Scope of Problem for Lymes Disease

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from http://www.tandfonline.com/doi/full/10.1586/14787210.2014.940900

The burden of Lyme disease for individuals and society remains high. Despite the availability of numerous preventative measures [21,22] Corapi KM, White MI, Phillips CB, et al. Strategies for primary and secondary prevention of Lyme disease. Nat Clin Pract Rheumatol 2007;3(1):20-5
Clark RP, Hu LT. Prevention of lyme disease and other tick-borne infections. Infect Dis Clin North Am 2008;22(3):381-96; vii 
, the incidence of acute Lyme disease is significant. The CDC currently estimates that the annual number of new cases of Lyme disease in the USA exceeds 300,000 [23] Reported cases of Lyme disease by year, United States, 1995-2009. Available from: www.cdc.gov/lyme/stats/chartstables/casesbyyear.html [Last accessed 1 March 2014] ; how these individual patients fare is an important consideration and ILADS is primarily interested in preventing and reducing the morbidity associated with chronic disease. Although some prospective studies found long-term outcomes were good, many had significant limitations [24–26] Vazquez M, Sparrow SS, Shapiro ED. Long-term neuropsychologic and health outcomes of children with facial nerve palsy attributable to Lyme disease. Pediatrics 2003;112(2):e93-7
Seltzer EG, Gerber MA, Cartter ML, et al. Long-term outcomes of persons with Lyme disease. JAMA 2000;283(5):609-16
Gerber MA, Zemel LS, Shapiro ED. Lyme arthritis in children: clinical epidemiology and long-term outcomes. Pediatrics 1998;102(4 Pt 1):905-8 
. There is substantial evidence of varying quality demonstrating that the severity [16–18,27–29] Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology 2008;70(13):992-1003
Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology 2003;60(12):1923-30
Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345(2):85-92
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 1994;121(8):560-7
Skogman BH, Glimaker K, Nordwall M, et al. Long-term clinical outcome after Lyme neuroborreliosis in childhood. Pediatrics 2012;130(2):262-9
Eikeland R, Mygland A, Herlofson K, Ljostad U. European neuroborreliosis: quality of life 30 months after treatment. Acta Neurol Scand 2011;124(5):349-54 
, duration [16,18,27,29,30] Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology 2008;70(13):992-1003
Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345(2):85-92
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 1994;121(8):560-7
Eikeland R, Mygland A, Herlofson K, Ljostad U. European neuroborreliosis: quality of life 30 months after treatment. Acta Neurol Scand 2011;124(5):349-54
Asch ES, Bujak DI, Weiss M, et al. Lyme disease: an infectious and postinfectious syndrome. J Rheumatol 1994;21(3):454-61 
and cost [15,31] Zhang X, Meltzer MI, Pena CA, et al. Economic impact of Lyme disease. Emerg Infect Dis 2006;12(4):653-60
Meltzer MI, Dennis DT, Orloski KA. The cost effectiveness of vaccinating against Lyme disease. Emerg Infect Dis 1999;5(3):321-8 
of persistent manifestations of Lyme disease can be profound. While the etiology of these manifestations is uncertain, their impact is clear. Two retrospective cohorts [27,30] 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 1994;121(8):560-7
Asch ES, Bujak DI, Weiss M, et al. Lyme disease: an infectious and postinfectious syndrome. J Rheumatol 1994;21(3):454-61 
, two case series [32,33] Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med 1990;323(21):1438-44
Logigian EL, Kaplan RF, Steere AC. Successful treatment of Lyme encephalopathy with intravenous ceftriaxone. J Infect Dis 1999;180(2):377-83 
, a meta-analysis [34] Cairns V, Godwin J. Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms. Int J Epidemiol 2005;34(6):1340-5[CrossRef], [PubMed], [Web of Science ®], [Google Scholar], two prospective European studies and four NIH-sponsored clinical trials [16–18] Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology 2008;70(13):992-1003
Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology 2003;60(12):1923-30
Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345(2):85-92 
describe significant long-term consequences of Lyme disease. Findings include:

  • Thirty-four percent of a population-based, retrospective cohort were ill an average of 6.2 years after antibiotic treatment [27] 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 1994;121(8):560-7[CrossRef], [PubMed], [Web of Science ®], [Google Scholar];

  • Sixty-two percent of a retrospective evaluation of 215 Lyme disease patients from Westchester County, NY, remained ill an average of 3.2 years after antibiotic treatment [30] Asch ES, Bujak DI, Weiss M, et al. Lyme disease: an infectious and postinfectious syndrome. J Rheumatol 1994;21(3):454-61[PubMed], [Web of Science ®], [Google Scholar];

  • A meta-analysis of 504 patients treated for Lyme disease found this group had more fatigue, musculoskeletal pain and neurocognitive difficulties than 530 controls [34] Cairns V, Godwin J. Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms. Int J Epidemiol 2005;34(6):1340-5[CrossRef], [PubMed], [Web of Science ®], [Google Scholar]. Additionally, it demonstrated that persistent Lyme disease symptoms were a distinct set of symptoms, which differed from those of fibromyalgia, chronic fatigue syndrome and depression [34] Cairns V, Godwin J. Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms. Int J Epidemiol 2005;34(6):1340-5[CrossRef], [PubMed], [Web of Science ®], [Google Scholar];

  • Among 23 European pediatric patients with objective findings of Lyme neuroborreliosis sequelae, daily activities or school performance were negatively impacted in 10 (43%) [28] Skogman BH, Glimaker K, Nordwall M, et al. Long-term clinical outcome after Lyme neuroborreliosis in childhood. Pediatrics 2012;130(2):262-9[CrossRef], [PubMed], [Web of Science ®], [Google Scholar];

  • A European study of adults treated for neuroborreliosis found that at 30 months post-treatment, 16% were cognitively impaired [29] Eikeland R, Mygland A, Herlofson K, Ljostad U. European neuroborreliosis: quality of life 30 months after treatment. Acta Neurol Scand 2011;124(5):349-54 [Google Scholar];

  • On entrance, patients enrolling in the four NIH-sponsored clinical trials on antibiotic retreatment had experienced poor long-term outcomes from their prior therapy. Participants in the two trials by Klempner et al. had persistent symptoms, which were sufficiently severe as to interfere with daily functioning [18] Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345(2):85-92[CrossRef], [PubMed], [Web of Science ®], [Google Scholar];

  • Using a combined total of 22 standardized measures of QoL, fatigue, pain and cognition [16–18] Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology 2008;70(13):992-1003
    Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology 2003;60(12):1923-30
    Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345(2):85-92 
    , the investigators of the four NIH-sponsored retreatment trials documented that the patients’ QoL was consistently worse than that of control populations [16–18] Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology 2008;70(13):992-1003
    Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology 2003;60(12):1923-30
    Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345(2):85-92 
    and equivalent to that of patients with congestive heart failure [18] Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345(2):85-92[CrossRef], [PubMed], [Web of Science ®], [Google Scholar]; pain levels were similar to those of post-surgical patients and fatigue was on par with that seen in multiple sclerosis [16,18] Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology 2008;70(13):992-1003
    Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345(2):85-92 
    . Table 1 compares the QoL scores of the NIH Lyme disease participants at the time of their study enrollment to those of patients with other chronic diseases, including diabetes, heart disease, depression, osteoarthritis, rheumatoid arthritis, lupus, fibromyalgia and epilepsy [35–40] Jones KD, Burckhardt CS, Deodhar AA, et al. A six-month randomized controlled trial of exercise and pyridostigmine in the treatment of fibromyalgia. Arthritis Rheum 2008;58(2):612-22
    Schaefer C, Chandran A, Hufstader M, et al. The comparative burden of mild, moderate and severe fibromyalgia: results from a cross-sectional survey in the United States. Health Qual Life Outcomes 2011;9(1):71
    Tang S, Calkins H, Petri M. Neurally mediated hypotension in systemic lupus erythematosus patients with fibromyalgia. Rheumatology 2004;43(5):609-14
    Ware JE, Kosinski M. SF-36 physical & mental health summary scores: a manual for users of version 1. 2nd edition; 1994. p. 1-238
    Calandre EP, Morillas-Arques P, Molina-Barea R, et al. Trazodone plus pregabalin combination in the treatment of fibromyalgia: a two-phase, 24-week, open-label uncontrolled study. BMC Musculoskelet Disord 2011;12:95
    Burckhardt CS, Jones KD. Effects of chronic widespread pain on the health status and quality of life of women after breast cancer surgery. Health Qual Life Outcomes 2005;3:30 
    .

Table 1. Long-term consequences (or impairments) of Lyme disease.