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A 38-year-old female from Montreal, Canada, consulted for sudden, painless vision loss in her left eye 5 days before presentation. Her medical history was known for bipolar disease, hypothyroidism, and clinically diagnosed truncal tinea versicolor (Fig. 1).
Her history was largely unremarkable except for occasional ingestion of beef tartar. She denied any chills or fever and was afebrile upon physical examination. At initial visit, her visual acuity was 20/20 OD and counting fingers OS. Slit-lamp examination of the left eye showed 1+ cells and 1+ flare in the anterior chamber as well as 2+ vitreous cells and 1+ vitreous haze as per the Standardization of Uveitis Nomenclature working group grading scheme.
Dilated fundus examination revealed an exophytic white lesion in the macula (Fig. 2).
A clinical diagnosis of panuveitis caused by probable ocular toxoplasmosis OS was established. Baseline uveitis workup was initiated while empirical therapy with pyrimethamine (25 mg PO daily), folinic acid (10 mg PO every second day), and clindamycin (300 mg PO QID) was started on the day of the initial presentation. The patient also received routine topical uveitis treatment (prednisolone 1% q1hr, dexamethasone ointment 0.1% qHS, and homatropine 2% BID) in her left eye and oral prednisone 60 mg daily, started 48 hours after the initiation of antiprotozoal treatment. Her initial workup was notable for mild absolute eosinophilia and negative Toxoplasma gondii serology (immunoglobin [Ig]M and IgG). Results of screening for HIV, syphilis, cytomegalovirus (IgG), and tuberculosis (interferon-gamma release assay) were negative. Baseline workup was done for sarcoidosis even though the clinical picture was more suggestive of an infectious etiology; both chest x-ray and angiotensin-converting enzyme level were within normal limits.
After 2 weeks of clinical stability, the patient’s vision deteriorated and the fundus lesion had worsened significantly. Prednisone was suspended and a diagnostic vitrectomy was performed promptly. Calcofluor-white stain showed presence of pseudohyphae in the vitreous a few hours after the vitrectomy (Fig. 3). The vitreal culture subsequently confirmed Candida albicans growth the next day.
Upon further questioning, in addition to her chronic skin lesions, the patient also reported chronic white buccal lesions, as well as recurrent vulvovaginitis. Furthermore, on review of systems, she described symptoms suggesting left-sided neglect for the last few weeks.
On subsequent investigations, direct examination of skin lesion scrapings showed pseudohyphae consistent with Candida species, and buccal culture grew Candida albicans. Serum (1 to >3) β-D-glucan, a marker of invasive fungal infection, was elevated at >500 pg/mL though blood cultures remained negative. Cerebral magnetic resonance imaging (MRI) showed multiple active right parietal microabscesses (Fig. 4) and an old frontal lesion suggesting previous infection. Spinal MRI was consistent with spondylodiscitis at the level of L4–L5. The diagnosis was established as chronic mucocutaneous candidiasis (CMCC) complicated by invasive candidiasis, with the eye as the presenting infection site.
Intravenous liposomal amphotericin B (5 mg/kg/day) was started but had to be stopped 2 weeks later due to renal toxicity. This was followed by oral fluconazole (800 mg daily) for 1 year, leading to complete resolution of mucocutaneous symptoms and of the cerebral and spinal lesions on subsequent MRIs. The daily dose of fluconazole was then reduced to 400 mg daily for the following 6 months before further being tapered to 200 mg daily. She will likely continue on this prophylactic dosage for life. In addition to the systemic treatments, the patient also received 4 weekly intravitreal antifungal injections (amphotericin B, 5 μg/0.1 mL, n = 1; voriconazole, 100 μg/0.1 mL, n = 3) OS, quieting down the panuveitis. However, her visual acuity stayed at counting fingers as a result of extensive macular scarring. Her right eye remained free of disease with normal visual acuity.
In light of her unusual clinical presentation, the patient was referred for genetic testing, which revealed bi-allelic CARD9 mutations (manuscript in preparation).
The clinical presentation of ocular candidiasis spans over a continuous spectrum. Whereas chorioretinitis involves only the chorioretinal layers, manifesting as cotton wool spots, Roth spots, retinal hemorrhages, or deep retinal focal white infiltrates, the diagnosis of Candida endophthalmitis also requires the presence of vitritis and/or fluffy vitreal lesions extending from chorioretinal infiltrates.
In addition to ocular candidiasis, the differential diagnosis of a focal chorioretinal lesion with associated vitreous cells includes toxoplasmosis, toxocariasis, tuberculosis, cat-scratch disease, onchocerciasis, cysticercosis, sarcoidosis, syphilis, and masquerade syndrome.
By definition, endogenous Candida endophthalmitis occurs in association with transient or persistent candidemia, yet it remains an infrequent complication of invasive candidiasis. Even though the aforementioned wide spectrum of signs of ocular candidiasis was detected in up to 26% of patients with proven candidemia,
Conversely, not all Candida endophthalmitis have proven candidemia at presentation. The reported rates of positive blood culture in patients diagnosed with Candida endophthalmitis are highly variable, ranging from 11% to 100% depending on the population.
To our knowledge, our patient is the first reported case of endophthalmitis associated with CMCC, a condition characterized by persistent or recurrent superficial candidal infection of skin, mucous membranes, and nails.
Finally, this case emphasizes the importance of performing an in-depth workup and of screening for immunodeficiencies when managing atypical cases presenting with “spontaneous” deep Candida infections such as endophthalmitis. Multiple genetic mutations, including CARD9, have been reported to cause impaired Th17 immunity against Candida species, predisposing to superficial and/or deep infections.
The presence of CMCC and its associated genetic susceptibilities are often overlooked but are important for several reasons. Recognition of such susceptibilities not only ensures prompt short-term and long-term treatments for patients, but also provides the opportunity for novel adjunctive therapy targeting specific mutations.
Furthermore, as some of these mutations are inheritable, appropriate genetic counselling would also be beneficial and necessary.
The authors have no proprietary or commercial interest in any materials discussed in this article.
Q.W., S.F.D., and M.-J.A. have no financial or proprietary interest to declare. D.C.V. has received an unrestricted educational grant from CSL Behring Canada; an investigator-initiated grant from Astellas Canada; and honoraria from CSL Behring Canada, Sunovion, Pfizer Canada, and Merck Canada. He has received research funding support from the McGill University Health Centre/Research-Institute and is a Chercheur-Boursier clinicien junior 1 (Fondation de recherche Santé-Québec, FRQS).
This case report received no funding.
Chorich III, L.J.
Diagnosis of uveitis.
in: Foster C.S. Vitale A.T. Diagnosis and treatment of uveitis. 2nd ed. Jaypee Brothers Medical Publishers,
New Delhi2013: 101-122