Page 119 - Human Lyme Neuroborreliosis

Treatment 103

progression and recovery. With the general recognition that early in the
disease process there is the potential for infectious-related toxic, metabolic,
and autoimmune manifestations that can contribute to disease progression and
clinical manifestations, the avenues for treatment can be conceptually
broadened. Steere and colleagues [20] called attention to concomitant immune
processes in infectious Lyme disease in the investigation of treatment-resistant
Lyme arthritis, a complication rarely noted in Europe. With only about 10% of
patients presenting with persistent joint inflammation for months to years after
standard courses of antibiotic treatment, Steere and colleagues [21] studied the
binding of OspA and human lymphocyte function-associated antigen 1 (hLFA-
1) peptides to 5 major MHC molecules noting the OspA (163-175) identified
the critical epitope in triggering antibiotic treatment-resistant Lyme arthritis.
The hypothesis of infection-induced autoimmunity [22] was based on T-cell
epitope mimicry between a spirochetal and host protein of bystander activation
of a T-cell response to a self-epitope unrelated to spirochetal proteins. Either
way, the T-cell response or linked antibody response to the self-protein could
stimulate persistent synovial inflammation. Only some MHC molecules bound
particular autoantigens accounting for the HLA association with autoimmune
diseases, which made it all the more important that most patients with
treatment-resistant Lyme arthritis were found to have HLA-DRB1*0401 or
HLA-DRB1*001 alleles, and to a lesser degree, the HLA-DRB1*0404 allele.
These three alleles, which have a similar sequence in the third hypervariable
region of the HLA-DRB1 chain were are also associated with increased
severity of adult rheumatoid arthritis. However, in a study of European Lyme
disease [23] there was no noted association among 283 patients between HLA
determinants and any of the various early or late infectious manifestations.
There is very limited information on post-infectious autoimmune syndromes
of the nervous system caused or mediated by the Lyme spirochete. However
early susceptibility and protracted involvement, combined with the presence of
serological markers of altered immunity in affected patients with LNB [24],
should lead to a consideration of appropriate oral or parenteral immune
modulatory immunotherapy to enhance recovery and treat autoimmune disease
manifestations.

Conclusion

LNB is amenable to treatment with oral and parenteral antibiotic in
uncomplicated patients, and combined with immune modulatory therapy for

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