BILATERAL SIMULTANEOUS ENDOGENOUS ASPERGILLUS ENDOPHTHALMITIS IN AN IMMUNOCOMPETENT PATIENT Nishant Sachdev, MD,* Pawan Gupta, MD,* Ramandeep Singh, MD,* Arunaloke Chakrabarti, MD,† Vishali Gupta, MD,* Amod Gupta, MD*

Purpose: To report a case of bilateral endogenous Aspergillus endophthalmitis in an immunocompetent patient. Methods: We report a young immunocompetent 26-year-old Indian woman who presented with bilateral simultaneous endogenous endophthalmitis and was managed with pars plana vitreous surgery in both the eyes. Results: Smear examination of the vitrectomy specimen from the left eye identified septate hyphae with acute-angle branching, which on culture showed growth of Aspergillus fumigatus. A detailed systemic evaluation failed to reveal any systemic focus or predisposing factor for fungal infection. The patient had received an intravenous dextrose infusion 2 weeks before this episode while being treated at a rural hospital for malarial infection. During follow-up, she developed bilateral rhegmatogenous retinal detachment requiring revised pars plana vitreous surgery with silicon oil tamponade. Conclusion: An immunocompetent patient can present with bilateral simultaneous endogenous Aspergillus endophthalmitis after receiving an intravenous infusion of presumably contaminated dextrose solution. RETINAL CASES & BRIEF REPORTS 4:14 –17, 2010

ment for minor ailments.8 Although all previously reported cases were unilateral, we report for the first time a bilateral simultaneous onset of endogenous Aspergillus endophthalmitis in an immunocompetent adult individual.

From the Departments of *Ophthalmology and †Microbiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

A

spergillus species are ubiquitous saprophytic molds that are found in soil and decaying vegetation. Despite universal exposure, infections in humans are relatively uncommon. Endogenous Aspergillus endophthalmitis is a rare disease and is mostly reported in immunocompromised patients with heart transplants,1 endocarditis,2 lung, liver and renal transplants,3–5 leukemia6 and in intravenous drug abusers.7 Interestingly, we reported a series of 12 immunocompetent patients who developed endogenous fungal endophthalmitis after receiving presumably contaminated dextrose infusions while undergoing treat-

Case Report A 26-year-old woman presented with sudden painless loss of vision in both eyes for 5 days. There was no history of ocular trauma or previous ocular surgery. Two weeks before the onset of symptoms, the patient had developed a high-grade fever with chills and rigors and was suspected to be suffering from malaria. During the course of treatment, she received multiple intravenous dextrose infusions. Although the fever subsided, she developed rapidly progressive loss of vision in both eyes. At presentation, her visual acuity was counting fingers close to the face in both eyes. She had a bilateral symmetrical clinical picture with severe anterior chamber inflammation (4⫹ cells, 4⫹ flare, hypopyon), and dense vitritis with obscuration of retinal details. There was no history of oral or genital ulcers. Her systemic examination was unremarkable. On B-scan ultrasonography, there was presence of a bilateral subreti-

Reprint requests: Amod Gupta, MD, Department of Ophthalmology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India; e-mail: [email protected]

14

15

BILATERAL ASPERGILLUS ENDOPHTHALMITIS

Fig. 1. A, Intraoperative fundus picture of the right eye showing presence of yellowish confluent subretinal abscess with few overlying superficial fundal hemorrhages. B, Intraoperative fundus picture of the left eye showing presence of yellowish vitreous exudates adherent to the retina with underlying subretinal abscess. C and D, Fundus pictures of both the right and left eyes, respectively, 14 months after presentation showing healed macular lesions with atrophic retina in both the eyes.

nal abscess in the posterior pole with overlying dense vitreous exudates. With a possible diagnosis of bilateral endogenous endophthalmitis, the patient was subjected to pars plana vitrectomy with intravitreal antibiotic injections (vancomycin 1 mg/0.1 mL, ceftazidime 2.25 mg/0.1 mL, and amphotericin B 5 ␮g/0.1 mL) in the right eye and 1 day later in the left eye. Intraoperatively a large yellowish, confluent, subretinal abscess was noted in the posterior pole in both eyes (Figure 1). The smear examination of the vitrectomy specimen from the right eye was noncontributory. However, the vitreous sample from the left eye showed septate hyphae with acute-angle branching that was later confirmed as Aspergillus fumigatus by culture on Sabouraud dextrose agar media (Figure 2). The patient was started on oral itraconazole 200 mg twice a day for 2 weeks followed by 100 mg twice a day for the next 12 weeks. Her complete systemic evaluation including blood counts, fasting blood sugar, blood and urine cultures, echocardiography, chest x-ray, and abdominal ultrasound failed to identify any focus of infection or any predisposing factors.

Fig. 2. A, Calcofluor staining of the vitrectomy specimen from the left eye showing presence of acute angle branching septate hyphae. B, Sabouraud dextrose agar media with growth of A. fumigatus from the same vitrectomy specimen.

During the follow-up, she developed bilateral rhegmatogenous retinal detachment at 2 months and 6 months in the left and right eye, respectively, for which she underwent successful pars plana vitreous surgery with silicon oil tamponade. At the 14-month follow-up, she maintained a best-corrected visual acuity of 20/80 in the right eye and 20/200 in the left eye with healed retinitis lesions and atrophic macula in both eyes (Figure 1).

Discussion Endogenous endophthalmitis comprises 2% to 8% of all cases of infectious endophthalmitis and can be bacterial or fungal in origin.9 Fungal endogenous endophthalmitis is most commonly caused by Candida albicans followed by Aspergillus species.10 Candida endogenous endophthalmitis is characterized by the

16

RETINAL CASES & BRIEF REPORTSℜ

presence of vitreous fluff balls/abscesses and multiple, chorioretinitis lesions. Aspergillus endogenous endophthalmitis, however, is more fulminant, and the chorioretinal lesions are often confluent with indistinct margins located in the macular area. The severity of retinal involvement ranges from subretinal infiltrates to full-thickness retinal necrosis. The infection spreads and leads to formation of an overlying abscess that eventually breaks into the vitreous cavity, and finally, the anterior segment becomes involved as well.11 Moreover, Aspergillus infection is associated with a poor visual outcome with a higher chance of evisceration compared with infection by Candida species, which are more frequently bilateral and are associated with a better visual and anatomical outcome.10,11 Aspergillus fumigatus, a common environmental spore-forming mold, enters the human body mostly through the inhalational route wherein spores lodge in the terminal airways. Although the majority of the spores are phagocytosed by alveolar macrophage in the terminal airways itself, few spores may escape to germinate and infiltrate the tissue. They are then taken care of by the increased recruitment and activation of neutrophils, a process mediated by the T-lymphocytes.12,13 However, in patients who have undergone organ transplant and are on prolonged steroid therapy, the disabled macrophage function and the defective T-lymphocyte response allows the fungus to invade and disseminate via the hematogenous route. Invasive aspergillosis is seen in 5% to 10% of patients who undergo allogenic stem cell transplantation.14 Rarely, the Aspergillus may infiltrate the human body by direct hematogenous route as seen in intravenous drug abusers by the use of contaminated needles, in patients with prolonged indwelling catheters, and those who receive contaminated intravenous dextrose infusions. The fungus may lodge in different organs including the eye, where it may present as endogenous endophthalmitis. Aspergillus endogenous endophthalmitis is very rare in healthy adults and presents as a unilateral disease. Bilateral Aspergillus infection is usually associated with debilitating illnesses such as cardiac/ valvular disease, prematurity,15 disseminated tuberculosis,16 and organ transplant.4 It has also been reported in a 1-month-old apparently healthy infant (although the child had reduced T-helper cell count) in whom 1 eye became phthisical and required removal, whereas the other eye responded to treatment with intravenous amphotericin-B.17 The present case illustrates a possible bilateral simultaneous Aspergillus endogenous endophthalmitis in an immunocompetent adult in whom no obvious cause or predisposing factor could be identified other than the



2010



VOLUME 4



NUMBER 1

febrile illness for which the patient received antipyretics and antimalarials along with intravenous dextrose infusions. The patient was empirically treated for malaria based on the typical clinical features of highgrade fever with chills and rigors. The fever is highly unlikely to be due to systemic Aspergillus infection as invasive aspergillosis typically manifests with fever, cough, dyspnea, pleuritic chest pain, and, sometimes, hemoptysis with rapidly worsening hypoxemia in patients with prolonged neutropenia or immunosuppression, which was not the profile of our patient.18 Moreover, the fact that the fever settled with antimalarials is again in favor of this diagnosis. Hence, it is reasonably safe to assume that one of the dextrose infusions was contaminated with the fungus. The role of fever and antipyretics in altering the immune system is still controversial. Fröhlich et al19 recently found a downregulation of neutrophil function including reduced phagocytosis and oxidative killing of bacteria with hyperthermia. Moreover, Austin and Truant20 showed that commonly used antipyretics like salicylates also adversely affect neutrophil function with impaired intracellular killing of bacteria. These polymorphonuclear neutrophils are also essential in the initiation and execution of the acute inflammatory response to invasive Aspergillus infection and subsequently its resolution. We have previously reported a series of 12 immunocompetent patients with unilateral endogenous fungal endophthalmitis after receiving presumably contaminated dextrose infusions.8 The majority of these patients were similarly being treated for minor febrile illnesses. It can only be speculated that, in these patients, fever or antipyretics alter neutrophil function to a sufficient degree to predispose them to invasive fungal infections. Moreover, the neutrophils and other phagocytic defense mechanisms may be overcome even in a healthy host if the fungus enters the blood in a large invasive dose via a presumably contaminated dextrose infusion. The present problem of contaminated dextrose infusions leading to endophthalmitis is fast emerging as a public health problem in developing countries, a fact that we have highlighted previously as well.8 What is more disturbing is the fact that all the cases including this one were from various different rural hospitals and not from any one particular health center. Moreover, these infusion solutions were not prepared locally by the practioners themselves or in any regional pharmacy but were prepared commercially by various accepted pharmaceutical manufacturers. These rural hospitals/clinics were run by either qualified medical doctors or registered medical practioners. The preventive measures suggested to reduce this risk of receiving contaminated intravenous dextrose infusions in-

17

BILATERAL ASPERGILLUS ENDOPHTHALMITIS

clude a careful inspection of the infusion bottles for any contaminant before infusing the same and the use of special epidural filters while giving intravenous fluids to the patient.21,22 Such infections have been demonstrated in other organ systems as well in both clinical and experimental studies including infections in the kidneys, brain, and myocardium and can even lead to life-threatening septicemia.23–25 Key words: bilateral simultaneous endogenous Aspergillus endophthalmitis, dextrose infusion, immunocompetent, subretinal abscess.

12.

13.

14.

15.

References 1. 2. 3.

4.

5.

6.

7.

8.

9.

10.

11.

Darell RW. Endogenous Aspergillus uveitis following heart surgery. Arch Ophthalmol 1967;78:354 –357. Boldrey EE. Bilateral endogenous Aspergillus endophthalmitis. Retina 1981;1:171–174. Graham DA, Kinyoun JL, George DP. Endogenous Aspergillus endophthalmitis after lung transplant. Am J Ophthalmol 1995;119:107–109. Hunt KE, Glasgow BJ. Aspergillus endophthalmitis. An unrecognized endemic disease in orthotopic liver transplantation. Ophthalmology 1996;103:757–767. Naidoff MA, Green WR. Endogenous Aspergillus endophthalmitis occurring after kidney transplant. Am J Ophthalmol 1975;79:502–509. Kalina PH, Campbell RJ. Aspergillus terreus endophthalmitis in a patient with chronic lymphocytic leukemia. Arch Ophthalmol 1991;109:102–103. Doft BH, Clarkson JG, Rebel G, Forster RK. Endogenous Aspergillus endophthalmitis in drug abusers. Arch Ophthalmol 1980;98:859 – 862. Gupta A, Gupta V, Dogra MR, et al. Fungal endophthalmitis after a single intravenous administration of presumably contaminated dextrose infusion fluid. Retina 2000;20:262–268. Okada AA, Johnson RP, Liles WC, et al. Endogenous bacterial endophthalmitis: report of a ten year retrospective study. Ophthalmology 1994;101:832– 838. Ness T, Pelz K, Hansen LL. Endogenous endophthalmitis: microorganisms, disposition and prognosis. Acta Ophthalmol Scand 2007;85:852– 856. Weishaar PD, Flynn HW Jr, Murray TG, et al. Endogenous

16. 17. 18. 19.

20.

21.

22.

23.

24.

25.

Aspergillus endophthalmitis. Clinical features and treatment outcomes. Ophthalmology 1998;105:57– 65. Rivera A, Hohl T, Pamer EG. Immune responses to Aspergillus fumigatus infections. Biol Blood Marrow Transplant 2006;12:47– 49. Schaffner A, Douglas H, Braude A. Selective protection against conidia by mononuclear and against mycelia by polymorphonuclear phagocytes in resistance to Aspergillus. Observations on these two lines of defense in vivo and in vitro with human and mouse phagocytes. J Clin Invest 1982;69: 617– 631. Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002;34:909 – 917. Paradis AJ, Roberts L. Endogenous ocular aspergillosis: report of a case in an infant with cytomegalic inclusion disease. Arch Ophthalmol 1963;69:765–769. Friedman AH, Chishti MI, Henkind P. Endogenous ocular aspergillosis. Ophthalmologica 1974;168:197–205. Sihota R, Aggarwal HC, Grover AK, Sood NN. Aspergillus endophthalmitis. Br J Ophthalmol 1987;71:611– 613. Denning DW. Invasive aspergillosis. Clin Infect Dis 1998; 26:781– 803. Fro¨hlich D, Wittmann S, Rothe G, Sessler DI, Vogel P, Taeger K. Mild hyperthermia downregulates receptor-dependent neutrophil function. Anesth Analg 2004;99:284 –292. Austin TW, Truant G. Hyperthermia, antipyretics and function of polymorphonuclear leukocytes. Can Med Assoc J 1978;118:493– 495. Biswas J. Fungal endophthalmitis after a single intravenous administration of presumably contaminated dextrose infusion fluid. Retina 2001;21:93–94. Newall F, Ranson K, Robertson J. Use of in-line filters in pediatric intravenous therapy. J Intraven Nurs 1998;21:166 – 170. Useh MF, Mbouda B. Risk of contamination from air vents during intravenous fluid administration. East Afr Med J 1998; 75:322–326. Maki DG, Martin WT. Nationwide epidemic of septicemia caused by contaminated infusion products. IV. Growth of microbial pathogens in fluids for intravenous infusions. J Infect Dis 1975;131:267–272. Omuta J, Uchida K, Yamaguchi H, Shibuya K. Histopathological study on experimental endophthalmitis induced by bloodstream infection with Candida albicans. Jpn J Infect Dis 2007;60:33–39.

Bilateral simultaneous endogenous Aspergillus endophthalmitis in an immunocompetent patient.

To report a case of bilateral endogenous Aspergillus endophthalmitis in an immunocompetent patient...
460KB Sizes 3 Downloads 9 Views