Peripheral neuropathy in acrodermatitis chronica atrophicans - effect of treatment.

Forty-seven patients with the late borrelial manifestation acrodermatitis chronica atrophicans (ACA) and with objective neurological and/or neurophysiological findings were followed up after antibiotic treatment with dermatological, serological, neurological and neurophysiological controls. Despite a good therapeutic effect on ACA lesions, specific antibody values and symptoms of irritative nerve lesions, the objective neurological and neurophysiological findings of nerve deficit remained unchanged. There was no progress of neuropathy findings during the follow-up time. Our interpretation of the results is that the remaining neuropathy signs after treatment of ACA are neurological sequelae and not manifestations of persisting Borrelia infection.

Polyneuropathy in late Lyme borreliosis - a clinical, neurophysiological and morphological description.

In a prospective study, detailed clinical and neurophysiological examinations were performed in 17 patients with polyneuropathy associated with the late borrelial manifestation acrodermatitis chronica atrophicans (ACA). Similar clinical and neurophysiological signs were found in most of the patients. The findings were those of a sensory polyneuropathy, mainly affecting large nerve fibres. Marked abnormality of vibration threshold was a common finding and in 4 patients this raised a suspicion of spinal cord engagement, in addition to a polyneuropathy. Sural nerve biopsy, performed in 3 of the patients, showed a mainly axonal neuropathy. Biopsy findings did not confirm earlier reports of vasculitis of epineural vessels in ACA-associated polyneuropathy.

No evidence for specific in vitro lymphocyte reactivity to HgCl2 in patients with dental amalgam-related contact lesions.

Blood lymphocytes from 20 patients with oral contact lesions to dental amalgam and 10 healthy individuals were analyzed for HgCl2-induced proliferation in vitro, using both a modified assay and a conventional assay. The release of interferon-gamma (IFN-gamma) was measured in cell supernatants. Six patients displayed positive reactions in patch tests to mercuric compounds. No significant differences were recorded in HgCl2-induced proliferation in cells from patients and controls, since only few in the whole material responded to submitogenic concentrations. IFN-gamma was detectable in cell supernatants from some patients but also from controls and is not predictive of mercury allergy. Neither the phenotypes of peripheral lymphocyte subsets, the frequency of circulating cells expressing the interleukin-2 (IL-2) receptor, spontaneous lymphocyte proliferation nor concentrations of serum interleukin-6 differed between patient and control samples. In contrast to what has been claimed before, we did not find any evidence for specific in vitro lymphocyte reactivity in patients with oral contact lesions.

[Despite better knowledge of pathogenesis and treatment: atopic eczema--a disease with increasing incidence in Sweden]. / Trots bättre kunskaper om patogenes och behandling: atopiskt eksem--en sjukdom som ökar i Sverige.

The past twenty years have witnessed an increasing incidence of atopic dermatitis in Western Europe. The article consists in a discussion of the pathogenesis, clinical signs and treatment of this common skin disease. Both an IgE-mediated reaction on epidermal Langerhans cells, and a physiological/biochemical defect of the skin barrier structure may be crucial factors of the multifactorial pathogenesis. Local treatment with corticosteroids and moisturisers remains the basic approach, though the development of new more specific treatments is under way. Although much remains to be learned about atopic dermatitis, today all patients can be offered effective treatment resulting in improved quality of life.

Acrodermatitis chronica atrophicans: histopathologic findings and clinical correlations in 111 cases.

We studied 111 consecutive, untreated and serologically confirmed patients with acrodermatitis chronica atrophicans. Emphasis was on the histopathologic patterns of erythematous and fibrous lesions, and on an assay used to correlate histopathologic findings with such clinical features as fibrous nodules, ulnar bands and the pain reaction allodynia. There was a significant correlation between allodynia and signs of marked inflammation, but not between allodynia and neural and perineural cell infiltrates or fibrosis. Moreover, there was no significant correlation between serum IgG titers to Borrelia and the density of inflammatory cell infiltrates or the proportion of plasma cells in tissue. Histopathologic examination did not reveal any important differences between fibrous nodules, ulnar bands and sclerodermatous lesions. The histopathologic pattern is not diagnostic per se, but characteristic enough to alert the experienced pathologist.

Peripheral neuropathy in acrodermatitis chronica atrophicans - a late Borrelia manifestation.

Clinical and/or neurophysiological signs of peripheral neuropathy were found in 64% of 63 consecutive untreated patients with the late borrelial manifestation acrodermatitis chronica atrophicans (ACA). The neuropathy frequency was significantly higher in the patients than in 30 age- and sex-matched control persons of whom 27% had neuropathy findings. The most common neuropathy in ACA was a symmetric distal sensory polyneuropathy. In a subgroup of patients with localized or asymmetric neuropathy, the changes were found more often in extremities with than without visible ACA lesions. Neuropathy symptoms, most often pain and/or paresthesia, were present in 64% of the patients, compared to in 13% of the control persons. Thus, both symptoms and signs of neuropathy were significantly more frequent in patients with untreated ACA than in control subjects.

Polymerase chain reaction for detection of Borrelia burgdorferi DNA in skin lesions of early and late Lyme borreliosis.

The aim of this study was to evaluate the polymerase chain reaction (PCR) as a diagnostic tool for Lyme borreliosis on large numbers of samples from clinically well-defined cases of early and late cutaneous borreliosis. Skin biopsy specimens from patients with erythema migrans and acrodermatitis chronica atrophicans were analysed blindly together with an equal number of control biopsies. Using two different dilutions of each DNA specimen increased the number of total positives detected. All of the 76 control biopsies were PCR negative. Biopsy specimens from 18 of 26 (69%) erythema migrans lesions and from 22 of 36 (61%) acrodermatitis chronica atrophicans lesions were PCR positive. Fourteen post-therapy biopsies from patients with acrodermatitis chronica atrophicans were all negative, supporting the opinion that antibiotic therapy is successful in this chronic manifestation of Lyme borreliosis.

Roxithromycin in Lyme borreliosis: discrepant results of an in vitro and in vivo animal susceptibility study and a clinical trial in patients with erythema migrans.

A new semisynthetic macrolide roxithromycin was evaluated for its potential use in the treatment of Lyme borreliosis. Using a macro-dilution broth technique, Borrelia burgdorferi was shown to be susceptible to roxithromycin with a minimal bactericidal concentration (MBC) of 0.06-0.25 microgram/ml. A systemic B. burgdorferi infection was established in gerbils; a dosage of greater than or equal to 25 mg/kg/day roxithromycin for 10 days eliminated the infection. A single blind, randomized multicenter study was performed to evaluate the efficacy of roxithromycin 150 mg b.i.d. versus phenoxymethyl-penicillin 1 g b.i.d. for 10 days in patients with uncomplicated erythema migrans. The study was interrupted when 19 patients had enrolled because of five treatment failures. All 5 patients had received roxithromycin; three patients had persisting or recurrent erythema migrans, one developed a secondary erythema migrans-like lesion and severe arthralgia and one developed neuroborreliosis. B. burgdorferi was isolated from skin biopsies after roxithromycin therapy from two patients with persistent erythema migrans and both isolates were still highly susceptible to roxithromycin (MBC = 0.03 microgram/ml). No treatment failures were seen in 10 patients treated with phenoxymethyl-penicillin. Roxithromycin is thus not recommended for treatment of 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.

Comparison of four different serological methods for detection of antibodies to Borrelia burgdorferi in erythema migrans.

Three different enzyme-linked immunosorbent assays (ELISA) and Western blot were compared in regard to the detection of antibodies to Borrelia burgdorferi in sera from 100 patients with erythema migrans and from 100 controls. For IgG detection, a commercial indirect ELISA kit with flagellum antigen (flagellum ELISA) was significantly more sensitive than the routinely-used indirect ELISA with sonicated whole-cell antigen (sonicate ELISA) (p = 0.008). The difference in positivity in the IgM test was of borderline significance (p = 0.058). An IgM antibody-capture ELISA with sonicated whole-cell antigen (capture ELISA) was significantly more sensitive than either the IgM sonicate ELISA (p less than 0.001) or IgM flagellum ELISA (p less than 0.001). With the Western blot pattern chosen as the criterion for positivity, IgM Western blot was at least equal to IgM capture ELISA in terms of the number of positive erythema migrans sera, but a frequent discrepancy between these two tests was noted as to positivity in individual sera. IgG Western blot was considered to be of less value for the diagnosis of current disease due to a high occurrence of positivity among controls.

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.

Brainstem response audiometry in chronic Lyme borreliosis.

Auditory brainstem responses (ABR) were investigated in 26 patients with acrodermatitis chronic atrophicans, which is a late manifestation of Lyme borreliosis. Nine of the patients showed pathological ABR, four of them unilaterally and five bilaterally. The main pathological findings were: 1) Poor reproducibility of waves IV-V or of wave V; 2) Increased latency of wave V. After antibiotic treatment, ABR was improved in eight of the nine patients, and in three of them it was normal. In the five patients who did not completely recover, the improvement consisted in better reproducibility and a tendency towards normal wave V latencies. The results of this study indicate that the central nervous system may become involved in patients with acrodermatitis chronica atrophicans.

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.

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.