mg). He was discharged on amphotericin 470 mg/kg daily. Six weeks after discharge, the patient was restarted on his maintenance chemotherapy, consisting of vincristine and adriamycin, with the exclusion of prednisone secondary to his history of recent fungal
infection. Subsequent surveillance MRIs 6 weeks and 4 months postoperatively showed interval improvement in the mucosal thickening and chronic inflammatory changes. A screening MRI and CTat 5 months postoperative showed no change in the chronic inflammatory changes in the sinuses without evidence of invasion of fungal disease into the orbits or through the calvarium. His creatinine had begun to rise (from 0.7 mg/dL to 1.5 mg/dL) and the patient remained clinically clear of any signs or symptoms of recurrent fungal sinusitis, in addition to negative office endoscopic nasal exams. Therefore, the amphotericin treatment was discontinued and recommendations for surveillance of C-reactive protein were made.
Resolution of invasive fungal sinusitis in two pediatric patients
3. Discussion Invasive fungal sinusitis in the immunocompromised population is a serious mortality risk. A large proportion of survivors are left with permanent neurological, visual and cosmetic deformities. One study which included Aspergillus and other fungal species showed that the mortality rate from the initial fungal infection was 62% and 27% die from other causes after resolving the initial infection. The expected mortality from mucormycosis alone would be expected to be higher. The medical management of these diseases combined with prompt surgical intervention is still no predictor of survival for the same study showed that 61% of the patients who died of the initial infection had undergone extensive surgical procedures [1]. A high level of suspicion for this disease process must be kept in this patient population. CT and MR imaging studies are indicated to help with the diagnosis in conjunction with endoscopy and biopsies for culture. Most patients do not have the classic CT findings of bone erosion or extrasinus extension in the early course of invasive fungal sinusitis. It has been shown that in immunocompromised patients, severe unilateral thickening of the nasal cavity mucosa was most suggestive of invasive fungal disease, but is a nonspecific finding [2]. Although mucormycosis is most frequently identified among immunocompromised patients as a lung infection, orbito-sinus-facial disease is a significant second locality. Patients may demonstrate facial pain or headache, orbital cellulitis, paresis of extraocular muscles, proptosis or chemosis [3]. Mucormycosis spores penetrate tissue and have a predilection for the internal elastic lamina of the arteries, with subsequent angioinvasion. This angioinvasion produces thromboses with secondary ischemic infarction and hemorrhagic necrosis resulting in its rapid progression. Pathologic specimens demonstrate tissue invasion by non-septate hyphae with right- or obtuse-angle branching [4]. As with our case reports, the best chance for control involves a combination of aggressive medical and surgical treatment including the early administration of amphotericin and surgical debridement of all suspicious and affected tissues. The treatment course with amphotericin should be titrated to the patient’s recovery and both clinical and radiographic parameters should be incorporated. The duration of treatment can vary from 4 to 6 weeks or as long as 2—3
127
months with 4—8 weeks being average [4]. Resolution of CT changes, clinical improvement and as in Case one, endoscopic visualization and culture should be used to direct treatment. The continuation of chemotherapy should be maintained with a close eye to neutrophil counts and prudent judgment used to determine whether to hold doses on a day to day basis. Sinus imaging studies alone may not be enough to make the diagnosis of invasive fungal sinusitis and a high index of suspicion especially with immunocompromised patients must be maintained. Early sinus endoscopy and biopsies and initiation of appropriate medical and surgical treatment will ensure the greatest chance of recovery. Surgical treatment principles include aggressive debridement of all gross disease. Ideally, patients’ chemotherapy regimens should be managed to maximize their own defense mechanisms to help fight the infection. Part of the reason for the second look in Patient one was that the patient was scheduled to begin chemotherapy as a part of regularly scheduled treatment for his ALL. It was felt that it was necessary to document no further gross or microscopic disease before embarking on a therapy which would decrease his counts and thereby make it more difficult for him to fight off infection. Although these cases are rare, they can result in significant morbidity and mortality. These patients are best managed with a team approach involving the oncologists, infectious disease specialists, and otolaryngologists. Due to the relatively rare incidence of these cases, it is important for clinicians to share these experiences and outcomes to be able to develop practice guidelines for this potentially lethal disease in the pediatric immunocompromised patient population.
References [1] C.A. Kennedy, G.L. Adams, J.P. Neglia, G.S. Giebink, Impact of surgical treatment on paranasal fungal infections in bone marrow transplant patients, Otolaryngol. Head Neck Surg. 116 (1997) 610—616. [2] J.M. DelGaudio, R.E. Swain, T.T. Kingdom, S. Muller, P.A. Hudgins, Computed tomographic findings in patients with invasive fungal sinusitis, Arch. Otolaryngol. Head Neck Surg. 129 (2003) 236—240. [3] L. Pagano, M. Offidani, L. Fianchi, et al., Mucormycosis in hematologic patients, Haematologica 89 (2004) 207—214. [4] M.A. Sohail, M.A. Khabori, J. Hyder, A. Verma, Acta Trop. 80 (2001) 177—185.
www.elsevier.com/locate/ijporl
CASE REPORT
Resolution of invasive fungal sinusitis in two pediatric patients with acute lymphoblastic leukemia Kristin Egan *, Elizabeth Robbins, Peggy Weintrub, Cynthia Chin, Kristina Rosbe University of California San Francisco, Department of Otolaryngology, 400 Parnassus Ave. Suite A730, San Francisco, 94143 CA, United States Received 4 January 2006; received in revised form 10 February 2006; accepted 10 February 2006
KEYWORDS Mucormycosis; Acute lymphoblastic leukemia; Immunocompromised; Invasive fungal sinusitis
Summary Two cases of invasive fungal sinusitis are presented which occurred in immunocompromised pediatric patients and were successfully resolved. The management of these cases can provide important recommendations in regards to identification and interventions, both medical and surgical, as well as the timing of treatment. # 2006 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Case reports
Invasive fungal sinusitis is an important concern among the immunocompromised pediatric population. The significant morbidity and mortality associated with this condition and the rapidity of its progression make diagnosis and prompt treatment crucial. We present case reports of pediatric patients recently diagnosed with acute lymphoblastic leukemia that were successfully treated for invasive fungal sinusitis. We also reviewed the current literature to provide the most up to date treatment guidelines for invasive fungal sinusitis in the immunocompromised patient population.
2.1. Patient one
* Corresponding author. Tel.: +1 415 566 6728. E-mail address: [email protected] (K. Egan).
A 9-year-old Caucasian male recently diagnosed with acute lymphoblastic leukemia (ALL) was admitted to the hospital after being presented with increasing pain and swelling at the medial aspect of the left eye over the course of 1 week. He also had a fever of low grade persisting for 3 days prior to admission and received a dose of intravenous (i.v.) ceftriaxone 2 days prior to admission for this. The patient had been receiving induction chemotherapy consisting of daily dexamethasone at 6 mg/m2, weekly vincristine, and a single dose of pegaspargase starting 1 month prior to admission. Symptoms of sinusitis, primarily eye pain with facial pain and pressure, developed at about day 22 of a 28-day induction period. The
1871-4048/$ — see front matter # 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pedex.2006.02.002
124
Fig. 1 Non-enhanced axial (A) and coronal (B) CT scan through the orbits demonstrates opacification of the maxillary and ethmoid sinuses bilaterally. Intrinsic high density within the thickened sinus mucosa and retained sinus secretions are characteristic for fungal infection. There is destruction of the left middle turbinate and extension of disease into the left lacrimal fossa with abscess formation and subperisoteal extension.
patient was never neutropenic at any point during induction chemotherapy or during consolidation chemotherapy. His lowest absolute neutrophil count (ANC) was 740 thirteen days prior to admission. On admission, his ANC was 2320 (Figs. 1—3). The chief complaint was eye pain and initial examination revealed the patient to be afebrile with no gross distortion of vision. There was tenderness and edema over the left lateral nasal bridge with mild erythema and no scleral injection or proptosis. The patient was empirically started on i.v. nafcillin, zosyn, and tobramycin. A computed tomography scan (CT) of the sinuses done on admission revealed an edematous left lacrimal gland, with a small rim enhancing fluid collection along the left
K. Egan et al. lacrimal fossa extending through the ethmoid sinus on the left. An MRI was done which showed mucosal thickening of the ethmoid and maxillary sinuses with a mild postseptal enhancement along the left lamina papyracea, likely representing a subperiosteal enhancement. There was no evidence for frank abscess. There was no evidence for cavernous sinus or intraconal extension of the disease. The patient was taken to the operating room for a bone marrow biopsy and a maxillary sinus aspirate was performed which grew mucormycosis. Liposomal amphotericin (10 mg/kg/day) was begun and a CT performed 2 days later revealed interval worsening of sinus opacification and of the subperiosteal abnormal soft tissue in the postseptal medial left orbit. His exam remained unchanged with left eye pain and edema over the nasal bridge. The low attenuation area within the left anterior ethmoid, left nasal mucosa, and left maxillary sinus was felt to be concerning for abscess-like collection. There remained no evidence for intraconal, cavernous sinus, or intracranial extension of disease and no evidence for bony erosion. The patient was then taken back to the operating room for a more definitive procedure given the results of the sinus aspirate and CT scans. The patient subsequently underwent endoscopic bilateral total ethmoidectomies, bilateral maxillary antrostomies and during the operation, it was noted that the left middle turbinate appeared necrotic and it was therefore removed and sent for pathology. Bilateral procedures were done to examine the right sinus cavities for evidence of disease. Thickened mucosa was noted in the ethmoids bilaterally along with bilateral maxillary polypoid mucosa. Pathology of the samples taken during the operative procedure revealed mucormycosis infiltrating respiratory mucosa bilaterally. On the left middle turbinate, it was noted that the mucormycosis was infiltrating underlying bone. A KOH showed rare non-septate hyphae consistent with Mucor. The patient was continued on amphotericin and remained afebrile. The postoperative course demonstrated a resolution of the pain and edema over the left lateral nasal bridge with stable vision and no pain on movement of extraocular muscles. The patient remained hospitalized to undergo treatment with i.v. antifungal, antibiotic, and chemotherapeutic medications. On hospital day 18, the patient was scheduled for a second look in the operating room due to the difficulty of evaluating him at the bedside. Repeated endoscopic visualization revealed no evidence of necrotic tissue. Given the previous positive cultures, a small amount of tissue adjacent to the attachment of the middle turbinate near the maxillary sinus in addition to debris in the left maxillary sinus was removed and sent for pathology. These specimens
Resolution of invasive fungal sinusitis in two pediatric patients
125
Fig. 2 Coronal (A) and axial (B) T2 sequences of the sinuses demonstrate low T2 signal intensity characteristic of fungal infection within the bilateral ethmoid sinuses, with left lacrimal fossa abscess and subperiosteal extension. There is an associated enhancement on the postgadolinium T1 images.
revealed no fungal hyphae. The patient continued to do well throughout the remainder of his hospital course and was discharged home on hospital day 23 to begin the interim maintenance phase of his chemotherapy protocol. Throughout the hospitalization, methotrexate therapy was continued, though two doses of mercaptopurine were held the day of the endoscopic sinus procedures. The mercaptopurine was resumed on postoperative day 2 without incident. A bone marrow biopsy was performed at the onset of this hospitalization as scheduled to assess response to the chemotherapeutic agents and revealed remission with blasts <5%. Approximately 1 month after discharge, concern about Patient one’s rising creatinine (from 0.4 mg/dL to 1.2 mg/dL, three times baseline) was raised and his amphotericin dose was held. After a week, his creatinine dropped to about 1½ times baseline (0.6 mg/dL). Amphotericin was then restarted on a Monday—Wednesday—Friday schedule for a duration of 4 weeks (so a total of 10 weeks of amphotericin from his last negative surgery). At the completion of amphotericin, the patient was taken back to the operating room for endoscopic examination and biopsies which were all negative for mucormycosis. Three months after his initial presentation, the patient was admitted to the hospital for edema of the skin overlying the frontal sinuses and was taken to the operating room for endoscopic examination and cultures which were again negative for mucormycosis.
2.2. Patient two An 18-year-old Hispanic male with a history of pre Bcell acute lymphoblastic leukemia undergoing che-
motherapy consisting of vincristine (1.5 mg/m2), adriamycin, and dexamethasone presented with shaking chills and right sided retro-orbital pain and headache with a temperature of 1028 and an ANC of 160. The patient had a past medical history significant for aspergilloma of the left thigh during induction therapy. Approximately 8 months prior to admission, he was hospitalized for fever and neutropenia and taken to the operating room for a CaldwellLuc right maxillary antrostomy and anterior ethmoidectomy during which biopsy specimens were taken which revealed no evidence of fungal elements. An MRI done on hospital day 2 revealed abnormal soft tissue development within the right maxillary sinus with hypointense T2 signal and partial opacification of the right anterior ethmoid sinus with areas of decreased T2 signal concerning for fungal sinusitis. He was empirically begun on voriconazole. He underwent bedside nasal biopsies which showed fungal elements with branching septate hyphae. The fungal culture grew rare Rhizopus species and the morphology of the pathological specimens was consistent with this. Therefore, on hospital day 3, the patient was taken to the operating room where he underwent endoscopic right maxillary antrostomy and total ethmoidectomy. During the procedure, a large black mass was observed in the right sinonasal cavity which was removed along with cultures sent from the operating room which revealed Rhizopus species. At this point, his antifungal coverage was switched to liposomal amphotericin since Rhizopus is not sensitive to voriconazole. The patient underwent an MRI on postoperative day 5 which when compared with the preoperative
126
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Fig. 3 Coronal (A) and axial (B) T2 sequences through the sinuses 8 months later demonstrate postsurgical changes of a right maxillary antrostomy. New soft tissue within the right maxillary sinus which is T2 hypointense and enhances on postgadolinium T1 coronal (C) and axial (D) sequences is characteristic for fungal sinus disease. This obstructs the right osteomeatal unit and extends into the right pterygopalatine foramen.
MRI was interpreted as unchanged but with areas that were consistent with chronic sinusitis and calcifications. No intracranial or orbital, skull base or cavernous sinus extension was visualized. The chemotherapeutic regimen for this patient was put on hold during his hospitalization and on postoperative day 10, he received a modified regimen that was consistent with what he would have received at the end of delayed intensification treatment consisting of vincristine (1.5 mg/m2, total 2 mg) and pegaspargase (2500 mg/m2, total 3700 mg). He was discharged on amphotericin 470 mg/kg daily. Six weeks after discharge, the patient was restarted on his maintenance chemotherapy, consisting of vincristine and adriamycin, with the exclusion of prednisone secondary to his history of recent fungal
infection. Subsequent surveillance MRIs 6 weeks and 4 months postoperatively showed interval improvement in the mucosal thickening and chronic inflammatory changes. A screening MRI and CTat 5 months postoperative showed no change in the chronic inflammatory changes in the sinuses without evidence of invasion of fungal disease into the orbits or through the calvarium. His creatinine had begun to rise (from 0.7 mg/dL to 1.5 mg/dL) and the patient remained clinically clear of any signs or symptoms of recurrent fungal sinusitis, in addition to negative office endoscopic nasal exams. Therefore, the amphotericin treatment was discontinued and recommendations for surveillance of C-reactive protein were made.
Resolution of invasive fungal sinusitis in two pediatric patients
3. Discussion Invasive fungal sinusitis in the immunocompromised population is a serious mortality risk. A large proportion of survivors are left with permanent neurological, visual and cosmetic deformities. One study which included Aspergillus and other fungal species showed that the mortality rate from the initial fungal infection was 62% and 27% die from other causes after resolving the initial infection. The expected mortality from mucormycosis alone would be expected to be higher. The medical management of these diseases combined with prompt surgical intervention is still no predictor of survival for the same study showed that 61% of the patients who died of the initial infection had undergone extensive surgical procedures [1]. A high level of suspicion for this disease process must be kept in this patient population. CT and MR imaging studies are indicated to help with the diagnosis in conjunction with endoscopy and biopsies for culture. Most patients do not have the classic CT findings of bone erosion or extrasinus extension in the early course of invasive fungal sinusitis. It has been shown that in immunocompromised patients, severe unilateral thickening of the nasal cavity mucosa was most suggestive of invasive fungal disease, but is a nonspecific finding [2]. Although mucormycosis is most frequently identified among immunocompromised patients as a lung infection, orbito-sinus-facial disease is a significant second locality. Patients may demonstrate facial pain or headache, orbital cellulitis, paresis of extraocular muscles, proptosis or chemosis [3]. Mucormycosis spores penetrate tissue and have a predilection for the internal elastic lamina of the arteries, with subsequent angioinvasion. This angioinvasion produces thromboses with secondary ischemic infarction and hemorrhagic necrosis resulting in its rapid progression. Pathologic specimens demonstrate tissue invasion by non-septate hyphae with right- or obtuse-angle branching [4]. As with our case reports, the best chance for control involves a combination of aggressive medical and surgical treatment including the early administration of amphotericin and surgical debridement of all suspicious and affected tissues. The treatment course with amphotericin should be titrated to the patient’s recovery and both clinical and radiographic parameters should be incorporated. The duration of treatment can vary from 4 to 6 weeks or as long as 2—3
127
months with 4—8 weeks being average [4]. Resolution of CT changes, clinical improvement and as in Case one, endoscopic visualization and culture should be used to direct treatment. The continuation of chemotherapy should be maintained with a close eye to neutrophil counts and prudent judgment used to determine whether to hold doses on a day to day basis. Sinus imaging studies alone may not be enough to make the diagnosis of invasive fungal sinusitis and a high index of suspicion especially with immunocompromised patients must be maintained. Early sinus endoscopy and biopsies and initiation of appropriate medical and surgical treatment will ensure the greatest chance of recovery. Surgical treatment principles include aggressive debridement of all gross disease. Ideally, patients’ chemotherapy regimens should be managed to maximize their own defense mechanisms to help fight the infection. Part of the reason for the second look in Patient one was that the patient was scheduled to begin chemotherapy as a part of regularly scheduled treatment for his ALL. It was felt that it was necessary to document no further gross or microscopic disease before embarking on a therapy which would decrease his counts and thereby make it more difficult for him to fight off infection. Although these cases are rare, they can result in significant morbidity and mortality. These patients are best managed with a team approach involving the oncologists, infectious disease specialists, and otolaryngologists. Due to the relatively rare incidence of these cases, it is important for clinicians to share these experiences and outcomes to be able to develop practice guidelines for this potentially lethal disease in the pediatric immunocompromised patient population.
References [1] C.A. Kennedy, G.L. Adams, J.P. Neglia, G.S. Giebink, Impact of surgical treatment on paranasal fungal infections in bone marrow transplant patients, Otolaryngol. Head Neck Surg. 116 (1997) 610—616. [2] J.M. DelGaudio, R.E. Swain, T.T. Kingdom, S. Muller, P.A. Hudgins, Computed tomographic findings in patients with invasive fungal sinusitis, Arch. Otolaryngol. Head Neck Surg. 129 (2003) 236—240. [3] L. Pagano, M. Offidani, L. Fianchi, et al., Mucormycosis in hematologic patients, Haematologica 89 (2004) 207—214. [4] M.A. Sohail, M.A. Khabori, J. Hyder, A. Verma, Acta Trop. 80 (2001) 177—185.