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lou mal of Clinical Neuro-ophthalmology 8(2):79-80, 1988. INVITED EDITORIAL Ambiguous Serologies in Active Lyme Borreliosis In 1975, Lyme disease meant arthritis to physicians in southern Connecticut. Twelve years later, Lyme disease means an infectious disease with potential manifestations in multiple organ systems due to the spirochete Borrelia burgdorferi. It has many similarities to syphilis. Protean clinical manifestations include inflammatory, degenerative, transplacental, and demyelinating illnesses, which in the past have been treated with corticosteroids, vitamins, or tincture of time. Only antibiotic therapy offers the prospect, but not the guarantee, of a cure for this spirochetosis. Correct diagnosis of Lyme borreliosis often, but not always, is dependent on serology methods. Borrelia burgdorferi is nearly unique among borrelia spirochetes because serology techniques for its detection are available to the clinician. Sixteen other borreliae species require direct visualization of spirochetes in blood smears for the diagnosis of the relapsing fevers, which they cause in human and animal hosts. Before the current serological methods, with their shortcomings, are reviewed it is worthwhile to say a word about seronegative, culture-positive disease, serovariable disease, and seronegative disease which is diagnosed by the pathognomonic skin lesion erythema migrans. Culture of the spirochete Borrelia burgdorferi from body fluids or tissue is a tedious procedure with a very low yield. Rawlings and associates (1) reported a series of patients from Texas in which cultures of synovium, skin, cerebrospinal fluid, or blood yielded spirochetes. Acute Lyme serology and follow-up examination 12 months later yielded persistently seronegative results in seven cases. Berger and colleagues (2) isolated spirochetes from the pathognomonic skin lesion erythema migrans in nine patients. None of the patients were seropositive at presentation when biopsies of the erythema migrans lesions were obtained for culture, and two of eight were seronegative in convalescent specimens obtained 3 months later. 79 '91988 Raven Press, Ltd., New York Serovariable disease means that one laboratory will test an aliquot of your patient's serum and report that Lyme disease antibodies cannot be detected, but a second laboratory will test the same aliquot and detect antibodies at a significant titer. A recent report of transplacental Lyme borreliosis illustrates such a situation. Maternal postpartum serum was strongly reactive by two independent methods (indirect immunofluorescence and enzyme- linked immunosorbent assay) at the Centers for Disease Control, and the New York State Department of Health but was nonreactive at the Yale School of Medicine. The mother had the diagnostic skin lesion, erythema migrans followed by arthritis. The fetus was stillborn. Spirochetes were obtained from cultures of fetal liver and heart, and spirochetes were found in fetal heart, brain, adrenal gland, placenta, and other organs using a variety of histochemical methods (silver impregnation, immunohistochemistry, and monoclonal antibody techniques) (3). An interlaboratory study of Lyme serology using aliquots from 12 patients demonstrated that in some cases a patient will be called unequivocally reactive at one laboratory and nonreactive at another laboratory (4). Erythema migrans (formerly called erythema chronicum migrans) is a skin lesion uniquely associated with Lyme borreliosis (5) and is proof positive of the infection. Physicians at Yale studied a group of patients with Lyme disease who showed the erythema migrans lesion. Convalescent sera from patients with cutaneous manifestations only showed reactivity with IgG in one of ten patients, with IgM in three of ten patients, and in disseminated disease, 12 of 22 patients reacted with IgM and 15 of 22 were seropositive with IgG methods (6). The likelihood of serologic reactivity in a situation where the diagnosis of B. burgdorferi infection is made by firm independent clinical criteria (the erythema migrans lesion) is somewhere between 40 and 60%. Based on these data, it does not ap- 80 INVITED EDITORIAL pear prudent to expect that present serology methods will identify 100% of cases of Lyme borreliosis with neurologic or ophthalmologic manifestations. Problems with presently available methods for antibody detection in Lyme borreliosis are lack of sensitivity (false negative results) and to a much lesser extent some lack of specificity (false positive results). There is no standardization of reagents for serology testing; each laboratory may make their own reagents or may purchase them from a variety of vendors. No matter who makes the products for serology testing, the manufacturing process requires that the spirochete be cultivated in vitro. The proteins that are believed to be antigenic for the human host are controlled by plasmids (7,8), which are lost after serial subculture in the laboratory. Schwan and Burgdorfer report the loss of spirochetal antigenic proteins after serial subcultures of Borrelia burgdorferi in the laboratory (9). Cross reactions of sera from patients wth Lyme borreliosis in nonreaginic syphilis serology methods should be anticipated and should not mislead the clinician. A recent comparison study from the Centers for Disease Control showed that 3 of 12 Lyme sera were cross reactive in the FTAABS test. Some syphilitic sera showed cross reaction in Lyme immunofluorescence tests. The syphilitic cross-reacting sera never were positive at the usual CDC screening dilution (1/256); but some very high titer Lyme sera were cross reactive in the FTA-ABS at the usual screening dilution (1/5) (10). Leptospirosis, yaws, and pinta have been proposed as other diseases with potential cross reactions in Lyme serology methods (11), but results of blind comparison testing of coded specimens have not yet been published. Should corticosteroids be used to treat Lyme borreliosis under any circumstances, and if so, what conditions mandate their use? Some physicians reserve corticosteroids for the management of Herxheimer reactions. The experience with the Herxheimer reaction in syphilotherapy demon- 1CUrl Neuro-ophlhalmof, Vol. 0, i\itl. ~. 1)0'0 strates the prudence of this approach. Corticosteroid therapy in Lyme borreliosis without antibiotic coverage, either by choice or by misintention, might be deleterious to the clinical situation in the short or long term, if the lessons of experimental syphilis are recalled. One physician's eulogy for syphilis was" ... it is forgotten but not gone." There is much to learn about Lyme borreliosis. Our task will be less tedious if we heed the lessons of syphilis. Alan B. MacDonald, M.D. Southampton Hospital Southampton, New York REFERENCES I. Rawlings JA, Fournier PV, Teltow GJ. Isolation of Borrelia spirochetes from patients in Texas. J Clin Microbial 1987;25:1148-50. 2. Berger BW, MacDonald AB, Benach JL. The use of a homologous antigen in the serologic testing of patients with erythema chronicum migrans of Lyme disease. JAm Acad Dermatal 1987, in press. 3. MacDonald AB, Benach JL, Burgdorfer W. Stillbirth following maternal Lyme disease. NY State J Med 1987;87: 615-6. 4. Hedberg CW, Osterholm MT, MacDonald KL. An interlaboratory study of antibody to Borrelia burgdorferi. J Infect Dis 1987;55:1325-7. 5. Berger BW. Erythema chronicum migrans of Lyme disease. Arch Dermatol 1984;120:1017-21. 6. Shresta M, Grodzicki RL, Steere AC. Diagnosing early Lyme disease. Am JMed 1985;78:235-40. 7. Howe TR, Mayer LW, Barbour AG. A single recombinant plasmid expressing two major outer surface proteins of the Lyme disease spirochete. Science 1985;227:645-6. 8. Barbour AG, Tessier SL, Hayes SF. Variation in a major surface protein of Lyme disease spriochetes. Infect Immun 1984;45:94-100. 9. Schwan TG, Burgdoder W. Antigenic changes of Borrelia burgdorfen as a result of in vitro culture. JInfect Dis 1987, in press. 10. Hunter EF, Russell HF, Farshy CE, et al. Evaluation of sera from patients with Lyme disease in fluorescent treponemal antibody-absorption test for syphilis. Sex Transm Dis 1986;13:232-6. II. Craft JE~ Grodzicki RL, Steere AC. Antibody response in Lyme disease: evaluation of diagnositic tests. J Infect Dis 1984;149:789-95. |
