First isolations of Borrelia burgdorferi from rodents collected in northern Europe.

Spirochetes were found in 13% of Ixodes ricinus collected from an island, near Stockholm where human borreliosis is endemic. Borrelia burgdorferi was cultivated from the kidney and/or spleen of wild rodents (Clethrionomys glareolus and Apodemus flavicollis) from the same island. Spirochetes were identified as Borrelia burgdorferi by indirect immunofluorescence assays using species and genus specific monoclonal antibodies. In these tests the spirochetes could not be differentiated from strains previously cultured from Swedish patients with Ixodes-borne borreliosis. The results show that small rodents in Europe may harbour borreliae and indicate that C. glareolus and A. flavicollis may be important reservoirs for the spirochetes causing Ixodes-borne borreliosis in humans and domestic animals in Europe.

Erythema chronicum migrans Afzelius and acrodermatitis chronica atrophicans. Early and late manifestations of Ixodes ricinus-borne Borrelia spirochetes.

In the present thesis consecutive patients, 231 with ECMA, 41 with ACA and 20 with facial palsy (Bell's palsy), have been studied. It has been shown that spirochetes, transmitted by the tick Ixodes ricinus, are involved in the etiology of ECMA and ACA. This has been shown through the isolation and cultivation of spirochetes from ticks and from the skin of patients with ECMA and ACA. The spirochetes have morphological characteristics similar to those of the genus Borrelia. No antigenic differences have been found between ECMA and ACA strains by the use of four different monoclonal antibodies against Borrelia burgdorferi. In serological studies, with the indirect IF test and with the ELISA, elevated antibody titers against these spirochetes were found in sera from patients with ECMA and ACA. Significantly increasing titers were found in sera from patients who developed extracutaneous complications and decreasing titers as a response to therapy. The serological tests are of good diagnostic help for patients with ACA and in many of the patients with ECMA-related extracutaneous complications, but in the present study only 15-28% of the patients with uncomplicated ECMA were seropositive. The study has shown that a tick bite and/or an untreated ECMA may be followed by symptoms from the nervous system (facial palsy, meningoradiculitis), the joints and from the heart as well. It has also been shown that ACA may sometimes be preceded by an untreated ECMA and that manifestations from the nervous system and/or the joints may precede or accompany ACA. There may be a long period of latency (several years) between a spontaneously healing ECMA and the development of ACA lesions. In ACA patients with abnormalities of joints or bones the concordance in site of the cutaneous involvement and changes in the underlying joints or bones may in these cases be consistent with a progressive localized spirochetal infection. Lichen sclerosus et atrophicus-like lesions found in patients with ACA indicate that a Borrelia infection may result in lichen sclerosus et atrophicus-like reactions. The recognition of ACA may be difficult and a combination of clinical, histopathological and serological findings may be necessary to secure the diagnosis. Clinical differences between ECMA-related disorders in Sweden an Lyme disease in the United States have been found and there may also be antigenic differences between the spirochetes involved.(ABSTRACT TRUNCATED AT 400 WORDS)

Tick-borne borreliosis and facial palsy.

During a one-year period, 82 consecutive patients seeking medical attention for facial palsy primarily of unknown etiology were examined for underlying Ixodes ricinus-borne borreliosis. Evidence of the infection was found in 16 (20%) of the patients, most of whom had cerebrospinal fluid findings indicating meningeal involvement. Among 9 children included in the study, borreliosis was found in 6 cases. Bilateral facial palsy occurred in 3 of the borrelia-infected patients, as compared with none of the patients without borreliosis. It is suggested that, in areas where the tick vector is present, borreliosis should be regularly sought in patients with facial palsy of otherwise unknown etiology. As regards the serological diagnosis, it is emphasized that normal borrelia antibody titres in serum and cerebrospinal fluid at the time of the first consultation do not exclude the infection. A careful serological follow-up of patients with facial palsy is therefore recommended in order not to miss an underlying borreliosis which, if allowed to go untreated, implies a risk of other organ involvement and a protracted course.

Cutaneous manifestations of Lyme borreliosis. Clinical definitions and differential diagnoses.

At the IVth international Conference on Lyme borreliosis the cutaneous manifestations and differential diagnoses were reviewed. Erythema migrans (EM) is a spontaneously healing erythematous lesion occuring at the site of borrelial inoculation. Typically it is homogeneous or is annular with centrifugal spreading. Atypical variants may also occur. Borrelial lymphocytoma (BL) generally presents as a bluish-red nodule. Histologically there is a dense polyclonal lymphocytic infiltrate. Predilection sites are the ear and the breast. It may appear secondarily to EM or be the first manifestation of Lyme borreliosis. EM and BL are early, localized cutaneous manifestations, but sometimes extracutaneous signs or symptoms of disseminated disease may appear simultaneously with either of these lesions. Multiple EM-like lesions, occurring as a result of hematogenous spread, are the cutaneous markers of disseminated disease. Acrodermatitis chronica atrophicans is a chronic skin lesion which is generally seen on the extremities. It starts with an inflammatory phase with bluish-red discoloration, which years to decades later may be followed by an atrophic phase. Sclerotic skin lesions may also develop. Important differential diagnoses are granuloma annulare, malignant lymphoma, benign lymphoreticular infiltrations and sclerotic lesions of non-borrelial origin, collagenoses and circulatory insufficiency.

Successful cultivation of spirochetes from skin lesions of patients with erythema chronicum migrans Afzelius and acrodermatitis chronica atrophicans.

Spirochetes could be cultivated from 9 out of 13 skin biopsies from patients with erythema chronicum migrans Afzelius (ECMA) and from 2 out of 5 biopsies from patients with acrodermatitis chronica atrophicans (ACA) by using a newly modified serumless Kelly's medium. The different spirochete strains grew best at a low oxygen tension. Attempts to grow spirochetes from blood and cerebrospinal fluid failed. The cultivation of spirochetes from secondary ECMA lesions favours the presumption that a spirochetemia may occur in ECMA. The isolation of spirochetes from an ACA patient who had a disease duration of greater than 10 years proves that the spirochetes may survive in the human body for a considerable time.

Lyme borreliosis: aspects of tick-borne Borrelia burgdorferi infection from a dermatologic viewpoint.

During this decade, Lyme borreliosis has emerged as an important health problem, especially in Europe and in the United States, and there has been an explosive growth of knowledge about this condition. The true incidence of lxodes-borne borrelial infection is probably increasing, at least in parts of the world, but the reported increase is also partly attributable to a greater recognition and awareness of this infection. This paper reviews the basic knowledge about Borrelia burgdorferi, its vectors, and its reservoirs. The tendency for Lyme borreliosis to mimic other diseases and the similarities to syphilis are described. The nomenclature of the dermatologic manifestations and the staging of the disease as a localized, disseminated, and chronic infection are summarized. The clinical manifestations, from the dermatologist's point of view, and the sometimes difficult task of diagnosis both at the clinical and laboratory level are reviewed. The dermatologic manifestations erythema migrans, secondary, multiple erythema migranslike skin lesions, borrelial lymphocytoma, and acrodermatitis chronica atrophicans may serve as helpful landmarks in the identification of Lyme borreliosis.

Serodiagnosis of erythema migrans and acrodermatitis chronica atrophicans by the Borrelia burgdorferi flagellum enzyme-linked immunosorbent assay.

The diagnostic performance of an enzyme-linked immunosorbent assay (ELISA) using purified Borrelia burgdorferi flagella as test antigen was compared with that of a B. burgdorferi sonic extract ELISA. We tested sera from 200 healthy controls, 107 patients with erythema migrans (EM), 50 patients with acrodermatitis chronica atrophicans (ACA), and 98 patients with various dermatological disorders without clinical evidence of active Lyme borreliosis. The flagellum ELISA was significantly more sensitive than the sonic extract ELISA. With sera from patients with EM, the diagnostic sensitivity for immunoglobulin G (IgG) antibody detection increased from 11.2 to 35.5% (P less than 0.001) and for IgM antibody detection it increased from 16.6 to 44.8% (P less than 0.001). In the flagellum ELISA, the number of positive tests increased significantly (P less than 0.005) when the duration of EM exceeded 1 month, but still only about 50% of patients with longstanding (1 to 12 months) untreated EM were IgG seropositive. Concomitant general symptoms did not affect the antibody level, whereas patients with multiple erythema were more frequently seropositive. All sera from patients with EM which were positive in the sonic extract ELISA were also positive in the flagellum ELISA. Not only did the overall number of positive tests increase, but the flagellum ELISA yielded a significantly better quantitative discrimination between seropositive patients and controls (P less than 0.002). IgG antibodies to the B. burgdorferi flagellum were found in all sera from patients with ACA, indicating persistence of an antiflagellum immune response in late stages of Lyme borreliosis. IgM reactivity in sera from patients with ACA was shown to be unspecific and the result IgM rheumatoid factor. A rheumatoid factor was detected in sera from 32% of patients with ACA, compared with 7.5% of patients with EM. The improved diagnostic performance, the ease of standardization of the flagellum antigen, and the lack of strain variation make the B. burgdorferi flagellum a needed reference antigen for growing routine serology in Lyme borreliosis.

Comments on the course and classification of Lyme borreliosis.

On the basis of answers by clinicians to a questionnaire concerning the classification and staging of Lyme borreliosis, the following classification is proposed: EARLY LYME BORRELIOSIS Localized infection: Erythema migrans and borrelial lymphocytoma without signs or symptoms of disseminated infection. (Regional lymphadenopathy and/or minor constitutional symptoms may be present). Early disseminated infection: Multiple erythema migrans-like skin lesions. Early manifestations of neuroborreliosis, arthritis, carditis or other organ involvement. LATE LYME BORRELIOSIS Chronic infection: Acrodermatitis chronica atrophicans. Neurologic, rheumatic or other organ manifestations--persistent or remitting for at least 12 (or 6) months.