A Review of Post-treatment Lyme Disease Syndrome and Chronic Lyme Disease for the Practicing Immunologist

Wong, Katelyn H; Shapiro, Eugene D.; Soffer, Gary

doi:10.1007/s12016-021-08906-w

Cited by 35 publications

(44 citation statements)

References 70 publications

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“…Accurate diagnosis of PTLDS is complicated by the employment of two-tier serological tests that detect antibodies against B. burgdorferi even after spirochetes are cleared. To some extent, posttreatment Lyme arthritis in individuals could be attributed to dysregulated immune responses due to both the slow release of spirochete peptidoglycan and triggered autoimmunity as indicated by detection of high levels of proinflammatory cytokines and chemokines in the synovial fluid of such patients ( 47 ). Therefore, the successful treatment of late Lyme disease could be facilitated by a combination of both antimicrobial and anti-inflammatory therapeutic approaches.…”

Section: Discussionmentioning

confidence: 99%

Sciatic–Vagal Nerve Stimulation by Electroacupuncture Alleviates Inflammatory Arthritis in Lyme Disease-Susceptible C3H Mice

et al. 2022

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Lyme disease is caused by Borrelia burgdorferi, and the pathogenesis of the disease is complex with both bacterial and host factors contributing to inflammatory responses. Lyme disease affects different organs including joints and results in arthritis. Immune responses stimulated by B. burgdorferi through toll-like receptors cause infiltration of leukocytes, which produce inflammatory cytokines and facilitate spirochete clearance. However, arthritic manifestations and chronic fatigue syndrome-like symptoms persist long after completion of antibiotic treatment regimens in a significant number of patients. To counter the effects of inflammation, treatment by non-steroidal anti-inflammatory drugs, hydroxychloroquine, or synovectomy to eradicate inflammatory arthritis in the involved joint could be employed; however, they often have long-term consequences. Acupuncture has been used for a long time in Asian medicine to diminish pain during various ailments, but the effects and its mechanism are just beginning to be explored. Control of inflammation by neuronal stimulation has been exploited as a systemic therapeutic intervention to arrest inflammatory processes. Our objective was to determine whether activation of the sciatic–vagal network by electroacupuncture on ST36 acupoint, which is used to control systemic inflammation in experimental models of infectious disorders such as endotoxemia, can also alleviate Lyme arthritis symptoms in mice. This aim was further strengthened by the reports that sciatic–vagal neuronal network stimulation can lead to dopamine production in the adrenal medulla and moderate the production of inflammatory factors. We first assessed whether electroacupuncture affects spirochete colonization to attenuate Lyme arthritis. Interestingly, bioluminescent B. burgdorferi burden detected by live imaging and qPCR were similar in electroacupuncture- and mock-treated mice, while electroacupuncture induced a lasting anti-inflammatory effect on mice. Despite the discontinuation of treatment at 2 weeks, the simultaneous decrease in neutrophils in the joints and inflammatory cytokine levels throughout the body at 4 weeks suggests a systemic and persistent effect of electroacupuncture that attenuates Lyme arthritis. Our results suggest that electroacupuncture-mediated anti-inflammatory responses could offer promising healthcare benefits in patients suffering from long-term Lyme disease manifestations.

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Section: Discussionmentioning

confidence: 99%

Sciatic–Vagal Nerve Stimulation by Electroacupuncture Alleviates Inflammatory Arthritis in Lyme Disease-Susceptible C3H Mice

et al. 2022

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“…Despite the discovery of Lyme disease over 40 years ago [ 9 ], the etiology of symptoms in chronic Lyme disease (CLD)/Post-Treatment Lyme Disease (PTLDS) is still a highly controversial topic [ 10 , 11 ]. The most frequent scientific hypotheses to explain persistent symptoms in CLD/PTLDS include immune evasion of Borrelia [ 12 ] with persistence of borrelial infection [ 13 , 14 , 15 ] or antigenic debris [ 16 ], persistent tick-borne co-infections including Babesia [ 17 ] and/or Bartonella [ 18 ], ongoing inappropriate immune activation and inflammation, or some combination of these [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Short-Term High Dose Pulsed Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-Infections: A Report of Three Cases and Literature Review

Horowitz¹,

Freeman²

2022

Antibiotics

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Lyme disease and associated co-infections are increasing worldwide and approximately 20% of individuals develop chronic Lyme disease (CLD)/Post-Treatment Lyme Disease Syndrome (PTLDS) despite early antibiotics. A seven- to eight-week protocol of double dose dapsone combination therapy (DDDCT) for CLD/PTLDS results in symptom remission in approximately 50% of patients for one year or longer, with published culture studies indicating higher doses of dapsone demonstrate efficacy against resistant biofilm forms of Borrelia burgdorferi. The purpose of this study was, therefore, to evaluate higher doses of dapsone in the treatment of resistant CLD/PTLDS and associated co-infections. A total of 25 patients with a history of Lyme and associated co-infections, most of whom had ongoing symptoms despite several courses of DDDCT, took one or more courses of high dose pulsed dapsone combination therapy (200 mg dapsone × 3–4 days and/or 200 mg BID × 4 days), depending on persistent symptoms. The majority of patients noticed sustained improvement in eight major Lyme symptoms, including fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating, where dapsone dosage, not just the treatment length, positively affected outcomes. High dose pulsed dapsone combination therapy may represent a novel therapeutic approach for the treatment of resistant CLD/PTLDS, and should be confirmed in randomized, controlled clinical trials.

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“…Investigation has identi ed overlapping symptom presentations of PASC with ME/CFS, PTLD and other post-infectious chronic in ammatory disorders [1][2][3] . However, clear etiological and pathophysiological differences exist in these conditions that necessitate precision medicine tailored therapies.…”

Section: Introductionmentioning

confidence: 99%

Cytokine Hub Classification of PASC, ME-CFS and other PASC-like Conditions

Patterson

Guevara-Coto

Francisco

et al. 2022

Preprint

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Background Post-acute sequelae of COVID-19 (PASC) is a growing healthcare and economic concern affecting as many as 10%-30% of those infected with COVID-19. Though the symptoms have been well-documented, they significantly overlap with other common chronic inflammatory conditions which could confound treatment and therapeutic trials. Methods A total of 236 patients including 64 with post-acute sequelae of COVID-19 (PASC), 50 with myalgic encephalomyelitis-chronic fatigue syndrome (ME-CFS), 29 with post-treatment Lyme disease (PTLD), and 42 post-vaccine individuals with PASC-like symptoms (POVIP) were enrolled in the study. We performed a 14-plex cytokine/chemokine panel previously described to generate raw data that was normalized and run in a decision tree model using a Classification and Regression Tree (CART) algorithm. The algorithm was used to classify these conditions in distinct groups despite their similar symptoms. Results PASC, ME-CSF, POVIP, and Acute COVID-19 disease categories were able to be classified by our cytokine hub based CART algorithm with an average F1 score of 0.61 and high specificity (94%). Conclusions Proper classification of these inflammatory conditions with very similar symptoms is critical for proper diagnosis and treatment.

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A Review of Post-treatment Lyme Disease Syndrome and Chronic Lyme Disease for the Practicing Immunologist

Cited by 35 publications

References 70 publications

Sciatic–Vagal Nerve Stimulation by Electroacupuncture Alleviates Inflammatory Arthritis in Lyme Disease-Susceptible C3H Mice

Sciatic–Vagal Nerve Stimulation by Electroacupuncture Alleviates Inflammatory Arthritis in Lyme Disease-Susceptible C3H Mice

Efficacy of Short-Term High Dose Pulsed Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-Infections: A Report of Three Cases and Literature Review

Cytokine Hub Classification of PASC, ME-CFS and other PASC-like Conditions

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