Int

A 22-year-old Malay male who was previously well, presented to the eye casualty department with the complaint of blurring of vision of the right eye associated with redness, photophobia and mild pain for one week. He denied any joint pain, rashes, ulcers or hearing loss. On examination, the visual acuity of the right eye was counting finger 1 foot and for the left eye was 6/6. Near vision of the right eye was more than N48 and for the left eye was N6. Relative afferent pupillary defect was not present in both eyes. The right conjunctiva was diffusely injected and the right cornea showed fresh inferior keratic precipitates, occasional cells in the anterior chamber and anterior vitreous cells (figure 1). The left conjunctiva and cornea were clear. The Intraocular pressure (IOP) was 13 in both eyes. Fundoscopic examination of the right eye showed yellowish chorioretinal lesion located about 2-disc diameters from the optic disc involving the fovea with fluffy edges measuring about 1 disc diameter with overlying vitiritis. The optic disc appeared hyperaemic with normal cup disc ratio and there was evidence of vascular sheathing (figure 2). Left fundoscopy revealed old chorioretinal scar at superiotemporal arcade about 2-disc diameters in size and located about 1 disc diameter from the optic disc (figure 3). No retinitis seen around the scar. On general examination, he was afebrile with no lymphadenopathy.

Investigations revealed positive serology for toxoplasmosis IgG and toxoplasmosis IgM. RPR, VDRL, anti HIV 1, anti HIV 2 and Candida antibody were negative. The ESR was 26ml/hr. CXR was clear and the Mantoux test was negative. Other initial baseline investigations were within normal range.

Based on the appearance of the lesions in both eyes and the serological results, a diagnosis of right ocular toxoplasmosis was made. The presence of chorioretinal scars in the left eye suggests that patient had previous toxoplasmosis infection.

He was started on Oral Fansidar (pyrimethamine and sulfadoxine) one tablet twice daily, oral. Leucovorin 3mg three times a week, gutt Mydriacyl tds, gutt Betnesol qid. oral Prednisolone 40mg daily and oral Zantac 150mg bd were given 48 hours later.

The size of the lesion in the right eye and the vitritis improved after few days of medication (figure 4). However, in the second week of treatment, he developed maculo- papular erythematous rashes of the face, limbs and trunks associated with oral ulcers and bilateral conjunctivitis (figure 5). A diagnosis of Steven Johnson Syndrome was made and patient was admitted to the ward. Oral Fansidar was immediately stopped. The medication then was changed to oral Azithromycin 250mg bd, oral Prednisolone 30mg and oral chlopheniramine 4 mg tds.

He was admitted to High Dependency Ward for close observation. His condition worsens for a few days after admission, with spreading and increasing number of vesiculobullous lesion all over the body. There was no internal organ involvement noted. Regular eye checkup was done to detect the presence of ocular complications. Rodding was performed and intensive topical lubrication were given to prevent the formation of symblepharon..

His condition improved steadily over three weeks. Oral Azithromycin was stopped at the fourth week. He was discharged stable after four weeks of inpatient treatment. Oral Prednisolone was tailed down over a period of two months. His right eye vision improved to 6/60 and the near vision was N8.

DISCUSSION

Toxoplasmosis is an infection caused by the protozoan Toxoplasma gondii. It is the most common cause of intraocular inflammation world wide. It is a common belief in ophthalmology that the vast majority of cases of ocular toxoplasmosis were caused by congenital rather than a postnatal infection¹. It is now known that this assumption is not necessarily true and certainly not applicable in all populations. Observations by a family of ophthalmologists in southern Brazil clearly showed that the disease is acquired postnatally in that region². Recent serologic studies indicated that ocular toxoplasmosis was more commonly associated with acquired infection than previously believed¹. Although this patient could have been infected before, his IgM level suggested that this episode was a newly acquired infection rather than reactivation.

The aim of the treatment is to stop the multiplication of tachyzoites during active retinochoroiditis and to reduce inflammatory reaction. It has been shown that medical treatment failed to shorten the duration of inflammatory activity or to prevent recurrences. However, treatment did reduce the size of the ultimate chorioretinal scar³. There is lack of randomized controlled studies that definitively demonstrate the efficacy or superiority of any of the anti-toxoplasmic treatment regimens. Thus the choice of treatment is determined by the presence of contraindication in the patient, the availability of the medications, the patient’s tolerance to treatment and clinician’s preference and experience.

Although no consensus on the optimal drug combination or duration of drug therapy exists, a 4 to 6 week course of pyrimethamine, sulfadiazine and leucovorin is considered to be effective regimen⁴. Our patient was started with this regimen.

Corticosteroids are given in combination with antiparasitic drugs to reduce the inflammatory reaction during active chorioretinitis and to minimize tissue damage.

However the used of oral corticosteroids without antibiotic coverage may produce an immunodeficiency state that results in rapid spread of tachyzoites and wide spread of retinitis. They should never be used without antiparasitic coverage in the treatment of ocular toxoplasmosis⁵. Realizing all the abovementioned issues, our patient was started with oral Fansidar and oral Prednisolone. Although they are very effective, side effect of these medications can cause serious problems and consequences.

Fansidar is a combination of pyrimethamine and sulfadoxine (subgroup of sulfonamide). Pyrimethamine is a diaminopyrimidine that acts as a potent inhibitor of dihydrofolate reductase and is synergistic with sulfonamides. Sulfadiazine exerts bacteriostatic action through competitive antagonism with para-aminobenzoic acid (PABA). Side effects of Pyrimethamine include increase risk of bone marrow suppression. Sulfadiazine adverse effects include drugs hypersensitive syndrome (DHS) and renal crystallization⁶.

One of DHS spectrum is Steven Johnson Syndrome, which occurred in our patient. Reactions classically begin 1 to 8 weeks into drug therapy. The syndrome usually starts with fever, and over the next few days a cutaneous eruption develops, often accompanied by lymphadenopathy and pharyngitis^.The severity of cutaneous changes does not necessary reflect the severity of internal organ involvement. Our patient developed mucocutanoeus target and vesicobullous lesions, which correlates with Steven Johnson Syndrome. In this case, internal organ condition was monitored but not noted to be involved.

Replacement therapy for toxoplasmosis was not a clear-cut choice since most of anti-parasitic agents available are also associated with Steven Johnson Syndrome. Further more the therapy has to be effective to control infection, which was previously achieved by oral Fansidar in this patient. Oral Azithromycin was seen as a drug of choice for these reasons. Corticosteroids were maintained since it was relatively indicated in both toxoplasmosis and SJS.

Both conditions can results in visual impairment. SJS can be a life threathening condition and its ocular complications include conjunctivitis, ectropion or entropion, symblepharon, vascularization of the cornea, chronic dry eyes, and ankylosymblepharon. Proper management in dealing with both diseases is mandatory in order to prevent mortality and minimize the ocular complications.

It has been shown in this case that the challenging part in managing patient with both diseases is to balance out between prevention of fatal consequences and the need control to the infection and preserving vision. Decisions on medical treatment for both conditions will remain controversial till reliable prospective randomized control trials are done to address the issues.

Figure 1 Photo of anterior segment showing inferior distribution of whitish keratic precipitates

Figure 2 Fundus photograph of the left eye showing chorioretinal lesion on in macula region with hyperaemic disc and vascular sheathing

Figure 3 Fundus photograph of the right eye showing old chorioretinal scar at the superior arcade. No fresh lesion noted

Figure 4 Fundus photograph of the left eye showing reduction in the size of lesion with less vitritis

Figure 5 Photo showing macular papular erythematous rashes around the trunk

Case Report

DISCUSSION