Case report: persistently seronegative neuroborreliosis in an immunocompromised patient

Abstract

BackgroundInfection with Borrelia burgdorferi sensu lato complex (B. b. sl) spirochetes can cause Lyme borreliosis, manifesting as localized infection (e.g. erythema migrans) or disseminated disease (e.g. Lyme neuroborreliosis). Generally, patients with disseminated Lyme borreliosis will produce an antibody response several weeks post-infection. So far, no case of neuroborreliosis has been described with persistently negative serology one month after infection.Case presentationWe present a patient with a history of Mantle cell lymphoma and treatment with R-CHOP (rituximab, doxorubicine, vincristine, cyclofosfamide, prednisone), with a meningo-encephalitis, who was treated for a suspected lymphoma relapse. However, no malignant cells or other signs of malignancy were found, and microbial tests did not reveal any clues, including Borrelia serology. He did not recall being bitten by ticks, and a Borrelia PCR on CSF was negative. After spontaneous improvement of symptoms, he was discharged without definite diagnosis. Several weeks later, he was readmitted with a relapse of symptoms of meningo-encephalitis. This time however, a Borrelia PCR on CSF was positive, confirmed by two independent laboratories, and the patient received ceftriaxone upon which he partially recovered. Interestingly, during the diagnostic process of this exceptionally difficult case, a variety of different serological assays for Borrelia antibodies remained negative. Only P41 (flagellin) IgG was detected by blot and the Liaison IgG became equivocal 2 months after initial testing.ConclusionsTo the best of our knowledge this is the first case of neuroborreliosis that is seronegative on repeated sera and multiple test modalities. This unique case demonstrates the difficulty to diagnose neuroborreliosis in severely immunocompromised patients. In this case, a delay in diagnosis was caused by broad differential diagnosis, an absent known history of tick bites, negative serology and the low sensitivity of PCR on CSF. Therefore, awareness of the diagnostic limitations to detect Borrelia infection in this specific patient category is warranted.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3273-8) contains supplementary material, which is available to authorized users.

Ceftriaxone and Doxycycline induced Seroconversion in Previously Seronegative Patient with Clinically Suspected Disseminated Lyme Disease: Case Report

“…In patients who do not develop EM, the diagnosis of Lyme disease is sometimes very difficult to make due to nonspecific symptoms and possible false negative laboratory test results [ 3 4 5 6 7 ], which was the case in the patient presented here. Patient's initial symptoms progressed over the time, and the patient underwent extensive diagnostic process ( Table 1 ), which didn't result with exact diagnosis.…”

“…The decision was based on studies which showed that CSF pleocytosis or other CSF abnormalities, including presence of anti- Borrelia antibodies, are not necessarily present in individuals with Lyme disease who have symptoms of central nervous system involvement, like headache, neck stiffness, memory or concentration problems [ 1 12 ]. Furthermore, only around 30% of patients with early localized, and around 60% of those with late disseminated Lyme disease, will show positive results for anti- Borrelia antibodies by two-step serological algorithm [ 4 5 6 7 ].…”

“…Considering that up to 50% of patients in the first and second stage of the disease are seronegative ( i.e. , negative IgM and IgG anti- Borrelia antibodies) [ 5 6 7 8 ], many authors believe that negative results on serologic tests should not exclude diagnosis of Lyme disease if it is clinically strongly supported.…”

Erythema Migrans: Course and Outcome in Patients Treated With Rituximab

“…These comprise individual case reports, and in all 4 cases CSF pleocytosis was present. The diagnosis of Lyme neuroborreliosis was based on demonstration of borrelial antibodies in CSF in 1 patient [3] and the presence of borrelial DNA in CSF in the other 3 patients, using polymerase chain reaction [1, 2, 4]. It is of interest that B. burgdorferi sensu lato antibodies in serum were not detected in any of these 4 patients.…”

Under-Detection of Lyme Disease in Canada

“…Failure of serological testing can result from a number of factors. Serology is not infallible and its reliability is influenced by time since infection, early antibiotic treatment, immunomodulatory and anti-inflammatory therapies, inhibition of class switching, a decline in the vigor of the IgG response over time, as well as other factors, all of which will influence first- and second-tier serology [94,95,96,97,98,99,100]. Additionally, there will be cases where neither patient nor physician considers Lyme disease as a diagnosis.…”