0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letters |

Recalcitrant Candida Endophthalmitis Associated With Mannose-Binding Lectin Deficiency FREE

Ana-Maria Oliva, MD; Peter R. Pavan, MD; Curtis E. Margo, MD, MPH; Scott E. Pautler, MD
Arch Ophthalmol. 2009;127(6):819-828. doi:10.1001/archophthalmol.2009.107.
Text Size: A A A
Published online

Mannose-binding lectin (MBL) is an acute-phase reactant that binds microbial surface carbohydrates and participates in opsin-mediated phagocytosis. An important component of the innate immune system, MBL also activates the lectin complement pathway.1 Low serum levels of MBL have been associated with serious bacterial, fungal, and viral infections.2 We describe an otherwise healthy man with MBL deficiency and recalcitrant Candida endophthalmitis.

A 43-year-old man of Middle Eastern descent had a 1-week history of blurred vision in the right eye. He and several siblings had a history of recurrent oral thrush but no diagnosed immunodeficiency. He had no history of intravenous drug abuse or recent symptoms of oral thrush. On examination, vision in the affected eye was 20/200. A 1.5-mm focal white retinal infiltrate was seen along the superior-temporal arcade with neurosensory macular detachment. He was treated with a varying regimen of sulfadiazine, daraprim, leucovorin calcium, clindamycin hydrochloride, and prednisone in the ensuing 7 weeks (Figure 1A). Results of rapid plasma reagin, fluorescent treponemal antibody absorption, human immunodeficiency virus enzyme-linked immunosorbent assay, blood cultures, and Bartonella and anti-Toxoplasma IgG and IgM titers were either within the normal range or negative. Five weeks after the patient's initial visit, his visual acuity decreased and the retinal lesion was nearly twice its original size (Figure 1B). The prednisone dosage was increased but the lesion continued to enlarge (Figure 1C). Vitrectomy performed 7 weeks after his initial visit revealed yeasts and pseudohyphae on Gram staining. At the conclusion of surgery, 50 μg of voriconazole in 0.1 mL of sterile water was injected intravitreously. Cultures grew Candida albicans sensitive to voriconazole and fluconazole. Oral voriconazole at a dosage of 200 to 300 mg by mouth twice a day and later oral fluconazole at a dosage of 800 mg by mouth daily failed to slow progression. Treatment with intravitreous voriconazole at a dose of 100 μg in 0.1 mL of sterile water was started, but the lesion progressed despite 6 more injections every 3 to 4 days during the next month. A second pars plana vitrectomy with excision of the entire white lesion in the macula was followed by endolaser and gas-fluid exchange. Cultures yielded Candida albicans still sensitive to voriconazole and fluconazole. Urine and blood culture results were negative. Postoperatively, the patient was treated with intravenous fluconazole and micafungin. Further studies were performed, including transesophageal echocardiography, lymphocyte subset analysis, thyroid stimulation hormone level, serum cortisol level, and lumbar puncture with cerebral spinal fluid analysis and culture, all of which had unremarkable results. The patient was not anergic to a Candida skin test; lymphocyte transformation to Candida antigen and neutrophil function test results were normal. One month later, a new retinal infiltrate was seen in the midperiphery, followed by a second focus the next week. The patient received a series of 16 injections of intravitreous voriconazole every 1 to 3 days with alternating doses of 100 μg and 200 μg in 0.1 mL of sterile water. Four satellite lesions developed, followed by a partial retinal detachment, lens capsular opacification, and anterior chamber inflammation. The left eye remained healthy. The affected eye was enucleated and examined histologically in its entirety. The specimen revealed persistent growth of yeasts in the cortical vitreous (Figure 2). Extensive testing of immune function disclosed a severe deficiency of MBL (6 ng/mL; reference range, ≥100 ng/mL]).

Place holder to copy figure label and caption
Figure 1.

Fundus photographs of the right eye. A, A 1–disc area white lesion of the retina with neurosensory detachment in the superior macula was seen shortly after the patient started treatment. B, Five weeks later, the lesion and macular exudate progressed in size. New hemorrhages appeared in the retina peripheral to the infiltrate. C, Seven weeks after the initial visit, the lesion involved the entire retina from superior to inferior vascular arcades. There was moderate posterior vitritis.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

The enucleated eye had luxuriant growth of yeasts and pseudohyphae in the remaining cortical vitreous (periodic acid–Schiff, original magnification ×175).

Graphic Jump Location

Deficiency of MBL has been correlated with a variety of infections in otherwise healthy individuals but may also enhance susceptibility to certain infections in persons receiving chemotherapy or those with secondary immunosuppression for other reasons.3 Genetic polymorphism explains the range of serum concentrations of MBL found in the general population, with severe serum MBL deficiency associated with homozygosity of yet unnamed minority alleles.3 We are unaware of any previous reports of recalcitrant Candida endophthalmitis associated with MBL deficiency in an otherwise healthy individual. Mannose-binding lectin replacement therapy using plasma-derived or recombinant lectin is under investigation but is not currently available for clinical use.1,4

Correspondence: Dr Margo, Department of Pathology, University of South Florida, 12901 Bruce B. Downs Blvd, MDC Box 11, Tampa, FL 33612 (cmargo@hsc.usf.edu).

Financial Disclosure: None reported.

This article was corrected online for error in data on 7/21/2009, prior to publication of the correction in print.

Eisen  DPMinchinton  RM Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis 2003;37 (11) 1496- 1505
PubMed Link to Article
Neth  OJack  DLDodds  AWHolzel  HKlein  NJTurner  MW Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition. Infect Immun 2000;68 (2) 688- 693
PubMed Link to Article
Kilpatrick  DC Mannan-binding lectin and its role in innate immunity. Transfus Med 2002;12 (6) 335- 352
PubMed Link to Article
Summerfield  JA Clinical potential of mannose-binding lectin-replacement therapy. Biochem Soc Trans 2003;31 (pt 4) 770- 773
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Fundus photographs of the right eye. A, A 1–disc area white lesion of the retina with neurosensory detachment in the superior macula was seen shortly after the patient started treatment. B, Five weeks later, the lesion and macular exudate progressed in size. New hemorrhages appeared in the retina peripheral to the infiltrate. C, Seven weeks after the initial visit, the lesion involved the entire retina from superior to inferior vascular arcades. There was moderate posterior vitritis.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

The enucleated eye had luxuriant growth of yeasts and pseudohyphae in the remaining cortical vitreous (periodic acid–Schiff, original magnification ×175).

Graphic Jump Location

Tables

References

Eisen  DPMinchinton  RM Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis 2003;37 (11) 1496- 1505
PubMed Link to Article
Neth  OJack  DLDodds  AWHolzel  HKlein  NJTurner  MW Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition. Infect Immun 2000;68 (2) 688- 693
PubMed Link to Article
Kilpatrick  DC Mannan-binding lectin and its role in innate immunity. Transfus Med 2002;12 (6) 335- 352
PubMed Link to Article
Summerfield  JA Clinical potential of mannose-binding lectin-replacement therapy. Biochem Soc Trans 2003;31 (pt 4) 770- 773
PubMed Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

428 Views
62 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs