As many as one-third of patients with Lyme disease are ill on long-term follow-up. A population-based, retrospective cohort study in Massachusetts found that 34% of patients suffered from arthritis or recurrent arthralgias, neurocognitive impairment, and neuropathy or myelopathy an average of six years after treatment for Lyme disease. [1] These limits on antibiotics for Lyme disease leave many patients and physicians navigating uncertainty when symptoms persist.

Meanwhile, 62% of a cohort of 215 consecutively treated Lyme disease patients in Westchester County, New York were found to have arthralgias, arthritis, and cardiac or neurologic involvement with or without fatigue an average of 3.2 years after treatment. [2]

These patients suffer from a broad range of complications. Logigian and colleagues noted, “Twenty-four of 27 chronic Lyme disease patients presented with a mild encephalopathy that began 1 month to 14 years after the onset of the disease and was characterized by memory loss, mood changes, and sleep disturbances.” The symptoms also included fatigue, headaches, depression, irritability, and difficulty finding words.

Other complications include Lyme encephalopathy [3,4] diffuse axonal peripheral neuropathy, [5,6] post-Lyme syndrome, [7] [8] and postural orthostatic tachycardia syndrome (POTS), [8] and Post-treatment Lyme Disease Syndrome (PTLDS). [9]

Signs of Lyme disease may disappear immediately following treatment but re-emerge months later. [9]

The complication, however, may not be apparent at the end of the initial course of treatment. Aucott described post-treatment symptomatology and functional impact of PTLDS over time. “Signs of Lyme disease disappeared post-treatment; however, new-onset patient-reported symptoms increased or plateaued over time,” Aucott and colleagues noted. “At 6 months, 36% of patients reported new-onset fatigue, 20% widespread pain, and 45% neurocognitive difficulties.” [9]

There is evidence that Lyme disease is more complex than when first described.  For example, “Borrelia uses the immunoprivileged site produced by tick saliva to facilitate its transmission,” according to Bernard and colleagues in the latest issue of Experimental Dermatology.[10] Wormser et al. reported that the particular genotype of Bb “predicts the capacity for hematogenous dissemination during early Lyme disease.”[11]

Coinfection with Babesia can increase the severity and duration of Lyme disease. [12] Diuk-Wasser from Columbia University reported “Epidemiologic studies have documented that up to 40% of patients with Lyme disease experience concurrent Babesiosis.” [13]

There are doctors who limit treatment to 14 to 28 days and those who do not. In a recent All Things Lyme blog, a study by Tseng and colleagues based on insurance claims data concluded that the use of extended courses of antibiotics and multiple antibiotics in the treatment of Lyme disease has increased in recent years. This trend reflects how limits on antibiotics for Lyme disease influence real-world clinical decision-making when patients fail to improve. [14]

According to the review, 18% of Lyme disease patients were treated for more than 5 weeks (defined as extended therapy by the authors). The actual length of time patients were prescribed antibiotics was much longer with an average of 86 days. Treatment duration ranged from 35 to 404 days.

Two medical societies offer guidelines for the treatment of Lyme disease — the Infectious Diseases Society of America (IDSA) and the International Lyme and Associated Diseases Society (ILADS). Yet doctors remain in limbo as discussions between the two societies stall, leaving physicians uncertain about how best to care for patients with persistent symptoms. These limits on antibiotics for Lyme disease leave many patients and clinicians navigating uncertainty when symptoms do not resolve as expected.

References:

1. Asch ES, Bujak DI, Weiss M, Peterson MG, Weinstein A. Lyme disease: an infectious and post-infectious syndrome. J Rheumatol, 21(3), 454-461 (1994).
2. Shadick NA, Phillips CB, Logigian EL et al. The long-term clinical outcomes of Lyme disease. A population-based retrospective cohort study. Ann Intern Med, 121(8), 560-567 (1994).
3. Logigian EL, Kaplan RF, Steere AC. Successful treatment of Lyme encephalopathy with intravenous ceftriaxone. J Infect Dis, 180(2), 377-383 (1999).
4. Fallon BA, Keilp JG, Corbera KM et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology, 70(13), 992-1003 (2008).
5. Halperin JJ. Neuroborreliosis: central nervous system involvement. Semin Neurol, 17(1), 19-24 (1997).
6. Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med, 323(21), 1438-1444 (1990).
7. Krupp LB, Hyman LG, Grimson R et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology, 60(12), 1923-1930 (2003).
8. Kanjwal K, Karabin B, Kanjwal Y, Grubb BP. Postural orthostatic tachycardia syndrome following Lyme disease. Cardiol J, 18(1), 63-66 (2011).
9. Aucott JN, Rebman AW, Crowder LA, Kortte KB. Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here? Qual Life Res, 22(1), 75-84 (2013).
10. Bernard Q, Gallo RL, Jaulhac B et al. Ixodes tick saliva suppresses the keratinocyte cytokine response to TLR2/TLR3 ligands during early exposure to Lyme borreliosis. Exp Dermatol, 25(1), 26-31 (2016).
11. Wormser GP, Brisson D, Liveris D et al. Borrelia burgdorferi genotype predicts the capacity for hematogenous dissemination during early Lyme disease. J Infect Dis, 198(9), 1358-1364 (2008).
12. Krause PJ, Telford SR, 3rd, Spielman A et al. Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. Jama, 275(21), 1657-1660 (1996).
13. Diuk-Wasser MA, Vannier E, Krause PJ. Coinfection by Ixodes Tick-Borne Pathogens: Ecological, Epidemiological, and Clinical Consequences. Trends Parasitol, (2015).
14. Tseng YJ, Cami A, Goldmann DA, DeMaria A, Jr., Mandl KD. Incidence and Patterns of Extended-Course Antibiotic Therapy in Patients Evaluated for Lyme Disease. Clin Infect Dis, (2015).