The Stages And Symptoms of Lyme Disease

One of the difficulties with diagnosing Lyme Disease, is that the early symptoms of the illness, immediately following tick bite can be mild and easily overlooked, especially if you do not live in known areas where Lyme is common (which officially is all of Australia).

If you have travelled to known Lyme Disease endemic areas, such as the East Coast of the US, and you experience any of the following symptoms, seek medical treatment immediately and inform them of the location you travelled to. This will help the medical professional (usually a GP) diagnose Lyme Disease.

Early localized stage (3 to 30 days post-tick bite) (CDC)

The first symptom is usually an expanding “bull’s-eye” rash (called erythema migrans, EM, see Figure 2) which, in the US, is thought to occur in 70% to 90% of all LD cases (CDCAmerican Lyme Disease FoundationDandache et al. 2008). An EM rash generally has the following characteristics (American Lyme Disease Foundation):

  • Usually (but not always) radiates from the site of the tick bite – ticks will attach anywhere on the body, but prefer body creases such as the armpit, groin, back of the knee, and nape of the neck; rashes will therefore often appear in (but are not restricted to) these areas;

    Bullseye_Lyme_Disease_Rash

    Figure 2. A “Textbook Bull’s-Eye” Erythema Migrans Rash.

  • Appears either as a solid red expanding rash or blotch, OR a central spot surrounded by clear skin that is in turn ringed by an expanding red rash (looks like a bull’s-eye);
  • Appears an average of 1 to 2 weeks (range = 3 to 30 days) after disease transmission;
  • Has an average diameter of 13 to 15 cm, (range = 5 to 60 cm);
  • Persists for about 3 to 5 weeks;
  • May or may not be warm to the touch;
  • Is usually not painful or itchy.

Usually, about the time that the rash occurs (or would occur) other symptoms (flu-like symptoms) become apparent (CDC):

  • Fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes.

If you observe any of the above symptoms you should seek immediate medical treatment.

Early disseminated stage (days to weeks post-tick bite) (CDC)

As the LD spirochete bacteria continue to spread throughout the body a number of other symptoms can start to develop and may come and go (CDC and American Lyme Disease Foundation):

  • Additional EM rashes on other areas of the body;
  • Facial or Bell’s palsy (loss of muscle tone on one or both sides of the face);
  • Severe headaches and neck stiffness due to meningitis (inflammation of the spinal cord);
  • Pain and swelling in the large joints (such as knees)/tendons;
  • Tingling or numbness in extremities;
  • Multiple enlarged lymph glands;
  • Abnormal pulse;
  • Shooting pains that may interfere with sleep;
  • Heart palpitations and dizziness due to changes in heartbeat (Lyme carditis);
  • Sore throat;
  • Changes in vision;
  • Fver of 38 to 39 ºC;
  • Severe fatigue.

According to the CDC and Steere et al., 2004, many of these symptoms will resolve over a period of weeks to months, even without treatment. However, lack of treatment can result in additional, more debilitating, complications (see below). So again, seek medical treatment immediately if you have any of these symptoms.

Late disseminated stage (months to years post-tick bite) (CDC)

Later-stage Lyme Disease symptoms can be very debilitating. These may occur weeks, months or in some cases years after the initial tick bite. These can include severe headaches, painful arthritis and swelling of joints, cardiac abnormalities, and central nervous system (CNS) involvement leading to cognitive (mental) disorders (American Lyme Disease Foundation).

According to the CDC and Steere et al., 1987 approximately 60% of patients with an untreated infection may begin to have intermittent bouts of arthritis with severe joint pain and swelling. The larger joints are most often affected, especially the knees.

Approximately 5 % of untreated patients (Auwaerter, et al., 2004) go on to develop the more severe chronic neurological complaints months to years after infection (American Lyme Disease Foundation):

  • Disabling neurological disorders (disorientation; confusion; dizziness; short-term memory loss; inability to concentrate, finish sentences or follow conversations; mental “fog”);
  • Numbness in arms/hands or legs/feet.

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Websites And Links

Centers for Disease Control and Prevention (CDC) page on Lyme Disease

American Lyme Disease Foundation

Infectious Diseases Society of America

University of Sydney’s Tick Borne Diseases Unit

US National Institute of Health

US National Institute of Allergy and Infectious Diseases (Lyme Disease Page)

Books

Institute of Medicine (US) Committee on Lyme Disease and Other Tick-Borne Diseases: The State of the Science. Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases: The Short-Term and Long-Term Outcomes: Workshop Report. Washington (DC): National Academies Press (US); 2011. Available from: http://www.ncbi.nlm.nih.gov/books/NBK57020/

Lyme Disease: the Great Controversy Halperin, J.J., Baker, P., and Wormser, G.P. In, “Lyme Disease: An Evidence-based Approach”(American Lyme Disease Foundation) (Link to Chapter 17 pdf)

Wang, G. (2015). Chapter 104 – Borrelia burgdorferi and other Borrelia species, Molecular Medical Microbiology (Second Edition), Pages 1867–1909, Elsevier Ltd.

Radolf, J. D., et al. (2010). Lyme disease in humans, Caister Academic Press.

Journal Articles

Halperin, J. J. “Nervous system Lyme disease, chronic Lyme disease, and none of the above.” Acta Neurol Belg, 2016, 116(1): 1-6.

Lantos, P. M. “Chronic Lyme disease.” Infect Dis Clin North Am, 2015, 29(2): 325-340.

Aucott, J. N. “Posttreatment Lyme disease syndrome.” Infect Dis Clin North Am, 2015, 29(2): 309-323.

Mayne, P. J. “Clinical determinants of Lyme borreliosis, babesiosis, bartonellosis, anaplasmosis, and ehrlichiosis in an Australian cohort.” Int J Gen Med, 2015, 8: 15-26.

Gofton, A. W., et al. “Inhibition of the endosymbiont “Candidatus Midichloria mitochondrii” during 16S rRNA gene profiling reveals potential pathogens in Ixodes ticks from Australia.” Parasit Vectors, 2015, 8: 345.

Gofton, A. W., et al. “Bacterial profiling reveals novel “Ca. Neoehrlichia”, Ehrlichia, and Anaplasma species in Australian human-biting ticks.” PLoS One, 2015, 10(12): e0145449/0145441-e0145449/0145416.

Patrick, D. M., et al. “Lyme Disease Diagnosed by Alternative Methods: A Phenotype Similar to That of Chronic Fatigue Syndrome.” Clin Infect Dis, 2015.

Ostfeld, R. S. and J. L. Brunner. “Climate change and Ixodes tick-borne diseases of humans.” Philos Trans R Soc Lond B Biol Sci, 2015, 370(1665).

Aguero-Rosenfeld, M. E. and G. P. Wormser. “Lyme disease: diagnostic issues and controversies.” Expert Rev. Mol. Diagn., 2015, 15(1): 1-4.

Halperin, J. J. “Chronic Lyme disease: misconceptions and challenges for patient management.” Infect Drug Resist, 2015, 8: 119-128.

Borchers, A. T., et al. “Lyme disease: a rigorous review of diagnostic criteria and treatment.” J Autoimmun, 2015, 57: 82-115.

Mayne, P., et al. “Evidence for Ixodes holocyclus (Acarina: Ixodidae) as a Vector for Human Lyme Borreliosis Infection in Australia.” J Insect Sci, 2014, 14(1).

Lantos, P. M. and G. P. Wormser. “Chronic coinfections in patients diagnosed with chronic lyme disease: a systematic review.” Am J Med, 2014, 127(11): 1105-1110.

DeBiasi, R. L. “A concise critical analysis of serologic testing for the diagnosis of lyme disease.” Curr Infect Dis Rep, 2014, 16(12): 450.

Brissette, C. A. and R. A. Gaultney. “That’s my story, and I’m sticking to it–an update on B. burgdorferi adhesins.” Front Cell Infect Microbiol, 2014, 4: 41.

Groshong, A. M. and J. S. Blevins. “Insights into the biology of Borrelia burgdorferi gained through the application of molecular genetics.” Adv. Appl. Microbiol., 2014, 86: 41-143.

Lantos, P. M., et al. “A systematic review of Borrelia burgdorferi morphologic variants does not support a role in chronic Lyme disease.” Clin Infect Dis, 2014, 58(5): 663-671.

Pavia, C. S. and G. P. Wormser. “Culture of the entire mouse to determine whether cultivable Borrelia burgdorferi persists in infected mice treated with a five-day course of ceftriaxone.” Antimicrob. Agents Chemother., 2014, 58(11): 6701-6703, 6704 pp.

O’Day, D. H. and A. Catalano. “A lack of correlation between the incidence of lyme disease and deaths due to Alzheimer’s disease.” J Alzheimers Dis, 2014, 42(1): 115-118.

Strle, K., et al. “Elevated Levels of IL-23 in a Subset of Patients With Post-Lyme Disease Symptoms Following Erythema Migrans.” Clin. Infect. Dis., 2014, 58(3): 372-380.

Halperin, J. J., et al. “Common misconceptions about Lyme disease.” Am J Med, 2013, 126(3): 264.e261-267.

Klempner, M. S., et al. “Treatment trials for post-Lyme disease symptoms revisited.” Am J Med, 2013, 126(8): 665-669.

Kobayashi, Y., et al. “A novel macrolide solithromycin exerts superior anti-inflammatory effect via NF-κB inhibition.” J Pharmacol Exp Ther, 2013, 345(1): 76-84.

Ajamian, M., et al. “Serologic markers of lyme disease in children with autism.” JAMA, J. Am. Med. Assoc., 2013, 309(17): 1771-1772.

Burbelo, P. D., et al. “Lack of serum antibodies against Borrelia burgdorferi in children with autism.” Clin. Vaccine Immunol., 2013, 20(7): 1092-1093.

Krut, J. J., et al. “Cerebrospinal fluid Alzheimer’s biomarker profiles in CNS infections.” J. Neurol., 2013, 260(2): 620-626.

Barbour, A. “Remains of infection.J. Clin. Invest., 2012, 122(7): 2344-2346.

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Perronne, C. “Lyme disease antiscience.” Lancet Infect Dis, 2012, 12(5): 361-362; author reply 362-363.

Tuttle, C. “Lyme disease antiscience.” Lancet Infect Dis, 2012, 12(5): 362; author reply 362-363.

Auwaerter, P. G., et al. “Lyme disease antiscience – Authors’ reply.” Lancet Infect Dis, 2012, 12(5): 362-363.

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Chandra, A., et al. “Anti-Borrelia burgdorferi antibody profile in post-Lyme disease syndrome.” Clin. Vaccine Immunol., 2011, 18(5): 767-771.

Stricker, R. B. and L. Johnson. ““Lyme literacy” and physicians in Connecticut.” J Pediatr, 2011, 158(3): 518-519; author reply 519-520.

Lantos, P. M. “Chronic Lyme disease: the controversies and the science.” Expert Rev Anti Infect Ther, 2011, 9(7): 787-797.

Halperin, J. J. “Nervous system lyme disease: is there a controversy?” Semin Neurol, 2011, 31(3): 317-324.

Schutzer, S. E., et al. “Distinct cerebrospinal fluid proteomes differentiate Post-Treatment Lyme disease from Chronic Fatigue syndrome.” PLoS One, 2011, 6(2): e17287.

Kanjwal, K., et al. “Postural orthostatic tachycardia syndrome following Lyme disease.” Cardiol J, 2011, 18(1): 63-66.

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Johnson, M. and H. M. Feder, Jr. “Chronic Lyme disease: a survey of Connecticut primary care physicians.” J Pediatr, 2010, 157(6): 1025-1029.e1021-1022.

Holzbauer, S. M., et al. “Death due to community-associated Clostridium difficile in a woman receiving prolonged antibiotic therapy for suspected lyme disease.” Clin Infect Dis, 2010, 51(3): 369-370.

Feder, H. M., Jr. “Reply.” J Pediatr, 2010, 158(3): 519-520.

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Wormser, G. P. and E. D. Shapiro. “Implications of gender in chronic Lyme disease.” J Womens Health (Larchmt), 2009, 18(6): 831-834.

Wahlberg, P. and D. Nyman. “Chronic Lyme borreliosis–fact or fiction?” Duodecim, 2009, 125(12): 1269-1276.

Qureshi, M., et al. “Lyme disease serology in amyotrophic lateral sclerosis.” Muscle Nerve, 2009, 40(4): 626-628.

ALSUntangled update 1: investigating a bug (Lyme Disease) and a drug (Iplex) on behalf of people with ALS.” Amyotrophic Lateral Sclerosis, 2009, 10: 248-250.

Allan, E. J., et al. “Bacterial L-forms.” Adv. Appl. Microbiol., 2009, 68: 1-39.

Wormser, G. P. and I. Schwartz. “Antibiotic treatment of animals infected with Borrelia burgdorferi.” Clin. Microbiol. Rev., 2009, 22(3): 387-395.

Wormser, G. P., et al. “Impact of clinical variables on Borrelia burgdorferi-specific antibody seropositivity in acute-phase sera from patients in North America with culture-confirmed early lyme disease.” Clin. Vaccine Immunol., 2008, 15(10): 1519-1522.

Marques, A. “Chronic Lyme disease: a review.” Infect Dis Clin North Am, 2008, 22(2): 341-360, vii-viii.

Dandache, P. and R. B. Nadelman. “Erythema migrans.” Infect Dis Clin North Am, 2008, 22(2): 235-260, vi.

Steere, A. C., et al. “Prospective study of serologic tests for lyme disease.” Clin Infect Dis, 2008, 47(2): 188-195.

Fallon, B. A., et al. “A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy.” Neurology, 2008, 70(13, Pt. 1): 992-1003.

Hodzic, E., et al. “Persistence of Borrelia burgdorferi following antibiotic treatment in mice.” Antimicrob. Agents Chemother., 2008, 52(5): 1728-1736.

Wilske, B., et al. “Microbiological and serological diagnosis of Lyme borreliosis.” FEMS Immunol. Med. Microbiol., 2007, 49(1): 13-21.

Feder, H. M., Jr., et al. “A critical appraisal of “chronic Lyme disease”.” N. Engl. J. Med., 2007, 357(14): 1422-1430.

Auwaerter, P. G. “Point: antibiotic therapy is not the answer for patients with persisting symptoms attributable to lyme disease.” Clin. Infect. Dis., 2007, 45(2): 143-148.

Stricker, R. B. “Counterpoint: long-term antibiotic therapy improves persistent symptoms associated with lyme disease.” Clin. Infect. Dis., 2007, 45(2): 149-157.

Wormser, G. P. “Clinical practice. Early Lyme disease.” N Engl J Med, 2006, 354(26): 2794-2801.

Wormser, G. P., et al. “The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America.” Clin Infect Dis, 2006, 43(9): 1089-1134.

Steere, A. C. and S. M. Angelis. “Therapy for Lyme arthritis.” Arthritis Rheum., 2006, 54(10): 3079-3086.

Ivetic Tkalcevic, V., et al. “Anti-inflammatory activity of azithromycin attenuates the effects of lipopolysaccharide administration in mice.” Eur. J. Pharmacol., 2006, 539(1-2): 131-138.

Aguero-Rosenfeld, M. E., et al. “Diagnosis of Lyme borreliosis.” Clin. Microbiol. Rev., 2005, 18(3): 484-509.

Bratton, R. L. and R. Corey. “Tick-borne disease.” Am Fam Physician, 2005, 71(12): 2323-2330.

Rothstein, J. D., et al. “β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression.” Nature, 2005, 433(7021): 73-77.

Sanz, M.-J., et al. “Erythromycin exerts in vivo anti-inflammatory activity downregulating cell adhesion molecule expression.” Br J Pharmacol, 2005, 144(2): 190-201.

Cameron, D., et al. “Evidence-based guidelines for the management of Lyme disease.” Expert Rev Anti Infect Ther, 2004, 2(1 Suppl): S1-13.

Steere, A. C., et al. “The emergence of Lyme disease.” J. Clin. Invest., 2004, 113(8): 1093-1101.

Auwaerter, P. G., et al. “Lyme borreliosis (Lyme disease): molecular and cellular pathobiology and prospects for prevention, diagnosis and treatment.” Expert Rev Mol Med, 2004, 6(2): 1-22.

Domercq, M. and C. Matute. “Neuroprotection by tetracyclines.” Trends Pharmacol. Sci., 2004, 25(12): 609-612.

Tamaoki, J., et al. “Clinical implications of the immunomodulatory effects of macrolides.” Am. J. Med., 2004, 117(Suppl. 9A): 5S-11S.

Brownstein, J. S., et al. “A climate-based model predicts the spatial distribution of the Lyme disease vector Ixodes scapularis in the United States.” Environ Health Perspect, 2003, 111(9): 1152-1157

Krupp, L. B., et al. “Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial.” Neurology, 2003, 60(12): 1923-1930.

Kaplan, R. F., et al. “Cognitive function in post-treatment Lyme disease. Do additional antibiotics help?” Neurology, 2003, 60(12): 1916-1922.

Sood, S. K. “Effective retrieval of Lyme disease information on the Web.” Clin Infect Dis, 2002, 35(4): 451-464.

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Collignon, P. J. “11 Antibiotic resistance.” Med J Aust, 2002, 177(6): 325-329.

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Klempner, M. S., 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.

Wooten, R. M. and J. J. Weis. “Host-pathogen interactions promoting inflammatory Lyme arthritis: Use of mouse models for dissection of disease processes.” Curr. Opin. Microbiol., 2001, 4(3): 274-279.

Steere, A. C. “Lyme disease.” N Engl J Med, 2001, 345(2): 115-125.

Lindgren, E. and R. Gustafson. “Tick-borne encephalitis in Sweden and climate change.” The Lancet, 2001, 358(9275): 16-18.

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