As a result of the recent interest in Lyme disease a large number of papers has been published on its different aspects. The purpose of this thesis is to present a comprehensive study of the most important histopathological manifestations based on the experience obtained during the last 11 years. In the first years, serology was not yet available in our laboratory, the histopathology and demonstration of spirochaetes in tissue were a part of the cliagnostic tools; till to day the recognition of the microorganisms in tissue is sometimes used in diagnostic and therapeutical problems. ... Zie: Summar

Koning, Johannes de

English

University of Groningen

   University of GroningenHispathologic aspects of Lyme Borreliosis.Koning, Johannes deIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1994Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Koning, J. D. (1994). Hispathologic aspects of Lyme Borreliosis. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 12-11-2019SUMMARYThe gradualunveilingof the spectre of "Lyme disease" or "Lymeborreliosis" traces backto the perseverance of two mothers in the village of Lyme, Connecticut, USA, who in1 9 75 drew attention to an epidemic of arthritis in children in their village. Epidemiologicstudies made it clear that the diseasernostlikelywas of infectious origin andtÍansmittedby a tick bite. AÍter the discovery of infection of the ticks by a spirochaete of genusBorrelia, it became apparent hat the arthritis was caused by inÍection with this microbe,Iater named Borrelia burgdorferi after its discoverer Burgdorfer.On tlre basis of observed reiations between "Lyrne disease" and other disease manifes-tations, a spectÍa of "Lyme disease" gradually developed.Chapter 2 provides an overview of the history of "Lyme disease", of the epidemiologyand aetiology and oÍ the different stages of the disease with the different clinicalmanifestations. Diseases like "Erythema chronicum migïans", " Lymphadenosis benignacutis", "Bannwarth's syndrome" and "Acrodermatitis chronica atrophicans " were aIIrecognized as a manifestation of Lyme borreliosis after the discovery of the spirochaetalnature of the disease and the cultivation of the microbe. B. burgdorferi can be dividedin three genetic types:B . burgdorferi sensu stricto, B. burgdorteri gafinii andthird groupnarned Borrelia burgdorfi Afzelius. These different genetic types aÍe respectivelyassociated with arthritis, neuroborreliosis and acrodermatitis chronica atrophicans.Only B. burgdorferi sensu stricto is found in the United States, in Europe all3 types ofBorrelia strains are present.Silver impregnation methods are routinely employed to demonstrate spirochaetes intissue samples. Because the organisms maybe sparse, amodificationof silverimpregnationwas developed with a better contrast.Chapter 3 and 4 describe the staining and detectingof B. burgdorfeilinthe tissue by theBosma-Steiner staining, a short-time high-concentrate silver impregnation methodpreceded by treatment of the slides with amylase. The spirochaetes show coiled,undulating, and long elongatedforms. TheBosma-steiner stairungappear more sensitivewhen compared to results published for other silver impregnation methods.DemonstrationofB. bwgdorferiinlymphvesselsandtheCsFofpatientswithBannwarth'ssyndrome has not been reported before.Cardiac involvement is reported in chapter 5. The most troublesome manifestations ofcardiac disease are the several degrees of atrioventricular block. Right ventricularbiopsies of these patients showed myocardial and subendocardial infiltrates consistingoÍ lymphocytes, histiocytes and plasma cells. Silver staining reveals spirochaetescharacteristíc of B, burgdo{eri near and in the in{iltrates. In one patient single fibrenecrosis was seen in the myocardium (chapter 5a). In chapter 5b a patient is reporteddying suddenly while being hospitalízed for suspected Lyme disease. Un autopsyshowed cardiac conducting system involvement with necrosis oÍ associated musclefibres in the sinoatrial node.In the last part of this chapter (5c) we report a patient with pericarditis. B, burgdorfericould be identified in the pericardial fluid by a monoclonal antibody method, the143immunogold-silver staining and by direct immunofluorescence using a serum of apatient with proven Lyrne disease.Involvement of skeletal muscles is relatively rare in Lyme-disease. In chapter 6 eightpatients are described with myositis. Muscle biopsies showed a focal nodular myositiswith perivascular and perimysial lymphohistiocytic and plasmacellular infiltrate.Degeneration of sorne muscle fibres was present near the inflarnmatory infiltrates. Onlyfew spirochaetes weïe found. The predorninance of B-cells and T-cells with helperphenotype suggests thepossibilitythatthe degenerationof the musclefibres is mediatedvia a humoral immune mechanism.A study of acrodermatitis chronica atrophicans is reported in chapter 7. Specialattention was given to changes in the elastic tissue and elastin plexus of the skin, to thenurnber of spirochaetes as detected by silver impregnation and to ultïastructuralchanges. Loss of elasticity oÍ the skin appeared to coincide with the disappearance oÍ theelastin plexus consisting of oxytalan fibres and the elaunin plexus. Quantification oÍspirochaetes revealed that they were especially rare in atrophic skin areas ancl easier tofind in inÍiltrative and nodular lesions. Ultrastructural studies showed not onlydegeneration oÍ collagen and elastic fibres, but also of nerve fibres. Again the scarcity ofrnicroorganisns in relation to the extent of the tissue damage is striking.Chapter 8 {ocuses on review of the histopathologic maniÍestations of Lyrne borreliosis.The disease starts with a typical skin lesion: Erytherna chronicum migrans. The secondstage is characterized by organ involvement, especially conducting disorders of the heartand meningoradiculitis. The main manifestations of the third stage are arthritis,acrodermatitis chronica atrophicans, chronic encephalitis and peripheral neuropathy.Borrelia bttrgdorferi seerns to cause direct tissue damage or to provoke immunemechanisms resulting in inflammation with focal necrosis, but diffuse involvement ofan organ may occur. The inflammatory inÍiltrate in stage I and II, consists predominantlyof lymphocytes usually localized around blood vessels and in the interstitiurn/ neutrophrlsseem to occur in recent onset of the disease (ECM) and in acute exaceïbations (hepatitisand arthritis ). Large atypical cells, resembling Reed-Sternberg cells can be found in activegerminal centers of Borrelial lymphocytoma. Plasrna cells and sornetilnes fibrosis arefeertures of third stage. There exist relative few staining techniques by which B . burgdorf erimay be demonstrated. The Bosrnir-Steiner method provides a high contrast betweenpositive staining spirochaetes and a negativebackground. Those usingirnrnunohistologywith antibodies are of course more speciÍic. The microorganisms are generally sparse ilndthey rnay be difficult to find in the tissue. In sorne lesions they have not beendernonstrated so far.From these studies, that especially concerned skeletal and cardiac muscular tissue andskin, it is quit clear that histopathological changes in Lyrne disease usually consist ofnonspecific infiammation which is accorrrpanied by tissue destruction. The possibilityof underlyin gB. bttrgdorferi infection can be suspectedwhen the pathoiogist is acquaintedwith the different manifestations of Lyme disease or when he or she is alerted to thepossibility on the basis of adequate clinical information. Because the microorganismsare toxic or (humorally) irnrnune mediated tissue damage is a possibility. Recovery, evenof chronic disease, after antibiotic treatment demonstrates however, that the presenceof viable microorganisms is needed for the disease to progÍess.t44Deborrekindrepideoorslgeinfvero(bttg'Doorhet sHcVETSCde s1mrgrchrorkzrn .stricltyperchrora 1 ; f  .Í  Í ^NLverbrgevo(Aavan Ívaninfiltinfiltvoor5a ) .Inh i i  icardde siPeri,vandirepailHhoonod

Hispathologic aspects of Lyme Borreliosis.

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