There are three important clinical features of this patient’s presentation:
- uveitis associated with meningoencephalitis
- subacute cognitive decline
- clinical improvement after the administration of antimicrobial therapy
A unique feature of this patient’s presentation is his exposure to rituximab, a humanized chimeric anti-CD20 monoclonal antibody that causes B-cell depletion. The effects of rituximab should be considered when interpreting the results of IgG and IgM serologic tests. This concern is relevant to testing for West Nile virus infection and eastern equine encephalitis, both of which can cause neuroinvasive viral encephalitis and are endemic in the northeastern United States. The antibody response during these infections can be delayed or absent in patients with B-cell depletion.4,5 Such a response may also occur in Powassan virus infection, an emerging cause of viral meningoencephalitis in the United States that is transmitted by ticks.6
A key question remains: What pathogen can cause uveitis and meningoencephalitis and result in rapid clinical improvement after the administration of vancomycin, ampicillin, ceftriaxone, and acyclovir?
The authors point out that spirochete infections can cause uveitis and meningoencephalitis.
Due to the patient’s history of living in an endemic area for tick-borne diseases, is an avid hunter, whose condition improved dramatically after IV antibiotics, infection with borrelia species seemed a logical diagnosis.
The authors point out the problem with testing:
Testing for Lyme disease occurs as a part of a two-tiered algorithm and measures a person’s antibody response to the spirochete. Whether treatment with rituximab delays formation of antibodies in blood and CSF is unknown, thus complicating the interpretation of this patient’s serologic test results.
They further state that those with neurological Lyme infection often have abnormal imaging findings of the head or spine but that this patient had neither.
Then they state that B. miyamotoi, another borrelia species, causes a symptom complex that is consistent with this patient and that there are two case reports of meningoencephalitis in immunocompromised patients receiving rituximab, where B. miyamotoi was the causative agent. These patients received rituximab for hematologic cancers, and in both, Wright-Giemsa staining of CSF showed spirochetes, and a definitive diagnosis of B. miyamotoi infection was made based on nucleic acid testing of the blood.
The authors state the patient’s recurrent fever but lack of rash also support a B. miyamotoi infection, but that the opthalmologic findings do not. They admit; however, that there is limited understanding of B. miyamotoi but since other spirochetes can cause eye issues, B. miyamotoi is likely no different. ( I must add here that I know many Lyme disease patients who get recurrent fevers and have never seen a rash. This is a perfect example of how researchers and doctors have falsely pigeon-holed Lyme symptoms into a box of their own making). For more: https://madisonarealymesupportgroup.com/2019/02/22/why-mainstream-lyme-msids-research-remains-in-the-dark-ages/
Regarding testing, a lumbar puncture targeting the glpQ gene of borrelia that causes relapsing fever, which is absent in Lyme disease, was positive. Serum showed strong reactivity on the ELISA that detects IgG antibodies directed against the GlpQ protein of B. miyamotoi. Corresponding IgM ELISA was negative, consistent of B. miyamotoi infection of several months duration.
Unfortunately there are no randomized controlled trials and no formal treatment recommendations. Patients typically receive Lyme disease treatment. An in vitro study showed B. miyamotoi was susceptible to doxycycline, azithromycin, and ceftriaxone but not amoxicillin. (Again, I must add that current Lyme disease treatment advocated by the CDC/IDSA only works for a small percentage of patients and that studies from the beginning have shown treatment failures using their approach. For more: https://madisonarealymesupportgroup.com/2016/02/13/lyme-disease-treatment/)
The patient was sent home with 4 weeks of IV ceftriaxone but developed a facial rash and was switched to doxycycline. After 3 weeks all symptoms had resolved but the blurry vision which improved slowly over 3 months.
This patient should be followed up for years, but won’t be.
And the question begging to be asked is: how many people with B. miyamotoi are falling through the cracks? It isn’t even reportable to the CDC yet (which notoriously undercounts all things tick-borne-related).