Case Reports Dacryocystitis As the Initial Presentation of Invasive Fungal Sinusitis in Immunocompromised Children Brett W. Davies, M.S., M.D.*, Mithra O. Gonzalez, M.D.†, Ryan C. Vaughn, M.D.‡, Gregory C. Allen, M.D.§, and Vikram D. Durairaj, M.D., F.A.C.S.║ Abstract: Sino-orbital fungal infection is a rare, but lifethreatening disease seen mainly in immunocompromised patients. While initial clinical impression may vary, dacryocystitis has rarely been described as the initial presenting sign. The authors present 2 pediatric cases of dacryocystitis as the initial sign of invasive fungal sinusitis. To their knowledge, this presenting sign has not been previously reported in the pediatric population. Management strategies and outcomes are discussed.
W
ithin the United States invasive sino-orbital fungal infection is a rare, but life-threatening disease seen mainly in immunocompromised patients. In most cases, the paranasal sinuses are involved. Diagnosis may be delayed because the signs and symptoms are nonspecific. Management classically includes surgical debridement and antifungals.1,2 We report 2 pediatric invasive sino-orbital fungal infections that presented acute dacryocystitis. To our knowledge, this presenting sign has not been previously reported in children. The Colorado Multiple Institutional Review Board approved this study in full compliance with the Declaration of Helsinki and current Health Insurance and Portability and Accountability Act regulations.
CASE REPORTS Case 1. A 9-year-old male with no previous history of congenital nasolacrimal duct obstruction was admitted to oncology service for chemotherapy after being diagnosed with acute myelogenous leukemia. His treatment started with IV antibiotics for neutropenic fever, and 2 days later, he developed OD pain, erythema, and epiphora. Physical examination revealed normal visual, motility, intraocular pressure, and pupil examination. An area of erythema and tenderness over the right medial canthus was noted, but no orbital signs were present. Given concern for fungal infection, the patient started taking oral fluconazole, and urgent CT imaging demonstrated enhancement of the right ethmoid sinus, bilateral maxillary sinuses, and right nasolacrimal duct (Fig. 1). CT imaging was chosen due to the urgency of the scan, as MRI was not available until the following day. After 24 hours without improvement, *Oculofacial Plastic and Orbital Surgery, Department of Ophthalmology, University of Colorado Hospital, Aurora, Colorado; †Oculofacial Plastic and Orbital Surgery, Department of Ophthalmology, University of Rochester, Rochester, New York; ‡Illinois Ear, Nose and Throat Specialists, Niles, Illinois; §Department of Otolaryngology, University of Colorado Hospital, Aurora, Colorado; and ║Texas Oculoplastic Consultants, Austin, Texas, U.S.A. Accepted for publication June 1, 2014. Case 1 presented at the ASOPRS 40th Annual Fall Scientific Symposium on October 22, 2009 in San Francisco, CA. Case 2 presented at the American Rhinologic Society 54th Annual Meeting on September 20, 2008 in Chicago, IL. The authors have no conflicts of interest to disclose. Address correspondence and reprint requests to Vikram Durairaj, MD, FACS, Texas Oculoplastic Consultants, 3705 Medical Pkwy #120, Austin, TX, 78705. E-mail: [email protected] DOI: 10.1097/IOP.0000000000000252
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2014
the patient was taken to the operating room for nasal endoscopy and dacryocystectomy. Biopsies of the right nasolacrimal sac, anterior inferomedial orbit, and sinuses with frozen sections and fungal cultures were performed (Fig. 2). A cast was identified in the nasolacrimal sac, further heightening the suspicion for a fungal etiology (Fig. 3). Frozen sections from the sinus mucosa did not show any fungal elements, but the nasolacrimal sac specimen cultured positive for Aspergillus niger. Amphotericin B, voriconazole, vancomycin, levaquin, and bactrim therapy was instituted. He responded well to medical management, and repeated imaging showed improvement in the disease. Several months later required a right dacryocystorhinostomy for persistent epiphora. This resolved his epiphora, and at 5 years after surgery, the patient remained asymptomatic and in remission of his acute myelogenous leukemia. Case 2. An 11-year-old neutropenic female with acute lymphoblastic leukemia and no previous history of congenital nasolacrimal duct obstruction was admitted for induction chemotherapy. During induction, she developed OD redness and pain concerning preseptal cellulitis. On examination, visual acuity, intraocular pressure, and pupil were normal. Motility was full although pain was reported. The right lower eyelid showed significant erythema and edema. Given concern for sinus involvement, the otolaryngology service was consulted, and bedside fiberoptic nasolaryngoscopy revealed pale mucosa of the right middle turbinate with necrotic ulceration of the left middle turbinate (Fig. 4). CT imaging revealed a fluid collection in the region of the right nasolacrimal sac and maxillary sinus opacification (Fig. 5). The patient was started on intravenous amphotericin B, caspofugin, and topical amphotericin B irrigations. The patient also received granulocyte infusions and hyperbaric oxygen therapy. Dacryocystectomy and biopsy of the sinus mucosa were performed, which demonstrated amphotericin-resistant Aspergillus fumigatus. Her medical regimen was then changed to voriconazole and caspofugin, to which the patient responded well. She remained asymptomatic until 5 years and later presented with several months of tearing on the right side. The examination revealed a lacrimal cutaneous fistula, medial canthal cicatrix, and complete nasolacrimal duct obstruction by irrigation. She subsequently underwent right external dacryocystorhinostomy with fistula closure and medial canthoplasty. Two years later, the patient remained disease free with recurrence of the fistula but no epiphora. The family elected to not pursue any further surgical treatment.
DISCUSSION Sino-orbital Aspergillus infections are either invasive or noninvasive. Invasive infections may be classified as localized or fulminant although both are potentially lethal. Localized infections typically start in the paranasal sinuses and spread via bony erosion or vessels in adjacent tissues.1,3 Fulminant sino-orbital Aspergillus infections involve multiple organs or organ systems. Noninvasive sino-orbital Aspergillus infections present as allergic sinusitis or as a sinonasal fungus ball with associated sinus mucosa destruction and bone expansion—by definition, they do not invade tissue or bone.3 Within the United States, invasive sino-orbital aspergillosis although rare is most commonly seen in immunocompromised patients.1 Risk factors include total neutrophil count of less than 1,000/mm3, AIDS, defects in phagocytosis, hematologic malignancy, steroids, immunosuppressives, diabetes mellitus, prosthetic devices, trauma, environmental exposure
e1
Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2014
Case Reports
FIG. 1. Axial CT of patient 1 through the inferior orbit demonstrating opacification of the maxillary sinuses with inflammation and enhancement around the right nasolacrimal sac.
FIG. 4. Necrotic ulceration on the leading edge of the left middle turbinate as seen through the view of a bedside fiberoptic nasal endoscopy.
FIG. 2. Intraoperative image of nasolacrimal sac biopsy site.
FIG. 5. Axial CT of patient 2 through the orbits demonstrating enhancement of the right nasolacrimal system.
FIG 3. Fungal cast submitted for culture and pathologic study.
(proximity to building demolition or restoration, yard work, compost heaps), and residence in endemic areas such as the Middle East especially Sudan, the Indian subcontinent and the
e2
southern United States.1 The 2 patients presented here were immunocompromised and received chemotherapy for hematologic malignancies. While lateral or retro-orbital pain is a common initial complaint of sino-orbital Aspergillus,3 acute dacryocystitis has only rarely been reported as the initial complaint. Most reported cases of lacrimal involvement have been caused by allergic fungal sinusitis and are present in immune-competent adults. Kim et al.4 recently reported a case of allergic fungal sinusitis presenting with epiphora. Their patient required multiple surgical procedures to control the infection and improve the nasolacrimal duct obstruction. Also, Petkar et al.5 reported a patient with epiphora as the only presenting sign of allergic fungal sinusitis. The patient had resolution of epiphora following sinus surgery and medical management. No lacrimal surgery was required. Finally, Facer et al.6 reported a case of bilateral nasolacrimal involvement from eosinophilic fungal sinusitis. The patient presented with a fluctuant mass just under the right medial canthus. Medical management, sinus surgery, and dacryocystorhinostomy were curative.
© 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2014
Imaging techniques such as CT and MRI aid in the diagnosis. Focal hypodense lesions and areas of enhancement or calcification may be appreciated in the orbit, paranasal sinuses or in our cases, the nasolacrimal duct of those affected. Focal bony destruction may occur.1,7 Beyond inspection, biopsies may be guided by imaging studies, and it has been recommended that hypodense lesions be particularly targeted as they often represent abscess.7 Repeat biopsies or multiple biopsies are sometimes required. As demonstrated in our second case, nasal endoscopy may give further evidence of an invasive fungal process. While this procedure can be a helpful adjunct, not all children can tolerate it at the bedside, even with sedation. The use of bedside nasal endoscopy is often at the discretion of the otolaryngologist. Treatment involves surgery and antifungal therapy. Antifungal options include amphotericin B, intraconazole, voriconazole, and lipid complex nystatin and echinocandins.3 Surgical treatment involves debridement either radical or conservative with the goal of clear surgical margins when possible. Aeration and drainage of the sinus with resection of involved tissue is commonly required.1 Radical versus conservative surgical excision remains a difficult decision as high mortality has been reported with central nervous system extension.1,3,7,8 Dhiwakar et al.7 advocate a conservative resection for anterior orbital processes while exenteration remains the treatment of choice for posterior disease. Our patients with anterior invasive sino-orbital fungal infections were treated with conservative debridement and antifungals. When the nasolacrimal
Case Reports
system is affected, dacryocystorhinostomy may be necessary to repair secondary obstruction. In conclusion, these cases demonstrate that dacryocystitis may be the initial presentation of invasive fungal sinusitis in children. While not a common presenting sign, the clinician should maintain a heightened clinical suspicion of fungal sinusitis when immune-compromised pediatric patients present with dacryocystitis.
REFERENCES 1. Levin LA, Avery R, Shore JW, et al. The spectrum of orbital aspergillosis: a clinicopathological review. Surv Ophthalmol 1996;41:142–54. 2. Mauriello JA Jr, Yepez N, Mostafavi R, et al. Invasive rhinosinoorbital aspergillosis with precipitous visual loss. Can J Ophthalmol 1995;30:124–30. 3. Sivak-Callcott JA, Livesley N, Nugent RA, et al. Localised invasive sino-orbital aspergillosis: characteristic features. Br J Ophthalmol 2004;88:681–7. 4. Kim C, Kacker A, Chee RI, et al. Allergic fungal sinusitis causing nasolacrimal duct obstruction. Orbit 2013;32:143–5. 5. Petkar A, Rao L, Elizondo DR, et al. Allergic fungal sinusitis with massive intracranial extension presenting with tearing. Ophthal Plast Reconstr Surg 2011;27:e98–100. 6. Facer ML, Ponikau JU, Sherris DA. Eosinophilic fungal rhinosinusitis of the lacrimal sac. Laryngoscope 2003;113:210–4. 7. Dhiwakar M, Thakar A, Bahadur S. Invasive sino-orbital aspergillosis: surgical decisions and dilemmas. J Laryngol Otol 2003;117:280–5. 8. deShazo RD. Fungal sinusitis. Am J Med Sci 1998;316:39–45.
© 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
e3
Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
W
ithin the United States invasive sino-orbital fungal infection is a rare, but life-threatening disease seen mainly in immunocompromised patients. In most cases, the paranasal sinuses are involved. Diagnosis may be delayed because the signs and symptoms are nonspecific. Management classically includes surgical debridement and antifungals.1,2 We report 2 pediatric invasive sino-orbital fungal infections that presented acute dacryocystitis. To our knowledge, this presenting sign has not been previously reported in children. The Colorado Multiple Institutional Review Board approved this study in full compliance with the Declaration of Helsinki and current Health Insurance and Portability and Accountability Act regulations.
CASE REPORTS Case 1. A 9-year-old male with no previous history of congenital nasolacrimal duct obstruction was admitted to oncology service for chemotherapy after being diagnosed with acute myelogenous leukemia. His treatment started with IV antibiotics for neutropenic fever, and 2 days later, he developed OD pain, erythema, and epiphora. Physical examination revealed normal visual, motility, intraocular pressure, and pupil examination. An area of erythema and tenderness over the right medial canthus was noted, but no orbital signs were present. Given concern for fungal infection, the patient started taking oral fluconazole, and urgent CT imaging demonstrated enhancement of the right ethmoid sinus, bilateral maxillary sinuses, and right nasolacrimal duct (Fig. 1). CT imaging was chosen due to the urgency of the scan, as MRI was not available until the following day. After 24 hours without improvement, *Oculofacial Plastic and Orbital Surgery, Department of Ophthalmology, University of Colorado Hospital, Aurora, Colorado; †Oculofacial Plastic and Orbital Surgery, Department of Ophthalmology, University of Rochester, Rochester, New York; ‡Illinois Ear, Nose and Throat Specialists, Niles, Illinois; §Department of Otolaryngology, University of Colorado Hospital, Aurora, Colorado; and ║Texas Oculoplastic Consultants, Austin, Texas, U.S.A. Accepted for publication June 1, 2014. Case 1 presented at the ASOPRS 40th Annual Fall Scientific Symposium on October 22, 2009 in San Francisco, CA. Case 2 presented at the American Rhinologic Society 54th Annual Meeting on September 20, 2008 in Chicago, IL. The authors have no conflicts of interest to disclose. Address correspondence and reprint requests to Vikram Durairaj, MD, FACS, Texas Oculoplastic Consultants, 3705 Medical Pkwy #120, Austin, TX, 78705. E-mail: [email protected] DOI: 10.1097/IOP.0000000000000252
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2014
the patient was taken to the operating room for nasal endoscopy and dacryocystectomy. Biopsies of the right nasolacrimal sac, anterior inferomedial orbit, and sinuses with frozen sections and fungal cultures were performed (Fig. 2). A cast was identified in the nasolacrimal sac, further heightening the suspicion for a fungal etiology (Fig. 3). Frozen sections from the sinus mucosa did not show any fungal elements, but the nasolacrimal sac specimen cultured positive for Aspergillus niger. Amphotericin B, voriconazole, vancomycin, levaquin, and bactrim therapy was instituted. He responded well to medical management, and repeated imaging showed improvement in the disease. Several months later required a right dacryocystorhinostomy for persistent epiphora. This resolved his epiphora, and at 5 years after surgery, the patient remained asymptomatic and in remission of his acute myelogenous leukemia. Case 2. An 11-year-old neutropenic female with acute lymphoblastic leukemia and no previous history of congenital nasolacrimal duct obstruction was admitted for induction chemotherapy. During induction, she developed OD redness and pain concerning preseptal cellulitis. On examination, visual acuity, intraocular pressure, and pupil were normal. Motility was full although pain was reported. The right lower eyelid showed significant erythema and edema. Given concern for sinus involvement, the otolaryngology service was consulted, and bedside fiberoptic nasolaryngoscopy revealed pale mucosa of the right middle turbinate with necrotic ulceration of the left middle turbinate (Fig. 4). CT imaging revealed a fluid collection in the region of the right nasolacrimal sac and maxillary sinus opacification (Fig. 5). The patient was started on intravenous amphotericin B, caspofugin, and topical amphotericin B irrigations. The patient also received granulocyte infusions and hyperbaric oxygen therapy. Dacryocystectomy and biopsy of the sinus mucosa were performed, which demonstrated amphotericin-resistant Aspergillus fumigatus. Her medical regimen was then changed to voriconazole and caspofugin, to which the patient responded well. She remained asymptomatic until 5 years and later presented with several months of tearing on the right side. The examination revealed a lacrimal cutaneous fistula, medial canthal cicatrix, and complete nasolacrimal duct obstruction by irrigation. She subsequently underwent right external dacryocystorhinostomy with fistula closure and medial canthoplasty. Two years later, the patient remained disease free with recurrence of the fistula but no epiphora. The family elected to not pursue any further surgical treatment.
DISCUSSION Sino-orbital Aspergillus infections are either invasive or noninvasive. Invasive infections may be classified as localized or fulminant although both are potentially lethal. Localized infections typically start in the paranasal sinuses and spread via bony erosion or vessels in adjacent tissues.1,3 Fulminant sino-orbital Aspergillus infections involve multiple organs or organ systems. Noninvasive sino-orbital Aspergillus infections present as allergic sinusitis or as a sinonasal fungus ball with associated sinus mucosa destruction and bone expansion—by definition, they do not invade tissue or bone.3 Within the United States, invasive sino-orbital aspergillosis although rare is most commonly seen in immunocompromised patients.1 Risk factors include total neutrophil count of less than 1,000/mm3, AIDS, defects in phagocytosis, hematologic malignancy, steroids, immunosuppressives, diabetes mellitus, prosthetic devices, trauma, environmental exposure
e1
Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2014
Case Reports
FIG. 1. Axial CT of patient 1 through the inferior orbit demonstrating opacification of the maxillary sinuses with inflammation and enhancement around the right nasolacrimal sac.
FIG. 4. Necrotic ulceration on the leading edge of the left middle turbinate as seen through the view of a bedside fiberoptic nasal endoscopy.
FIG. 2. Intraoperative image of nasolacrimal sac biopsy site.
FIG. 5. Axial CT of patient 2 through the orbits demonstrating enhancement of the right nasolacrimal system.
FIG 3. Fungal cast submitted for culture and pathologic study.
(proximity to building demolition or restoration, yard work, compost heaps), and residence in endemic areas such as the Middle East especially Sudan, the Indian subcontinent and the
e2
southern United States.1 The 2 patients presented here were immunocompromised and received chemotherapy for hematologic malignancies. While lateral or retro-orbital pain is a common initial complaint of sino-orbital Aspergillus,3 acute dacryocystitis has only rarely been reported as the initial complaint. Most reported cases of lacrimal involvement have been caused by allergic fungal sinusitis and are present in immune-competent adults. Kim et al.4 recently reported a case of allergic fungal sinusitis presenting with epiphora. Their patient required multiple surgical procedures to control the infection and improve the nasolacrimal duct obstruction. Also, Petkar et al.5 reported a patient with epiphora as the only presenting sign of allergic fungal sinusitis. The patient had resolution of epiphora following sinus surgery and medical management. No lacrimal surgery was required. Finally, Facer et al.6 reported a case of bilateral nasolacrimal involvement from eosinophilic fungal sinusitis. The patient presented with a fluctuant mass just under the right medial canthus. Medical management, sinus surgery, and dacryocystorhinostomy were curative.
© 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2014
Imaging techniques such as CT and MRI aid in the diagnosis. Focal hypodense lesions and areas of enhancement or calcification may be appreciated in the orbit, paranasal sinuses or in our cases, the nasolacrimal duct of those affected. Focal bony destruction may occur.1,7 Beyond inspection, biopsies may be guided by imaging studies, and it has been recommended that hypodense lesions be particularly targeted as they often represent abscess.7 Repeat biopsies or multiple biopsies are sometimes required. As demonstrated in our second case, nasal endoscopy may give further evidence of an invasive fungal process. While this procedure can be a helpful adjunct, not all children can tolerate it at the bedside, even with sedation. The use of bedside nasal endoscopy is often at the discretion of the otolaryngologist. Treatment involves surgery and antifungal therapy. Antifungal options include amphotericin B, intraconazole, voriconazole, and lipid complex nystatin and echinocandins.3 Surgical treatment involves debridement either radical or conservative with the goal of clear surgical margins when possible. Aeration and drainage of the sinus with resection of involved tissue is commonly required.1 Radical versus conservative surgical excision remains a difficult decision as high mortality has been reported with central nervous system extension.1,3,7,8 Dhiwakar et al.7 advocate a conservative resection for anterior orbital processes while exenteration remains the treatment of choice for posterior disease. Our patients with anterior invasive sino-orbital fungal infections were treated with conservative debridement and antifungals. When the nasolacrimal
Case Reports
system is affected, dacryocystorhinostomy may be necessary to repair secondary obstruction. In conclusion, these cases demonstrate that dacryocystitis may be the initial presentation of invasive fungal sinusitis in children. While not a common presenting sign, the clinician should maintain a heightened clinical suspicion of fungal sinusitis when immune-compromised pediatric patients present with dacryocystitis.
REFERENCES 1. Levin LA, Avery R, Shore JW, et al. The spectrum of orbital aspergillosis: a clinicopathological review. Surv Ophthalmol 1996;41:142–54. 2. Mauriello JA Jr, Yepez N, Mostafavi R, et al. Invasive rhinosinoorbital aspergillosis with precipitous visual loss. Can J Ophthalmol 1995;30:124–30. 3. Sivak-Callcott JA, Livesley N, Nugent RA, et al. Localised invasive sino-orbital aspergillosis: characteristic features. Br J Ophthalmol 2004;88:681–7. 4. Kim C, Kacker A, Chee RI, et al. Allergic fungal sinusitis causing nasolacrimal duct obstruction. Orbit 2013;32:143–5. 5. Petkar A, Rao L, Elizondo DR, et al. Allergic fungal sinusitis with massive intracranial extension presenting with tearing. Ophthal Plast Reconstr Surg 2011;27:e98–100. 6. Facer ML, Ponikau JU, Sherris DA. Eosinophilic fungal rhinosinusitis of the lacrimal sac. Laryngoscope 2003;113:210–4. 7. Dhiwakar M, Thakar A, Bahadur S. Invasive sino-orbital aspergillosis: surgical decisions and dilemmas. J Laryngol Otol 2003;117:280–5. 8. deShazo RD. Fungal sinusitis. Am J Med Sci 1998;316:39–45.
© 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
e3
Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
