Lyme disease: impact of the CDC surveillance criteria on patients

Townsend Letter for Doctors and Patients, June, 2004 by Marcus A. Cohen

My first Townsend column about Lyme disease (April 2004) opened with a startling fact: this tick-transmitted infection is the most prevalent vector-borne disease in the US. According to recent CDC statistics, Lyme cases constitute 95% of all reports for such diseases. (1) The remaining 5% includes the mosquito-transmitted West Nile Virus, sensationally publicized but by no measure affecting as many Americans as Lyme.

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That earlier Townsend column pointed to the narrowly-defined surveillance criteria for reporting cases issued by the Center for Disease Control and Prevention (CDC) as a significant reason for uncertainty over the incidence of Lyme.

This column reviews the CDC criteria, differentiates them from authoritative guidelines generally available for diagnosing Lyme, and spotlights the inadequacies and inherent problems in the two main serologic tests required by the CDC. It then describes how misuse of the CDC surveillance criteria has had an adverse impact on diagnosing and treating Lyme, and on the prevalence of persistent or recurrent cases.

CDC Surveillance Criteria

For Lyme Disease the CDC definition calls for a physician-diagnosed erythema migrans (EM) rash, a slightly flat or raised reddish lesion, or a positive antibody test together with one major system involvement. The EM lesion, which in less than half of all cases appears at the site of the tick bite shortly after infection and then spreads in the shape of a "bull's eye," is widely considered in itself pathognomonic for Lyme.

In patients with no EM who require serologic testing, the CDC calls for an Enzyme-Linked Immunosorbent Assay (ELISA). The ELISA indirectly detects antibodies in the patient's serum that react to antigens (proteins) present in the Lyme pathogen: such antibodies indicate exposure to the pathogen. Under the CDC surveillance criteria for Lyme, a negative ELISA is cause for rejection of a case report. If the ELISA is positive or equivocal, the CDC next requires Western blot tests for more definite evidence. The National Institute of Allergy and Infectious Disease (NIAID) regards this test as the most helpful in confirming exposure to Lyme.

Western blot tests (or immunoblot tests) look at antibodies directed against a broad range of antigens present in the Lyme pathogen. In a patient having antibodies to a particular antigen, a "band" will form at a certain place on the immunoblot. By reading the "band" patterns formed by the spectrum of antibodies to the Lyme pathogen, labs doing Western blots can determine with greater specificity than ELISAs do whether a patient's immune response is specific for Lyme infection.

Major Diagnostic Guidelines

Practice guidelines developed by the NIH and the Infectious Disease Society of America (IDSA) advise physicians suspecting Lyme disease to make a clinical diagnosis. A clinical diagnosis in Lyme should be based either on a history of exposure in an area endemic for Lyme-transmitting ticks and identification by a physician of the EM lesion (in the early stage of disease), or recognition by physicians of characteristic clinical signs and confirmation by lab findings.

Note: The CDC, in its own public statements, has advised that it has not issued guidelines for diagnosis of Lyme; the CDC guidelines concern only surveillance. A CDC representative made the distinctions clear at a hearing in Connecticut in 2004:

"Surveillance case definitions are created for the purpose of standardization, not patient care.... Whereas physicians appropriately err on the side of over-diagnosis, thereby assuring they don't miss a case, surveillance case definitions appropriately err on the side of specificity, thereby assuring that they do not inadvertently capture illnesses due to other conditions." (2)

Absence of EM and Uncharacteristic Forms

The first Townsend column about Lyme stressed that in one-fifth to one-half of patients the EM rash never appears or it appears in an atypical form. Because of the EM's complex, diverse presentation, even physicians evaluating patients in areas endemic for Lyme can fail to recognize this "signature" lesion.

At an FDA hearing on antimicrobials for early infection, Raymond Dattwyler, a rheumatologist at SUNY, Stony Brook, Long Island, told the FDA that "one guy at our hospital was teaching the house staff that erythema migrans was always a flat lesion ... if there was any edema in the lesion ... it couldn't be erythema migrans." Dattwyler showed his colleagues at Stony Brook culture-positive lesions that were raised, dispelling their misimpression. (3)

Lyme ELISAs: General Deficiencies

Crucial deficiencies of the Lyme ELISA are its relative lack of specificity and sensitivity. (Specificity refers to this test's ability to exclude patients without Lyme, sensitivity to its ability to detect patients with Lyme.) The ELISA can show false positive in patients with periodontal disease and syphilis, for example, which have certain proteins in common with Lyme spirochete. In addition to error caused by cross reactivity, different labs doing Lyme ELISAs vary in their results. (There is little standardization.)