98 LYME DISEASE AND OTHER SPIROCHETAL INFECTIONS
Harrison’s Manual of Medicine
LYME DISEASE AND OTHER SPIROCHETAL INFECTIONS
Yaws and Pinta
ETIOLOGY Borrelia burgdorferi, a fastidious spirochete, is the causative agent of Lyme disease. Three groups of B. burgdorferi organisms exist and are generally responsible for causing diseases with different manifestations in different parts of the world.
EPIDEMIOLOGY Lyme disease is a tick-transmitted illness; the distribution parallels the geographic range of certain ixodid ticks. The major areas of disease include the northeastern U.S. and Wisconsin and Minnesota in the Midwest. The principal vector in these regions is Ixodes scapularis (also called I. dammini); >20% of these ticks are infected with B. burgdorferi in these areas. Lyme disease also occurs in the western U.S., Europe, Asia, and Australia. The ticks have different animal hosts; the host of the immature I. scapularis is the white-footed mouse, while that of the mature tick is the white-tailed deer. The incidence of disease peaks during the summer. More than 100,000 cases have been reported to the CDC since 1982.
CLINICAL MANIFESTATIONS Early Infection: Stage 1 (Localized Infection) The principal site of stage 1 infection is the skin. After a 3- to 32- d incubation period, erythema migrans (EM) appears in ~75% of cases. Usually beginning as a red macule or papule at the site of the tick bite, EM expands to form a large annular lesion, often with a bright-red outer border and partial central clearing. Ixodid ticks are so small that most pts do not notice the initial tick bite. The lesion is warm but not usually painful.
Early Infection: Stage 2 (Disseminated Infection) Within days of the onset of EM, B. burgdorferi can spread hematogenously to many sites. Secondary annular skin lesions are similar in appearance to the primary lesion and are frequently accompanied by severe headache, mild neck stiffness, fever, chills, migratory musculoskeletal pain, arthralgias, and profound malaise and fatigue. These early symptoms usually resolve in several weeks, even without treatment. After several weeks or months, ~15% of pts develop neurologic abnormalities, including meningitis, subtle encephalitis, cranial neuritis (including facial palsy), motor or sensory radiculoneuropathy, mononeuritis multiplex, chorea, and/or myelitis. The CSF shows lymphocytic pleocytosis (~100 cells/µL), often with an elevated protein level and a normal or slightly low glucose level. Early neurologic abnormalities resolve completely in months, but chronic neurologic disease may occur later. Cardiac abnormalities develop in ~8% of pts within several weeks of onset of illness. The most common finding is fluctuating degrees of atrioventricular block. Some pts have myopericarditis. Like early neurologic findings, cardiac involvement usually resolves but may recur. Musculoskeletal pain is common during stage 2, with migratory pain in joints, tendons, bursae, muscles, or bones and without joint swelling.
Late Infection: Stage 3 (Persistent Infection) Months after the initial infection, ~60% of untreated pts in the U.S. develop arthritis, typically intermittent attacks of oligoarticular arthritis in large joints (especially the knees) lasting for weeks or months. Most pts have fewer recurrent attacks each year, but a few develop chronic arthritis of one or both knees, with erosion of cartilage and bone. Less commonly, chronic neurologic or skin involvement may develop months or years after initial infection.
DIAGNOSIS Lyme disease is diagnosed by the recognition of a characteristic clinical picture with serologic confirmation. Several weeks after infection, most pts develop an antibody response to B. burgdorferi that is detectable by ELISA. Western blotting in cases with equivocal or positive results is recommended to identify false-positive ELISAs. The persistence of serologic positivity in pts who have had Lyme disease is common and may cause confusion if another illness with similar manifestations develops. About 20–30% of acute- phase serum samples are positive. IgM- and IgG-specific assays are recommended in the first month of illness; thereafter, only IgG assays are of value. Polymerase chain reaction (PCR) for the organism may serve as a substitute for culture in cases of Lyme arthritis, with 85% of joint fluid samples PCR-positive in one study. The sensitivity of PCR for B. burgdorferi in the CSF is much lower, and there is little if any role for PCR in the testing of blood or urine samples.
TREATMENT See Fig. 98-1.
FIGURE 98-1. Algorithm for the treatment of the various acute or chronic manifestations of Lyme borreliosis. Relapse may occur with any of these regimens, and a second course of treatment may be necessary. AV, atrioventricular. (From AC Steere: HPIM-15, p. 1064.)
YAWS AND PINTA
CLINICAL MANIFESTATIONS Yaws is a chronic infectious disease of childhood caused by Treponema pallidum ssp. pertenue and transmitted by direct contact. The disease is characterized by one or more initial skin lesions (often a papule on the leg) followed by relapsing, nondestructive secondary lesions of skin and bone. In the late stages, destructive lesions of skin, bone, and joints develop.
Pinta, an infectious disease of the skin, is caused by Treponema carateum. The initial lesion is a small papule, located most often on the extremities, face, neck, or buttocks, that increases in size by peripheral extension and is accompanied by regional lymphadenopathy. Secondary pigmented lesions without adenopathy appear 1 month to 1 year after the initial lesion.
DIAGNOSIS Serologic tests are required for diagnosis of yaws, since clinical features have become less distinctive with the decreasing prevalence of the disease. However, there is no serologic test that can discriminate among the different treponemal infections. Nonvenereal treponemal infections should be considered in the evaluation of a reactive syphilis serology in any person who has immigrated from an endemic area.
Therapy with IM benzathine penicillin (1.2 million U for adults and 600,000 U for children) leads to rapid resolution of the lesions of yaws or pinta and prevents recurrence. Tetracycline, doxycycline, or erythromycin may be used in penicillin-allergic pts. Contacts of pts should be treated with antibiotics.
EPIDEMIOLOGY Leptospirosis is thought to be the most widespread zoonosis in the world, affecting at least 160 mammalian species. Infection in humans occurs mainly during the summer and fall in Western countries and in the tropics. Leptospirosis is acquired through incidental contact with contaminated water (two-thirds of cases) or through contact with urine or tissues of infected animals. Leptospiras enter through abraded skin or mucous membranes. Certain occupational groups are at especially high risk; included are veterinarians, agricultural workers, sewage workers, slaughterhouse employees, and workers in the fishing industry.
CLINICAL MANIFESTATIONS The incubation period ranges from 2 to 26 d. Leptospirosis typically is a biphasic illness in which an acute leptospiremic phase is followed by an “immune” leptospiruric phase. The initial phase of leptospiremia is characterized by an abrupt onset of headache (usually frontal), severe muscle aches (most prominent in the thighs and the lumbar area), cutaneous hyperesthesia, chills, and fever. The most common physical findings include fever with conjunctival suffusion. Less common findings include muscle tenderness, lymphadenopathy, hepatosplenomegaly, pharyngeal injection, and skin rashes. Most pts become asymptomatic within 1 week. The “immune” phase follows an asymptomatic period of 1–3 d and coincides with the appearance of antibodies. Symptoms in this phase vary but include those seen earlier; symptoms and signs of meningitis are present in 15% of cases. Even in the absence of meningeal signs, CSF pleocytosis is evident after the seventh day in 50–90% of cases. Although often less pronounced in the second phase, fevers can recur; they usually last only 1–3 d. Weil’s syndrome, the most severe form of leptospirosis, occurs in 5–10% of cases and is characterized by jaundice, renal dysfunction, hemorrhagic diathesis, and high mortality.
DIAGNOSIS The diagnosis is made by culture or serology. Leptospiras can be cultured in special semisolid medium from blood or CSF during the initial phase or from urine during the second phase. Shedding in the urine may continue from months to years. Specimens can be mailed to a reference laboratory for culture, since leptospiras remain viable in anticoagulated blood for up to 11 days. Antibodies to the organism appear in the second week of illness. For presumptive diagnosis of leptospirosis, an antibody titer in the microscopic agglutination test (MAT) of ³1:100 in the presence of a compatible clinical illness is required. ELISA can also be used. Serologic testing is not specific for the infecting serovar; thus it is important to culture for the organism.
TREATMENT See Table 98-1.
Table 98-1 Treatment and Chemoprophylaxis of Leptospirosis
EPIDEMIOLOGY Two types of relapsing fever are caused by Borrelia species: louse-borne (LBRF) and tick-borne (TBRF). Louse-borne disease is endemic in Central and East Africa. Tick-borne disease has a worldwide distribution.
CLINICAL MANIFESTATIONS The clinical manifestations of LBRF and TBRF are similar. After an incubation period of 2–18 d, the illness begins with an abrupt onset of rigors and fevers, headache, arthralgias, and myalgias. Fever is irregular in pattern. The pt develops dry mucous membranes and tender hepatosplenomegaly. Hemorrhagic complications can occur. Symptoms last 2– 7 d and end in a crisis. Survivors have relapses after 5–10 d of feeling relatively well; TBRF is associated with more relapses than LBRF.
DIAGNOSIS A definitive diagnosis is made by the demonstration of borreliae in peripheral blood films.
See Table 98-2. A Jarisch-Herxheimer reaction may develop within 1–4 h after the initiation of antibiotic therapy; its severity is correlated with the density of spirochetes in the blood.
Table 98-2 Antibiotic Treatment of Louse-Borne and Tick-Borne Relapsing Fever in Adults
For a more detailed discussion, see Lukehart SA: Endemic Treponematoses, Chap. 173, p. 1053; Speelman P: Leptospirosis, Chap. 174, p. 1055; Dennis DT, Campbell GL: Relapsing Fever, Chap. 175, p. 1058; and Steere AC: Lyme Borreliosis, Chap. 176, p. 1061, in HPIM-15.