Lyme borreliosis simile: an emergent and relevant disease to dermatology in Brazil

Abstracts

Neste trabalho de revisão são apresentadas doenças relacionadas com espiroquetas do gênero Borrelia, agentes etiológicos de diferentes enfermidades comuns ao homem e a animais. Enfatizou-se a Borrelia burgdorferi lato sensu, que inclui diferentes espécies causadoras de doenças e com envolvimento sistêmico, com interesse em várias especialidades médicas, como dermatologia, reumatologia, cardiologia e neurologia. Considerando que existem diferenças quanto ao agente etiológico, além dos aspectos clínicos e laboratoriais, quando comparada com a borreliose de Lyme causada pelas Borrelia burgdorferi, B. garinii e B. afzelli, a infecção no Brasil deve ser referida como borreliose de Lyme simile. O eritema migratório recidivante é a principal manifestação clínica da borreliose existente tanto no Brasil como nos demais países. Essa lesão clássica está relacionada com a picada do carrapato vetor e inicia-se como uma mácula ou pápula cutânea avermelhada, de caráter expansivo, eventualmente surgem lesões semelhantes múltiplas a distância. A manifestação clínica da enfermidade, em especial o envolvimento cutâneo, é o parâmetro diagnóstico mais relevante, e os exames complementares sorológicos confirmam a suspeita clínica.

Borrelia; Doença de Lyme; Eritema migratório

REVIEW ARTICLE

Lyme borreliosis simile: an emergent and relevant disease to dermatology in Brazil^*

Adivaldo Henrique da Fonseca^I; Roberto de Souza Salles^II; Simone de Abreu Neves Salles^III; Renata Cunha Madureira^IV; Natalino Hajime Yoshinari^V

^IPost Doctor - Medical and Veterinary Entomology University of Florida USA; Full Professor of Parasite Diseases, Department of Epidemiology and Public Health - Universidade Federal Rural do Rio de Janeiro (RJ)

^IIPh.D. degree in Veterinary Sciences, Universidade Federal Rural do Rio de Janeiro. Adjunct Professor (Level 4) of Microbiology, Department of Microbiology, Biomedical Institute, UFF (RJ)

^IIIM.Sc. degree in Dermatology from the Universidade Federal Fluminense. Assistant Professor of Dermatology, Department of Clinical Medicine of the Medical School, UFF (RJ)

^IVM.Sc. degree in Veterinary Sciences, Universidade Federal Rural do Rio de Janeiro. Ph.D. student in Veterinary Sciences, Universidade Federal Rural do Rio de Janeiro (RJ)

^VPost-doctor; Postdoctoral training from the Tufts School of Medicine, TSM, US. Associate Professor of Rheumatology of the Medical School, USP, Sao Paulo (SP)

^{Correspondence}

ABSTRACT

This review article presents diseases related to spirochetes of the genus Borrelia, which are the etiological agents of many human and animal diseases. Focus was given to the Borrelia burgdorferi sensu lato complex, including nine different species that cause diseases often with multisystemic involvement and raising interest to many medical specialties, such as Dermatology, Rheumatology, Cardiology and Neurology. Due to differences concerning the etiologic agent, clinical and laboratorial presentations, when comparing with Borrelia burgdorferi, B. garinii and B. afzelli, the infection must be referred as Lyme disease-like illness in Brazil. The recurrent erythema migrans is the main clinical manifestation of borreliosis observed in Brazil and in other countries. The classical reddish macular or papular skin lesion shows expanding features and is tick bite related; additionally, multiple secondary similar lesions may appear far from the original site. The clinical presentation of the disease, mainly skin manifestation, is the main diagnostic parameter, while serologic exams only confirm the clinical suspicion.

Keywords:Borrelia; Lyme disease; Erythema migrans.

INTRODUCTION

Several diseases transmitted by ticks, such as Lyme borreliosis and Lyme disease-like illness, may affect both wild and domestic animals as well as human beings. The intense agricultural and stock raising activities in Brazil, the interaction of human beings with domestic animals and the growing interest in outdoor activities favor the spread of infectious agents transmitted by ticks and contribute to the emergence and recurrence of different etiological agents.¹

Borrelia burgdorferi lato sensu complex comprises a group with a large number of infectious agents causing diseases that can affect several organs. Therefore, it has risen much interest in many medical specialties, such as Dermatology, Rheumatology, Cardiology, Neurology and Infectious diseases.^2-4 The spectrum of clinical presentation of this disease differs according to the geographical areas, and it is associated with the local antigenic characteristics of Borrelia spp as well as with its interaction with the ecosystem and the vector found in that area.² In North America, there is a predominance of skin and joint manifestations; in Europe, skin and neurological manifestations prevail, whereas in Asia the symptoms are basically skin-related.^4-7 Em qualquer situação o eritema migratório recidivante (EMR) é o mais relevante achado, permitindo a suspeita clínica.⁵

In any of these cases, the recurrent erythema migrans (EM) is the most relevant finding that raises the clinical suspicion. The pathogenic species of genus Borrelia may infect wild and domestic mammals, humans and birds.^8,9 As members of the order Spirochaetales, family Spirochaetaceae, they are morphologically different from Leptospira and Treponema, for being larger, having more periplasmic flagella and fewer spirilla.¹⁰ Members of genus Borrelia multiply by transverse binary fission, are microaerophilic and can be observed under optical microscopy with the silver nitrate impregnation technique and by visualization in dark-field or phase-contrast microscopy.^11,12

The currently known pathogenic Borrelia species account for five groups of distinct diseases:

(a) Epidemic relapsing fever, caused by B. recurrentis, and endemic relapsing fever, with more than 20 species of genus Borrelia, until recently named according to the tick responsible for its transmission;

(b) Avian borreliosis, which is caused by only one species, B. anserina, and produces anemia, fever, apathy and high morbidity rates in birds;

(c) Bovine borreliosis, caused by B. theileri. This is a cosmopolitan species that can cause mild anemia in ruminants and equines, and it has little pathogenic effect;

(d) Epizootic bovine abortion, a disease that affects cattle and deer caused by B. coriaceae;

(e) Lyme borreliosis (Lyme disease) and Lyme disease-like illness, that are caused by B. burgdorferi lato sensu⁷ (Chart).

Compared with the North American or European Lyme borreliosis and considering the etiological differences and the clinical and laboratorial aspects, the infection in Brazil must be referred as Lyme disease-like illness,¹³ and the first cases were published in the beginning of the 1990's.^14,15 To this day, the etiological agent in Brazil has not been isolated yet,^13,16 and the ticks likely to be involved in the wild cycle belong to the genus Ixodes. The genus Amblyomma would be implicated in the transmission to domestic animals and humans.^7,13,16

Skin manifestations of Lyme borreliosis and Lyme disease-like illness

EM is the main manifestation of Lyme borreliosis.^13,17,18 Although pathognomonic, the skin lesion is not present in all patients and occurs in 60-80% of patients infected with B. burgdorferi stricto sensu in the US. It is less frequently associated with B. garinii or B. afzelii, which are species found in Europe.^5,19

The classic lesion usually starts 8 to 9 days after the bite, at the inoculation site of Borrelia spp. A reddish, centrifugally expanding macule or papula is observed, and it classically reaches a diameter greater than 5cm (Figure 1). In Brazil, the available data suggest that EM appears, on average, 30 days after the tick bite and lasts for a period varying from few days to months.²⁰ The erythema is generally uniform in its initial phase, resulting in an reddish expanding plaque with different shades of this color; a papula can appear in the middle, corresponding to the site of the tick bite.²¹ Edematous urticaria-like lesions can occur in some cases.¹⁸

The newly formed EM consists of a reddish lesion that is very often ring-shaped, initially measuring 0.5-2.0cm corresponding to the tick bites. This erythema tends to progress via peripheral expansion of its borders with central clearing (Figure 2).²² The erythema is often circular, and it may show morphological variations such as triangular, oval or elongated shapes.^5,19 The size and shape of EM are variable, demonstrating a centrifugal and slow growth; however it can have a rapid expansion and become a plaque in a short period of time. Between 8 and 14 days after the tick bite, the lesion can reach a diameter greater than 15 cm.¹⁸

Although EM is normally found as a solitary lesion, multiple lesions can also occur, representing the dissemination of the microorganisms through the blood vessels and lymphatic system. They are called secondary annular lesions and are less expanding than the EM.^18,22,23

Skin changes in EM

At the site of the tick bite, a dermal inflammatory process occurs, with a central infiltrate composed of macrophages, mastocytes, neutrophils, plasmocytes, lymphocytes, and usually few eosinophils.^17,21,24

The main histopathological findings include proliferation and dilation of blood vessels, and vasculitis shows a primary lymphocyte infiltrate associated with plasma cells. As the lesion progresses, there is a reduction of the inflammatory process and marked atrophy of the epidermis and dermis.^25,26

In the histopathological study of biopsies of the core of the EM lesions, Steere et al.¹⁹ demonstrated a cuff-shaped dermal infiltrate composed of lymphocytes, histiocytes, plasma cells and mastocytes. Berger²² observed in the upper and deeper dermis the presence of perivascular and interstitial infiltrate mainly comprised of lymphocytes, plasmocytes and/or eosinophils. In biopsies of the edges on the lesion, the author found a predominance of plasmocytes, whereas in the center of the lesion, eosinophils prevail. There were lympho-histiocytic infiltrates in 38.23% of all biopsies in the superficial and deep dermis.

In skin biopsies of 31 patients from Manaus, Melo et al.²⁷ detected spongiosis in 15 (44.12%). When examining the dermis, 8 patients (15.69%) had an infiltrate composed of lymphocytes, histiocytes and eosinophils. In 9 patients (29.04%) they observed cuff-shaped infiltrate around the vessels. Borrelia spp was detected in one case (3.22%).²⁷ These biopsies were relevant to confirm the diagnosis of EM.

When EMR occurs isolate or accompanied by discreet symptoms it is considered as localized form, and when it presents multiple erythemas accompanied by more intense symptoms, it is deemed as disseminated EMR²² (Figure 3). The distinction between the two situations is important because, in individuals with localized lesion, the response to antibiotics is usually favorable, while in patients with disseminated disease, the treatment takes longer and has to be frequently repeated, with a poorer prognosis in terms of definitive cure.^22,23

The acrodermatitis chronica atrophicans^2,6,18 18 is the typical form that occurs in the chronic phase of the classic European Lyme borreliosis. Initially there is a red-bluish edematous lesion, usually in the feet or lower legs of elderly patients.² Erythema and edema significantly vary in intensity. With time, the skin in that site becomes atrophic with a wrinkled appearance, and the subcutaneous vessels are more evident.¹⁷

Extracutaneous manifestations in Lyme borreliosis and Lyme disease-like illness

According to Berger,18 the most frequent general extracutaneous symptoms in Lyme borreliosis were fever (55%), fatigue (48%), musculoskeletal discomfort (47%) and headache (38%). Joint pain and neurological symptoms were also observed. General manifestations such as malaise, neck rigidity, and photosensitivity, conjunctivitis, lymphadenopathies are described and may last several weeks or longer if not treated.²⁸

Secondary manifestations of Lyme borreliosis include neurological, joint and cardiac manifestations. Weeks or months after the onset of EMR, early neurological manifestations may be observed, such as aseptic meningitis, neuritis of cranial nerves, cerebellar ataxia, motor or sensory radiculoneuritis, myelitis and encephalitis.^29,30 Such manifestations may recur and last for months or become chonic.^29,30 Other publications mention the possibility of subluxations of small joints in the hands and feet associated with peripheral sensory neuropathy.^28,31,32 Cardiac disorders may also appear few weeks after EM, such as atrioventricular block, acute myocarditis or enlarged heart area.³³ Large-joint arthritis, especially in the knee, occur weeks or months after the initial stage and last few days or weeks, but they can relapse and evolve to a polyarticular involvement similar to that of rheumatoid arthritis.^13,15

Approximately 60% of untreated patients in the US develop arthritis within two years, which often presents with sudden onset, oligoarticular or monoarticular involvement, affecting large joints, and with periods of remission or activities.³ Mild fatigue and fever may accompany this stage. If left untreated, the joint condition may resolve spontaneously, but 10% of patients evolve to chronic erosive arthritis with synovial proliferation and no longer respond to antibiotics.³¹ Spirochete antigens and structures similar to B. burgdorferi, may be demonstrated in perivascular sites and synovia by means of the silver impregnation technique or monoclonal antibodies. The presence of bacterial components in the joints was demonstrated in the chronic forms using the polymerase chain reaction (PCR) technique.^29,34

The neurological involvement of Lyme borreliosis presents with clinical variations according to the stage of the disease. Fifteen percent of patients not treated in the primary stage evolved with central or peripheral neurological abnormalities, which had the potential to lead to irreversible damage.⁹ Therefore, in the initial stages patients complain of headache, irritability and sleep disorders. These symptoms generally disappear with remission of the disease.^9,28 In its latent stage, various abnormalities can be found, the most frequent including cranial neuropathy, especially facial paralysis, peripheral sensory or motor neuropathy and meningitis. The latter presents with severe headache, pain and neck rigidity, photophobia, nausea, vomiting and irritability.^9,28

Approximately 8% of untreated patients, within weeks or months after the primary infection, evolved into a cardiac condition consisting of variable degrees of atrioventricular block.¹⁹ The cardiac damage is reversible and it usually does not require a pacemaker. There are some rare reports of death as a consequence of myocarditis, with Borrelia present in the heart tissue.³⁵

There are reports of transplacental transmission of B. burgdorferi lato sensu leading to neonatal complications related to maternal infection during the first three months of pregnancy.^36,37

Lyme disease-like illness in humans in Brazil

In 1989, the first review article on borreliosis was published in the Brazilian medical literature warning physicians about the possible existence of this disease in Brazil.³⁸ In that year, a multidisciplinary team assembled at the Universidade de Sao Paulo in order to further investigate this disease. A laboratory was set up specifically for its diagnosis, aiming to perform serologic tests and culture of B. burgdorferi in a Barbour-Stoenner-Kelly (BSK) medium. In the beginning of the 1990's, some clinical cases of Lyme disease-like illness were reported in Rio de Janeiro,^14,39 Manaus,^40,41 São Paulo⁴² and Mato Grosso,^15,43 with a predominance of skin manifestations. The same situation was observed in Argentina.⁴⁴

The profile of Lyme disease-like illness was characterized with the report of 30 cases in humans, and the clinical manifestations, serum diagnosis, treatment and epidemiology with involvement of dogs, cattle, wild animals and ticks were discussed.²⁸

Patients with skin involvement and positive serology who were in suburban or rural areas in contact with small and/or big animals in the State of Rio de Janeiro presented positive serum reaction to B. burgdorferi, with a predominance of skin manifestations and a few cases of joint and cardiovascular abnormalities.⁴⁵

Studies conducted by Yoshinari¹³ concluded that in Brazil there is a form of Lyme borreliosis with clinical and epidemiological characteristics that are different from those found in Europe and North America. Skin manifestations were the most frequent ones and were present in different forms of the disease. Joint, neurological and cardiac involvement were also reported at comparable frequency as that found in other continents. The recurrent nature of the disease in Brazil stood out.²⁰

Lyme borreliosis in animals

Following the identification of the disease in humans, Lyme borreliosis was acknowledged as capable of infecting both wild and domestic animals. In the Northeastern region in the US, the agent is widely spread among rodents and deer,⁴⁶ constituting natural reservoirs.⁴⁷ Domestic animals such as dogs, horses and cattle act as carriers of the vectors to the domestic setting.^47-50 In contrast to the unnoticed infection of wild animals, this agent may cause clinical disease in domestic animals.^48,51,52

Salles et al.⁵³ observed that horses highly infected by ticks also had a higher prevalence of seropositivity in the indirect ELISA and Western blotting assays for B. burgdorferi, in contrast to the animals that underwent a stringent tick control program. According to these authors, the humoral response of the horses studied presented good antigen recognition for B. burgdorferi strain G39/40 in both tests used, and the frequency of serum positive animals corroborated the hypothesis that there is a type of borreliosis similar to the Lyme borreliosis affecting horses in Brazil.

The finding of Borrelia sp was reported in the peripheral blood and urine of marsupials.^54,55 Barboza et al.⁵⁴ ddetected skunks that were naturally infected, after immunosuppression with cyclophosphamide. Domestic and wild animals have a higher risk of becoming infected with the etiological agent because they are infested with a large number of ticks. In endemic areas, B. burgdorferi lato sensu was found in asymptomatic animals that can serve as a reservoir to humans.³³ Taking into account the potential transmission of the etiological agent through the urine of the host, Lyme borreliosis should be deemed as a serious public health problem.⁷

Diagnostic methods

The diagnosis of Borrelia spp can be made by peripheral blood smear, especially when spirochetemia is increased.^8,10 Smears can be performed with fragments of tick tissues, such as intestine, salivary gland and hemolymph, stained with Giemsa, as B. burgdorferi was originally discovered.^56,57 This technique has been very much used in the study of B. anserina and B. theileri in ticks and vertebrate hosts.^10,58

The finding of EM is relevant as a clinical and cutaneous marker of borreliosis. The histopathological exam of the skin biopsy or the culture in BSK medium as part of the search for the etiological agent are important tools for both specific and differential diagnosis.²⁷

Serological methods have been widely used in studies on anti-IgG and anti-IgM antibodies in humans and animals in risk or enzootic areas for borreliosis, serving as a support both to confirm clinical cases and to prepare an epidemiological profile of this disease.¹³

In Brazil, the indirect ELISA test to detect anti-B. burgdorferi gG has already been standardized for bovine,⁵⁹ canines⁶⁰ and equines⁵³ populations, with the use of total sonicated antigen of B. burgdorferi stricto sensu strain G39/40. Serological studies were performed using this assay; the frequency of anti-B.burgdorferi IgG antibodies was estimated at 72.51% in asymptomatic bovines in the Southeast region⁶¹ 20% in canines in the Baixada Fluminense region⁶⁰ and 9.80% in equines in the State of Rio de Janeiro.⁵³

The finding and the culture of the etiological agent provide a definitive diagnosis.¹² To this day it has still not been possible to cultivate the microorganism of the genus Borrelia responsible for the Lyme disease-like illness in mammals or ticks in Brazil.^13,16,34 Nevertheless, the results of the researches carried out showed the existence of a pathogenic agent related to ticks, which is able to boost the immune system of the host to produce antibodies against the North-American strain G39/40 of B. burgdorferi stricto sensu.^16,59,62,63

To establish the epidemiological pattern, the Center for Disease Control (CDC, Atlanta, US) determined the following diagnostic criteria:

1) In endemic areas, Lyme borreliosis is considered if, after exposure to ticks, the patient presents EM or, in its absence, there is a report of cardiovascular, nervous system or musculoskeletal disease;

2) In areas considered at risk for having reservoirs and vectors, the individuals are considered infected with Lyme borreliosis if they develop EM with positive serology by Western blotting (presence of two IgM bands or four IgG bands or the concomitance of one IgM band with two IgG bands).

The clinical diagnosis of EM must be confirmed by serologic and histopathological exams, as well as by culture in a specific medium. The patients are usually positive to antibody tests using ELISA and Western Blotting techniques; however, they must be carefully interpreted in view of false-positive serology with other infectious or autoimmune diseases.⁴⁴ The interpretation of serologic tests must be a cautious procedure because of the risks of false-negative and false-positive results; for example, patients who receive early treatment may present a negative serology.^7,62,64 The sensitivity of these tests is low in the acute phase, increases after some weeks of disease progression and tends to recur during flare or re-infections. It was reported that a portion of patients with chronic disease may remain serologically negative.^13,62 The specificity of the serologic test is low because it presents cross reactivity with syphilis, visceral leishmaniasis, rheumatoid disease, infectious mononucleosis, subacute bacterial endocarditis, scleroderma and systemic lupus erythematosus.⁶²q

ACKOWLEDGEMENT

Study carried out with the financial support of CNPq and FAPERJ.

REFERENCES

Received on August 14, 2004.

Approved by the Consultive Council and accepted for publication on February 25, 2005.

• 1. Massard CL, Fonseca AH. Carrapatos e doenças transmitidas comuns ao homem e aos animais. A Hora Veterinária. 2004; 23:15-23.
• 2. Abele DC, Ander KH. The many faces and phases of borreliosis I. Lyme disease. J Am Acad Dermatol. 1990; 23:167-86.
• 3. Steere AC, Grodzicki RL, Kornblatt AN. The spirochetal etiology of Lyme Disease. N Engl J Med. 1983; 308: 733-740.
• 4. Yoshinari NH, Barros PJL, Fonseca AH. Borreliose de lyme - zoonose emergente de interesse multidisciplinar. News Lab. 1995; 3:90-104.
• 5. Berger BW, Clemmenson OJ, Ackermann AB. Lyme disease is a spirochetosis: a review of the disease and evidence of its cause. Am J Dermatopathol. 1983; 5: 111.
• 6. Lipschultz B Über eine seltene Erythemform (Erythema chronicum migrans). Arch Derm Syph. 1913; 118:349.
• 7. Soares CO, Ishikawa, MM, Fonseca AH, Yoshinari NH. Borrelioses, Agentes e Vetores. Pesq Vet Bras 2000; 20: 1-19.
• 8. Hoogstraal H. Ticks and spirochetes. Acta Trop. 1979; 36:133-6.
• 9. Steere AC. Lyme disease. New Engl J Med. 1989; 31:586-597.
• 10. Balashov YS. A translation of bloodsucking ticks (Ixodoidea) vectors of diseases of man and animals. Misc Publicat Entomol Soc Am. 1972; 8: 159-356.
• 11. Barbour AG, Maupin GO, Teltow GJ, Carter CJ, Piesman J. Identification of an uncultivable Borrelia species in the hard tick Amblyomma americanum: possible agent of a lyme disease-like illness. J Infect Dis. 1996; 173:403-9.
• 12. Barbour AG. Isolation and cultivation of lyme disease spirochetes. Yale J Biol Med. 1984; 57:521-5.
• 13. Yoshinari NH, Abrão MG, Bonoldi VLN, Soares CO, Madruga CR, Scofield A, et al. Coexistence of antibodies to tick-borne agents of Babesiosis and Lyme Borreliosis in patients from Cotia County, State of São Paulo, Brazil. Mem Inst Oswaldo Cruz. 2003; 98:311-8.
• 14. Azulay RD, Abulafia L, Sodre CS. Lyme disease in Rio de Janeiro, Brazil. Int J Dermatol. 1991; 30:569-71.
• 15. Yoshinari NH, Barros PJL, Yassuda P, Baggio D, Steere AC, Cossermelle W. Estudo epidemiológico da doença de lyme no Brasil. Rev Hosp Clín Fac Med Sao Paulo. 1992; 47:71-5.
• 16. Abel IS, Marzagão G, Yoshinari NH, Schumaker TTS. Borrelia-like spirochetes recovered from ticks and small mammals collected in the Atlantic Forest Reserve, Cotia County, State of São Paulo, Brazil. Mem Inst Oswaldo Cruz. 2000; 95:621-4.
• 17. Berger BW. Cultivation of Borrelia burgdorferi from erythema migrans lesions and perilesional skin. J Clin Microbiol. 1992; 30:359-64.
• 18. Berger BW. Dermatologic manifestations of Lyme disease. Rev Infect Dis. 1989; 11: S1475.
• 19. Steere AC, Bartenhagen NH, Craft JE, Hutchinson GJ, Newman JA, Rahn DW, et al. The early clinical manifestation of Lyme disease. Ann Intern Med. 1983; 99:76-82.
• 20. Yoshinari NH, Barros PJL, Gauditano G, Fonseca AH. Report of 57 cases of Lyme-like disease (LLD) in Brazil. Arthritis Rheum. 2000; 43: S188.
• 21. Berger BW, Kaplan MH, Rothenberg IR, Barbour AG. Isolation and characterization of Lyme disease spirochete from the skin of patients with erythema chronicum migrans. J Am Acad Dermatol. 1985;13:444-9.
• 22. Berger BW. Erythema chronicum migrans of Lyme disease. Arch Dermatol. 1984;120:1017-21.
• 23. Berger BW. Treatament of erythema chronicum migrans of Lyme disease. Ann NY Acad Sci. 1988; 539:346.
• 24. De Koning J, Bosma RB, Hoogkamp-korstaje JAA. Demonstration of spirochetes in patients with Lyme disease with modified silver. J Med Microbiol. 1987; 23:261-7.
• 25. Cregh TM, Wright NA, Mckee PH. Inflammatory dermatoses. Erythema chronicum migrans. In: Marsden RA, Headington JT, Mackie R, editors. Pathology of the skin. London: Gower Medical;1989. p.802-14.
• 26. De Koning J, Hoogkamp-Korstaje JAA. Diagnosis of Lyme disease by demonstration of spirochetes in tissue biopsies. Zbl Bakt Hyg A. 1986; 263:179-88.
• 27. Melo IS, Gadelha AR, Ferreira LCL. Estudo histopatológico de casos de eritema crônico migratório diagnosticados em Manaus. An Bras Dermatol. 2003;78:169-77.
• 28. Yoshinari NH, Barros PJL, Bonoldi VLN, et al. Perfil da borreliose de lyme no Brasil. Rev Hosp Clín Fac Med Sao Paulo. 1997; 52:111-7.
• 29. Pachner AR, Steere AC. Neurological findings of lyme disease. Yale J Biol Med. 1984; 57:481-3.
• 30. Pirana S, Bento RF, Bogar P, Silveira JAM, Yoshinari NH. Paralisia facial e surdez súbita bilateral na doença de Lyme. Rev Bras Otorrinol. 1996; 62:500-2.
• 31. Steere AC, Malawista SE, Hardin JA, Ruddy S, Askenase W, Andiman WA. Erythema chronicum migrans and lyme arthritis: the enlarging clinical spectrum. Ann Intern Med. 1977; 86:685.
• 32. Stiernstedt GT, Granström M, Hederstedt B, Sköldenberg B. Diagnosis of spirochetal meningits by enzime-linked immunosorbent assay and indirect immunofluorescense assay in serum and and cerebrospinal fluid. J Clin Microbiol. 1985; 21:819-25.
• 33. Walker D. Tick- Transmitted infectious diseases in the United States. Ann Rev Public Health. 1998; 19:237-69.
• 34. Barros PJL, Levy LH, Monteiro FGV, Yoshinari NH. Doença de Lyme. Acometimento cutâneo e tratamento das fases iniciais. Rev Assoc Med Bras. 1993; 39:170-2.
• 35. Vlay SC. Cardiac manifestations of Lyme disease. Pratical Cardiol. 1990; 16:63-9.
• 36. Markowitz LE, Steere AC, Benach JL, Slade JD, Broome CV. Lyme disease during pregnancy. JAMA. 1986; 255:3394.
• 37. Osebold JW, Spezialetti R, Jennings MB. Congenital spirochetosis in calves: association with epizootic bovine abortion. J Am Vet Med Assoc. 1986; 188:371-5.
• 38. Yoshinari NH, Steere AC, Cossermelli W. Revisão da Borreliose de Lyme. Rev Ass Méd Brasil. 1989; 35: 34-7.
• 39. Briggs PL, Fraga S, Filgueira AL. Doença de Lyme: Apresentação de um caso com demonstração de Borrelia. In: Congresso Brasileiro Dermatologia, [resumo], Curitiba; 1993.
• 40. Talhari S, Schettine APM, Parreira VJ. Eritema crônico migrans. Doença de Lyme - Estudo de três casos. In: Anais do Congresso Brasileiro de Dermatologia, [resumo], Goiânia; 1987.
• 41. Talhari S, Talhari A, Ferreira LCL. Eritema cronicum migrans, eritema migratório, doença de Lyme ou borreliose de Lyme. An Bras Dermatol. 1992;67:205-9.
• 42. Yoshinari NH, Oyafuso LK, Monteiro FGV, Barros PJL, Cruz FCM, Ferreira LGE, et al. Doença de Lyme: Relato de um caso observado no Brasil. Rev Hosp Clin Fac Med São Paulo. 1993; 48:170-4.
• 43. Costa IP, Yoshinari NH, Barros PJL, Bonoldi VLN, Leon EP, Zeitune AD, et al. Doença de lyme em Mato Grosso do Sul: relato de três casos clínicos, incluindo o primeiro relato de meningite de lyme no Brasil. Rev Hosp Clin Fac Med Sao Paulo. 1996; 51:253-7.
• 44. Stanchi NO, Balague LJ. Lyme disease: antibodies against Borrelia burgdorferi in farm workers in Argentina. Rev Saúde Pública. 1993; 27:305-7.
• 45. Florião RA. Borreliose de Lyme. Determinação de manifestações peculiares a BL entre os pacientes que freqüentam o HUCFF. [tese]. Rio de Janeiro: Universidade Federal do Rio de Janeiro; 1994.
• 46. Magnarelli LA, Anderson JF, Apperson CS, Fish D, Johnsoon RC, Chappell WA. Spirochetes in ticks and antibodies to Borrelia burgdorferi in white tailed deer from Connecticut, New York state, and North Caroline. J Wildl Dis. 1986; 22:178-88.
• 47. Madigan JE. Lyme disease in horses. Vet Clin North Am Equine Pract. 1993; 9:429-34.
• 48. Fonseca AH, Ishikawa MM, Soares, C. Lyme borreliosis serology in cattle in Brasil. Rev Univ Rural. 1996; 18: 85-9.
• 49. Lissman BA, Bosler EM, Camay H, Ormiston BG, Benach JL. Spirochetes associated arthritis (lyme disease) in a dog. J Am Vet Med Assoc. 1984; 185:219-20.
• 50. Magnarelli LA, Anderson JF. Class-specific and polyvalent enzyme-linked immunosorbent assays for detection of antibodies to Borrelia burgdorferi in equids. JAMA. 1989;195:1365-8.
• 51. Magnarelli LA, Anderson JF, Schreier AB, Ficke CM. Clinical and serologic studies of canine borreliosis. J Am Vet Med Assoc. 1987;191:1089-94.
• 52. Parker JL, White KW. Lyme borreliosis in cattle and horses: a review of the literature. Cornell Vet. 1992; 82:253-74.
• 53. Salles RS, Fonseca AH, Scofield A, Madureira RC, Yoshinari NH. Sorologia para Borrelia burgdorferi latu sensu em eqüinos no estado do Rio de Janeiro. A Hora Veterinária. 2002; 22:46-9.
• 54. Barboza WGA, Almeida Jr DE, Silva LAM, Fonseca AH. Detecção de Borrelia sp. em gambás imunossuprimidos com ciclofosfamida. Rev Bras Med Vet. 1998; 20:241-3.
• 55. Fonseca AH, Soares CO, Ishikawa MM, Massard, CL, Yoshinari, NH. Detection of Borrelia sp. in opossum (Marsupialia: Didelphidae) in Brazil [abstract]. In: Congress World Veterinary Association, Yokohama, Japão; 1995. p.283.
• 56. Burgdorfer W, Barbour AG, Hayes SF, Peter O, Aeschilimann, A. Erythema chronicum migrans - tickborne spirochetosis. Acta Trop 1983; 40:79-83.
• 57. Burgdorfer W, Barbour AG, Hayes SF. Lyme disease: a tick-borne spiroquetosis? Science. 1982; 216:1317-9.
• 58. Magnarelli LA, Dumler JS, Anderson JF, Jonson RC, Fikrig E. Coexistence of antibodies to tick-borne pathogens of babesiosis, ehrlichiosis, and Lyme borreliosis in human sera. J Clin Microbiol. 1995; 33:3054-7.
• 59. Ishikawa MM, Fonseca AH, Soares CO, et al. Padronização de ensaio imunoenzimático ELISA indireto para pesquisa de anticorpos IgG contra Borrelia burgdorferi em bovinos. Rev Bras Med Vet 1997; 19:166-8.
• 60. Soares CO, Fonseca AH, Manera GB, Scofield A, Fonseca AH, Yoshinari NH. Sorologia para borreliose em cães procedentes da baixada fluminense, estado do Rio de Janeiro. Rev Brasil Med Vet. 1999; 21:111-3.
• 61. Ishikawa MM, Fonseca AH, Soares CO, Yoshinari NH. Estudo Sorológico comparativo da Borreliose de Lyme, Brucelose e Leptospirose em bovinos. Rev Patol Trop. 1999; 28:195-201.
• 62. Barros PJL. Caracterização clínica e laboratorial da doença de Lyme no Brasil, através de métodos imunológicos e reação em cadeia de polimerase. [tese]. Universidade de São Paulo; 2000. 163p.
• 63. Joppert AM, Hagiwara MK, Yoshinari NH. Borrelia burgdorferi antibodies in dogs from Cotia County, Sao Paulo State, Brazil. Rev Inst Med Trop Sao Paulo. 2001; 43:251-5.
• 64. Grodzick RL, Steere AC. Comparision of immunoblotting and indirect enzyme-linked immunosorbent assay using different antigen preparations for diagnosing early Lyme disease. J Infect Dis. 1988; 157:790-7.

Correspondence to

Adivaldo Henrique da Fonseca

Cx. Postal 74548

23890-970 - Seropédica – RJ

*

Work done at "Departamento de Epidemiologia e Saúde Pública da Universidade Federal Rural do Rio de Janeiro (UFRRJ)", "Departamento de Microbiologia e Parasitologia da Universidade Federal Fluminense (UFF)" and "Faculdade de Medicina da Universidade de São Paulo (FMUSP)", with support of CNPq.

Publication Dates

• Publication in this collection
  13 June 2005
• Date of issue
  Apr 2005

History

• Received
  14 Sept 2004
• Accepted
  25 Feb 2005