How to work up a patient with seizure disorder, left anterior uveitis, elevated IgG (Immunoglobulin G) toxoplasmosis levels, high normal S Ace (Serum Angiotensin-Converting Enzyme) levels, and bilateral parotidomegaly?

Workup of Anterior Uveitis with Elevated Toxoplasma IgG and Systemic Features

This patient requires immediate workup for sarcoidosis given the constellation of bilateral parotid enlargement, high-normal serum ACE, granulomatous anterior uveitis (mutton-fat KPs and Busacca nodules), and seizures—the elevated toxoplasma IgG with negative IgM indicates past infection, not active disease. 1, 2

Immediate Diagnostic Priorities

Sarcoidosis Evaluation (Primary Concern)

• Obtain chest X-ray or CT chest immediately to evaluate for hilar lymphadenopathy and pulmonary infiltrates, as these findings combined with bilateral parotid enlargement and granulomatous uveitis strongly suggest sarcoidosis 2, 3
• Measure serum ACE levels (already high-normal in this patient, which supports sarcoidosis) 3
• Consider tissue biopsy of accessible sites (parotid gland, conjunctiva if nodules present, or transbronchial if chest imaging abnormal) to confirm non-caseating granulomas 2
• Obtain serum calcium and 24-hour urinary calcium to assess for hypercalcemia/hypercalciuria associated with sarcoidosis 3

Rule Out Active Toxoplasmosis

• The positive IgG with negative IgM indicates past toxoplasma infection, not active disease 1, 4
• Anterior chamber paracentesis with PCR for Toxoplasma gondii should be considered if clinical suspicion for active ocular toxoplasmosis persists despite serologic findings suggesting past infection 4
• Note that IgM testing has limited utility given high false-positive rates and persistence for months to years after acute infection 4
• Lacrimal secretory IgA testing may help differentiate active from past infection if available, though this is not routinely performed 5

Neurologic Evaluation for Seizures

• Brain MRI with contrast to evaluate for neurosarcoidosis (leptomeningeal enhancement, white matter lesions, hypothalamic/pituitary involvement) or other structural causes of seizures 6, 7
• Lumbar puncture with CSF analysis including cell count, protein, glucose, ACE level, and Toxoplasma PCR if active CNS toxoplasmosis remains a consideration 6, 7
• EEG to characterize seizure activity and guide antiepileptic therapy 7

Additional Infectious Disease Workup

• Syphilis serology (RPR/VDRL and treponemal-specific test) as this is a routine investigation for granulomatous anterior uveitis 3
• Tuberculosis screening with interferon-gamma release assay (IGRA) or tuberculin skin test, as TB can mimic sarcoidosis 2
• HIV testing given the association with both toxoplasmosis and atypical presentations of uveitis 6

Clinical Reasoning

Why Sarcoidosis is the Leading Diagnosis

The combination of bilateral parotid enlargement, granulomatous anterior uveitis (mutton-fat KPs and Busacca nodules), high-normal ACE, and neurologic involvement (seizures) creates a highly specific pattern for sarcoidosis 2, 3. One case report specifically describes ocular sarcoidosis masked by positive toxoplasma serology, where the patient had bilateral eyelid edema, panuveitis, and increased lacrimal glands on imaging—ultimately responding to corticosteroids and methotrexate rather than anti-toxoplasma therapy 2.

Why Active Toxoplasmosis is Less Likely

• Toxoplasma typically causes posterior uveitis (chorioretinitis), not isolated anterior uveitis with granulomatous features 8, 1
• Positive IgG with negative IgM indicates past infection in the vast majority of cases 1, 4
• The clinical presentation lacks the characteristic focal necrotizing retinitis seen in ocular toxoplasmosis 8
• Seizures in toxoplasmosis typically occur with CNS lesions visible on imaging or in immunocompromised hosts 6, 7

Management Approach Pending Workup Results

If Sarcoidosis is Confirmed

• Topical corticosteroids for anterior uveitis management 6, 3
• Systemic corticosteroids (oral prednisone) for multisystem involvement including neurologic disease 2
• Consider steroid-sparing immunosuppression (methotrexate, azathioprine) for chronic disease requiring long-term control 2, 3
• Antiepileptic therapy for seizure management 7

If Active Toxoplasmosis is Confirmed (Less Likely)

• Pyrimethamine plus sulfadiazine plus folinic acid for 4-6 weeks would be indicated 8, 1
• Add corticosteroids only after 72 hours of antimicrobial therapy to avoid worsening infection 8, 1

Critical Pitfalls to Avoid

• Do not treat empirically for toxoplasmosis based solely on positive IgG serology—this represents past infection in most cases and the clinical picture strongly suggests sarcoidosis 2, 4
• Do not start corticosteroids before ruling out active infection if toxoplasmosis remains a diagnostic consideration 8
• Do not rely on serum IgM testing alone—it has poor specificity and can remain positive for months after acute infection 4
• Do not overlook neurosarcoidosis as a cause of seizures in patients with systemic sarcoidosis features 6, 2