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Figure.
Computed Tomographic Scan of Chest (Case 3)
Computed Tomographic Scan of Chest (Case 3)

Non–small cell adenocarcinoma of the lung (arrowhead) that caused symptoms attributed to chronic Lyme disease.

Table.  
Test Results and Treatments Prescribed for Patients Misdiagnosed With Chronic Lyme Disease
Test Results and Treatments Prescribed for Patients Misdiagnosed With Chronic Lyme Disease
1.
Wormser  GP, Dattwyler  RJ, Shapiro  ED,  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.
PubMedArticle
2.
Feder  HM  Jr, Johnson  BJ, O’Connell  S,  et al; Ad Hoc International Lyme Disease Group.  A critical appraisal of “chronic Lyme disease” [published correction appears in N Engl J Med. 2008;358(10):1084]. N Engl J Med. 2007;357(14):1422-1430.
PubMedArticle
3.
Patel  R, Grogg  KL, Edwards  WD, Wright  AJ, Schwenk  NM.  Death from inappropriate therapy for Lyme disease. Clin Infect Dis. 2000;31(4):1107-1109.
PubMedArticle
4.
Holzbauer  SM, Kemperman  MM, Lynfield  R.  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.
PubMedArticle
5.
Steere  AC, Taylor  E, McHugh  GL, Logigian  EL.  The overdiagnosis of Lyme disease. JAMA. 1993;269(14):1812-1816.
PubMedArticle
Research Letter
January 2015

Neoplasms Misdiagnosed as “Chronic Lyme Disease”

Author Affiliations
  • 1Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado
  • 2Upstate Infectious Disease Associates, Albany, New York
JAMA Intern Med. 2015;175(1):132-133. doi:10.1001/jamainternmed.2014.5426

Clinical features of Lyme disease include erythema migrans rash, facial palsy, arthritis, and peripheral neuropathy. In endemic areas, patients with erythema migrans can be diagnosed clinically. Otherwise, diagnosis is based on the history of possible exposure, compatible clinical features, and positive 2-tier serologic testing.1

Chronic Lyme disease is a loosely defined diagnosis given by a small number of physicians—who are not usually infectious disease experts—to patients with various nonspecific symptoms, including patients with no objective evidence of Lyme disease.2 In addition to adverse outcomes from unconventional treatments for chronic Lyme disease,3,4 patients misdiagnosed with chronic Lyme disease may be harmed when their actual condition remains untreated.

We report 3 cases in which diagnosis of the patients’ actual conditions was delayed due to the misdiagnosis of chronic Lyme disease. Institutional review board approval was not obtained for this case series because it did not meet the regulatory definition of research and was outside the scope of institutional review board requirements. All 3 patients gave written informed consent to share their medical records for this case series.

Report of Cases
Case 1

A man in his late 30s presented with a 12-year history of joint pain and memory loss, as well as 2 years of paresthesias in both hands. A physician diagnosed him with chronic Lyme disease and prescribed oral tetracycline hydrochloride after a telephone consultation despite negative Lyme serologic test results. Following an in-person evaluation 2 months later, the physician initiated extended antibiotic treatment (Table). The patient’s symptoms gradually worsened, and he developed syncope and visual field deficit. Evaluation by a different physician revealed a 1.4 × 0.8-cm pituitary tumor and elevated insulin-like growth factor 1 (835 ng/mL [to convert to nanomoles per liter, multiply by 0.131]), consistent with acromegaly. Successive Lyme serologic test results were negative. Only a portion of the tumor could be removed; the patient has permanent facial changes, cardiomyopathy, joint pain, and obstructive sleep apnea.

Case 2

A man in his late 30s presented with a 4-year history of fatigue, abdominal pain, and loose stools. Previous evaluations demonstrated stable mesenteric lymphadenopathy. Although he lived in an area where Lyme disease is rare, reported no history of erythema migrans, and had negative Lyme serologic test results, he was diagnosed with chronic Lyme disease by a physician and treated with antibiotics (Table). Subsequently, the patient discontinued treatment and was reevaluated by a gastroenterologist and an oncologist. Findings from a gastric biopsy demonstrated stage IV mucosa-associated lymphoid tissue lymphoma; successive Lyme serologic test results were negative. Findings from a mesenteric lymph node biopsy and positron emission tomographic scan demonstrated stage IV classic Hodgkin lymphoma, for which the patient underwent chemotherapy. He died 2 years later of complications of advanced lymphoma.

Case 3

A man in his late 50s presented with a 2-week history of fatigue and a 3-day history of fever, headache, and myalgias. He had no known tick bite but worked outdoors in a Lyme disease–endemic area. Serum enzyme immunoassay results for Lyme disease were positive, and he was prescribed doxycycline. Shortly afterward, an expanding 18 × 15-cm erythematous rash appeared below his left shoulder. The rash resolved but malaise and fatigue recurred. Two additional doxycycline courses provided only transient improvement. Five months after his initial diagnosis, the patient was referred to an infectious disease specialist for presumed chronic Lyme disease.

The results of the physical examination and laboratory evaluation were normal except for a slightly elevated white blood cell count. Results of serologic testing for Lyme disease were consistent with previous infection (Table). The patient had a remote 18 pack-year history of smoking. The chest radiograph revealed a 1.1-cm nodular mass in the right upper lobe confirmed by computed tomographic scan (Figure). Further evaluation demonstrated stage I non–small cell adenocarcinoma, which was successfully resected.

Discussion

Patients 1 and 2 had no evidence of ever having Lyme disease. Patient 3 likely had true Borrelia burgdorferi infection for which antibiotic therapy was appropriate; however, subsequent symptoms were incorrectly attributed to persistent infection.

Chronic Lyme disease is a misleading term that should be avoided.2Posttreatment Lyme disease syndrome is the proper term for patients with a verified previous B burgdorferi infection who experience fatigue, arthralgias, or other symptoms 6 months or more after antibiotic treatment when all other conditions have been ruled out.1,2,5

We are not suggesting that every patient with nonspecific symptoms, such as fatigue, joint pain, or abdominal pain, should be aggressively evaluated for cancer. Rather, we present these cases to demonstrate delays in diagnosis that come from assuming that patients have chronic Lyme disease.

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Article Information

Corresponding Author: Christina Nelson, MD, MPH, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, 3156 Rampart Rd, Mail Stop P-02, Fort Collins, CO 80521 (wje1@cdc.gov).

Published Online: November 3, 2014. doi:10.1001/jamainternmed.2014.5426.

Author Contributions: Dr Nelson had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Nelson, Elmendorf.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Nelson, Elmendorf.

Critical revision of the manuscript for important intellectual content: All authors.

Administrative, technical, or material support: Nelson, Elmendorf.

Study supervision: Mead.

Conflict of Interest Disclosures: None reported.

Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Additional Contributions: We are extremely grateful to the patients for sharing their experiences. We also thank Denise Levitan, MD, and Richard Krumdieck, MD, for their helpful input. Neither Dr Levitan nor Dr Krumdieck received compensation.

References
1.
Wormser  GP, Dattwyler  RJ, Shapiro  ED,  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.
PubMedArticle
2.
Feder  HM  Jr, Johnson  BJ, O’Connell  S,  et al; Ad Hoc International Lyme Disease Group.  A critical appraisal of “chronic Lyme disease” [published correction appears in N Engl J Med. 2008;358(10):1084]. N Engl J Med. 2007;357(14):1422-1430.
PubMedArticle
3.
Patel  R, Grogg  KL, Edwards  WD, Wright  AJ, Schwenk  NM.  Death from inappropriate therapy for Lyme disease. Clin Infect Dis. 2000;31(4):1107-1109.
PubMedArticle
4.
Holzbauer  SM, Kemperman  MM, Lynfield  R.  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.
PubMedArticle
5.
Steere  AC, Taylor  E, McHugh  GL, Logigian  EL.  The overdiagnosis of Lyme disease. JAMA. 1993;269(14):1812-1816.
PubMedArticle
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