CHRONIC LYME DISEASE
EARLY STUDIES
(Part 1)
Studies performed in the 1970's and 1980's clearly indicated Lyme disease could be a serious chronic infection. It was 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 today deny the existence of "chronic Lyme".
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.
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.
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.
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.
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]
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]
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]
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]
CONTINUED... Please see Page 2 located here.
Lucy Barnes