. 2019 Jul; 6(7): ofz292.
Published online 2019 Jun 19. doi: 10.1093/ofid/ofz292
PMCID: PMC6634433
PMID: 31334301

Erythema Migrans: Course and Outcome in Patients Treated With Rituximab



Information on Lyme borreliosis (LB) in patients treated with rituximab is limited to individual case reports.


We reviewed data on adult patients diagnosed with typical erythema migrans (EM) at the LB outpatient clinic of the University Medical Center Ljubljana, Slovenia, in the 10-year period 2008–2017. For all patients, clinical and laboratory information was acquired prospectively using a standardized questionnaire.


Among 4230 adult patients with a diagnosis of EM, 7 patients (0.17%), 5 women and 2 men with a median age of 65 years (range, 55–66 years), were receiving rituximab for an underlying medical condition. In these 7 patients, signs of disseminated LB (43%) and the isolation rates of borreliae from blood before antibiotic treatment (40%) were unusually high compared with corresponding findings in immunocompetent patients who had EM diagnosed at the same institution (8% vs <2%, respectively). The rates of LB-associated constitutional symptoms and borrelial antibodies in serum were lower than expected (14% and 29%, respectively, in patients receiving rituximab vs 25% and 65% in immunocompetent patients). One of the 7 patients (14%) experienced treatment failure; nevertheless, the outcome of early LB 1 year after antibiotic treatment, as used for immunocompetent patients with EM, was excellent in all 7 patients.


Findings in 7 patients with EM who were receiving rituximab for underlying disease suggest that although early LB in these patients is more often disseminated than in immunocompetent patients, the outcome 1 year after antibiotic treatment, as used for immunocompetent patients, is excellent.



There should be followed up done on these patients. A one year outcome, if you understand Lyme disease at all, is a short period of time.

Rituximab, a cancer medicine that interferes with the growth and spread of cancer cells, is used alone or in combination with other medicines to treat the following conditions in adults:

Rituximab may cause a serious brain infection that can lead to disability or death, as well as severe skin problems. You are supposed to tell your doctor if you have any of the following before using the drug:

  • liver disease or hepatitis (or if you are a carrier of hepatitis B)
  • kidney disease
  • lung disease or a breathing disorder
  • a weak immune system (caused by disease or by using certain medicines)
  • an active infection, including herpes, shingles, cytomegalovirus, chickenpox, parvovirus, West Nile virus, or hepatitis B or C
  • heart disease, angina (chest pain), or heart rhythm disorder
  • if you have used rituximab in the past
  • pregnancy – it can harm the unborn baby

According to this, Rituximab suppresses the immune system:

Biological drugs are becoming more popular as a treatment for rheumatoid arthritis (RA). Rituximab is one such drug that works by blocking the activity of immune cells. This then reduces the high level of inflammation seen in the joints of RA patients. Longer courses of treatment are needed for rituximab to be completely effective.

This prolonged treatment can weaken a patient’s immune response and can lead to a condition called hypogammaglobulinemia. This is an immune disorder where the body’s antibody levels are severely reduced, which increases the risk of serious infections.

LLMD’s typically do not recommend immune suppressants for Lyme/MSIDS patients unless they are on antibiotics in tandem. This research study shows why – those in Rituximab had more disseminated Lyme and more borrelia isolated from the blood.  By suppressing the immune system the infection has a greater ability to take over. The fact they had fewer constitutional symptoms and borrelia antibodies in serum means little.  Given time, this could change in a heart-beat. I suspect there were more treatment failures if they followed up on these patients up over years of time.

Patients in the study with solitary EM were prescribed oral antibiotics:

  • doxycycline (100 mg twice daily for 14 days)
  • cefuroxime axetil (500 mg twice daily for 15 days)
  • azithromycin (500 mg twice daily on the first day followed by 500 mg once daily for 4 subsequent days)
  • patients with multiple EM were treated with ceftriaxone (2 g once daily intravenously for 14 days)

For this study, treatment failure was defined as

  1. the occurrence of objective extracutaneous manifestations of LB within 1 year after the start of antibiotic treatment
  2. the appearance/persistence of subjective symptoms or their increased intensity (at the 1-year follow-up visit) that could not be attributed to other causes
  3. persistence of a skin lesion (ie, still visible EM) at a follow-up visit 2–3 months after commencement of treatment
  4. demonstration of borreliae by skin culture at the site of previous EM 2–3 months after the start of treatment (only patients with isolation of borreliae from skin before antibiotic treatment underwent repeated biopsy)

Patients with treatment failure were treated again with an alternative antibiotic.

By looking at the drugs listed, we can see right away that doxy has been shown to throw the spirochete into the non-cell wall form to reemerge later:

The emphasis on external lesions is a mistake. Research has shown that antibiotics clear the EM but won’t clear a systemic infection:

And something must be said about antibiotic levels as well.  In this timely video, Dr. Burrascano explains how some patients need higher drug levels to kill pathogens:

A one sized approach for Lyme/MSIDS is another mistake.

Sadly, the authors conclude that after one year everyone’s dandy, when nothing could be further from the truth.






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