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Conjunctival Aspergilloma with Multiple Mulberry Nodules: A Case Report
J.L. Chen, C.C. Wang, S.J. Sheu, and T.I. Yeh
CONJUNCTIVAL ASPERGILLOMA WITH MULTIPLE MULBERRY NODULES: A CASE REPORT Jiunn-Liang Chen, Cheng-Chiang Wang,1 Shwu-Jiuan Sheu,2 and Tzy-Ing Yeh Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung, 1 Department of Ophthalmology, Pao-Chien Hospital, Pingtung, 2 and National Yang-Ming University School of Medicine, Taipei, Taiwan.
A 30-year-old healthy female presented with a 1-year history of chronic mucous discharge, tearing, and irritation in the left eye. Slit-lamp examination revealed severe papillary and follicular reaction surrounding a movable subconjunctival mass on the left upper tarsal conjunctiva. Incision and curettage were performed to establish the diagnosis. Multiple peculiar black mulberry nodules were obtained. The clumps of septate hyphae seen with periodic acid-Schiff stain were characteristic of fungus ball (aspergilloma). The patient’s symptoms improved significantly after surgery without any antifungal therapy. Although rarely reported, aspergillus is a common fungus in the conjunctiva that may seed into the subconjunctiva. We present this case to remind ophthalmologists of such a rare cause of recalcitrant conjunctival inflammation in immunocompetent patients.
Key Words: aspergilloma, conjunctiva, immunocompetent (Kaohsiung J Med Sci 2005;21:286–90)
Ocular infection caused by fungi is less common than that caused by bacteria, but an increase in the reported incidence of ocular mycotic infections has been noticed in recent years. Although floral fungi are found in the healthy conjunctival sac, according to fungal cultures [1,2], they are rarely implicated in infections of the eyelid or conjunctiva, except in the presence of preexisting ocular disease, lower resistance to infection, or trauma involving organic matter in immunocompromised conditions. We report a conjunctival aspergilloma with a peculiar histologic appearance in a young, healthy female who presented with a 1-year history of recalcitrant ocular inflammation in her left eye.
Received: July 6, 2004 Accepted: March 22, 2005 Address correspondence and reprint requests to: Dr. Jiunn-Liang Chen, Department of Ophthalmology, Kaohsiung Veterans General st Hospital, 386 Ta-Chung 1 Road, Kaohsiung 813, Taiwan. E-mail: [email protected]
286
CASE PRESENTATION A 30-year-old female visited our hospital complaining of lid swelling with chronic mucous discharge, photophobia, and gradually increasing irritation in her left eye for 1 year. Previous ophthalmic medication used in other hospitals included topical steroids and antibiotics, but none alleviated the condition. Previous ocular history revealed neither contact lens use nor any treatment with systemic corticosteroids [3]. The patient denied ocular trauma or surgical history. General examination showed that she was in otherwise excellent health. At presentation, ocular examination showed that visual acuity with correction was 6/6 in the right and 6/6.7 in the left eye. When the upper lid of the left eye was everted, a 2 × 3 × 1-mm conjunctival mass surrounded by mucous discharge became visible. The superior tarsus showed a severe papillary and follicular reaction (Figure 1). Other ocular evaluations in both eyes were unremarkable. The impression was of bacterial conjunctivitis or internal hordeolum and the mass was thought to represent a pyogenic Kaohsiung J Med Sci June 2005 • Vol 21 • No 6 © 2005 Elsevier. All rights reserved.
Conjunctival aspergilloma with multiple mulberry nodules
Figure 1. A 2 × 3 × 1 mm subconjunctival mass surrounded by mucous discharge was found when the upper lid of the left eye was everted (original magnification × 30). The superior tarsus showed a severe papillary and follicular reaction.
Figure 2. Several black mulberry nodules with acute and chronic inflammatory infiltration and fibrous exudates were found within the subconjunctival mass.
granuloma or foreign body. Initial treatment included 0.25% chloramphenicol and 0.02% flumethasone eye drops three times daily and 0.3% gentamicin ointment at night. A small incision in the mass was made from the subconjunctival side under biomicroscopy. Some exudates with black debris were drained during manipulation and sent for bacterial culture, but the culture was negative. The patient had delayed resolution of the conjunctival mass. One month after surgical intervention, the mass appeared to have enlarged slightly with mucous discharge and persistent severe papillary reaction. Horizontal conjunctival incision and curettage of the mass under the surgical microscope in the operating theatre yielded several peculiar black mulberry nodules pressed out from the mass (Figure 2). After curetting the subconjunctival space, the wound was left open. Samples were collected for bacterial and fungal culture as well as further pathologic examination. Topical treatment was continued postoperatively. Pathologic examination showed clumps of septate hyphae compatible with fungus ball (mycosis) with periodic acid-Schiff stain (Figure 3). The cultures ultimately grew aspergillus, a fungus with filamented hyphae. Topical antifungal drugs were not administered because the patient’s condition dramatically improved after surgical intervention. After 2 weeks, the patient returned with no evidence of the nodular lesions and almost complete resolution of her conjunctival inflammation (Figure 4). She did not have any evidence of recurrence during a 1-year follow-up; ocular examination was unremarkable except for significant conjunctival scarring in the left eye (Figure 5). Immunologic
examinations produced negative results for anti-nuclear antibody, syphilis, and human immunodeficiency virus.
Kaohsiung J Med Sci June 2005 • Vol 21 • No 6
DISCUSSION Aspergillus species are ubiquitous molds in the environment in most areas of the world and are often nonpathogenic members of normal body flora [1,2,4]. However, such widely distributed fungi can cause various presentations of illness and infections, including of the ear, sinuses, eye [5,6], lung,
Figure 3. Within the black mulberry nodules, multiple septate hyphae with dichotomous acute angle branching and spores were identified with periodic acid-Schiff stain (original magnification × 200). The finding was compatible with aspergillosis.
287
J.L. Chen, C.C. Wang, S.J. Sheu, and T.I. Yeh
Figure 4. Two weeks postoperatively, there was only residual subconjunctival scarring without palpable nodular lesions (original magnification × 25).
Figure 5. Two years after cessation of medical treatment, ocular examination showed mild injection of left tarsal conjunctiva (original magnification × 16). There was no evidence of recurrence.
central nervous system, heart, gastrointestinal tract, skin, and bone. Aspergillus keratitis [7] and endophthalmitis are well known and can be caused by minor trauma [8] or surgery [9]. Endogenous aspergillus endophthalmitis [10–12] and aspergillus orbital cellulitis [13–15] have been reported in immunocompromised patients [16]. Conjunctival aspergilloma, though unusual, should be included in the differential diagnosis of chronic outer eye infection lasting longer than 4 weeks. A palpable lid mass with significant conjunctival infection in this case with no history of meibomian gland dysfunction reminds us to perform conjunctival swabs or incisions for a microscopic assay for hyphae. 288
Demonstration of aspergillus by culture and microscopic examination of biopsy tissue, using special stains such as periodic acid-Schiff stain to reveal septate hyphae, provides the most definitive diagnosis. Although it is rarely reported, aspergillus can opportunistically seed into the subconjunctiva. Combined therapy with surgical intervention and medical management has been successfully used to treat invasive and noninvasive aspergillosis colonization in a variety of manifestations, including the brain, keratitis, endophthalmitis, and paranasal sinus. When the deeper ocular structure is involved, systemic antifungal therapy is necessary. Hampton et al reported a case of conjunctival sporotrichosis in the absence of antecedent trauma [17]. The conjunctival infection resolved completely after excision of the mass and treatment with oral itraconazole and topical fluconazole. Perry et al reported a case of a retained aspergillus-contaminated contact lens inducing conjunctival mass in an immunocompetent patient [3]. Upon removal of the contact lens, the patient became asymptomatic and the conjunctival mass completely resolved without any additional therapy. In our case, removal of the subconjunctival aspergilloma by incision and curettage without any additional antifungal therapy also led to complete resolution of the conjunctival aspergillosis. The peculiar appearance of subconjunctival fungus balls (aspergilloma) in an immunocompetent patient may occur due to the accidental inoculation of an abundance of aspergillus. The filamented hyphae positive on periodic acid-Schiff staining were characteristic of aspergillus in this case, probably representing a pyogenic granuloma or an invasive reaction. We report this unusual case of subconjunctival aspergilloma that presented as chalazion with intensive conjunctival inflammation and remind ophthalmologists to keep in mind the possibility of mycotic conjunctival infection.
REFERENCES 1. Sehgal SC, Dhawan S, Chhiber S, et al. Frequency and significance of fungal isolations from conjunctival sac and their role in ocular infections. Mycopathologia 1981;73:17–9. 2. Ando N, Takatori K. Fungal flora of the conjunctival sac. Am J Ophthalmol 1982;94:67–74. 3. Perry HD, Donnenfeld ED, Grossman GA, et al. Retained Aspergillus-contaminated contact lens inducing conjunctival mass and keratoconjunctivitis in an immunocompetent patient. CLAO J 1998;24:57–8. 4. Sinski JT. The epidemiology of aspergillosis. In: The EpidemioKaohsiung J Med Sci June 2005 • Vol 21 • No 6
Conjunctival aspergilloma with multiple mulberry nodules
5. 6.
7.
8.
9.
10.
logy of Human Mycotic Disease. Springfield, IL: Charles C Thomas, 1975. Lapshina NA, Diadina UV. Imidazoles in the treatment of ocular mycoses. Antibiot Khimioter 1991;36:45–6. Mcdonnell PJ, McDonnell JM, Brown RH, Green WR. Ocular involvement in patients with fungal infections. Ophthalmology 1985;92:706–9. Wong TY, Fong KS, Tan DT. Clinical and microbial spectrum of fungal keratitis in Singapore: a 5-year retrospective study. Int Ophthalmol 1997;21:127–30. Panda A, Sharma N, Das G, et al. Mycotic keratitis in children: epidemiologic and microbiologic evaluation. Cornea 1997;16: 295–9. Tabbara KF, al Jabarti AL. Hospital construction-associated outbreak of ocular aspergillosis after cataract surgery. Ophthalmology 1998;105:522–6. Hunt KE, Glasgow BJ. Aspergillus endophthalmitis. An unrecognized endemic disease in orthotopic liver transplantation. Ophthalmology 1996;103:757–67.
Kaohsiung J Med Sci June 2005 • Vol 21 • No 6
11. Anteby I, Kramer M, Rahav G, Benezra D. Necrotizing choroiditisretinitis as presenting symptom of disseminated aspergillosis after lung transplantation. Eur J Ophthalmol 1997;7:294–6. 12. Weishaar PD, Flynn HW Jr, Murray TG, et al. Endogenous Aspergillus endophthalmitis. Clinical features and treatment outcomes. Ophthalmology 1998;105:57–65. 13. Framme C, Rosenfeld J, Sachs HG. Invasive aspergillosis of the orbit in immunocompetence. Ophthalmologe 2000;97:280– 4. [In German] 14. Kronish JW, Johnson TE, Gilberg SM, et al. Orbital infections in patients with human immunodeficiency virus infection. Ophthalmology 1996;103:1483–92. 15. Hutnik CM, Nicolle DA, Munoz DG. Orbital aspergillosis. A fatal masquerader. J Neuroophthalmology 1997;17:257–61. 16. Valluri S, Moorthy RS, Liggett PE, Rao NA. Endogenous Aspergillus endophthalmitis in an immunocompetent individual. Int Ophthalmol 1993;17:131–5. 17. Hampton DE, Adesina A, Chodosh J. Conjunctival sporotrichosis in the absence of antecedent trauma. Cornea 2002;21:831–3.
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J.L. Chen, C.C. Wang, S.J. Sheu, and T.I. Yeh
290
Kaohsiung J Med Sci June 2005 • Vol 21 • No 6
CONJUNCTIVAL ASPERGILLOMA WITH MULTIPLE MULBERRY NODULES: A CASE REPORT Jiunn-Liang Chen, Cheng-Chiang Wang,1 Shwu-Jiuan Sheu,2 and Tzy-Ing Yeh Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung, 1 Department of Ophthalmology, Pao-Chien Hospital, Pingtung, 2 and National Yang-Ming University School of Medicine, Taipei, Taiwan.
A 30-year-old healthy female presented with a 1-year history of chronic mucous discharge, tearing, and irritation in the left eye. Slit-lamp examination revealed severe papillary and follicular reaction surrounding a movable subconjunctival mass on the left upper tarsal conjunctiva. Incision and curettage were performed to establish the diagnosis. Multiple peculiar black mulberry nodules were obtained. The clumps of septate hyphae seen with periodic acid-Schiff stain were characteristic of fungus ball (aspergilloma). The patient’s symptoms improved significantly after surgery without any antifungal therapy. Although rarely reported, aspergillus is a common fungus in the conjunctiva that may seed into the subconjunctiva. We present this case to remind ophthalmologists of such a rare cause of recalcitrant conjunctival inflammation in immunocompetent patients.
Key Words: aspergilloma, conjunctiva, immunocompetent (Kaohsiung J Med Sci 2005;21:286–90)
Ocular infection caused by fungi is less common than that caused by bacteria, but an increase in the reported incidence of ocular mycotic infections has been noticed in recent years. Although floral fungi are found in the healthy conjunctival sac, according to fungal cultures [1,2], they are rarely implicated in infections of the eyelid or conjunctiva, except in the presence of preexisting ocular disease, lower resistance to infection, or trauma involving organic matter in immunocompromised conditions. We report a conjunctival aspergilloma with a peculiar histologic appearance in a young, healthy female who presented with a 1-year history of recalcitrant ocular inflammation in her left eye.
Received: July 6, 2004 Accepted: March 22, 2005 Address correspondence and reprint requests to: Dr. Jiunn-Liang Chen, Department of Ophthalmology, Kaohsiung Veterans General st Hospital, 386 Ta-Chung 1 Road, Kaohsiung 813, Taiwan. E-mail: [email protected]
286
CASE PRESENTATION A 30-year-old female visited our hospital complaining of lid swelling with chronic mucous discharge, photophobia, and gradually increasing irritation in her left eye for 1 year. Previous ophthalmic medication used in other hospitals included topical steroids and antibiotics, but none alleviated the condition. Previous ocular history revealed neither contact lens use nor any treatment with systemic corticosteroids [3]. The patient denied ocular trauma or surgical history. General examination showed that she was in otherwise excellent health. At presentation, ocular examination showed that visual acuity with correction was 6/6 in the right and 6/6.7 in the left eye. When the upper lid of the left eye was everted, a 2 × 3 × 1-mm conjunctival mass surrounded by mucous discharge became visible. The superior tarsus showed a severe papillary and follicular reaction (Figure 1). Other ocular evaluations in both eyes were unremarkable. The impression was of bacterial conjunctivitis or internal hordeolum and the mass was thought to represent a pyogenic Kaohsiung J Med Sci June 2005 • Vol 21 • No 6 © 2005 Elsevier. All rights reserved.
Conjunctival aspergilloma with multiple mulberry nodules
Figure 1. A 2 × 3 × 1 mm subconjunctival mass surrounded by mucous discharge was found when the upper lid of the left eye was everted (original magnification × 30). The superior tarsus showed a severe papillary and follicular reaction.
Figure 2. Several black mulberry nodules with acute and chronic inflammatory infiltration and fibrous exudates were found within the subconjunctival mass.
granuloma or foreign body. Initial treatment included 0.25% chloramphenicol and 0.02% flumethasone eye drops three times daily and 0.3% gentamicin ointment at night. A small incision in the mass was made from the subconjunctival side under biomicroscopy. Some exudates with black debris were drained during manipulation and sent for bacterial culture, but the culture was negative. The patient had delayed resolution of the conjunctival mass. One month after surgical intervention, the mass appeared to have enlarged slightly with mucous discharge and persistent severe papillary reaction. Horizontal conjunctival incision and curettage of the mass under the surgical microscope in the operating theatre yielded several peculiar black mulberry nodules pressed out from the mass (Figure 2). After curetting the subconjunctival space, the wound was left open. Samples were collected for bacterial and fungal culture as well as further pathologic examination. Topical treatment was continued postoperatively. Pathologic examination showed clumps of septate hyphae compatible with fungus ball (mycosis) with periodic acid-Schiff stain (Figure 3). The cultures ultimately grew aspergillus, a fungus with filamented hyphae. Topical antifungal drugs were not administered because the patient’s condition dramatically improved after surgical intervention. After 2 weeks, the patient returned with no evidence of the nodular lesions and almost complete resolution of her conjunctival inflammation (Figure 4). She did not have any evidence of recurrence during a 1-year follow-up; ocular examination was unremarkable except for significant conjunctival scarring in the left eye (Figure 5). Immunologic
examinations produced negative results for anti-nuclear antibody, syphilis, and human immunodeficiency virus.
Kaohsiung J Med Sci June 2005 • Vol 21 • No 6
DISCUSSION Aspergillus species are ubiquitous molds in the environment in most areas of the world and are often nonpathogenic members of normal body flora [1,2,4]. However, such widely distributed fungi can cause various presentations of illness and infections, including of the ear, sinuses, eye [5,6], lung,
Figure 3. Within the black mulberry nodules, multiple septate hyphae with dichotomous acute angle branching and spores were identified with periodic acid-Schiff stain (original magnification × 200). The finding was compatible with aspergillosis.
287
J.L. Chen, C.C. Wang, S.J. Sheu, and T.I. Yeh
Figure 4. Two weeks postoperatively, there was only residual subconjunctival scarring without palpable nodular lesions (original magnification × 25).
Figure 5. Two years after cessation of medical treatment, ocular examination showed mild injection of left tarsal conjunctiva (original magnification × 16). There was no evidence of recurrence.
central nervous system, heart, gastrointestinal tract, skin, and bone. Aspergillus keratitis [7] and endophthalmitis are well known and can be caused by minor trauma [8] or surgery [9]. Endogenous aspergillus endophthalmitis [10–12] and aspergillus orbital cellulitis [13–15] have been reported in immunocompromised patients [16]. Conjunctival aspergilloma, though unusual, should be included in the differential diagnosis of chronic outer eye infection lasting longer than 4 weeks. A palpable lid mass with significant conjunctival infection in this case with no history of meibomian gland dysfunction reminds us to perform conjunctival swabs or incisions for a microscopic assay for hyphae. 288
Demonstration of aspergillus by culture and microscopic examination of biopsy tissue, using special stains such as periodic acid-Schiff stain to reveal septate hyphae, provides the most definitive diagnosis. Although it is rarely reported, aspergillus can opportunistically seed into the subconjunctiva. Combined therapy with surgical intervention and medical management has been successfully used to treat invasive and noninvasive aspergillosis colonization in a variety of manifestations, including the brain, keratitis, endophthalmitis, and paranasal sinus. When the deeper ocular structure is involved, systemic antifungal therapy is necessary. Hampton et al reported a case of conjunctival sporotrichosis in the absence of antecedent trauma [17]. The conjunctival infection resolved completely after excision of the mass and treatment with oral itraconazole and topical fluconazole. Perry et al reported a case of a retained aspergillus-contaminated contact lens inducing conjunctival mass in an immunocompetent patient [3]. Upon removal of the contact lens, the patient became asymptomatic and the conjunctival mass completely resolved without any additional therapy. In our case, removal of the subconjunctival aspergilloma by incision and curettage without any additional antifungal therapy also led to complete resolution of the conjunctival aspergillosis. The peculiar appearance of subconjunctival fungus balls (aspergilloma) in an immunocompetent patient may occur due to the accidental inoculation of an abundance of aspergillus. The filamented hyphae positive on periodic acid-Schiff staining were characteristic of aspergillus in this case, probably representing a pyogenic granuloma or an invasive reaction. We report this unusual case of subconjunctival aspergilloma that presented as chalazion with intensive conjunctival inflammation and remind ophthalmologists to keep in mind the possibility of mycotic conjunctival infection.
REFERENCES 1. Sehgal SC, Dhawan S, Chhiber S, et al. Frequency and significance of fungal isolations from conjunctival sac and their role in ocular infections. Mycopathologia 1981;73:17–9. 2. Ando N, Takatori K. Fungal flora of the conjunctival sac. Am J Ophthalmol 1982;94:67–74. 3. Perry HD, Donnenfeld ED, Grossman GA, et al. Retained Aspergillus-contaminated contact lens inducing conjunctival mass and keratoconjunctivitis in an immunocompetent patient. CLAO J 1998;24:57–8. 4. Sinski JT. The epidemiology of aspergillosis. In: The EpidemioKaohsiung J Med Sci June 2005 • Vol 21 • No 6
Conjunctival aspergilloma with multiple mulberry nodules
5. 6.
7.
8.
9.
10.
logy of Human Mycotic Disease. Springfield, IL: Charles C Thomas, 1975. Lapshina NA, Diadina UV. Imidazoles in the treatment of ocular mycoses. Antibiot Khimioter 1991;36:45–6. Mcdonnell PJ, McDonnell JM, Brown RH, Green WR. Ocular involvement in patients with fungal infections. Ophthalmology 1985;92:706–9. Wong TY, Fong KS, Tan DT. Clinical and microbial spectrum of fungal keratitis in Singapore: a 5-year retrospective study. Int Ophthalmol 1997;21:127–30. Panda A, Sharma N, Das G, et al. Mycotic keratitis in children: epidemiologic and microbiologic evaluation. Cornea 1997;16: 295–9. Tabbara KF, al Jabarti AL. Hospital construction-associated outbreak of ocular aspergillosis after cataract surgery. Ophthalmology 1998;105:522–6. Hunt KE, Glasgow BJ. Aspergillus endophthalmitis. An unrecognized endemic disease in orthotopic liver transplantation. Ophthalmology 1996;103:757–67.
Kaohsiung J Med Sci June 2005 • Vol 21 • No 6
11. Anteby I, Kramer M, Rahav G, Benezra D. Necrotizing choroiditisretinitis as presenting symptom of disseminated aspergillosis after lung transplantation. Eur J Ophthalmol 1997;7:294–6. 12. Weishaar PD, Flynn HW Jr, Murray TG, et al. Endogenous Aspergillus endophthalmitis. Clinical features and treatment outcomes. Ophthalmology 1998;105:57–65. 13. Framme C, Rosenfeld J, Sachs HG. Invasive aspergillosis of the orbit in immunocompetence. Ophthalmologe 2000;97:280– 4. [In German] 14. Kronish JW, Johnson TE, Gilberg SM, et al. Orbital infections in patients with human immunodeficiency virus infection. Ophthalmology 1996;103:1483–92. 15. Hutnik CM, Nicolle DA, Munoz DG. Orbital aspergillosis. A fatal masquerader. J Neuroophthalmology 1997;17:257–61. 16. Valluri S, Moorthy RS, Liggett PE, Rao NA. Endogenous Aspergillus endophthalmitis in an immunocompetent individual. Int Ophthalmol 1993;17:131–5. 17. Hampton DE, Adesina A, Chodosh J. Conjunctival sporotrichosis in the absence of antecedent trauma. Cornea 2002;21:831–3.
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J.L. Chen, C.C. Wang, S.J. Sheu, and T.I. Yeh
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Kaohsiung J Med Sci June 2005 • Vol 21 • No 6