Lyme Disease in Taiwan: First Human Patient with Characteristic Erythema Chronicum Migrans Skin Lesion

Abstract

We report herein the first laboratory-diagnosed case of Lyme disease in a human in Taiwan. A 45-year-old Taiwanese man living in Taipei, in northern Taiwan, had an expanding skin lesion (measuring 23 by 15 cm) on his abdomen for 2 to 3 weeks and recurrent attacks of pain and swelling of the knee joint. Serologic tests indicated a significantly elevated titer of antibody to Borrelia burgdorferi. After appropriate antibiotic treatment for 3 weeks, the skin lesion was cured and the joint swelling was improved. Although several strains of Borrelia spirochetes had been isolated from rodents (Rattus losea) in Taiwan, the tick vector responsible for the transmission remains to be identified.

Lyme disease is an emerging tick-borne spirochetal infection (2) that can cause multisystem human illness; it usually begins with an expanding annular skin lesion known as erythema chronicum migrans (ECM) (12, 13). The etiologic agent of Lyme disease, Borrelia burgdorferi sensu lato, is transmitted mainly by ticks of the Ixodes ricinus complex in North America and Europe (6) and by Ixodes persulcatus and Ixodes ovatus ticks in the countries of Far East Asia (1, 5). Although Lyme disease is the most common vector-borne human infection in Europe and the United States, new cases and regions of endemicitis may be identified due to the worldwide distribution of vector ticks (8).

For surveillance, the diagnosis of Lyme disease is defined as the presence of an erythema migrans rash >5 cm in diameter or laboratory confirmation of infection with evidence of at least one manifestation of musculoskeletal, neurologic, or cardiovascular disease (4). In the absence of a skin lesion, serological tests that demonstrate diagnostic levels of immunoglobulin M (IgM) and IgG antibodies to the Lyme disease spirochete in serum or a significant change in IgM or IgG antibody response to B. burgdorferi in paired acute- and convalescent-phase serum samples were used as criteria for confirmatory diagnosis (3).

Although several strains of Borrelia spirochetes had been isolated from rodents (Rattus losea) in Taiwan (9), no laboratory-confirmed case of Lyme disease in humans had been reported in Taiwan. We report herein the first case of Lyme disease in Taiwan involving a person who had a typical ECM skin lesion and objective joint swelling.

A 45-year-old man living in Taipei, in northern Taiwan, presented to the local private clinic in late December 1996 with the chief complaints of an expanding skin rash on the lateral side of his abdomen and recurrent attacks of asymmetric swelling and pain in his left knee joint. This patient stated that the skin lesion was initially seen as red macule and expanded peripherally over a period of 2 to 3 weeks to form a large oval lesion without pain or itch. The lesion appeared like a red ring and measured 23 by 15 cm, with a bright erythematous margin and a central clearing area (Fig. 1). He did not recall a previous tick bite but was suspected of having one.

FIG. 1.

Photograph of an ECM skin lesion on the abdomen of a 45-year-old Taiwanese man. The lesion began as a red macule and expanded peripherally over a period of 2 to 3 weeks to form a large oval (measuring 23 by 15 cm) with a bright red border and a central clearing area.

On 7 January 1997, one tube of blood was collected from the patient, and routine hematologic and serologic examinations were performed. They revealed that the patient had an elevated erythrocyte sedimentation rate (35 mm/h) and an increased level of serum aspartate transaminase (55 U/ml). He also had a significantly elevated titer of antibody to B. burgdorferi as determined by indirect immunofluorescent-antibody assay with the strains B31 (ATCC 35210) and JD1 (Massachusetts isolate) of B. burgdorferi as antigens. In addition, an improved enzyme-linked immunosorbent assay kit (ImmunoWell Lyme test; General Biometrics, Inc., San Diego, Calif.) combined with a purified cell lysate of B. burgdorferi and the recombinant 39-kilodalton (P39) protein as antigens was also performed to verify the evidence of spirochetal infection (10, 11). The patient’s serum antibody to B. burgdorferi had a positive optical density at 405 nm with an enzyme immunoassay microplate reader, on the basis of the guidelines of the manufacturer (Dynatech Laboratories, Inc., Chantilly, Va.), and a serologic test (Treponema pallidum Haemagglutination Test; Murex Diagnostics Limited, Dartford, England) for syphilis was negative.

Therefore, the patient was diagnosed as possibly having Lyme disease and was subsequently treated with oral doxycycline (100 mg twice daily) for 3 weeks, as previously recommended (7). After treatment, the joint disorder of the patient was significantly improved, and the skin lesion was cured at 1 week following antibiotic therapy. For surveillance, another tube of blood was collected from the patient on 31 May 1997 (3 months after treatment), and routine hematologic and serologic tests were performed to follow up the condition of infection.

As indicated in Table 1, the laboratory findings revealed that the patient’s hematologic indices (both erythrocyte sedimentation rate and aspartate transaminase level) had become normal and the enzyme immunoassay for seroreactivity to B. burgdorferi was negative following antibiotic treatment. In addition, the serum titer of antibody to Lyme disease spirochetes dropped dramatically, from 1:512 to 1:32 at 3 months after antibiotic treatment. These results suggest that early Lyme disease can be cured by appropriate antibiotic therapy.

TABLE 1.

Hematologic and serologic findings for a patient with Lyme disease before and after antibiotic therapy

Date of blood specimen collection	Erythrocyte sedimentation rate (mm/h)	Aspartate transaminase level (U/ml)	Titer of antibody to B. burgdorferia		ImmunoWell Lyme testb result	TPHA testc result
			IgG	IgM
7 January 1997 (before treatment)	35	55	1:512	1:128	Positive	Negative
31 May 1997 (after treatment)	21	38	1:32	1:16	Negative	Negative

^aFluorescein isothiocyanate-conjugated goat anti-human IgG (F0132; Sigma) and IgM (F5384; Sigma) were used for analysis by the indirect immunofluorescent-antibody assay. 

^bAn improved enzyme-linked immunosorbent assay kit with a cell lysate of B. burgdorferi and recombinant P39 protein as antigens. 

^cSerologic test for syphilis. TPHA, Treponema pallidum Haemagglutination Test. 

Although the dermatologic manifestations of Lyme disease, particularly ECM, had been recognized as the unique clinical marker for diagnosing early Lyme disease infection, further analysis by Western blotting would increase the specificity of serologic testing for Lyme disease. Because of the routine hematologic and serologic tests performed for the patient described here, none of this patient’s serum was available for further analysis. However, it has been reported that most patients with Lyme disease in areas of endemicity did not remember a tick bite; the ECM skin lesion was the primary sign appearing during the illness characterizing the early phase of infection, and recurrences of ECM occurred frequently in patients with Lyme arthritis (13–15). Indeed, the patient described here also had recurrences of the skin lesion on his abdomen during the last 3 years. Whether the recurrence of skin lesions may imply reinfection by B. burgdorferi or reexposure to an infective tick needs to be determined.

The prevalence of Borrelia infection among rural populations in Taiwan has not yet been investigated. Most recently, we have conducted a general survey to investigate the prevalence of tick-borne spirochetal infection in small mammals. Several strains of Borrelia spirochetes had been isolated from rodents (R. losea) in Taiwan (9), and the prevalence of spirochetal infection was relatively high (ranging from 12 to 28%) among rodents captured in rural areas (unpublished observations). Thus, a serologic survey with antigens prepared from Borrelia isolates from Taiwan would be required to determine the prevalence of spirochetal infection among rural populations in Taiwan.

Elucidation of the risk of acquiring spirochetal infection by rural populations will depend on the identification of animal reservoirs and the vector ticks responsible for the transmission of spirochetal infection in Taiwan. Although two strains of Ixodes ticks (Ixodes granulatus and I. ovatus) were collected from the captured rodents mentioned above, whether these ticks are responsible for zoonotic transmission in Taiwan remains to be determined.

In conclusion, this report describes the first laboratory-confirmed case of human Lyme disease in Taiwan. The tick vector as well as the strain of spirochete responsible for transmission in Taiwan remain undetermined. This report also highlights the increasing evidence of the existence of tick-borne zoonotic infections in Taiwan and the fact that new cases of Lyme disease in Taiwan can be expected.