Persisting Symptoms/”Post-Lyme Syndrome”

[itsybitsyone]

1: Neurology. 2003 Jun 24;60(12):1923-30.
Comment in: Neurology. 2003 Jun 24;60(12):1888-9.
Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial.
Krupp LB, Hyman LG, Grimson R, Coyle PK, Melville P, Ahnn S, Dattwyler R, Chandler B.
Department of Neurology, Stony Brook University Medical Center, Stony Brook, NY 11794-8121, USA. [e-mail]
OBJECTIVE: To determine whether post Lyme syndrome (PLS) is antibiotic responsive. METHODS: The authors conducted a single-center randomized double-masked placebo-controlled trial on 55 patients with Lyme disease with persistent severe fatigue at least 6 or more months after antibiotic therapy. Patients were randomly assigned to receive 28 days of IV ceftriaxone or placebo. The primary clinical outcomes were improvement in fatigue, defined by a change of 0.7 points or more on an 11-item fatigue questionnaire, and improvement in cognitive function (mental speed), defined by a change of 25% or more on a test of reaction time. The primary laboratory outcome was an experimental measure of CSF infection, outer surface protein A (OspA). Outcome data were collected at the 6-month visit. RESULTS: Patients assigned to ceftriaxone showed improvement in disabling fatigue compared to the placebo group (rate ratio, 3.5; 95% CI, 1.50 to 8.03; p = 0.001). No beneficial treatment effect was observed for cognitive function or the laboratory measure of persistent infection. Four patients, three of whom were on placebo, had adverse events associated with treatment, which required hospitalization. CONCLUSIONS: Ceftriaxone therapy in patients with PLS with severe fatigue was associated with an improvement in fatigue but not with cognitive function or an experimental laboratory measure of infection in this study. Because fatigue (a nonspecific symptom) was the only outcome that improved and because treatment was associated with adverse events, this study does not support the use of additional antibiotic therapy with parenteral ceftriaxone in post-treatment, persistently fatigued patients with PLS.


Arthritis Rheum. 2007 Nov 29;56(12):4216-4225
Antibody responses to Borrelia burgdorferi in patients with antibiotic-refractory, antibiotic-responsive, or non-antibiotic-treated lyme arthritis.
Kannian P, McHugh G, Johnson BJ, Bacon RM, Glickstein LJ, Steere AC.

Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts.

OBJECTIVE: To compare the pattern of antibody responses to Borrelia burgdorferi in patients with antibiotic-refractory, antibiotic-responsive, or non-antibiotic-treated Lyme arthritis as an indirect measure of spirochetal persistence or eradication.

METHODS: At least 3 serial serum samples from 41 patients with antibiotic-refractory arthritis and 23 patients with antibiotic-responsive arthritis, and samples from 10 non-antibiotic-treated, historical control patients were tested for IgG reactivity with B burgdorferi sonicate and 4 differentially expressed outer surface lipoproteins of the spirochete, by enzyme-linked immunosorbent assay.

RESULTS: Among non-antibiotic-treated patients, antibody titers to B burgdorferi antigens remained high throughout a 2-5-year period of arthritis. In contrast, in patients with antibiotic-responsive arthritis, in whom joint swelling usually resolved during a 1-month course of oral antibiotic therapy, the median antibody titers to most of the spirochetal antigens remained steady or decreased during the first 1-3 months after starting antibiotic therapy. In patients with antibiotic-refractory arthritis, who had persistent joint swelling for a median duration of 10 months despite 2-3 months of oral or intravenous antibiotics, the median titers to most antigens increased slightly during the first 1-3 months. However, by 4-6 months after starting antibiotic therapy, reactivity with all antigens declined similarly in both antibiotic-treated groups.

CONCLUSION: Whereas the antibody titers to B burgdorferi remained high in non-antibiotic-treated patients, the titers declined similarly 4-6 months after starting therapy in patients with antibiotic-responsive or antibiotic-refractory arthritis, suggesting that synovial inflammation persisted in patients with antibiotic-refractory arthritis after the period of infection.

[itsybitsyone]

Pol Merkur Lekarski. 2001 Jan;10(55):36-7.
Psychologic disorders in acute and persistent neuroborreliosis]
Article in Polish
Pop³awska R, Konarzewska B, Gudel-Trochimowicz I, Szulc A.
Klinika Chorób Psychicznych AM w Bia³ymstoku.
In the risk group, inhabiting endemic areas, even non-specific symptoms should alert the physician to the possibility of infection caused by the spirochete. The invasion of central nervous system (neuroborreliosis) may be the cause for persisting, irreversible intellectual impairment and memory deficits. Brain lesions are the result of misdiagnosis and delayed antibiotic treatment. This paper describes a case of neuroborreliosis with atypical beginning and diagnostic difficulties.

Petrovic M; Vogelaers D; Van Renterghern L;Carton D; et al.
1998
Lyme borreliosis – A review of the late stages and treatment of four cases.
Acta Clinica Belgica, 53(3):178-83.
A five-week treatment with doxycycline at a dose of 200 mg daily was prescribed. Fatigue, arthralgia en myalgia seemed to respond positively to
the initiated therapy. However, they reappeared two weeks after cessation of doxycycline. ...it was decided to treat with ceftriaxone IM 2 g daily for three weeks.
This resulted in a complete resolution of the general symptoms. However, three weeks later arthralgia of the knees and myalgia in both legs recurred. ...
Symptoms and signs may improve only temporarily shortly after treatment, but re-emerge within weeks or months.



Mol Immunol. 2008 Jan;45(1):180-9. Epub 2007 Jun 6.
Human homologues of a Borrelia T cell epitope associated with antibiotic-refractory Lyme arthritis.
Drouin EE, Glickstein L, Kwok WW, Nepom GT, Steere AC.
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. [e-mail]

Antibiotic-refractory Lyme arthritis, which may result from infection-induced autoimmunity, is associated with HLA-DR molecules that bind an epitope of Borrelia burgdorferi (Bb) outer-surface protein A (OspA(165-173)) and with T cell reactivity with this epitope.

One potential mechanism to explain these associations is molecular mimicry between OspA(165-173) and a self-peptide. Here, we searched the published human genome for peptides with sequence homology with OspA(165-173).

The two peptides identified with the greatest sequence homology with the OspA epitope were MAWD-BP(276-288), which had identity at eight of the nine core amino acid residues, and T-span7(58-70), which had identity at six residues.

MAWD-BP mRNA was expressed by synoviocytes, while T-span7 mRNA was not. However, neither peptide bound all of the HLA-DR molecules associated with antibiotic-refractory Lyme arthritis. Among 11 patients, 9 had T cell reactivity with OspA(161-170), 6 had responses to MAWD-BP(276-288), and 3 had reactivity with T-span7(58-70), but reactivity with the self-peptides was lower than that induced by the spirochetal epitope.

Thus, there remains an association between OspA(165-173) and antibiotic-refractory Lyme arthritis, and infection-induced autoimmunity is an attractive hypothesis to explain this outcome.

However, molecular mimicry due to sequence homology between OspA(165-173) and a human peptide seems unlikely to be the critical mechanism.