Lyme Disease: Diagnostic Challenge, Treatment Enigma
By Joan Unger, RN, MS, ARNP-C
Summary-Sixty percent of patients seen at the Yale University Lyme Disease Clinic had no evidence of current or previous infection, and 19% had previous but no active disease. Only 21% had active Lyme disease (LD). In spite of this number, 75% (94) had received a total of 232 courses of antibiotic treatment. Sixty-nine patients with no evidence of LD (55%) had at least one minor adverse drug reaction.
· LD is transmitted by tick bite and affects multiple body systems. It usually presents with a typical bull's-eye rash, often accompanied by flu-like symptoms.
· Serologic testing with ELISA commonly returns false-positive results, which must be confirmed with Western blot.
· Treatment consists of 10-21 days of antibiotic therapy with tetracycline, doxicycline, or ampicillin.
· Advanced practice nurses play a critical role in educating patients about prevention of tick bites.
(Editor's note: In this first of a two-part series on Lyme disease, we discuss prevalence, diagnosis, and treatment. In next month's issue, we'll outline results of two large multicenter trials of a promising Lyme disease vaccine.)
Tick bite. Lyme disease. The words evoke an image of fatal or chronic illness accompanied by devastating neurologic, cardiologic, or myalgic disability for life. More than 103,000 cases of Lyme disease (LD) were reported from 1982-1997.1 We cannot know how many were misdiagnosed as a result of false-positive serology or the total cost of treating LD that was in fact not LD.
A study reported by Reid, Schoen, and Evans, et al of the Yale University School of Medicine found 60% of patients seen at the Yale University Lyme Disease Clinic had no evidence of current or previous infection, and 19% had previous but no active disease.2 Only 21% had active LD .
"In general, patients with active Lyme disease (who were not the focus of this study) had good outcomes," the authors said. Patients with previous or no evidence of LD used considerable health resources, including office visits, serologic tests, and antibiotic treatment. They reported significant disability, during which normal activities could not be carried out. Patients acknowledged a high rate of stress (52% of those with previous LD and 45% of those with no evidence of LD) as well as depression (38% of those with previous LD and 42% of those with no evidence of LD).
Reid et al reported that of 209 study patients, 125 lacked evidence of current or previous infection. In spite of this, 94 (75%) of the 125 had previously received a total of 232 courses of antibiotic treatment. Thirty-nine (31%) had received antibiotics for more than 100 days, and 28 (22%) had received parenteral therapy.
Of those who received antibiotics, 69 (55%) of the patients with no evidence of current or previous LD had at least one minor adverse drug reaction, including gastrointestinal irritation, diarrhea, or yeast infection. Seven patients (6%), all of whom had received parenteral therapy, suffered major adverse events, including antibiotic associated colitis, neutropenia, serum sickness, or septic thrombophlebitis.
Is Fear Driving Treatment Decisions?
How could this happen? Why were there so many inappropriate diagnoses and treatments? Could fear of Lyme disease be the real culprit? LD is caused by a tick-borne spirochete, Borrelia burgdorferi, and affects multiple body systems. Diagnosis can be difficult because many symptoms mimic other illnesses. LD has a characteristic rash with a bull's-eye appearance called erythema migrans, which occurs in 86-100% of persons with symptomatic LD, between one and 30 days (median: seven days) after a bite by an infected tick. This rash may be accompanied by flu-like symptoms. After several months, if untreated, the disease may progress to arthritic and neurological symptoms.
The LD microbe is difficult to isolate or culture from body tissues or fluids. In the early weeks following infection, antibody tests are not reliable because the patient's immune system has not produced enough antibodies to be detected. But antibiotics given early during infection may prevent antibodies from reaching detectable levels, even if the LD bacterium is causing the patient's symptoms.
Some Tests Are Unreliable
Because some tests are poorly standardized or cannot distinguish between LD antibodies and antibodies from similar organisms, false-positive results are common. These generate considerable anxiety for the patient and place the health care provider in a difficult position.
The cost in terms of suffering and anxiety as well as dollars and cents is staggering. Fix, Strickland of the University of Maryland School of Medicine, and Grant of the Kent Country Health Department in Chestertown, MD, investigated this aspect of LD.3 They identified 142 subjects diagnosed with tick bites, 40 with LD, and 50 with suspected LD.
Of the tick-bite patients, 95 (67%) had serologic testing and 93 (66%) had initial negative or equivocal results. Twenty-four (26%) of the 93 had follow-up testing with one seroconversion. Seventy-eight tick-bite patients (55%) received antibiotics. None developed clinical LD.
Direct charges for diagnosing and treating the 232 patients totaled $47,595. One-third of the cost was for serologic testing. The researchers concluded that "Most patients with tick bites are undergoing costly serologic testing of no benefit, and the majority are receiving prophylactic antibiotic therapy . . . of unproven benefit." They found serologic testing did not appear to influence the treatment of patients actually diagnosed with LD.
Implications for Practice
Anticipatory education and counseling of patients regarding management of tick bites need to be a priority, especially in areas where LD is endemic. (See patient education handout, enclosed in this issue.) Both barrier and chemical protection from tick bites should be stressed. (See box, above left.)
Clinicians need to become skilled in recognition and management of LD, especially in highly endemic areas of the United States such as Minnesota, Wisconsin, New York, Massachusetts, Rhode Island, Connecticut, New Jersey, and Maryland.4 It is equally important to recognize what is not LD and test and treat appropriately. (See table, p. 18.)
Serological tests include enzyme-linked immunoabsorbent assay (ELISA), which is poorly standardized and commonly returns false-positives, according to The Washington Manual of Medical Therapeutics, 29th Edition (Lippincott-Raven Publishers, Philadelphia). Positive ELISA must be confirmed by Western blot. When ordering serological tests to diagnose LD, remember that early antibiotic treatment may inhibit antibody response.
Treatment options for early LD, isolated seventh nerve palsy, and first-degree atriventricular (AV) block include:
· tetracycline, 250 mg PO qid for 10-21 days;
· doxicycline, 100 mg PO bid for 10-21 days;
· amoxicillin, 500 mg PO tid for 10-21 days with or without probenecid 500 mg PO tid.
Ten-day therapy is usually reserved for isolated erythema migrans. A regimen for early disseminated and chronic LD is not established but might include PO doxycycline, IV penicillin-G, or IV ceftriaxone. Parenteral therapy is recommended for high-grade AV block.5
References
1. Centers for Disease Control and Prevention. Fact sheet: Lyme disease. 1998; Atlanta.
2. Reid MC, Schoen RT, Evans J, et al. The consequences of overdiagnosis and overtreatment of Lyme disease: An observational study. Ann Int Med 1998;128: 354-362.
3. Fix AD, Strickland GT, Grant J. Tick bites and Lyme disease in an endemic setting. JAMA 1998;279: 206-210.
4. Verdon ME, Sigal LH. Recognition and manage- ment of Lyme disease. Am Fam Phys 1997;56: 427-440.
5. Carey CF, Lee HH, Woeltje KF. The Washington Manual of Medical Therapeutics, 29th Edition. Philadelphia, Lippincott-Raven Publishers. 1998; 284.
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