Chronic granulomatous disease (CGD) is a rare (1/200 000–1 000 000 births) primary immunodeficiency that affects phagocytes leading to intracellular bacterial and fungal infections and granuloma formation. Chronic granulomatous disease manifests typically as pneumonia, infectious dermatitis and abscess formation in the absence of antibiotic prophylaxis (Johnston 2001). Blepharoconjunctivitis and chorioretinitis are the most common manifestations in the eye (Goldblatt et al. 1999; Kim et al. 2003).
A 38-year-old male patient with known X-linked CGD was remitted to our clinic and presented with bilateral red eyes and pain especially in his left eye, which began 1 week earlier. He also suffered from ulcerative colitis and was receiving treatment with oral trimethoprime with sulphonamide. His symptoms worsened with time. He had already received local treatment (fucidic acid and later chloramphenicol drops) from the local GP without any improvement. BCVA was 7/10 and 4/10 at the right (RE) and left eye (LE), respectively.
Slit-lamp examination of the RE showed no signs of blepharitis or secretion but mild conjunctival injection. Limbal neovascularization was seen, both deep and superficial, predominantly at the inferior half of cornea with a mild corneal thinning. A slight opacity was seen in the peripheral cornea. No other finds in the cornea, anterior chamber or the posterior segment were observed.
The LE showed no signs of blepharitis but severe chemosis and injection, mild purulent secretion and neovascularization, both deep and superficial, along with a discrete corneal thinning over the same area as in the RE. Paracentrally inferiorly in the left cornea, a large infiltrate was noticed (1.5–2 mm ∅), under a superficial erosion (Fig. 1). A mild to moderate inflammation with precipitates, some flare and cells, was observed in the anterior chamber. The posterior segment was unremarkable except for an inactive chorioretinal scar. A standard conjunctival culture and corneal scraping were taken, and levofloxacin drops were prescribed at high doses together with oral tetracycline.
The patient came for control the day after. He reported a mild improvement in his symptoms but the examination showed two satellite lesions next to the large infiltrate in the LE. During the following days, the conjunctival injection and the size, appearance and density of the infiltrate diminished. BCVA rose to 7/10 and 6/10 in the RE and LE, respectively. Approximately 17 days after the beginning of treatment, dexamethasone drops (three times daily) added.
Two weeks after the infiltrate had completely vanished, the cornea showed a thinning with mild fibrosis (Fig. 2). The deep limbal blood vessels had regressed but not the superficial ones, which had spread to the area of thinness. The final BCVA was 8–9/10 and 8/10 in the RE and LE, respectively, with no subjective symptoms. The cultures showed no bacteria, fungi and acanthamoeba.
Immunodeficient patients have a higher incidence of lid and conjunctival infections. Our patient presented with severe symptoms in spite of antibiotic treatment. The clinical diagnosis was a bacterial/infectious keratitis with a large infiltrate–this was not supported by the negative culture. More potent antibiotics were given topically and orally and a certain improvement was observed over time. Complete resolution and healing of the infiltrate occurred with a certain corneal thinning. The finding of the mild corneal thinning at the periphery along with the presence of moderate to severe neovascularization into the cornea can be interpreted as earlier marginal and perhaps ulcerative lesions/keratitis which obviously healed without treatment, apparently noninfectious.
One case of peripheral ulcerative keratitis (Leroux et al. 2004) and one case of paralimbal keratitis caused by candida glabrata (Djalilian et al. 2001) have been reported in patients with CGD. However, no case with so centrally positioned infiltrate and such deterioration of BCVA has been reported. The negative culture can be interpreted as noninfectious infiltrate in the left cornea, but the profound clinical and subjective improvement after the prescription of levofloxacin drops implies the opposite. The fact that antibiotic drops were prescribed 2 days earlier can perhaps explain the negative culture, as this can interfere with microbiology testing. The other possibility but less likely would be a sterile inflammatory keratitis (maybe related to granuloma formations already known in other organs), which has not been described earlier in such patients. Regarding other possible systemic causes of granulomas, the patient has regular contact with infection clinic, and no other infections have been diagnosed.