Acrodermatitis Chronica Atrophicans Research Articles

Neurologice manifestations in Lyme borreliosis

Neurologic manifestations may occur in early disseminated or late chronic Lyme borreliosis. Signs and symptoms of peripheral neuropathy had already been reported in patients with acrodermatitis chronica atrophicans (ACA), the principal dermatologic manifestation of late chronic Lyme borreliosis, at the turn of this century 1,2 (see review in Ref 3). The first case report of a patient with Bannwarth's syndrome, a painful radiculoneuritis that follows tick bite and erythema migrans (EM), was published in 1922 by Garin and Bujadoux. 4 Unfortunately, the authors were not aware that the enlarging erythema they observed was virtually identical to the EM described in 1909 by Afzelius 5 and in 1913 by Lipschütz. 6 A case report on EM followed by meningitis was first published in 1930 by Hellerström. 7 In the 1960s, Schaltenbrand 8 and other European neurologists 9–13 studied large cohorts of patients, all of whom developed painful radiculoneuritis, cranial neuritis, or lymphocytic meningoencephalitis as a sequela of tick bite and EM. Although the pathogenesis was unknown, it seemed clear that these patients suffered from a clinically characteristic disease, which was named meningopolyneuritis Garin-Bujadoux-Bannwarth 14 or Bannwarth's syndrome. 13 Despite reports that showed a beneficial effect of penicillin on EM-meningitis, 15,16 most European neurologists thought an arbovirus was the cause of Bannwarth's syndrome. 8–10,12,13 This concept was drawn from the knowledge of the viral etiology of central European encephalitis, another tick-transmitted neurologic disease observed in Europe. Yet dermatologists, familiar with the long-known therapeutic effect of antibiotics in EM and ACA, continued to postulate that bacterial agents caused Bannwarth's syndrome. 16 In the 1960s, Hopf found signs and symptoms of peripheral neuropathy in 40% of 92 patients with ACA. 3,17 This particular feature is known as ACA-associated neuropathy and represents a characteristic neurologic manifestation of late chronic Lyme borreliosis. 18–20 Neurologic abnormalities in Lyme disease were also observed in the United States. Eleven percent of patients with EM or Lyme arthritis were found to suffer from radiculoneuritis similar to Bannwarth's syndrome or from encephalitis. 21,22 Shortly after Borrelia burgdorferi was identified to be the causative agent of Lyme disease, 23,24 the pathogenesis of Bannwarth's syndrome 25,26 as well as of ACA and ACA-associated neuropathy 20,27 could also be disclosed. Subsequently, neurologic syndromes such as a chronic debilitating encephalomyelitis, 19,28,29 cerebral vasculitis, 30–33 and focal myositis 34–36 could reliably be linked to borrelial infection by several investigators. On the other hand, the frequent and “defensive” use of serodiagnostic tests to “rule out” Lyme borreliosis in patients with unclear neurologic phenomena has led to an increasing amount of anecdotal reports, which ascribe a large variety of neurologic conditions to Lyme borreliosis. Many of these reports lack evidence of borrelial infection except for the demonstration of serum antibodies to B. burgdorferi. It must be kept in mind that in endemic areas, as much as 10 to 30% of the clinical normal population have been found to be seropositive. 37–40 The increasing number of patients who undergo serodiagnostic testing for uncharacteristic symptoms of presumed Lyme borreliosis will subsequently lead to an increasing number of false-positive results. The overabundance of such “atypical” — in many instances, probably “falsepositive” — cases in the literature has led to a misconception of the clinical picture of neuroborreliosis. This has also led to potentially dangerous or useless extended therapeutic trials. 41–43 If the diagnosis is based on reliable criteria 44–46 neuroborreliosis will generally present with characteristic manifestations. A carefully performed prospective study has proven that atypical neurologic cases play no role in a large cohort of patients with neuroborrelfiosis. 47

Acrodermatitis chronica atrophicans

Acrodermatitis chronica atrophicans (ACA) has hitherto mainly been described from northern, central and eastern parts of Europe. In recent years, there have been a few American case reports on ACA in connection with Lyme disease (Lavoie et al. 1986; Kaufman et al. 1989). Previously the majority of cases described from the United States referred to immigrants from Europe (Montgomery and Sullivan 1945).

Cutaneous fibroses induced by Borrelia burgdorferi

Three cases of chronic infection with Borrelia burgdorferi are described. The patients presented with nodular or discoid fibrosis, partly in conjunction with acrodermatitis chronica atrophicans (ACA). Juxta-articular fibrotic nodules may develop within a few months of the onset of ACA. Nodular, discoid morphoea-like, and widespread cutaneous fibroses in chronic Borrelia infection may be provoked by trauma, surgery or electromagnetic radiation. They respond well to antibiotic therapy. These lesions offer an in vivo model for studying the evolution of immunologically induced fibrosis.

Further Evidence for Borrelia burgdorferi Infection in Morphea and Lichen Sclerosus et Atrophicus Confirmed by DNA Amplification

We present further evidence in support of the notion that Borrelia burgdorferi is possibly involved in the pathogenesis of morphea and lichen sclerosus et atrophicus (LSA). Running a nested polymerase chain reaction (PCR) with a primer set specific for the flagellin gene of B. burgdorferi enabled us to demonstrate the presence of Borrelia DNA in skin biopsies of patients with morphea (nine of nine) of LSA (six of six). Biopsy specimens obtained from patients with erythema chronicum migrans (two patients, four of four samples) and acrodermatitis chronica atrophicans (one patient, one of one sample) also showed positive PCR results. By contrast, there was no amplification of Borrelia DNA in control biopsies either from patients with chronic eczema (three of three) or psoriasis (two of two) or from normal skin (three of three). Antibodies directed against B. burgdorferi were only detected in the serum of patients with erythema chronicum migrans (two of two) and acrodermatitis chronica atrophicans (one of one) but were not present in cases of morphea (five of five), LSA (three of three), or in control subjects (three of three). These data suggest that B. burgdorferi may play a role in the pathogenesis of both morphea and LSA. Furthermore, we conclude that PCR analysis provides an important diagnostic tool, even in seronegative Borrelia infections.

Western blot analysis of sera from Lyme borreliosis patients according to the genomic species of the Borrelia strains used as antigens.

Sera of 52 Lyme borreliosis patients classified according to their clinical features were analysed by Western blot using as antigens Borrelia strains belonging to three recently described genomic species. The antibody response was demonstrated to be homologous within each genospecies. Serum reactivity was studied for each of the type strains Borrelia burgdorferi sensu stricto (strain B31T), Borrelia garinii (strain 20047T) and group VS461. Seven of 15 sera (46.6%) of patients with meningoradiculitis showed preferential reactivity with Borrelia garinii (strain 20047T), all of 8 sera (100%) of patients with acrodermatitis chronica atrophicans showed preferential reactivity with group VS461 (strain VS461) and 8 of 16 sera (50%) of patients with arthritis showed preferential reactivity with Borrelia burgdorferi sensu stricto (strain B31T). The presence of a strong response to OspA and OspB proteins of Borrelia burgdorferi sensu stricto was found only in this last group of patients. These results suggest that there are clinical implications of the recently described modifications in the taxonomy of Borrelia burgdorferi.

Acrodermatitis chronica atrophicans: A chronic T-cell-mediated immune reaction against Borrelia burgdorferi?: Clinical, histologic, and immunohistochemical study of five cases

Acrodermatitis chronica atrophicans (ACA) is a late manifestation of infection caused by Borrelia burgdorferi. Our purpose was to study the clinical, histopathologic, and immunohistochemical findings in patients with ACA to understand better the pathogenesis of the disease. Five patients were studied. Skin biopsy specimens were obtained from active lesions for histologic and immunohistochemical studies. Clinical lesions included an initial erythematous discoloration in one patient and violaceous infiltrated plaques and nodules in four patients, three of whom also had late atrophic lesions. Biopsy specimens showed a dermal perivascular and interstitial lymphocytic infiltrate with plasma cells. There was a predominance of CD3+, CD4+ T cells in the dermal infiltrate. B cells were present in three patients. The dermal infiltrate showed an intense expression of lymphocyte function-associated antigen. The intercellular adhesion molecule type 1 was expressed on endothelial cells, perivascular mononuclear cells, and focally on basal keratinocytes. Our findings suggest that a chronic, T-cell-mediated immune reaction against B. burgdorferi is involved in the pathogenesis of ACA.

Effects of Adequate Versus Inadequate Treatment of Cutaneous Manifestations of Lyme Borreliosis on the Incidence of Late Complications and Late Serologic Status

Eighty-two patients who were treated at the Department of Dermatology, Innsbruck, Austria, from 1980 to 1987 for cutaneous manifestations of Lyme disease were subjected to a clinical follow-up investigation aimed at detecting dermatologic, neurologic, and internal late complications of borreliosis. Only 54 of these patients had received adequate antibiotic treatment according to current standards. Also, their sera were investigated for the presence of immunoglobulin G (IgG) and IgM Borrelia burgdorferi antibodies by an indirect immunofluorescence assay, three different enzyme-linked immunosorbent assays, and immunoblotting. As a control, the sera of 126 healthy blood donors were investigated with the same assays. Results showed no unambiguous clinical late complications of Lyme borreliosis, even in inadequately treated or untreated patients. Seropositivity varied considerably according to the assay used; the indirect immunofluorescence assay yielded the highest scores. The proportion of seropositive results (immunofluorescence assay) was 59% in patients with erythema chronicum migrans, 69% in those with lymphocytoma cutis, and 100% in those with acrodermatitis chronica atrophicans (overall 63%); in contrast, only 31% of the blood donor control group were found to be seropositive. Seropositivity did not correlate with adequacy of treatment, interval between onset of symptoms and treatment, time span since treatment, age of patients, and presence of antinuclear antibodies. Immunoblot pattern showed high incidence of antibodies against the 29/31-kD (outer surface proteins OspA and OspB) and 55/58-kD antigens in general and against the 41-kD protein (flagellin) in patients with acrodermatitis chronica atrophicans only.

Monoclonal Antibodies for Identification of Borrelia afzelii sp. nov. Associated with Late Cutaneous Manifestations of Lyme Borreliosis

Borrelia isolates associated with Lyme borreliosis were previously divided into 3 genospecies, B. burgdorferi sensu stricto, B. garinii and group VS461, on the basis of DNA homology. B. burgdorferi sensu stricto and B. garinii were identified by monoclonal antibodies (MAbs), H3TS and D6 respectively, but no MAbs were available to identify group VS461. Two MAbs were produced, I 17.3 and J 8.3 which reacted with OspB and OspA proteins, respectively, of strains belonging to group VS461, which should be named B. afzelii sp. nov. 24 strains were assigned to B. afzelii sp. nov., 11 of them being isolated from skin lesions, 6 from acrodermatitis chronica atrophicans (ACA) and 5 from erythema chronicum migrans (ECM). Although quite unknown in the USA, ACA has frequently been reported in northern Europe where B. afzelii sp. nov. is commonly isolated. This study documents the involvement of B. afzelii sp. nov. as a specific aetiological agent of ACA.

Acrodermatitis Chronica Atrophicans

To the Editor.— We report a possible case of acrodermatitis chronica atrophicans (ACA), a spirochetal disease almost entirely limited to Europe. Report of a Case.— A 68-year-old native of New York, NY, reported a 20-year history of thinning of the skin with easy bruising and fragility. Eight years after the onset of skin changes, hepatosplenomegaly, thrombocytosis, an increased serum IgM level, and an uncharacterized dysproteinemia were discovered, all of unknown cause and asymptomatic. These problems all were without long-term follow-up. He had also noted the recent onset of mild hearing loss. He had traveled only to Great Britain 15 years before the onset of symptoms. Findings from his physical examination revealed diffuse thinning of the scalp and body hair and generalized thinning of the skin, especially prominent over the extensor surfaces of the limbs and joints that was characterized by a cigarette paper appearance (Fig 1). Intertriginous skin was violaceous

Amplification of Borrelia burgdorferi DNA in skin biopsies from patients with Lyme disease

To determine whether the polymerase chain reaction could contribute to a better diagnosis of Lyme disease, skin biopsy samples from patients suffering from erythema chronicum migrans or acrodermatitis chronica atrophicans were tested for the presence of Borrelia burgdorferi by a polymerase chain reaction assay, which was specific for European strains. The spirochete could not be detected microscopically in any of the 15 biopsy samples obtained from nine patients. However, B. burgdorferi could be isolated from seven of eight of these samples, which indicated the presence of spirochetes. Using a nested polymerase chain reaction, we were able to detect B. burgdorferi-specific sequences in 12 of the 15 biopsy samples. Biopsy samples from three of four patients with erythema chronicum migrans and four of five patients with acrodermatitis chronica atrophicans were found to be positive for B. burgdorferi. The spirochete could be isolated from the biopsy sample, from a patient with erythema chronicum migrans who tested negative, which suggests a false-negative polymerase chain reaction result probably on account of the low number of spirochetes present in the lesion. The positive polymerase chain reaction for lesions from patients with acrodermatis chronica atrophicans supports the concept that B. burgdorferi can persist in the skin over a long period of time. From these results, it was concluded that the polymerase chain reaction is a valuable technique for the diagnosis of Lyme disease.

A Clinical, Histological, and Immunohistochemical Comparison of Acrodermatitis Chronica Atrophicans and Morphea

We compared 19 patients with acrodermatitis chronica atrophicans (ACA), a dermatosis caused by Borrelia burgdorferi infection, and 40 patients with morphea, a disease of heterogeneous origin where a borrelia etiology has been suggested in some cases, both clinically and histologically to define the differences between these two dermatoses. Clinically, ACA involves acral body sites with lower temperatures, is seen mostly in elderly persons, and presents as a livid discoloration that is not sharply demarcated. Morphea can be localized in embryonal structures, affects any age and body site, and exhibits extension at the periphery of the lesions. Histologically, ACA shows atrophy of collagen and elastic tissue as well as hypertrophic basophilic elastic tissue; whereas in morphea, sclerosis and polarizing elastic tissue are prominent. Graft-versus-host-like reactions may be present in both dermatoses. Immunohistochemical testing with different lymphocyte markers showed differences only in the expression of HLA-DR antigens. These conditions can be distinguished from each other on a clinical and histological basis in most cases. In 17% of morphea biopsy specimens, however, histological differentiation from ACA was not possible. Moreover, the histological pattern of morphea was not associated with a positive borrelia serology.

Spirochetes in atrophic skin lesions accompanied by minimal host response in a child with Lyme disease

Acrodermatitis chronica atrophicans, which has rarely been observed in the United States, is a late skin manifestation of Lyme borreliosis. A 12-year-old girl who spent summers on Cape Cod presented with a 2-year history of hyperpigmentation and atrophy of the skin on the hands, wrists, and ankles. The skin biopsy specimen of an affected area showed mild dermal fibrosis, a few inflammatory cells, and spirochetes morphologically compatible with Borrelia burgdorferi. An IgG antibody response to B. burgdorferi could be elicited by immunoblotting, but not by enzyme-linked immunosorbent assay. We conclude that this patient had chronic Lyme borreliosis manifested only by indolent infection of the skin.

Hautmanifestationen der Lyme-Borreliose

The dermatological symptoms of Lyme borreliosis present with a typical clinical pattern and characteristic time of appearance. In contrast to other manifestations of Lyme borreliosis they are easily recognizable in most of the cases. In the first stage, erythema migrans arises at the tick bite site. With this symptom the diagnosis of Lyme borreliosis can be established. During all manifestations of Lyme borreliosis the history of erythema migrans is an important parameter to verify the diagnosis. In the early stage of disease a lymphocytic proliferation can appear at the tick bite site, at the ear lobe, or at the mamilla. Borrelia lymphocytoma can be diagnosed when antibodies against Borrelia burgdorferi are positive. Years after infection, acrodermatitis chronica atrophicans arises at distal body sites causing livid swelling and gradually skin atrophy. Skin lesions can be accompanied by neuropathies, mostly of the lower legs, which in contrast to the skin lesions, do not respond well to antibiotic therapy. There is evidence that some cases of Shulman syndrome, morphea and lichen sclerosus et atrophicus might be related to a borrelia infection as indicated by cultivation of B. burgdorferi from skin biopsies of morphea and response to antibiotic treatment in some cases. The classical dermatological symptoms of Lyme borreliosis, erythema migrans, borrelia lymphocytoma and acrodermatitis chronica atrophicans respond to oral antibiotic treatment. In acrodermatitis chronica atrophicans parenteral antibiotic therapy is sometimes necessary.

Periarticular fibrous nodules in Lyme borreliosis

Periarticular fibrous nodules have been described in patients with late-phase acrodermatitis chronica atrophicans (ACA) in the setting of Lyme borreliosis. We report the clinical and histopathological study of two patients with periarticular fibrous nodules and with Lyme borreliosis and discuss the relationship between these nodules and ACA.

Lyme borreliosis: Ten years after discovery of the etiologic agent, Borrelia burgdorferi

Since the recovery of its causative agent, Borrelia burgdorferi, in 1981, Lyme borreliosis has become the most prevalent tick-borne disease in the United States as well as in Europe. Its steadily increasing clinical spectrum now includes erythema migrans, acrodermatitis chronica atrophicans, lymphadenosis beniga cutis, arthritis, myocarditis, progressive meningoencephalitis, myositis, and various ocular and skin disorders. The true incidence of Lyme borreliosis in the world is unknown. In the United States, it has increased from 2,000 cases in 1987, to more than 8,000 in 1989. It occurs now in regions where the tick vectors, Ixodes dammini and Ixodes pacificus, are absent and where other species of ticks may be responsible for maintaining and distributing the spirochete. In Europe, Lyme borreliosis has been reported from 19 countries; its occurrence coincides with the distribution of the vector tick, Ixodes ricinus and possibly Ixodes hexagonus. Specific and dependable serological tests are still not available, but development of probes for specific antigens and the polymerase chain reaction appear promising in detecting ongoing infections and in identifying B. burgdorferi in ticks, animal, and human hosts. Brief reference is made to advances in the preparation of whole cell and genetically engineered vaccines.

Borrelia burgdorferi—associated cutaneous B cell lymphoma: Clinical and immunohistologic characterization of four cases

Four patients with low-grade malignant B cell lymphoma of the skin in association with chronic Borrelia burgdorferi infection are presented. Plaque-shaped or nodular erythematous lesions with ill-defined borders were seen. Clinical progression was slow; the skin tumors occurred for up to 7 to 15 years. Extracutaneous involvement was found in only one case. Immunohistologic investigations showed an expression of B cell markers with restriction to only one light chain type and absence of T cell antigens. The growth fraction was 5% to 30%, as shown with the monoclonal antibody Ki-67. The immunoarchitecture of the tumors in three patients was unusual compared with established criteria for cutaneous B cell lymphoma and revealed similarities to mucosa-associated B cell lymphoma. Some immunohistologic heterogeneity may indicate the development of monoclonal proliferation that originated from different phases of B lymphocytic differentiation. In three cases no clinical signs of B. burgdorferi infection were found; in one patient acrodermatitis chronica atrophicans was present. The occurrence of acrodermatitis chronica atrophicans and malignant lymphomas was frequently reported in the European literature before B. burgdorferi was recognized. These findings suggest a relation between B. burgdorferi infection and cutaneous B cell lymphoma. In geographic regions where infected ticks are present, borreliosis should be considered in patients with cutaneous B cell lymphoma.

Diagnosis of Lyme Disease Based on Dermatologic Manifestations

Lyme disease, or Lyme borreliosis, is an infection caused by the spirochete Borrelia burgdorferi, which is most commonly transmitted to humans by a tick bite. Characterized by early and late phases, Lyme disease is a multisystem illness involving the skin, heart, joints, and nervous system. Diagnosis is based predominantly on clinical manifestations, the most specific being dermatologic. Thus, recognizing the dermatologic manifestations of Lyme disease is important for diagnosis and institution of appropriate, effective therapy. Approximately 75% of patients with Lyme disease present with the pathognomonic skin lesion erythema migrans, an expanding erythematous lesion. During early infection, secondary erythema migrans lesions or Borrelia lymphocytoma may occur. Borrelia lymphocytoma commonly presents as an erythematous nodule on the ear lobe or nipple. During late infection, acrodermatitis chronica atrophicans, an erythematous, atrophic plaque unique to Lyme disease may appear; it has been described in about 10% of patients with Lyme disease in Europe. Fibrotic nodules associated with acrodermatitis chronica atrophicans as well as other sclerotic and atrophic lesions, such as morphea, lichen sclerosus et atrophicus, anetoderma, and atrophoderma of Pasini and Pierini, have been seen late in the course of Lyme disease. In a few cases, other sclerodermatous lesions, such as eosinophilic fasciitis and progressive facial hemiatrophy, have been linked to B. burgdorferi infection. We review the cutaneous lesions associated with Lyme disease.

Lyme Borreliosis

The skin diseases Erythema (chronicum) migrans (ECM, EM), Lymphadenosis benigna cutis (LABC), and Acrodermatitis chronica atrophicans (ACA) have long been described in northern Europe, and dermatologists are very familiar with these manifestations, which have been successfully treated with penicillin for about 40 years without the causative agent being known. Certain neurologic symptoms could be linked to tickbites during the 1920's and later also to EM. In 1977, Steere et al. reported a new form of inflammatory arthritis, mainly in school children in the community of Lyme, Connecticut, U.S.A., which they could also associate with preceding erythema and tickbites. Five years later, Burgdorfer was able to isolate Borrelia spirochetes from Ixodes ticks, which are known to be vectors of Lyme disease as well as of EM and ACA. The following year, Borrelia spirochetes were also isolated from Ixodes ticks and from skin lesions of patients in Sweden and Germany. These findings resulted in a large number of reports of new discoveries related to this infection, which is now known under the names of tick-borne or Lyme borreliosis and, in the U.S., also as Lyme disease or Lyme arthritis. It has proven to be a great imitator disease, mainly through its involvement of the neurological system, and to be far more widespread than previously thought. The full course of the disease is not yet known, however it is clinically, like another spirochetosis, syphilis, divided into early and late stages. Manifestations involve mainly the skin, the joints, the nervous system (Neuroborreliosis), and the heart. Antibiotic treatment is effective, especially in the early stages. Like syphilis, the disease can be self-healing without treatment. People who are exposed to ticks should be aware of the risk of contracting this disease, also in Japan where Ixodes ticks have been shown to be carriers of Borrelia spirochetes. Cases, particularly of EM, but also with neurological symptoms, have already been diagnosed in Hokkaido, Honshu, Shikoku, and Kyushu. As Lyme borreliosis is now proven to exist in Japan, it is beneficial for dermatologists to know about the various presentations of this disease. This paper will briefly summarize the historical background, the clinical stages, the diagnosis, and the treatment of Lyme borreliosis, with a summary of the present situation in Japan.

Improved immunoglobulin M serodiagnosis in Lyme borreliosis by using a mu-capture enzyme-linked immunosorbent assay with biotinylated Borrelia burgdorferi flagella

A mu-capture enzyme-linked immunosorbent assay (ELISA) for detection of serum immunoglobulin M (IgM) antibodies to Borrelia burgdorferi by using biotinylated purified B. burgdorferi flagella was developed. The diagnostic performance of the mu-capture ELISA was compared with that of a conventional indirect ELISA. Sera from untreated patients with erythema migrans (n = 50), neuroborreliosis (n = 100), and acrodermatitis chronica atrophicans (ACA; n = 48) were investigated. The cutoff of the ELISAs was adjusted to a diagnostic specificity of 98% on the basis of examination of 200 serum specimens from healthy controls. The mu-capture ELISA increased the diagnostic sensitivity in patients with erythema migrans from 32 to 48% (P less than 0.01) and in patients with neuroborreliosis from 37 to 57% (P less than 0.001). Because of an increased signal/noise ratio, the mu-capture ELISA yielded a significantly better quantitative discrimination of individual positive measurements from the cutoff (P less than 0.001). The increased signal/noise ratio was most likely a consequence of the elimination of IgG competition for the test antigen. This may also explain why 12% of patients with ACA showed significantly increased specific IgM levels only by the mu-capture ELISA. Of patients with ACA, 27% had IgM rheumatoid factor. The mu-capture principle with a directly labeled antigen showed no interference with IgM rheumatoid factor, in contrast to the indirect ELISA. The high diagnostic performance and ease of this three-step mu-capture ELISA make it suitable for routine anti-B. burgdorferi IgM serodiagnosis.

Intrathecally produced antibodies to Borrelia burgdorferi measured by IgG-capture ELISA

An IgG-capture enzyme-linked immunosorbent assay (ELISA) which directly measures the intrathecal production of Borrelia burgdorferi-specific IgG in neuroborreliosis is described. The method is based on the simultaneous measurement of IgG-specific antibodies in paired cerebrospinal fluid (CSF) and serum samples. Sixty-nine paired CSF/serum samples from 64 patients with neuroborreliosis or other neurological disorders and six samples from acrodermatitis chronica atrophicans (ACA) patients were analysed by IgG-capture ELISA. Of 12 samples from patients with early neuroborreliosis, intrathecal production of B. burgdorferi-specific IgG could be demonstrated in 11 samples. Of 56 patients with other neurological disorders of known or unknown etiology, intrathecal production of B. burgdorferi-specific IgG was demonstrated in one patient who had a history compatible with a previous neuroborreliosis. No intrathecal production was found in the samples from ACA patients in spite of high Borrelia titres in their CSF as measured by indirect ELISA. In conclusion, the B. burgdorferi IgG-capture ELISA is a sensitive and reliable method for the detection of intrathecal production of IgG antibodies to B. burgdorferi. It is advantageous in comparison to the indirect ELISA as it does not require correction for leakage across the blood/CSF barrier.