Scleroderma Information » Scleroderma » Lymphoproliferative responses to Borrelia burgdorferi in circumscribed scleroderma
Question:
Lymphoproliferative responses to Borrelia burgdorferi in circumscribed scleroderma Breier F.; Klade H.; Stanek G.; Poitschek C.; Kirnbauer R.; Dorda W.; Aberer E. Department of Dermatology, University of Vienna Medical School, Waehringer Guertel 18-20,A-1090 Vienna Austria British Journal of Dermatology (United Kingdom) 1996, 134/2 (285-291) Humoral immune responses to Borrelia burgdorferi (Bb) have been reported to occur in certain patients with circumscribed scleroderma (CS) (morphoea). Together with the isolation of spirochaetes from CS skin biopsies, this finding was taken to suggest Bb as the aetiological agent of CS. Since there is cellular immunoreactivity to Bb in patients with chronic Lyme borreliosis (LB), Bb-specific lymphocytic responses were tested in patients with CS. For this purpose, peripheral blood mononuclear cells from CS patients and, as controls, from patients with various manifestations of LB, and from healthy volunteers without any evidence of Bb infection, were exposed to Bb organisms for 5 days and then assayed for DNA synthesis. Stimulation indices (SI) > 10 were scored positive. By performing lymphocyte proliferation tests we found: (i) that not only patients with various manifestations of LB but also a considerable percentage of seropositive (five of 13 = 38%) and seronegative (six of 26 = 23%) CS patients exhibit an elevated Bb-induced lymphocyte proliferation; (ii) that the magnitude of the cellular response seen in CS patients is comparable to that encountered in patients with established Bb manifestations; and (iii) that, within a given patient, antibiotic therapy can result in a significant reduction of this response. These results support a causative role of Bb in at least some CS patients. Bb-induced lymphocyte responses were also seen in both seropositive and seronegative erythema chronicum migrans patients. These findings show that the pattern of Bb-specific immune responses is more complex than previously thought, and underscore the importance of lymphocyte function assays in evaluating the diagnosis of potential Bb infection in seronegative patients.
Response:
From British Journal of Dermatology October 2000 (Volume 142, Number 4) Morphoea Is Neither Associated With Features of Borrelia Burgdorferi Infection, Nor Is This Agent Detectable in Lesional Skin by Polymerase Chain Reaction Weide B, Schittek B, Klyscz T, et al Br J Dermatol. 2000;143:780-785 In 1985, Aberer and colleagues submitted a letter to the Lancet proposing a causative link between spirochetal infection and morphea,[1] and since then the topic has been highly controversial. During the past decade and a half, evidence has accumulated both in support of and against the association.[2-5] Weide and colleagues now provide compelling data that may finally settle the controversy about "Borrelia-induced morphea." They conclude that there is no association. To reach such a definitive statement, Weide and colleagues attacked the hypothesis that Borrelia and morphea are linked on several levels, using a combination of clinical, serologic, and DNA evidence. A total of 54 patients with morphea were prospectively enrolled in their study, and 52 of these completed a questionnaire designed to assess the likelihood of Borrelia exposure. All patients included in the study presented to the University Department of Dermatology in Tubingen, Germany, between January 1998 and March 1999 (38 women, 16 men; mean age 42.8 years). A total of 21 of these patients had not received any form of antibiotic therapy since disease onset, and 2 patients had coexisting acrodermatitis chronica atrophicans (ACA). A total of 52 of 54 morphea patients, in addition to 104 age- and sex-matched general dermatology patient controls and 25 patients with known late-stage Borrelia infection manifesting as ACA were asked the following questions: Have you had any tick bites within 10 years before onset of disease? Any tick bites (generally) in the last 20 years before examination? Any skin rashes suspicious for erythema migrans (EM) within 10 years before onset of disease? (Illustrative clinical photographs were shown.) Do you spend time frequently in forests? Do you have a garden at your place of residence? Impressively, there was no difference in response between the morphea and negative control groups. In contrast, the ACA group reported a statistically significant, much higher prevalence of tick bites (60.0% vs 15.3% within 10 years), skin rashes suspicious for EM (52.0% vs 6.1%), time spent in the forest (96.0% vs 40.0%), and presence of a garden at the place of residence (96.0% vs 73.1%). For the next phase of the study, 53 patients with morphea had their serum checked for IgG and IgM reactivity against Borrelia burgdorferi. IgM titers were negative in all cases, and IgG titers were positive in only 3 of 53 cases — 2 of which also had ACA. Therefore, only 1 patient with plaque morphea alone had a positive IgG anti-borrelial titer. As a final step, Weide and colleagues performed polymerase chain reaction (PCR) analysis on punch biopsy samples taken from lesional skin of 33 patients with morphea, including 2 patients with concurrent ACA. Amplification was done using nested PCR for 2 different borrelial gene sequences — ospA and the borrelial ribosomal RNA gene. This technique provides high sensitivity for detection of all known borrelial subtypes. None of the results of the sampled morphea lesions were positive for borrelial DNA. In contrast, borrelial DNA was successfully amplified from 1 patient with ACA and 1 patient with EM. Discussion Weide and colleagues have provided compelling data that a large group of patients with clinical and biopsy-confirmed morphea show no clinical, serologic, or PCR evidence of concurrent or antecedent borrelial infection. Furthermore, their questionnaire data suggest that a tick-borne, as yet unidentified causative infectious agent is also unlikely. Perhaps, a decade and a half after the controversial hypothesis by Aberer and coworkers first surfaced, it is finally time to put the question to rest. References Aberer E, Neumann R, Stanek G. Is localized scleroderma a Borrelia infection? [letter]. Lancet. 1985;ii:278. Schempp C, Bocklage H, Lange T, et al. Further evidence for Borrelia burgdorferi infection in morphoea and lichen sclerosis et atrophicus confirmed by DNA amplification. J Invest Dermatol. 1993;100:717-720. Wienecke R, Schlupen EM, Zochling N, et al. No evidence for Borrelia burgdorferi-specific DNA in lesions of localized scleroderma. J Invest Dermatol. 1995;104:23-26. Fujiwara H, Fujiwara K, Hashimoto K, et al. Detection of Borrelia burgdorferi DNA (B garinii or B afzelii) in morphoea and lichen sclerosis et atrophicus tissues of German and Japanese but not of US patients. Arch Dermatol. 1997;133:41-44. Weide B, Walz T, Garbe C. Is morphoea caused by Borrelia burgdorferi? a review. Br J Dermatol. 2000;142:636-644
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