Studies performed in the 1970's and 1980's clearly indicated Lyme disease could be a serious chronic infection. They also determined seronegative Lyme was a concern and the disease was not cured with what was thought to be adequate antibiotic therapy. Below is a collection of some of these studies, many by the same authors who deny the existence of "chronic Lyme" today.

Hosp Pract. 1978 Apr;13(4):143-58.

Lyme arthritis: a new clinical entity.

Steere AC, Hardin JA, Malawista SE.

Named for the Connecticut town where the first identified cases occurred in 1972, this disorder has since been found elsewhere and may be caused by a virus transmitted by ticks. Attacks are often preceded by erythema chronicum migrans and are seldom prolonged, though they may recur. Symptomatic treatment only is advised, except in the rare instances of severe neurologic complications or myocardial conduction abnormality.

PMID: 658948 [PubMed - indexed for MEDLINE]

Arthritis Rheum. 1980 May;23(5):591-9.

Elevated levels of collagenase and prostaglandin E2 from synovium associated with erosion of cartilage and bone in a patient with chronic Lyme arthritis.

Steere AC, Brinckerhoff CE, Miller DJ, Drinker H, Harris ED Jr, Malawista SE.

A patient with chronic Lyme arthritis and roentgenographic evidence of bony erosion underwent a synovectomy; proliferative synovium (pannus), containing aggregates of small lymphocytes, was found adherent to eroded cartilage and bone. During 8 days in tissue culture, the synovial cells produced large amounts of collagenase and prostaglandin E2, but only low levels of both neutral and acid proteinases. Sixty-seven percent of the lymphocytes from the synovium were T cells; 19% were B cells. Attempts to identify agent/antigen in the synovial cells were unsuccessful. Thus, the synovium of this patient, whose disease appears to be tick-transmitted, resembles that of rheumatoid arthritis. This finding further supports the hypothesis that many possible agents, including infectious ones, trigger a common pathway in synovium, which leads to joint destruction.

PMID: 6246904 [PubMed - indexed for MEDLINE]

Yale J Biol Med. 1984 Jul-Aug;57(4):453-61.

The clinical spectrum and treatment of Lyme disease.

Steere AC, Malawista SE, Bartenhagen NH, Spieler PN, Newman JH, Rahn DW, Hutchinson GJ, Green J, Snydman DR, Taylor E.

Lyme disease was recognized as a separate entity because of close geographic clustering of affected children in Lyme, Connecticut, with what was thought to be juvenile rheumatoid arthritis. It then became apparent that Lyme disease is a complex, multisystem disorder. The illness usually begins in summer with erythema chronicum migrans and associated symptoms (stage 1). Weeks to months later, some patients develop neurologic or cardiac abnormalities (stage 2), and weeks to years later, many patients develop intermittent attacks of arthritis (stage 3), which may become chronic, with erosion of cartilage and bone. Patients with severe and prolonged illness have an increased frequency of the B-cell alloantigen, DR2. For patients with early Lyme disease, tetracycline appears to be the most effective drug, then penicillin, and finally erythromycin. High-dose intravenous penicillin is effective for the later stages of the disease.

PMID: 6516448 [PubMed - indexed for MEDLINE]

Radiology. 1985 Jan;154(1):37-43.

Lyme arthritis: radiologic findings.

Lawson JP, Steere AC.

Lyme disease is a newly recognized, multi-system disorder that may be associated with chronic arthritis. Of 25 patients with severe arthritic manifestations the most frequent radiographic finding was knee joint effusion. Intra-articular edema was often accompanied by a continuum of soft-tissue changes involving the infrapatellar fat pad, periarticular soft tissues, and the entheses, which were sometimes thickened, calcified, or ossified. Later in the illness, the joints of some patients showed typical changes of an inflammatory arthritis, including juxta-articular osteoporosis, cartilage loss, and cortical or marginal bone erosions. Less commonly, other patients demonstrated changes more characteristic of degenerative arthritis, including cartilage loss, subarticular sclerosis, and osteophytosis. Joint involvement of Lyme disease has similarities to juvenile arthritis and Reiter syndrome, but can usually be distinguished clinically and serologically from these entities.

PMID: 3964949 [PubMed - indexed for MEDLINE]

Ann Intern Med. 1986 Jun;104(6):798-800.

Borrelia burgdorferi in joint fluid in chronic Lyme arthritis.

Snydman DR, Schenkein DP, Berardi VP, Lastavica CC, Pariser KM.

Although indirect evidence suggests that chronic Lyme arthritis is caused by persistent infection with Borrelia burgdorferi, direct visualization has been lacking. We report the demonstration of B. burgdorferi from synovial fluid aspirated from the right knee of a 31-year-old man with Lyme arthritis for more than 1 year. After 6 days, culture medium inoculated with synovial fluid showed one motile and several nonmotile spirochetes. Direct immunofluorescence staining showed reactivity with anti-B. burgdorferi serum. Spirochetes were not seen in subcultured material. The patient's arthritis improved with high-dose intravenous penicillin. Identification of B. burgdorferi from the joint fluid of a patient with long-standing arthritis supports the concept that the arthritis is due to persistent infection.

PMID: 3518562 [PubMed - indexed for MEDLINE]

J Bone Joint Surg Am. 1986 Sep;68(7):1057-61.

Chronic arthritis of the knee in Lyme disease. Review of the literature and report of two cases treated by synovectomy.

McLaughlin TP, Zemel L, Fisher RL, Gossling HR.

The arthritis that may be a part of Lyme disease, a spirochetal infection transmitted by ticks, has not been widely reported in the orthopaedic literature. Established chronic arthritis in patients who have Lyme disease most commonly affects the knee and may cause erosive joint disease. Antibiotics given early in the course of the disease can prevent chronic arthritis. When the arthritis is established, penicillin administered intravenously is curative in as many as 55 per cent of patients, but medical therapy alone may be insufficient to successfully treat the chronic stage of arthritis.

Zentralbl Bakteriol Mikrobiol Hyg A. 1986 Dec;263(1-2):201-5.

Clinical manifestations of Lyme disease.

Steere AC, Bartenhagen NH, Craft JE, Hutchinson GJ, Newman JH, Pachner AR, Rahn DW, Sigal LH, Taylor E, Malawista SE.

Lyme disease typically begins with a unique skin lesion, erythema chronicum migrans (ECM) (stage 1). Patients with this lesion may also have headache, meningeal irritation, mild encephalopathy, multiple annular secondary lesions, malar or urticarial rash, generalized lymphadenopathy and splenomegaly, migratory musculoskeletal pain, hepatitis, sore throat, non-productive cough, conjunctivitis, periorbital edema, or testicular swelling. After a few weeks to months (stage 2), about 15% of patients develop frank neurologic abnormalities, including meningitis, encephalitis, cranial neuritis (including bilateral facial palsy), motor or sensory radiculoneuritis, mononeuritis multiplex, or myelitis.

At this time, about 8% of patients develop cardiac involvement--AV block, acute myopericarditis, cardiomegaly, or pancarditis. Throughout this stage, many patients continue to experience migratory musculoskeletal pain in joints, tendons, bursae, muscle, or bone. Months to years after disease onset (stage 3), about 60% of patients develop frank arthritis, which may be intermittent or chronic. Recently evidence suggests that Lyme disease may also be associated with chronic neurologic or skin involvement. Thus, Lyme disease occurs in stages with different clinical manifestations at each stage, but the course of the illness in each patient is highly variable.

PMID: 3554839 [PubMed - indexed for MEDLINE]

Zentralbl Bakteriol Mikrobiol Hyg A. 1986 Dec;263(1-2):169-78.

The spectrum of organ and systems pathology in human Lyme disease.

Duray PH, Steere AC.

Lymphocytes, plasma cells, and mononuclear phagocytes are frequently found in human tissues infected by the Lyme disease spirochete, Borrelia burgdorferi. Experience has shown that these cells comprise the tissue bed inflammatory infiltrate in Lyme disease affecting the joint synovia, myocardium, and skin. While many differences otherwise exist, Lyme synovitis has lymphoplasmacellular similarities with rheumatoid synovitis, lymphoplasmacellular epimyocarditis similarities with syphilitic myocarditis, and occasionally synovial endarteritis obliterans. Silver staining can demonstrate the spirochete if a careful search is done.

PMID: 3577479 [PubMed - indexed for MEDLINE]

Arthritis Rheum. 1987 Apr;30(4):448-50.

Failure of tetracycline therapy in early Lyme disease.

Dattwyler RJ, Halperin JJ.

We describe the clinical courses of 5 patients with Lyme disease who developed significant late complications, despite receiving tetracycline early in the course of their illness. All 5 patients had been treated for erythema chronicum migrans with a course of tetracycline that met or exceeded current recommendations. The late manifestations of Lyme disease included arthritis, cranial nerve palsy, peripheral neuropathy, chronic fatigue, and changes in mental function. Our findings suggest that the use of tetracycline at a dosage of 250 mg, 4 times a day for 10 days, as a treatment for early Lyme disease should be reconsidered. To determine optimal therapy for early Lyme disease, a study that compares an increased dosage of tetracycline with alternative treatments is indicated.

PMID: 3580012 [PubMed - indexed for MEDLINE]

Am J Surg Pathol. 1987;11 Suppl 1:47-60.

The surgical pathology of human Lyme disease. An enlarging picture.

Duray PH.

Lyme disease is a multisystems infectious disorder caused by the spirochete, Borrelia burgdorferi. Infection occurs by ticks feeding on mammalian hosts, including humans. The distribution of the tick and spirochete is world-wide and is especially prevalent where there are large deer populations. The disease is seen in three stages.

Stage I is a cutaneous rash (erythema chronicum migrans) consisting of lymphoplasmacytic infiltrates around dermal vessels. Stage II is characterized by varying forms of meningopolyradiculitis, with or without Bell's palsy or cardiac involvement (complete or incomplete heart block) and with interstitial endomyocarditis of lymphocytes and plasma cells. Lymphoplasmacellular infiltration is seen in the meninges, ganglia, and peripheral nerves.

Chronic and intermittent oligoarthritis is the hallmark of stage III disease, characterized by hypertrophic synovitis, often with fibrinaceous deposits and synovial vascular occlusion. Stage III chronic dermatologic syndromes (lymphadenosis benigna cutis, acrodermatitis chronicum atrophicans) consist of cutaneous lymphoid hyperplasia and vascular changes. Neurologic demyelination syndromes also occur in stage III. Plasma cells occur in all stages, but are more prominent in stages II and III. Spirochetes can be demonstrated by silver impregnation stains in some cases.

PMID: 3812878 [PubMed - indexed for MEDLINE]

J Neurol. 1987 Jan;234(1):40-3.

Chronic progressive neurological involvement in Borrelia burgdorferi infection.

Weder B, Wiedersheim P, Matter L, Steck A, Otto F.

Five patients with chronic meningitis were hospitalized several times for progressive neurological symptoms. The clinical manifestations included cranial neuritis, radiculoneuritis, myelitis and encephalitis. In two cases cerebral infarction occurred. The course was commonly characterized by a tendency to deteriorate. From the clinical point of view, it was repeatedly difficult to exclude multiple sclerosis or tuberculous meningitis. Finally, specific antibodies against Borrelia burgdorferi were detected by indirect immunofluorescence assay.

The diagnosis of a borreliosis was not considered initially because there was no history of tick-bite or erythema chronicum migrans, and the neurological involvement of the central nervous system seemed unusual. The latency between the first symptoms and diagnosis varied from 3 months to 5 years. After a parenteral, high-dose therapy with penicillin, there was a significant improvement in all patients. In two cases, there was evidence of intrathecally produced antibodies to myelin basic protein.

PMID: 3819785 [PubMed - indexed for MEDLINE]

Presse Med. 1987 Jan 24;16(2):72-5.

[Neurologic aspects of Lyme disease]

[Article in French]

Masson C.

The neurological manifestations of Lyme disease--a condition caused by a spirochete (Borrelia burgdorferi) and transmitted by a tick Ixodes dammini)--consist of chronic lymphocytic meningitis, cranial neuritis and radiculoneuritis associated to varying degrees. The tick-borne meningoradiculitis well known in Europe (Garin-Bujadoux-Bannwarth syndrome) appears, with very slight differences, as equivalent to the neurological manifestations of Lyme disease. Lesions of the central nervous system, which occur long after the B. burgdorferi infection, are thought to represent a tertiary stage of Lyme disease.

PMID: 2949311 [PubMed - indexed for MEDLINE]

Nervenarzt. 1987 Sep;58(9):564-7.

[Chronic Borrelia disease of the central nervous system]

[Article in German]

Behringer A, Wirbatz A.

Neurologische Klinik, Justus-Liebig-Universität Giessen.

A few years ago meningoradiculitis Garin-Bujadoux-Bannwarth (Bannwarth's syndrome) was discovered to be a neurological manifestation of Lyme disease transmitted by tick-bites and caused by Ixodes-ricinus-spirochaete (borrelia burgdorferi). Not enough attention is given to the fact that more serious and chronic disease of the central nervous system may be entailed. Two cases are reported in which detection of the borrelian-antibodies corroborated the diagnosis. After parenteral treatment with penicillin there was a drastic improvement in both patients.

PMID: 3670517 [PubMed - indexed for MEDLINE]

Ann Intern Med. 1987 Nov;107(5):725-31.

The clinical evolution of Lyme arthritis.

Steere AC, Schoen RT, Taylor E.

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.

To determine the clinical evolution of Lyme arthritis, 55 patients who did not receive antibiotic therapy for erythema chronicum migrans were followed longitudinally for a mean duration of 6 years. Of the 55 patients, 11 (20%) had no subsequent manifestations of Lyme disease. From 1 day to 8 weeks after disease onset, 10 of the patients (18%) began to have brief episodes of joint, periarticular, or musculoskeletal pain for as long as 6 years, but they never developed objective joint abnormalities.

From 4 days to 2 years after disease onset, 28 (51%) had one episode or began to have intermittent attacks of frank arthritis, primarily in large joints; a few had polyarticular movement. The total number of these patients who continued to have recurrences decreased by 10% to 20% each year. The remaining 6 patients (11%) developed chronic synovitis later in the illness; of these, 2 (4%) had erosions, and 1 (2%), permanent joint disability. The spectrum of Lyme arthritis ranges from subjective joint pain, to intermittent attacks of arthritis, to chronic erosive disease.

PMID: 3662285 [PubMed - indexed for MEDLINE]

J Neurol. 1988 Jan;235(3):140-2.

Chronic borrelia encephalomyeloradiculitis with severe mental disturbance: immunosuppressive versus antibiotic therapy.

Kollikowski HH, Schwendemann G, Schulz M, Wilhelm H, Lehmann HJ.

Neurologische Universitätsklinik und Poliklinik Essen, Federal Republic of Germany.

A 57-year-old male was repeatedly admitted to hospital because of complex neurological symptoms, including radicular pain, disturbance of micturition, seizures, and severely impaired mental state. The diagnosis was encephalomyeloradiculitis possibly of viral origin, and treatment with immunosuppressants was initiated. An alternating course with a tendency towards improvement ensued. Two and a half years after the occurrence of the initial symptoms, identification of specific antibodies in the blood and CSF led to the diagnosis of borreliosis with CNS involvement. High-dose therapy with penicillin rapidly reduced the symptoms, beginning with those of radicular pain and followed by an improvement of the mental state. Attention is directed to the wide spectrum of clinical symptoms of chronic borreliosis with CNS involvement. Previous reports that immunosuppression may result in some improvement but with a tendency towards relapse are confirmed. Our encouraging treatment results support those of other reports that penicillin therapy may lead to improvement even at late chronic stages in patients with severe CNS deficits.

PMID: 3367160 [PubMed - indexed for MEDLINE]

Arthritis Rheum. 1988 Apr;31(4):487-95.

Spirochetal antigens and lymphoid cell surface markers in Lyme synovitis. Comparison with rheumatoid synovium and tonsillar lymphoid tissue.

Steere AC, Duray PH, Butcher EC.

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.

Using monoclonal antibodies to spirochetal antigenes and lymphoid cell surface markers, we examined the synovial lesions of 12 patients with Lyme disease, and compared them with rheumatoid synovium and tonsillar lymphoid tissue. The synovial lesions of Lyme disease patients and rheumatoid arthritis patients were similar and often consisted of the elements found in normal organized lymphoid tissue. In both diseases, T cells, predominantly of the helper/inducer subset, were distributed diffusely in subsynovial lining areas, often with nodular aggregates of tightly intermixed T and B cells. IgD-bearing B cells were scattered within the aggregates, and a few follicular dendritic cells and activated germinal center B cells were sometimes present.

Outside the aggregates, many plasma cells, high endothelial venules, scattered macrophages, and a few dendritic macrophages were found. HLA-DR and DQ expression was intense throughout the lesions. In 6 of the 12 patients with Lyme arthritis, but in none of those with rheumatoid arthritis, a few spirochetes and globular antigen deposits were seen in and around blood vessels in areas of lymphocytic infiltration. Thus, in Lyme arthritis, a small number of spirochetes are probably the antigenic stimulus for chronic synovial inflammation.

PMID: 3258751 [PubMed - indexed for MEDLINE]

Neurology. 1988 Jun;38(6):863-7.

Chronic central nervous system involvement in Lyme borreliosis.

Kohler J, Kern U, Kasper J, Rhese-Küpper B, Thoden U.

Department of Neurology, University of Freiburg, Federal Republic of Germany.

We describe four patients with marked chronic meningoencephalomyelitis caused by tick-transmitted Borrelia burgdorferi infection. Imaging techniques showed either MS-like lesions or evidence of vascular involvement, as in other spirochetal infections, especially in meningovascular syphilis.

PMID: 3368066 [PubMed - indexed for MEDLINE]

Rev Rhum Mal Osteoartic. 1988 Jul-Sep;55(9):647-53.

[Lyme disease. Clinical, biological and developmental aspects. 29 cases in the Orléans region]

[Article in French]

Benhamou CL, Gauvain JB, Calamy G, Lemaire JF, Kervran JP, Bardet M, Caplan F, Luthier F.

Service de Rhumatologie, Hôpital de la Source, Orléans.

The description of Lyme's disease (LD) in 3 stages (like syphilis), has now become classical. 29 cases of LD, between June 1981 and November 1986, have been recorded at the Hospital in Orleans. The first twelve patients that were clinically diagnosed before the serology was introduced in France, have been recalled in order to search for possible late forms and assay their antibody level of anti-Borrelia burgdorferi. The preponderance of neurological forms (22 cases) and the scarcity of peripheral and/or arthralgic arthritis (8 cases) are emphasized by this study.

Radiculalgias (18 cases in 22 meningo-radiculitis), especially in the lower extremities (14 cases), required hospitalization in rheumatology in 21 instances. Spinal algias (16 cases), were only isolated, at the time of hospitalization, in one case. The intense and nocturnal nature of the radiculalgias and spinal algias was noted in 17 of 18 cases, and 16 of 16 cases, respectively. Two atrio-ventricular blocks required hospitalization in cardiology. The long-term follow-up (3 to 5 years) of 12 patients revealed only 2 cases of severe asthenia and swelling at the puncture site in one case. There were no entesopathies nor chronic arthritis. The search for anti-Borrelia burgdorferi antibodies in the serum, was positive 24 times in 28. In the 4 cases where the serology was negative, the samplings were taken after a follow-up of more than three years in 3 instances.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 3055243 [PubMed - indexed for MEDLINE]

Hautarzt. 1988 Oct;39(10):647-51.

[Acrodermatitis chronic atrophicans and sclerodermiform skin changes in Borrelia infection]

[Article in German]

Langer K, Diem E.

I. Universitäts-Hautklinik Wien.

A female patient with acrodermatitis chronica atrophicans and widespread sclerodermiform skin lesions with a high IgG antibody titer against Borrelia burgdorferi is presented. The rapid improvement after high-dose penicillin G therapy and the course of the Borrelia antibody titer suggest a persistence of the causative organism.

PMID: 3235338 [PubMed - indexed for MEDLINE]

N Engl J Med. 1988 Dec 1;319(22):1441-6.

Seronegative Lyme disease. Dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi.

Dattwyler RJ, Volkman DJ, Luft BJ, Halperin JJ, Thomas J, Golightly MG.

Department of Medicine, State University of New York, School of Medicine, Stony Brook 11794-8161.

Comment in:

The diagnosis of Lyme disease often depends on the measurement of serum antibodies to Borrelia burgdorferi, the spirochete that causes this disorder. Although prompt treatment with antibiotics may abrogate the antibody response to the infection, symptoms persist in some patients. We studied 17 patients who had presented with acute Lyme disease and received prompt treatment with oral antibiotics, but in whom chronic Lyme disease subsequently developed.

Although these patients had clinically active disease, none had diagnostic levels of antibodies to B. burgdorferi on either a standard enzyme-linked immunosorbent assay or immunofluorescence assay. On Western blot analysis, the level of immunoglobulin reactivity against B. burgdorferi in serum from these patients was no greater than that in serum from normal controls. The patients had a vigorous T-cell proliferative response to whole B. burgdorferi, with a mean ( +/- SEM) stimulation index of 17.8 +/- 3.3, similar to that (15.8 +/- 3.2) in 18 patients with chronic Lyme disease who had detectable antibodies.

The T-cell response of both groups was greater than that of a control group of healthy subjects (3.1 +/- 0.5; P less than 0.001). We conclude that the presence of chronic Lyme disease cannot be excluded by the absence of antibodies against B. burgdorferi and that a specific T-cell blastogenic response to B. burgdorferi is evidence of infection in seronegative patients with clinical indications of chronic Lyme disease.

PMID: 3054554 [PubMed - indexed for MEDLINE]

Ann N Y Acad Sci. 1988;539:324-45.

Antibiotic therapy of early European Lyme borreliosis and acrodermatitis chronica atrophicans.

Weber K, Preac-Mursic V, Neubert U, Thurmayr R, Herzer P, Wilske B, Schierz G, Marget W.

Department of Microbiology, University of Munich, Federal Republic of Germany.

In a study on 121 consecutive patients with erythema migrans, 65 patients obtained oral penicillin, 36 tetracyclines, and 20 amoxicillin-clavulanic-acid. Follow-up was carried out for a median of 29, 17, and 7 months, respectively. In another limited trial on 29 patients with acrodermatitis chronica atrophicans (ACA), 14 patients received oral penicillin, 9 parenteral penicillin, and 6 tetracyclines. There was no statistically significant difference among treatment groups in both therapeutic trials, with the exception of different follow-ups due to the nonrandomized study design and different occurrence of the Jarisch-Herxheimer reaction in patients with erythema migrans.

Later extracutaneous manifestations developed in 27% of the patients with erythema migrans and in 47% of the patients with ACA despite antibiotic therapy. We could not prove the superiority of any antibiotic tested in either early or late European Lyme borreliosis.

PMID: 3056202 [PubMed - indexed for MEDLINE]

Rev Neurol (Paris). 1988;144(12):765-75.

[Multiple neurologic manifestations of Borrelia burgdorferi infection]

[Article in French]

Dupuis MJ.

Clinique St-Pierre, Ottignies, Belgique.

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.

PMID: 3070690 [PubMed - indexed for MEDLINE]

Ann N Y Acad Sci. 1988;539:346-51.

Treatment of erythema chronicum migrans of Lyme disease.

Berger BW.

Department of Dermatology, New York University School of Medicine, New York 10016.

Between June 1981 and July 1987 the efficacy of antibiotic treatment of 215 patients with erythema chronicum migrans of Lyme disease was evaluated in terms of the necessity for retreatment and the prevention of the late manifestations of Lyme disease. The principal antibiotics utilized to treat 161 patients through 1986 were varying doses of tetracycline, or penicillin alone or in combination with probenecid. Two of 80 patients with a minor form of the illness and 17 of 81 patients with a major form of the illness required retreatment. There were four patients who did not respond to retreatment with their original medication. A 15- to 30-day course of amoxicillin (500 mg q.i.d.) and probenecid (500 mg q.i.d.) or doxycycline (100 mg t.i.d.), and on three occasions ceftriaxone (2-4 g/day i.v.), were used to treat 54 patients in 1987. Although it is too early to judge the efficacy of treatment in these patients, increases in the incidence of Herxheimer reactions and drug eruptions were observed. Strict compliance with treatment protocols and the possibility of reactions to medications should be thoroughly discussed with patients.

PMID: 3190102 [PubMed - indexed for MEDLINE]

Scand Audiol. 1989;18(4):205-10.

Brainstem response audiometry in chronic Lyme borreliosis.

Sandström M, Bredberg G, Asbrink E, Hovmark A, Holmkvist C.

Department of Audiology, Södersjukhuset, Stockholm, Sweden.

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.

PMID: 2609097 [PubMed - indexed for MEDLINE]

Am J Clin Pathol. 1989 Jan;91(1):95-7.

Spirochetes in the spleen of a patient with chronic Lyme disease.

Cimmino MA, Azzolini A, Tobia F, Pesce CM.

Istituto Scientifico di Medicina Interna, Università di Genova, Italy.

A 54-year-old man had intermittent evening fever, arthralgia, transient erythematous macular eruption on the skin, and splenomegaly of two year's duration. Immunofluorescence tests for Borrelia burgdorferi serum antibodies had positive results, but G-penicillin treatment was ineffective. Splenectomy with lymph node biopsy was performed to rule out lymphoproliferative disorders. Borrelia-like spirochetes were identified histologically in the spleen; this finding was consistent with persistence of B. burgdorferi organisms in inner organs in chronic Lyme disease.

PMID: 2910019 [PubMed - indexed for MEDLINE]

Monatsschr Kinderheilkd. 1989 Feb;137(2):101-4.

[Neuroborreliosis: progressive encephalomyelitis with cerebral vasculitis]

[Article in German]

Lock G, Berger G, Gröbe H.

Kinderklinik, Stadt Nürnberg.

Encephaloborreliosis is described in a 16 year old patient. Besides the progressive encephalopathy this case presents symptoms and findings of a cerebral vasculitis. During and after antibiotic treatment all clinical symptoms and pathological changes in the cerebrospinal fluid almost completely disappeared.

PMID: 2716736 [PubMed - indexed for MEDLINE]

Trends Neurosci. 1989 May;12(5):177-81.

Lyme disease.

Pachner AR.

Lyme disease is of interest to the neurologist and neuroscientist for a variety of reasons. As more arthropod hosts throughout the world are infected with the causative organism, Borrelia burgdorferi, the illness in humans is becoming more prevalent; in addition, recognition of the disease in humans and susceptible animals is increasing. The neurological manifestations include acute and chronic forms, and it has become clear that B. burgdorferi has joined Treponema pallidum, herpes simplex virus, and human immunodeficiency virus (HIV) as an agent of persistent infection of the brain.

Recent strides in the understanding of antigenic variation in Borrelia have provided insights into how this agent may survive in the human host. Preliminary work in animal models has provided information about the relationships between strain-dependent tropisms, spirochetemia, the development of specific antibody, and nervous system invasion. Finally, the history of the development of understanding of the disease has been a fascinating mixture of parental concern, serendipitous discovery, and correlation of clinical syndromes and serological evaluations across continents.

PMID: 2472690 [PubMed - indexed for MEDLINE]

N Engl J Med. 1989 Aug 31;321(9):586-96.

Lyme disease.

Steere AC.

Division of Rheumatology/Immunology, Tufts University School of Medicine, New England Medical Center, Boston, MA 02111.

Comment in:

Within the last decade, Lyme borreliosis has emerged as a complex new infection whose distribution is worldwide. The disorder is caused by a recently recognized spirochete, B. burgdorferi, transmitted by ticks of the I. ricinus complex. Certain species of mice are critical in the life cycle of the spirochete, and deer appear to be crucial to the tick. Although the disorder's basic outlines are similar everywhere, there are regional variations in the causative spirochete, animal hosts, and clinical manifestations of the illness. In the United States, Lyme disease commonly begins in summer with a characteristic skin lesion, erythema migrans, accompanied by flu-like or meningitis-like symptoms. Weeks or months later, the patients may have neurologic or cardiac abnormalities, migratory musculoskeletal pain, or arthritis, and more than a year after onset, some patients have chronic joint, skin, or neurologic abnormalities. After the first several weeks of infection, almost all patients have a positive antibody response to the spirochete, and serologic determinations are currently the most practical laboratory aid in diagnosis. Treatment with appropriate antibiotics is usually curative, but longer courses of therapy are often needed later in the illness, and some patients may not respond.

PMID: 2668764 [PubMed - indexed for MEDLINE]

Rev Infect Dis. 1989 Sep-Oct;11 Suppl 6:S1518-25.

A perspective on the treatment of Lyme borreliosis.

Luft BJ, Gorevic PD, Halperin JJ, Volkman DJ, Dattwyler RJ.

Department of Medicine, University of New York, Stony Brook 11794-8153.

Lyme borreliosis has become the most common tick-borne infection in the United States. Although both beta-lactam and tetracycline antibiotics have been shown to be effective in the treatment of this spirochetosis, the development of optimal therapeutic modalities has been hampered by the lack of reliable microbiologic or immunologic criteria for the diagnosis or cure of this infection. In vitro sensitivity studies have been performed by several laboratories, but there has been no standardization of the methodology for measuring either inhibitory or bactericidal levels.

Clinical studies have documented the efficacy of antibiotics, but therapy has failed in as many as 50% of cases of chronic infection. Although new antibiotic regimens appear promising, the optimal treatment of this infectious disease remains to be determined. In this report we review the clinical and experimental rationale for the antibiotic regimens that we currently use and the need for a more standardized approach to treatment trials.

PMID: 2682965 [PubMed - indexed for MEDLINE]

Rev Infect Dis. 1989 Sep-Oct;11 Suppl 6:S1487-93.

Clinical pathologic correlations of Lyme disease.

Duray PH.

Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.

The multisystem effects caused by Borrelia burgdorferi in Lyme disease are multiple, varied, and unpredictable. In some patients, the full extent of the infection consists of a stage I acute systemic viral-like illness. Stage II primarily involves the cardiovascular system (myocarditis) and/or the central nervous system (CNS) (meningoencephalitis, polyradiculitis). More inflammatory cells are found in the heart and nervous system structures during this intermediate stage than are found in any tissues involved during stage I. Stage III is characterized by peripheral neuropathy and CNS disorders such as dementia or transverse myelitis and arthritis and synovitis of large joints such as the knee. Chronic Lyme disease is also associated with multiple and seemingly unrelated cutaneous manifestations such as acrodermatitis chronica atrophicans, sclerodermoid-like reactions, lichen sclerosus et atrophicus, subcuticular fibrous nodules, eosinophilic fasciitis-like lesions of the extremities, and, possibly, granuloma annulare. With care, spirochetes can be recovered or demonstrated by silver staining in most of the above lesions. Spirochetes have yet to be seen in the tissues of autonomic ganglia or peripheral nerves.

PMID: 2814170 [PubMed - indexed for MEDLINE]

Infection. 1989 Nov-Dec;17(6):355-9.

Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis.

Preac-Mursic V, Weber K, Pfister HW, Wilske B, Gross B, Baumann A, Prokop J.

Neurologische Klinik Grosshadern, München, FR Germany.

The persistence of Borrelia burgdorferi in patients treated with antibiotics is described. The diagnosis of Lyme disease is based on clinical symptoms, epidemiology and specific IgG and IgM antibody titers to B. burgdorferi in serum. Antibiotic therapy may abrogate the antibody response to the infection as shown in our patients. B. burgdorferi may persist as shown by positive culture in MKP-medium; patients may have subclinical or clinical disease without diagnostic antibody titers to B. burgdorferi. We conclude that early stage of the disease as well as chronic Lyme disease with persistence of B. burgdorferi after antibiotic therapy cannot be excluded when the serum is negative for antibodies against B. burgdorferi.

PMID: 2613324 [PubMed - indexed for MEDLINE]

Rheum Dis Clin North Am. 1989 Nov;15(4):649-56.

Lyme disease: musculoskeletal manifestations.

Kolstoe J, Messner RP.

Section of Rheumatology, University of Minnesota School of Medicine, Minneapolis.

A previously unrecognized musculoskeletal syndrome led to the recognition of this "new" infectious disease. Several distinct patterns of musculoskeletal involvement can be seen throughout the course of untreated Lyme disease. Diffuse, nonspecific muscle achiness and stiffness can be seen early to be followed by characteristically brief, recurrent episodes of LIMP and transient arthritis that help to differentiate LD from other arthropathies. Chronic oligoarticular arthritis is seen in a few. Lyme arthropathy most closely resembles the reactive arthropathies. In a few cases, LD has mimicked other connective tissue disorders such as juvenile rheumatoid arthritis, rheumatoid arthritis, myositis, and scleroderma. It would appear that the full spectrum of musculoskeletal LD is still being defined.

PMID: 2685923 [PubMed - indexed for MEDLINE]

Rheum Dis Clin North Am. 1989 Nov;15(4):679-90.

Lyme disease in children.

Belani K, Regelmann WE.

Lyme disease is an increasing health risk for children. Pediatricians should become familiar with the different clinical syndromes caused by the Borrelia burgdorferi. Appropriate antibiotic therapy must be initiated and follow-up of these children should be a part of the management as some may develop (tertiary) chronic borreliosis. Lyme disease should be considered in the diagnostic work-up of heart block, childhood arthritis and in undiagnosed peripheral and central nervous system disease. Serologic tests appear to be quite specific and sensitive in children with late stage disease in our experience. Newer diagnostic tests to detect infection during the early stage will optimize the management of Lyme disease and further decrease the incidence of long-term sequelae.

PMID: 2685925 [PubMed - indexed for MEDLINE]

Rheum Dis Clin North Am. 1989 Nov;15(4):691-710.

Histopathology of clinical phases of human Lyme disease.

Duray PH.

Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Acute, subacute, or chronic persistent human Lyme borreliosis is an inflammatory disorder composed pathologically of lymphocytes, plasma cells, macrophages, and mast cells. The lymphoplasmocellular infiltrates can at times be seen in the skin, subcutaneous tissues, lymph nodes, spleen, liver, myocardium, brain, autonomic ganglia, and peripheral nerves. The joints in arthritic cases have proliferative synovitis, fibrinaceous deposits, lymphoplasmocellular aggregates, and mast cells. Varying degrees of vascular damage does occur in these sites; however, usually only in late, chronic disease. Spirochetes are present in most sites, in an extracellular location, but are sparse.

PMID: 2685926 [PubMed - indexed for MEDLINE]

Ann Neurol. 1989 Dec;26(6):732-7.

Molecular mimicry and Lyme borreliosis: a shared antigenic determinant between Borrelia burgdorferi and human tissue.

Aberer E, Brunner C, Suchanek G, Klade H, Barbour A, Stanek G, Lassmann H.

Department of Dermatology II, University of Vienna, Austria.

Comment in:

The pathogenesis of chronic manifestations in Lyme borreliosis, a disease induced by Borrelia burgdorferi, is at present unresolved. By testing monoclonal antibodies directed against various borrelia antigens, we found an antigenic determinant shared by the 41 kDa flagella protein and human tissue, especially prominent on myelinated fibers of human peripheral nerve, on nerve cells and axons of the central nervous system, as well as on certain epithelial cells (including joint synovia) and on heart muscle cells. Immune reactions against such a shared antigen could play a pathogenetic role in chronic organ manifestations of Lyme borreliosis.

PMID: 2481425 [PubMed - indexed for MEDLINE]

Rheum Dis Clin North Am. 1989 Nov;15(4):635-47.

Nervous system manifestations of Lyme disease.

Halperin JJ.

Department of Neurology, State University of New York, Stony Brook.

Neurologic involvement is commonplace in Lyme borreliosis. Neuropathies can be acute or chronic, focal or disseminated, but are predominantly axonal. CNS infection can also be acute or indolent, focal or disseminated; meningitis, encephalitis, and cranial nerve palsies occur. A mild encephalopathy is also common, but only occasionally due to CNS infection.

PMID: 2555847 [PubMed - indexed for MEDLINE]

Rev Infect Dis. 1989 Sep-Oct;11 Suppl 6:S1460-9.

Epidemiology and clinical similarities of human spirochetal diseases.

Schmid GP.

Division of Sexually Transmitted Diseases, Centers for Disease Control, Atlanta, Georgia 30333.

Lyme disease, first identified in 1975, is the most recently recognized of the seven human spirochetal diseases; the evolving clinical picture of Lyme disease indicates it shares many features with the other diseases. These similarities are striking in view of the diverse epidemiology of the seven diseases, which are caused by Treponema species (spread by human-to-human contact) or Leptospira or Borrelia species (zoonoses). These similarities include the following: (1) skin or mucous membrane as portal of entry; (2) spirochetemia early in the course of disease, with wide dissemination through tissue and body fluid; and (3) one or more subsequent stages of disease, often with intervening latent periods. Lyme disease shares with many spirochetal diseases a tropism for skin and neurologic and cardiovascular manifestations, whereas chronic arthritis is unique to Lyme disease. These similarities and dissimilarities offer opportunities to discover which properties unique to the pathogenic spirochetes are responsible for clinical manifestations and suggest that certain clinical features of patients with spirochetal diseases other than Lyme disease may someday be recognized in patients with Lyme disease.

PMID: 2682958 [PubMed - indexed for MEDLINE]

Rheum Dis Clin North Am. 1989 Nov;15(4):747-55.

Treatment of Lyme borreliosis.

Luft BJ, Dattwyler RJ.

Department of Medicine, State University of New York, Stony Brook.

The infectious process of Lyme disease can appear as chronic dermatologic, rheumatologic, or neurologic. To rationally select a treatment regimen, the physician must have an appreciation of the clinical manifestations of the illness and of the systemic nature of the infection. The authors discuss the proper treatment protocols for each stage in the progression of Lyme disease.

PMID: 2555849 [PubMed - indexed for MEDLINE]

Rheum Dis Clin North Am. 1989 Nov;15(4):747-55.

Treatment of Lyme borreliosis.

Luft BJ, Dattwyler RJ.

Department of Medicine, State University of New York, Stony Brook.

The infectious process of Lyme disease can appear as chronic dermatologic, rheumatologic, or neurologic. To rationally select a treatment regimen, the physician must have an appreciation of the clinical manifestations of the illness and of the systemic nature of the infection. The authors discuss the proper treatment protocols for each stage in the progression of Lyme disease.

PMID: 2555849 [PubMed - indexed for MEDLINE]