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[Borreliosis--increasing clinical problem].

Lyme disease (LD) is due to infection with Borrelia burgdorferi (B. burgdorferi). We analysed some aspects of epidemiology and clinical manifestation of borreliosis. We tried to estimate the efficiency of diagnostic methods and treatment. We analyzed medical documentation of 300 patients with LD treated in our department between 1993-2001. The diagnosis was made according to Lyme Disease Foundation's criteria. Patients suffering from LD were divided into 3 groups according to stages of the disease. The most frequent manifestation of LD was erythema migrans (EM). The number of LD cases had increased during the observation time. The exposition to tick-bites was greater during summer and early autumn. The great number of patients with EM was observed at the same time. Cases of Lyme arthritis (LA), disseminated EM, Lyme carditis (LC) and neuroborreliosis represented the group number 2. LA, uveitis and acrodermatitis chronica atrophicans (ACA) were diagnosed in the third group of patients. Serological markers of B. burgdorferi infection were found in about 50% of cases of EM and in each patient in group 2 and 3. Complete recovery after antibiotic therapy was observed in every case in early LD and partial one in the late stage.

Adolescent↗

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.

Erythema Chronicum Migrans↗

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.

Diagnosis, Differential↗

Joint manifestations of Lyme borreliosis in Europe.

Our clinical and serological studies have shown that Lyme arthritis is not a rare manifestation of Lyme borreliosis in Europe. The significance of serological findings for Lyme arthritis have more often remained uncertain in consideration of potential differential diagnoses than was to be expected on the basis of specificity controls. Various joint manifestations in the course of Lyme borreliosis have been distinguished. The succession or the coexistence of intermittent attacks of arthralgias and arthritis has been pointed out as particular indications of Lyme arthritis. We have noted diffuse hand and finger swelling as a striking feature of early Lyme arthritis. Generally, Lyme arthritis has been attributable to Stage 3 of the disease. The most pathognomonic manifestation has been intermittent knee arthritis. The pattern of joint involvement has shown similarities to that in postenteric and postveneral reactive arthritides, in particular as regards the occurence of dactylitis (sausage digits) and heel involvement. However, we have not seen sacroiliitis and Reiter's syndrome. As distinguished from typical Lyme arthritis, peculiar joint manifestations have been noted in association with acrodermatitis chronica atrophicans. Typing of Class I and II histocompatibility antigens did not give evidence of any immunogenetic basis for Lyme arthritis.

Arthritis, Infectious↗

Detection of serum antibodies against Borrelia burgdorferi with some commercially available serological tests.

Sixty-three sera were analysed for antibodies against Borrelia burgdorferi with an in-house indirect immunofluorescence assay. Thirty-nine sera were positive (titer greater than or equal to 256), seven borderline (titer 128) and 17 negative (titer less than or equal to 64). These results were compared with results obtained with four different commercial assays for detection of such antibodies. Indirect immunofluorescence tests yielded most positive results. The flagellin ELISA test detected antibodies in patients with erythema chronicum migrans (ECM) more often than the other test systems. Sera from patients with acrodermatitis chronica atrophicans (ACA) were positive in all systems. The serological diagnosis of borreliosis is difficult and direct methods for detecting the presence of the microbe are highly needed.

Antibodies, Bacterial↗

[Lyme borreliosis: underdiagnosed?--overtreated?].

Lyme borreliosis is a tick-borne mediated systemic inflammatory disorder caused by a newly recognized spirochete, Borrelia burgdorferi. Its clinical hallmark is an early expanding skin lesion, erythema chronicum migrans (ECM) which may be followed weeks to months later by neurological, cardiac, or joint abnormalities. Symptoms may be associated with any of these systems alone or in combination. All stages of Lyme borreliosis may respond to antibiotics, but treatment of early disease is the most successful. Foci of Lyme borreliosis are widely distributed within the USA and Europe and the disorder appears to be worldwide. Although there are some variations in clinical expression between the USA and Europe, the various syndromes, Erythema migrans (Afzelius), Meningopolyneuritis [Garin-Bujadoux, Bannwarth (MPN)] are now generally subsumed under the name Lyme borreliosis. B. burdorferi is also responsible for an early skin lesion, Borrelia lymphozytom [Lymphadenosis cutis benigna (LCB)], and for a late one, Acrodermatitis chronica atrophicans (ACA), both seen primarily in Europe. In the USA joint abnormalities are the leading abnormalities in the later manifestation of the disease. Lyme borreliosis grew up in the last ten years as a new nosologic entity with some aspects for an infectious etiology of rheumatic disease.

Anti-Bacterial Agents↗

[Lyme disease].

Lyme disease is a multisystem disorder caused by a tick-transmitted spirochete, Borrelia burgdorferi. Clinical manifestations typically begin with characteristic skin lesions, erythema (chronicum) migrans. Weeks to months later, some patients develop the second stage of the illness characterized by neurologic abnormalities, migratory joint pain, cardiac involvement. Months to years later, in many patients the disease progresses to the third stage of manifestation such as chronic arthritis, chronic encephalomyelitis, acrodermatitis chronica atrophicans and keratitis. Zoonotic infection with B. burgdorferi is also widespread within endemic regions among domestic as well as wild animals. The diagnosis is based on clinical and epidemiological findings in most patients, particularly those with erythema migrans or tick bites. Detection of specific antibodies to B. burgdorferi is a useful confirmatory test in many patients. In atypical cases, a positive test result can be valuable for determining the diagnosis. However, serologic testing in Lyme disease is not yet standardized and the results obtained from different assay systems or commercial kits may vary. Moreover, because of poor agreement in sensitivity and/or specificity, data obtained from different laboratories are not comparable. We emphasize that serologic findings must be interpreted with caution; the physician must beware of its strengths and limitations.

Animals↗

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.

Animals↗

[Antibiotic therapy of Lyme borreliosis].

There are still no definite patterns for antibiotic therapy of Lyme borreliosis. Recent studies have shown that ceftriaxone or tetracyclines are superior to the conventional penicillin. Against erythema chronica migrans (stage I) oral therapy, preferably with tetracycline, is sufficient. In cases with stage II symptoms, such as arthritis or neurological affections, high dose parenteral treatment, preferably with ceftriaxone, is recommended, although its effect on the neurologic symptoms is not yet proven. Carditis also calls for high dose parenteral administration of antibiotics, even though there are no published studies on this treatment as yet. Opinion is divided on the cutaneous symptoms such as acrodermatitis chronica atrophicans, morphea, lichen sclerosus et atrophicus (acute inflammatory stage) and lymphadenitis cutis benigna. Even if oral penicillin or tetracycline can cure existing symptoms, in the absence of longterm observations, it remains an open question whether oral treatment can prevent further complications or evolution to chronicity (stage III). For these clinical pictures there is also a tendency to give high dose parenteral antibiotics, and ceftriaxone is likely to win favour. In stage II Lyme borreliosis, autoimmune processes occur which scarcely respond to antibiotics any longer. Nevertheless, parenteral administration of high dose antibiotics remains sensible as a means of eradicating pathogens from the tissues, CSF or synovial fluids, and to avoid further complications. Evaluation of the therapeutic effects of corticosteroids or other immunosuppressive agents would require prospective studies.

Anti-Bacterial Agents↗

Evidence for spirochetal origin of circumscribed scleroderma (morphea).

Acrodermatitis chronica atrophicans (ACA) and morphea are clinically distinct skin diseases with some common features and possible coexistence. We found antibodies to Borrelia burgdorferi in eight of fifteen patients with morphea. Six of them had IgG antibodies and two both IgG and IgM antibodies. Four of the eight seropositive and five of the seven seronegative patients had been treated with high dose penicillin previously. Spirochetal organisms could be cultured in Barbour-Stoenner-Kelly's medium from a skin biopsy of one seropositive untreated patient. Spirochetes were recovered from histological sections in three of eight, two seropositive and one seronegative morphea and in one of three erythema chronicum migrans patients by an avidin-biotin immunoperoxidase method. The similar clinical picture of ACA and morphea, the response to penicillin therapy in both entities, the presence of antispirochetal antibodies, the isolation of spirochetes in culture and the detection of spirochetal organisms on histological sections suggest a close relationship among these diseases. We conclude that morphea may represent a Borrelia infection. The correlation to ACA is discussed.

Adolescent↗

Antibodies to the Borrelia burgdorferi flagellum in patients with scleroderma, granuloma annulare and porphyria cutanea tarda.

It is generally accepted that cutaneous Lyme borreliosis comprises erythema chronicum migrans, lymphadenosis benigna cutis, and acrodermatitis chronica atrophicans. In recent years the tick-borne spirochete Borrelia burgdorferi has been associated with a number of other cutaneous disorders. We therefore investigated sera from 175 patients with localized scleroderma (morphea) (n = 64), systemic sclerosis (n = 74), granuloma annulare (n = 16) and porphyria cutanea tarda (n = 21) with the new, highly sensitive and specific Borrelia burgdorferi flagellum ELISA assay. As controls (n = 297) served normal healthy volunteers and patients with other skin diseases. It was found that the distribution of individual antibody values and the median antibody levels were identical in controls and in patients with scleroderma, granuloma annulare and porphyria cutanea tarda. These data do not support the hypothesis of an etiological association between Borrelia burgdorferi infection and scleroderma, granuloma annulare or porphyria cutanea tarda.

Adolescent↗

[Investigation of Lyme disease in northeast of China].

In 1987-1988, we conducted investigation of Lyme disease in Northeast of China. The disease was widespread in the forest areas of Heilonjiang and Jilin provinces where Ixodes persulcatus population thrives. The disease occurred at Daqing tree farm where 628 people were inquired and examined among them, 37 cases including 23 cases of ECM, 6 cases of neurological abnormalities, 7 cases of arthritis and 1 case of acrodermatitis chronica atrophicans were confirmed being Lyme disease. The sera of patients suspected with the disease and that of the residents at Xiaobai tree farm were tested for antibodies against Borrelia burgdorferi (B31) by ELISA. Seventeen out of 22 patients were positive and 54 out of 240 residents had significant IgG titers. Samples of tick midgut were inoculated into BSK medium and cultivated. Three isolates of spirochetes were cultivated from Ixodes persulcatus. One of them (M7) was confirmed being Borrelia burgdorferi. Recently another isolate was cultivated from a patient with ECM.

Animals↗

[Borrelia burgdorferi, clinical aspects, cultivation and identification of the pathogen in erythema migrans in Berlin].

Among other manifestations, the following diseases caused by Borrelia burgdorferi in Europe are transmitted by ticks of the species ixodes ricinus: erythema migrans (EM), lymphadenosis benigna cutis (LBC), lymphocytic meningo-radiculitis (Bannwarth's syndrome), and acrodermatitis chronica atrophicans (ACA). We report on a female patient, who developed EM 10 days after a-tick bite in Berlin. Borrelia burgdorferi could be cultivated from a skin biopsy specimen taken from the periphery of the EM. The isolates were identified as Borrelia burgdorferi by indirect immunofluorescence using the monoclonal antibodies H 9724 and H 5332.

Animals↗

[Unusual manifestations of Lyme borreliosis. A contribution to the clinical spectrum of this disease group].

Since the discovery that EM (erythema migrans), ACA (acrodermatitis chronica atrophicans) and BL (borrelial lymphocytoma) have an infectious etiology, these syndromes have been receiving particular attention. This report describes four patients whose dermatological symptoms did not at first indicate borreliosis. In all four cases serological antibody tests proved that they were caused by Borrelia burgdorferi. In two of these cases these findings were confirmed by bacterial cultures. The unusual skin symptoms, i.e. multiple disseminated erythema, erysipelas-like manifestations, swelling and discoloration of the eyelids and lichenoid papules, extend the known clinical spectrum of cutaneous borreliosis in Europe.

Adult↗

[Acute and chronic borreliosis transmitted by ticks in Europe].

Ticks are direct pathogenic agents, and also transmit some infectious diseases such as borreliosis. Clinical manifestations of borreliosis are multiple. They most often affect the skin, nervous system, joints and heart. Cutaneous pseudolymphomas, erythema chronicum migrans of Afzelius, acrodermatitis chronica atrophicans of Pick-Herxheimer, meningo-radiculitis and various arthropathies are the most commonly encountered diseases.

Acute Disease↗

[Multiple neurologic manifestations of Borrelia burgdorferi infection].

The neurological spectrum of Borrelia burgdorferi infections is still enlarging. We review epidemiological, pathological and serological data of Lyme disease. The course of the disease is divided in three stages: stage 1 during the first month is characterised by erythema chronicum migrans and associated manifestations; stage 2 includes not only the classical European meningoradiculitis but also less specific neurological symptoms: isolated lymphocytic meningitis with an acute or even relapsing course, apparently idiopathic facial palsy, neuritis of other cranial nerves, polyneuritis cranialis, Argyll-Robertson sign, peripheral nerve involvement, acute transverse myelitis, severe encephalitis, myositis. During stage 3, three to five months or longer after the onset of the disease, chronic arthritis, acrodermatitis chronica atrophicans and various neurological symptoms can be observed: chronic neuropathy with mainly sensory or motor signs, recurrent strokes due to cerebral angiopathy and progressive encephalomyelitis; this third stage the central nervous system involvement is characterised by slowly progressive or fluctuating course during months or years, ataxic or spastic gait disorder, bladder disturbances, cranial nerve dysfunction including optic atrophy and hypoacusia, dysarthria, focal and diffuse encephalopathy. This chronic central nervous system disease can mimic multiple sclerosis, anorexia nervosa, psychic disorders or subacute presenile dementia. It is often associated with pleiocytosis, abnormal EEG and evoked potentials, sometimes multifocal and mainly periventricular white matter lesions visualised by CT or MRI, and as a rule high antibody titers against Borrelia burgdorferi. High doses of penicillin can halt the disease, sometimes induce spectacular regression of symptoms or sometimes be inefficient; ceftriaxone could be a more powerful therapy. Similarities between syphilis and Borreliosis are multiple: both of these spirochetes contain plasmids, can be transmitted through the placenta and progress for many years through successive stages, with multiorgan symptoms, including parenchymatous and vascular lesions of the central nervous system. Borrelia burgdorferi is the new great imitator.

Animals↗

[Cutaneous B cell lymphoma in chronic Borrelia burgdorferi infection. Report of 2 cases and a review of the literature].

Low-grade malignant B-cell lymphomas of the skin can be distinguished from lymphadenosis benigna cutis (Bäfverstedt) by immunohistological methods developed in the last few years. Its coexistence with Borrelia burgdorferi infection can be shown by clinical and serological findings. In the chronic stage of this infection, lymphocytic cell infiltrations consistent with histological and immunohistological findings of malignant B-cell lymphoma can be found. Predominantly at the extremities, multiple plaque-shaped or nodular lesions are seen, showing a follicular pattern in their periphery. The tumors do not respond to antibiotic therapy. They regress totally after X-ray treatment, but local recurrences are rather common. They show a long persistent course with only slow progression and seem to be of low-grade malignancy independent from the cytological findings. In most cases the tumors remain limited to the skin and to one anatomical site; nevertheless, the development of systemic involvement has been reported. We present two cases of malignant B-cell lymphoma of the skin in patients with chronic B. burgdorferi infection. Both cases showed the typical clinical and histological features of this entity. Similar reports from the literature indicate close relationships with the chronic stage of Borrelia infection, with the simultaneous presence of acrodermatitis chronica atrophicans as an indicator. We conclude that an elevated titer indicating Borrelia infection is an important finding for the diagnosis and prognosis of this particular type of cutaneous B-cell lymphoma.

Aged↗

[Clinical aspects of erythema migrans (Lyme) borreliosis].

Erythema migrans or Lyme borreliosis may be classified according to 3 stages. Erythema migrans is the typical initial lesion of the disease, often associated with general symptoms. Carditis, meningitis, musculoskeletal symptoms including arthralgia may develop in stage 2; arthritis (arthralgia), acrodermatitis chronica atrophicans (ACA), and encephalomyelitis may occur in stage 3. Borrelial lymphocytoma may be seen either in the early phase of the disease or along with the ACA. However, there is no definite therapeutical concept, so far. We recommend tetracyclines during the first stage, and high doses of penicillin G during stages 2 and 3 as well as for pregnant women.

Humans↗