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Vasculitis of the central nervous system is a rare complication of Lyme borreliosis.1 2 We now report a case of early onset borrelia associated encephalitis followed by systemic vasculitis. Antibiotics failed to improve the clinical course and remission was only reached after extensive immunosuppressive treatment.
A 52 year old man was admitted because of fever, headache, tinnitus, and painful joints. He reported a tick bite on his left arm, which had occurred three weeks earlier and which was followed by a reddish skin eruption. His general practitioner started treatment with doxycycline, but the patient's condition worsened. The patient had a fever of 39.9°C; further physical examination showed no other abnormalities. Except for an erythrocyte sedimentation rate of 51 mm/1st h and a leucocyte count of 16.1×109/l, routine blood analysis was normal. Cultures (blood, urine, stool) were negative. Enzyme linked immunosorbent assays (ELISAs) showed an increased anti-borrelia-IgM titre of 322.5 EU/ml (normal <30) with normal IgG levels, suggestive of early stage Lyme borreliosis. This was supported by western immunoblotting, with reactivity towards anti-borrelia-IgM.3 4 Intravenous ceftriaxone (2 g daily) was started. Because of signs of meningoencephalitis the patient was transferred to the intensive care unit (ICU). Analysis of the cerebrospinal fluid (CSF) showed anti-borrelia-IgM antibodies, pleocytosis, and an increased protein level, consistent with neuroborreliosis.5 An artificially increased IgM level in the CSF owing to the introduction of blood during the spinal tap was ruled out, because few erythrocytes were seen.
Shortly upon arrival at the ICU the patient was intubated and mechanically ventilated because of respiratory insufficiency due to muscle fatigue. Examination now disclosed numerous splinter haemorrhages distributed over the whole body. Ceftriaxone was continued for 10 days and then replaced by doxycycline. After 18 days antibiotic treatment was discontinued because of lack of improvement. Fever persisted and generalised epileptic seizures complicated the course. Cultures remained negative. An ELISA was repeated after four weeks: the anti-borrelia-IgM was then raised to 800 EU/ml; the IgG level was also above normal. The number of splinter haemorrhages increased and a non-oliguric renal insufficiency developed, resembling a glomerulonephritis with microscopic haematuria, granular casts, and proteinuria (0.9 g/24 h). Screening markers of autoimmune diseases (antineutrophil cytoplasmic antibodies, antinuclear antibodies, cryoglobulins) were negative. A skin-fascia-muscle biopsy sample taken from the right leg showed vasculitis of medium sized arteries (fig 1). No spirochaetes were detected in this sample. Treatment with prednisolone (1 mg/kg/day) did not improve the condition of the patient within one week, therefore, cyclophosphamide (2 mg/kg/day) was added. Within two days the patient regained normal neurological functions. Renal function improved within four weeks (serum creatinine decreasing from 249 to 130 μmol/l, blood urea nitrogen decreasing from 56.4 to 24.4 mmol/l of urea) and the patient was weaned from the ventilator. Follow up was uneventful.
Vasculitis may develop within weeks after infection and complicate the clinical course of Lyme borreliosis. To our knowledge, this is the first description of a systemic vasculitis including cerebral and renal disease after B burgdorferi infection in a human being. Histological proof for vasculitis was assessed in a skin-fascia-muscle sample; the absence of spirochaetes therein suggests an autoimmune based pathogenesis.2 6 As in this case, laboratory support for acute B burgdorferiinfection is an important issue, especially for endemic areas like the Netherlands.7 8 Whether elicited directly by the micro-organism or by secondary autoimmune mechanisms, vasculitis occurs in association with disseminated organ failure. Cyclophosphamide, successful in a case of B burgdorferiinduced cerebral vasculitis,9 was effective for this case of systemic vasculitis as well.
In conclusion, persisting vasculitic activity should be suspected whenever antibiotic treatment does not improve the clinical course in Lyme borreliosis. When borrelia associated vasculitis has been histologically established, and does not respond to corticosteroid treatment alone, we suggest the combined use of prednisolone and cyclophosphamide.
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