Trimethoprim-induced aseptic meningitis and uveitis

We wish to report a case of trimethoprim-related uveitis and aseptic meningitis confirmed by rechallenge. An 18-year-old woman presented with a recent history of recurrent urinary tract infections. The first infection, 5 months previously, was treated with a 7-day course of trimethoprim. She made an uneventful recovery. 2 months later a recurrent urinary tract infection was diagnosed and trimethoprim was again prescribed. Within hours of the first dose of trimethoprim, she described the onset of headache, red and sore eyes, and neck ache. She was reviewed in the emergency department and her therapy was changed to co-amoxyclav. She completed a 7-day course. Her eye pain endured for 2 weeks. A subsequent urinary tract infection, 1 month later, was again treated with co-amoxyclav and she made an uncomplicated recovery. 2 months later she presented to the emergency department with headache, fever, painful red eyes, and photophobia. Earlier in the day she had attended her local medical officer, with a recurrence of urinary tract symptoms. A clinical diagnosis of cystitis was made and she was prescribed trimethoprim. She took her first dose about 4 h before her hospital presentation. On examination, she appeared unwell but was orientated and responsive. Her temperature was 37·5oC. Neck stiffness and a positive Kernig’s sign were both elicited and slit-lamp examination of both eyes revealed white cells in the anterior chamber and a proteinaceous “flare”, consistent with a bilateral anterior uveitis. Small non-tender anterior and posterior cervical lymph nodes were palpable. Her large joints were tender on passive movement. Investigations revealed an ESR of 22, a normal full blood count, white cell count, electrolytes, urea, creatinine, and liver function tests. Urine microscopy showed 11 to 100 10 white cells. Urine cultures yielded a mixed growth. A high vaginal swab showed no growth. For Chlamydia trachomatis, direct fluorescence on a cervical swab and C trachomatis urinary PCR were negative. Cerebrospinal fluid (CSF) microscopy showed 1 red cell, 3 polymorphonuclear cells, and 2 monocytes 10/L. The CSF was sterile. The CSF protein was elevated at 0·66 g/L. Blood cultures were negative. Immunological studies showed a negative antinuclear antibody, and a normal rheumatoid factor. There was no history of previously diagnosed sexually transmitted diseases in either the patient or her sexual partner. She denied any recreational illicit drug use and only occasionally drank alcohol. She was a non-smoker. Her only regular medication was the oral contraceptive pill. In the absence of other infectious or autoimmune diagnoses, an adverse drug reaction to trimethoprim is most likely. Trimethoprim-induced aseptic meningitis has been described in previous case reports. The potential to produce this adverse effect has been shown to occur independently of the combination with sulphonamide drugs. Uveitis, by contrast, has been attributed to the systemic use of sulphonamide derivatives. Of interest, most of these cases were reported in people treated with co-trimoxazole, and none was re-challenged with trimethoprim alone to determine if this drug was capable of inducing uveitis. To our knowledge this is the first case report of trimethopriminduced uveitis. It is possible that this diagnosis is missed due to the frequent use of this drug in combination with sulphamethoxazole for which this particular adverse drug reaction has been well described.