What has Allen Steere said in published articles regarding Lyme disease?
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                                                   as of 28 October 1999
As primary author in collaboration with others:

31 citations, 3 have "NO ABSTRACT AVAILABLE".

TITLE: 
Vaccination against Lyme disease with recombinant Borrelia burgdorferi
outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study
Group [see comments]
AUTHORS: Steere AC; Sikand VK; Meurice F; Parenti DL Fikrig E; 
Schoen RT; Nowakowski J; Schmid CH; Laukamp S;Buscarino C; Krause DS
AUTHOR AFFILIATION:
Division of Rheumatology and Immunology, Tufts University School of
Medicine, New England Medical Center, Tupper Research Institute,
Boston, MA 02111, USA.
COMMENTS:
Comment in: N Engl J Med 1998 Jul 23;339(4):263-4
Comment in: N Engl J Med 1998 Nov 26;339(22):1637; discussion 1638-9
Comment in: N Engl J Med 1998 Nov 26;339(22):1637-8; discussion 1638-9
Comment in: N Engl J Med 1998 Nov 26;339(22):1638-9
ABSTRACT:
BACKGROUND: The risk of acquiring Lyme disease is high in areas in
which the disease is endemic, and the development of a safe and
effective vaccine is therefore important. METHODS: We conducted a
multicenter, double-blind, randomized trial involving 10,936 subjects
who lived in areas of the United States in which Lyme disease is
endemic. Participants received an injection of either recombinant
Borrelia burgdorferi outer-surface lipoprotein A (OspA) with adjuvant
or placebo at enrollment and 1 and 12 months later. In cases of
suspected Lyme disease, culture of skin lesions, polymerase-chain-
reaction testing, or serologic testing was done. Serologic testing
was performed 12 and 20 months after study entry to detect
asymptomatic infections. RESULTS: In the first year, after two
injections, 22 subjects in the vaccine group and 43 in the placebo
group contracted definite Lyme disease (P=0.009); vaccine efficacy
was 49 percent (95 percent confidence interval, 15 to 69 percent). In
the second year, after the third injection, 16 vaccine recipients and
66 placebo recipients contracted definite Lyme disease (P<0.001);
vaccine efficacy was 76 percent (95 percent confidence interval, 58
to 86 percent). The efficacy of the vaccine in preventing
asymptomatic infection was 83 percent in the first year and 100
percent in the second year. Injection of the vaccine was associated
with mild-to-moderate local or systemic reactions lasting a median of
three days. CONCLUSIONS: Three injections of vaccine prevented most
definite cases of Lyme disease or asymptomatic B. burgdorferi
infection.
NLM PUBMED CIT. ID: 9673298 NLM CIT. ID: 98328627
SOURCE:  N Engl J Med 1998 Jul 23;339(4):209-15
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9673298&form=6&db=m&Dopt=b

TITLE: Treatment of Lyme arthritis.
AUTHORS: Steere AC; Levin RE; Molloy PJ; Kalish RA
Abraham JH 3rd; Liu NY; Schmid CH
AUTHOR AFFILIATION:
New England Medical Center, Tufts University School of Medicine,
Boston, Massachusetts.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-40576/AR/NIAMS AR-07570/AR/NIAMS
ABSTRACT:
OBJECTIVE. To test treatment regimens for Lyme arthritis. METHODS.
Patients were randomly assigned to treatment with doxycycline or
amoxicillin plus probenecid for 30 days. Patients who had persistent
arthritis for at least 3 months after treatment with oral antibiotics
or parenteral penicillin were given intravenous ceftriaxone for 2
weeks. RESULTS. Eighteen of the 20 patients treated with doxycycline
and 16 of the 18 patients who completed the amoxicillin regimen had
resolution of the arthritis within 1-3 months after study entry.
However, neuroborreliosis later developed in 5 patients, 4 of whom
had received the amoxicillin regimen. Of 16 patients (2 from the oral
antibiotic study and 14 additional patients) who had persistent
arthritis despite previous oral antibiotics or parenteral penicillin,
none had resolution of the arthritis within 3 months after
ceftriaxone therapy. The HLA-DR4 specificity and OspA reactivity were
associated with a lack of response. CONCLUSION. Lyme arthritis can
usually be treated successfully with oral antibiotics, but patients
may still develop neuroborreliosis. Patients with certain genetic and
immune markers may have persistent arthritis despite treatment with
oral or intravenous antibiotics.
NLM PUBMED CIT. ID: 8003060 NLM CIT. ID: 94271287
SOURCE:  Arthritis Rheum 1994 Jun;37(6):878-88
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8003060&form=6&db=m&Dopt=b

TITLE: The overdiagnosis of Lyme disease [see comments]
AUTHORS: Steere AC; Taylor E; McHugh GL; Logigian EL
AUTHOR AFFILIATION:
Division of Rheumatology/Immunology, New England Medical Center,
Boston, MA 02111.
COMMENTS:
Comment in: JAMA 1993 Dec 8;270(22):2682; discussion 2683
Comment in: JAMA 1993 Dec 8;270(22):2682-3
Comment in: JAMA 1993 Dec 8;270(22):2683
GRANT/CONTRACT ID: AR-20358/AR/NIAMS
ABSTRACT:
OBJECTIVE--To analyze the diagnoses, serological test results, and
treatment results of the patients evaluated in a Lyme disease clinic,
both prior to referral and from current evaluation. DESIGN--
Retrospective case survey of prescreened patients. SETTING--Research
and diagnostic Lyme disease clinic in a university hospital.
PATIENTS-- All 788 patients referred to the clinic during a 4.5-year
period who were thought by the referring physician or the patient to
have a diagnosis of Lyme disease. MAIN OUTCOME MEASUREMENTS--Symptoms
and signs of disease, immunodiagnostic tests of Lyme disease, and
tests of neurological function. RESULTS--Of the 788 patients, 180
(23%) had active Lyme disease, usually arthritis, encephalopathy, or
polyneuropathy. One hundred fifty-six patients (20%) had previous
Lyme disease and another current illness, most commonly chronic
fatigue syndrome or fibromyalgia; and in 49 patients, these symptoms
began soon after objective manifestations of Lyme disease. The
remaining 452 patients (57%) did not have Lyme disease. The majority
of these patients also had the chronic fatigue syndrome or
fibromyalgia; the others usually had rheumatic or neurological
diseases. Of the patients who did not have Lyme disease, 45% had had
positive serological test results for Lyme disease in other
laboratories, but all were seronegative in our laboratory. Prior to
referral, 409 of the 788 patients had been treated with antibiotic
therapy. In 322 (79%) of these patients, the reason for lack of
response was incorrect diagnosis. CONCLUSIONS--Only a minority of the
patients referred to the clinic met diagnostic criteria for Lyme
disease. The most common reason for lack of response to antibiotic
therapy was misdiagnosis.
NLM PUBMED CIT. ID: 8459513 NLM CIT. ID: 93210851
SOURCE:  JAMA 1993 Apr 14;269(14):1812-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8459513&form=6&db=m&Dopt=b

TITLE: 
Association of chronic Lyme arthritis with HLA-DR4 and HLA-DR2 alleles
[published erratum appears in N Engl J Med 1991 Jan 10;324(2):129]
[see comments]
AUTHORS: Steere AC; Dwyer E; Winchester R
AUTHOR AFFILIATION:
Division of Rheumatology/Immunology, New England Medical Center, Tufts
University School of Medicine, Boston, MA 02111.
COMMENTS:
Comment in: N Engl J Med 1991 Jan 10;324(2):129
GRANT/CONTRACT ID: AM-20358/AM/NIADDK RR-00125/RR/NCRR AI-19411/AI/NIAID
ABSTRACT:
BACKGROUND AND METHODS. A small percentage of patients infected with
Borrelia burgdorferi have chronic Lyme arthritis that does not
respond to antibiotic therapy. To learn whether genetically
determined variations in the host immune response might account for
such outcomes, we determined the immunogenetic profiles of 130
patients with various manifestations of Lyme disease. RESULTS. Of the
80 patients with arthritis, 57 percent of those with chronic
arthritis (12 to 48 months in duration) had the HLA-DR4 specificity;
only 23 percent of those with arthritis of moderate duration (6 to 11
months) and only 9 percent of those with arthritis of short duration
(1 to 5 months) had this specificity (P = 0.003). After the
HLA-DR4-positive patients were excluded from each group, a secondary
association was noted with HLA- DR2, which was found in 75 percent of
the remaining patients with chronic arthritis and in 50 percent of
those with arthritis of moderate duration, but in only 20 percent of
those with arthritis of short duration (P = 0.023). Altogether, 25 of
the 28 patients with chronic arthritis (89 percent) had HLA-DR2 or
HLA-DR4, or both, as compared with 27 percent of those with arthritis
of short duration (relative risk, 22; P = 0.00006). These HLA
specificities appeared to act as independent, dominant markers of
susceptibility. Nucleotide-sequence typing, performed in five
patients with chronic arthritis, identified the HLA-DR2 allele as Dw2
(DR beta 1*1501), and the HLA-DR4 alleles as Dw4, Dw14, and Dw13 (DR
beta 1*0401, DR beta 1*0404, and DR beta 1*0403, respectively). The
presence of HLA-DR4 in patients with arthritis was associated with a
lack of response to antibiotic therapy (P = 0.01). CONCLUSIONS.
Particular Class II major histocompatibility genes determine a host
immune response to B. burgdorferi that results in chronic arthritis
and lack of response to antibiotic therapy.
NLM PUBMED CIT. ID: 2078208 NLM CIT. ID: 90309909
SOURCE:  N Engl J Med 1990 Jul 26;323(4):219-23
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2078208&form=6&db=m&Dopt=b

TITLE: Evaluation of the intrathecal antibody response to Borrelia
burgdorferi as a diagnostic test for Lyme neuroborreliosis.
AUTHORS: Steere AC; Berardi VP; Weeks KE; Logigian EL
Ackermann R
AUTHOR AFFILIATION:
Division of Rheumatology/Immunology, New England Medical Center, Tufts
University School of Medicine, Boston, MA 02111.
GRANT/CONTRACT ID: AM-20358/AM/NIADDK
ABSTRACT:
The intrathecal antibody response to Borrelia burgdorferi was
evaluated in American and West German patients with Lyme
neuroborreliosis. By an antibody capture enzyme immunoassay, 12 (92%)
of 13 patients from the USA with Lyme meningitis were found to have
intrathecal antibody production to B. burgdorferi, usually of
multiple isotypes, most commonly IgA. Of 12 patients with putative
late central nervous system manifestations of Lyme disease, 5 (42%)
had local production of IgG or IgA spirochetal antibody, but
cerebrospinal fluid (CSF) abnormalities could not be demonstrated in
6 patients with late peripheral nervous system manifestations of the
disorder. Compared with American patients, 30 European patients with
neuroborreliosis had significantly higher CSF:serum ratios of
specific antibody both early and late in the illness. Intrathecal
antibody determinations are the most specific diagnostic test
currently available for Lyme neuroborreliosis, but local antibody
production in CSF is an inconsistent finding in American patients
with late neurologic manifestations of the disorder.
NLM PUBMED CIT. ID: 2345301 NLM CIT. ID: 90264739
SOURCE:  J Infect Dis 1990 Jun;161(6):1203-9
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2345301&form=6&db=m&Dopt=b

TITLE: Spirochetal antigens and lymphoid cell surface markers in Lyme
synovitis. Comparison with rheumatoid synovium and tonsillar lymphoid
tissue.
AUTHORS: Steere AC; Duray PH; Butcher EC
AUTHOR AFFILIATION:
Department of Internal Medicine, Yale University School of Medicine,
New Haven, Connecticut.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS RR-00125/RR/NCRR AI-19957/AI/NIAID
ABSTRACT:
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.
NLM PUBMED CIT. ID: 3258751 NLM CIT. ID: 88192747
SOURCE:  Arthritis Rheum 1988 Apr;31(4):487-95
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3258751&form=6&db=m&Dopt=b

TITLE: The clinical evolution of Lyme arthritis.
AUTHORS: Steere AC; Schoen RT; Taylor E
AUTHOR AFFILIATION:
Department of Internal Medicine, Yale University School of Medicine,
New Haven, Connecticut.
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
RR-05443/RR/NCRR
ABSTRACT:
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.
NLM PUBMED CIT. ID: 3662285 NLM CIT. ID: 88022242
SOURCE:  Ann Intern Med 1987 Nov;107(5):725-31
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3662285&form=6&db=m&Dopt=b

TITLE: Treatment of Lyme disease.
AUTHORS: Steere AC; Green J; Hutchinson GJ; Rahn DW
Pachner AR; Schoen RT; Sigal LH; Taylor E; Malawista SE
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
RR-00125/RR/NCRR
ABSTRACT:
We compared phenoxymethyl penicillin, erythromycin, and tetracycline,
in each instance 250 mg four times a day for 10 days, for the
treatment of early Lyme disease (stage 1). None of 39 patients given
tetracycline developed major late complications compared with 3 of 40
penicillin- treated patients and 4 of 29 given erythromycin (p =
0.07). However, with all three antibiotic agents, nearly half of
patients had minor late symptoms. For neurologic abnormalities (stage
2), 12 patients were treated with high-dose intravenous penicillin,
20 million U a day for 10 days. Pain usually subsided during therapy,
but a mean of 7 to 8 weeks was required for complete recovery of
motor deficits. For the treatment of established arthritis (stage 3),
20 patients were assigned treatment with intramuscular benzathine
penicillin (7.2 million U) and 20 patients received saline. Seven of
the 20 penicillin-treated patients (35%) were apparently cured, but
all 20 patients given placebo continued to have attacks of arthritis
(P less than 0.02). Of 20 arthritis patients treated with intravenous
penicillin G, 20 million U a day for 10 days, 11 (55%) were
apparently cured. Thus, all 3 stages of Lyme disease can be treated
with antibiotic therapy, but some patients with late disease may not
respond.
NLM PUBMED CIT. ID: 3109144 NLM CIT. ID: 87237041
SOURCE:  Zentralbl Bakteriol Mikrobiol Hyg [A] 1987 Feb;263(3):352-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3109144&form=6&db=m&Dopt=b

TITLE: Historical perspective of Lyme disease.
AUTHORS: Steere AC; Snydman D; Murray P; Mensch J; Main AJ Jr
Wallis RC; Shope RE; Malawista SE
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK
RR-00125/RR/NCRR
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 3554843 NLM CIT. ID: 87208553
SOURCE:  Zentralbl Bakteriol Mikrobiol Hyg [A] 1986 Dec;263(1-2):3-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3554843&form=6&db=m&Dopt=b

TITLE: Clinical manifestations of Lyme disease.
AUTHORS: Steere AC; Bartenhagen NH; Craft JE; Hutchinson GJ
Newman JH; Pachner AR; Rahn DW; Sigal LH; Taylor E; Malawista SE
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK
RR-00125/RR/NCRR
ABSTRACT:
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.
NLM PUBMED CIT. ID: 3554839 NLM CIT. ID: 87208539
SOURCE:  Zentralbl Bakteriol Mikrobiol Hyg [A] 1986 Dec;263(1-2):201-5
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3554839&form=6&db=m&Dopt=b

TITLE: 
Longitudinal assessment of the clinical and epidemiological features
of Lyme disease in a defined population.
AUTHORS: Steere AC; Taylor E; Wilson ML; Levine JF
Spielman A
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK
AI-19693/AI/NIAID
ABSTRACT:
From 1979 to 1983, Lyme disease was studied longitudinally in the 162
long-term residents of Great Island, Massachusetts. In retrospect,
the index case occurred in 1962, and the peak years of disease
transmission (about three new cases per 100 residents per year) were
the late 1970s. Thereafter, during the period of active surveillance,
attack rates declined by half. Altogether, 26 (16%) of the 162
residents developed symptoms of the disease. Most of those affected
had erythema chronicum migrans, and when untreated, they subsequently
developed arthritis or, in one instance, myocarditis. A minority of
individuals, mostly children, had arthritis alone. Of 121
asymptomatic residents who gave blood samples, 10 adults (8%) had
high titers of IgG antibodies to the Lyme disease spirochete; these
titers sometimes persisted for years. From 1981 to 1983, the
estimated ratio of apparent-to-inapparent infection was 1:1. The high
frequency of Lyme disease on Great Island underscores the need for
surveillance and control programs.
NLM PUBMED CIT. ID: 3722867 NLM CIT. ID: 86252516
SOURCE:  J Infect Dis 1986 Aug;154(2):295-300
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3722867&form=6&db=m&Dopt=b

TITLE: Unilateral blindness caused by infection with the Lyme disease
spirochete, Borrelia burgdorferi.
AUTHORS: Steere AC; Duray PH; Kauffmann DJ; Wormser GP
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK
RR-00125/RR/NCRR
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 4026085 NLM CIT. ID: 85277667
SOURCE:  Ann Intern Med 1985 Sep;103(3):382-4
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=4026085&form=6&db=m&Dopt=b

TITLE: Successful parenteral penicillin therapy of established Lyme
arthritis.
AUTHORS: Steere AC; Green J; Schoen RT; Taylor E
Hutchinson GJ; Rahn DW; Malawista SE
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
RR-00125/RR/NCRR
ABSTRACT:
In a double-blind placebo-controlled trial carried out from 1980 to
1982, 20 patients with established Lyme arthritis were assigned
treatment with 2.4 million U of intramuscular benzathine penicillin
weekly for three weeks (total, 7.2 million U) and 20 patients
received saline. Seven of the 20 penicillin-treated patients (35 per
cent) had complete resolution of arthritis soon after the injections
and have remained well during a mean follow-up period of 33 months.
In contrast, all 20 patients given placebo continued to have attacks
of arthritis (P less than 0.02). In 1983, of 20 patients treated with
intravenous penicillin G, 20 million U a day for 10 days, 11 (55 per
cent) had complete resolution of arthritis and have remained well
since. As compared with nonresponders, penicillin-responsive patients
in both studies were more likely to have previously received
antibiotics for erythema chronicum migrans (P less than 0.02) and
less likely to have been given intraarticular corticosteroids during
or at the conclusion of parenteral therapy (P less than 0.1). The
Lyme spirochete was not cultured from synovium or joint fluid. We
conclude that established Lyme arthritis can often be treated
successfully with parenteral penicillin. However, neither of the
regimens that we tested is uniformly effective, and further
experience will be needed to determine the optimal course of therapy.
NLM PUBMED CIT. ID: 3883177 NLM CIT. ID: 85137775
SOURCE:  N Engl J Med 1985 Apr 4;312(14):869-74
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3883177&form=6&db=m&Dopt=b

TITLE: The clinical spectrum and treatment of Lyme disease.
AUTHORS: Steere AC; Malawista SE; Bartenhagen NH; Spieler PN
Newman JH; Rahn DW; Hutchinson GJ; Green J; Snydman DR; Taylor E
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK
AM-5639/AM/NIADDK
ABSTRACT:
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.
NLM PUBMED CIT. ID: 6516448 NLM CIT. ID: 85092772
SOURCE:  Yale J Biol Med 1984 Jul-Aug;57(4):453-64
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6516448&form=6&db=m&Dopt=b

TITLE: Recovery of Lyme disease spirochetes from patients.
AUTHORS: Steere AC; Grodzicki RL; Craft JE; Shrestha M
Kornblatt AN; Malawista SE
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK
AM-5639/AM/NIADDK
ABSTRACT:
Since the summer of 1982, we have cultured patient specimens for Lyme
disease spirochetes. Of 118 patients cultured, four specimens yielded
spirochetes: two from blood, one from a skin biopsy specimen of
erythema chronicum migrans (ECM), and one from cerebrospinal fluid.
All four isolates appeared identical when examined with a monoclonal
antibody. However, attempts to recover the spirochete from synovium
or synovial fluid were unsuccessful. In addition, the organism could
not be visualized in skin or synovial biopsy specimens using the
avidin- biotin peroxidase complex detection system. Thus, the current
yield in culturing spirochetes from patients is quite low, and it is
not yet known whether the organism is still alive later in the
disease when arthritis is present.
NLM PUBMED CIT. ID: 6393606 NLM CIT. ID: 85092786
SOURCE:  Yale J Biol Med 1984 Jul-Aug;57(4):557-60
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6393606&form=6&db=m&Dopt=b

TITLE: 
Neurologic abnormalities of Lyme disease: successful treatment with
high-dose intravenous penicillin.
AUTHORS: Steere AC; Pachner AR; Malawista SE
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK
AM-5639/AM/NIADDK
ABSTRACT:
Twelve patients were treated with high-dose intravenous penicillin for
neurologic abnormalities of Lyme disease. Headache, stiff neck, and
radicular pain usually began to subside by the second day of therapy
and were often gone by 7 to 10 days. Five of the 12 patients
continued to have intermittent mild headache for several more weeks,
but no patient relapsed after therapy was stopped. Compared to 15
previous patients treated with prednisone alone, the duration of
meningitic syndrome was significantly shorter in those given
penicillin (mean duration, 1 versus 29 weeks, p less than 0.000001).
However, in both groups, a mean of 7 to 8 weeks was required for
complete recovery of motor deficits. Despite antibiotic therapy, 3 of
the 12 patients treated with penicillin continued to have frequent
arthralgias, musculoskeletal pain, and fatigue. We conclude that
high-dose intravenous penicillin is effective therapy for neurologic
abnormalities of Lyme disease.
NLM PUBMED CIT. ID: 6316826 NLM CIT. ID: 84078045
SOURCE:  Ann Intern Med 1983 Dec;99(6):767-72
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6316826&form=6&db=m&Dopt=b

TITLE: The early clinical manifestations of Lyme disease.
AUTHORS: Steere AC; Bartenhagen NH; Craft JE; Hutchinson GJ
Newman JH; Rahn DW; Sigal LH; Spieler PN; Stenn KS; Malawista SE
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK
AM-5639/AM/NIADDK
ABSTRACT:
Lyme disease, caused by a tick-transmitted spirochete, typically
begins with a unique skin lesion, erythema chronicum migrans. Of 314
patients with this skin lesion, almost half developed multiple
annular secondary lesions; some patients had evanescent red blotches
or circles, malar or urticarial rash, conjunctivitis, periorbital
edema, or diffuse erythema. Skin manifestations were often
accompanied by malaise and fatigue, headache, fever and chills,
generalized achiness, and regional lymphadenopathy. In addition,
patients sometimes had evidence of meningeal irritation, mild
encephalopathy, migratory musculoskeletal pain, hepatitis,
generalized lymphadenopathy and splenomegaly, sore throat,
nonproductive cough, or testicular swelling. These signs and symptoms
were typically intermittent and changing during a period of several
weeks. The commonest nonspecific laboratory abnormalities were a high
sedimentation rate, an elevated serum IgM level, or an increased
aspartate transaminase level. Early Lyme disease can be diagnosed by
its dermatologic manifestations, rapidly changing system involvement,
and if necessary, by serologic testing.
NLM PUBMED CIT. ID: 6859726 NLM CIT. ID: 83229290
SOURCE:  Ann Intern Med 1983 Jul;99(1):76-82
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6859726&form=6&db=m&Dopt=b

TITLE: Treatment of the early manifestations of Lyme disease.
AUTHORS: Steere AC; Hutchinson GJ; Rahn DW; Sigal LH
Craft JE; DeSanna ET; Malawista SE
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK
AM-5639/AM/NIADDK
ABSTRACT:
During 1980 and 1981, we compared antibiotic regimens in 108 adult
patients with early Lyme disease. Erythema chronicum migrans and its
associated symptoms resolved faster in penicillin- or tetracycline-
treated patients than in those given erythromycin (mean duration, 5.4
and 5.7 versus 9.2 days, F = 3.38, p less than 0.05). None of 39
patients given tetracycline developed major late complications
(meningoencephalitis, myocarditis, or recurrent attacks of arthritis)
compared with 3 of 40 penicillin-treated patients and 4 of 29 given
erythromycin (chi square with 2 degrees of freedom = 5.33, p = 0.07).
In 1982, all 49 adult patients were given tetracycline; again, none
of them developed major complications. However, with all three
antibiotic agents nearly half of the patients had minor late symptoms
such as headache, musculoskeletal pain, and lethargy. These
complications correlated significantly with the initial severity of
illness. For patients with early Lyme disease, tetracycline appears
to be the most effective drug, then penicillin, and finally
erythromycin.
NLM PUBMED CIT. ID: 6407378 NLM CIT. ID: 83229279
SOURCE:  Ann Intern Med 1983 Jul;99(1):22-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6407378&form=6&db=m&Dopt=b

TITLE: The spirochetal etiology of Lyme disease.
AUTHORS: Steere AC; Grodzicki RL; Kornblatt AN; Craft JE
Barbour AG; Burgdorfer W; Schmid GP; Johnson E; Malawista SE
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK
AI-07174/AI/NIAID
ABSTRACT:
We recovered a newly recognized spirochete from the blood, skin
lesions (erythema chronicum migrans [ECM]), or cerebrospinal fluid of
3 of 56 patients with Lyme disease and from 21 of 110 nymphal or
adult lxodes dammini ticks in Connecticut. These isolates and the
original one from l. dammini appeared to have the same morphologic
and immunologic features. In patients, specific IgM antibody titers
usually reached a peak between the third and sixth week after the
onset of disease; specific IgG antibody titers rose slowly and were
generally highest months later when arthritis was present. Among 40
patients who had early disease only (ECM alone), 90 per cent had an
elevated IgM titer (greater than or equal to 1:128) between the ECM
phase and convalescence. Among 95 patients with later manifestations
(involvement of the nervous system, heart, or joints), 94 per cent
had elevated titers of IgG (greater than or equal to 1:128). In
contrast, none of 80 control subjects had elevated IgG titers, and
only three control patients with infectious mononucleosis had
elevated IgM titers. We conclude that the I. dammini spirochete is
the causative agent of Lyme disease.
NLM PUBMED CIT. ID: 6828118 NLM CIT. ID: 83141697
SOURCE:  N Engl J Med 1983 Mar 31;308(13):733-40
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6828118&form=6&db=m&Dopt=b

TITLE: Lyme carditis: cardiac abnormalities of Lyme disease.
AUTHORS: Steere AC; Batsford WP; Weinberg M; Alexander J
Berger HJ; Wolfson S; Malawista SE
ABSTRACT:
We studied 20 patients, mostly young adult men, with cardiac
involvement of Lyme disease. The commonest abnormality (18 patients)
was fluctuating degrees of atrioventricular block; eight of them
developed complete heart block. Thirteen patients had evidence of
more diffuse cardiac involvement: electrocardiographic changes
compatible with acute myopericarditis (11 patients), radionuclide
evidence of mild left ventricular dysfunction (five of 12 patients
tested), or frank cardiomegaly (one patient). Heart involvement was
usually preceded by erythema chronicum migrans and sometimes
accompanied by meningoencephalitis, facial palsy, arthritis, elevated
serum IgM levels, or cryoglobulins containing IgM. The duration of
cardiac involvement was usually brief (3 days to 6 weeks). The
clinical picture in these patients has similarities to acute
rheumatic fever; but in Lyme disease, complete heart block may be
commoner, myopericardial involvement tends to be milder, and valves
seem not to be affected.
NLM PUBMED CIT. ID: 6967274 NLM CIT. ID: 80240247
SOURCE:  Ann Intern Med 1980 Jul;93(1):8-16
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6967274&form=6&db=m&Dopt=b

TITLE: Antibiotic therapy in Lyme disease.
AUTHORS: Steere AC; Malawista SE; Newman JH; Spieler PN; Bartenhagen NH
ABSTRACT:
We studied antibiotic efficacy in 113 patients with erythema chronicum
migrans, the first manifestation of Lyme disease. Erythema chronicum
migrans and its associated symptoms resolved faster in patients given
penicillin or tetracycline (median duration, 4 and 2 days,
respectively) than in untreated patients (10 days; P less than 0.001
and P = 0.005, respectively). Erythromycin had no significant effect.
Although the frequency of subsequent neurologic and cardiac
abnormalities was similar in all four groups, significantly fewer
patients given penicillin developed arthritis than did untreated
patients (P = 0.001). Among 15 patients with arthritis who were
followed for at least 29 months, the total duration of joint
involvement was shorter in penicillin-treated patients (median, 4
weeks) than in untreated patients (17 weeks; P = 0.019). Although the
clinical manifestations of the disease may fluctuate in frequency
from year to year and influence apparent antibiotic effect, we
conclude that penicillin therapy shortens the duration of erythema
chronicum migrans and may prevent or attenuate subsequent arthritis.
NLM PUBMED CIT. ID: 6967272 NLM CIT. ID: 80240204
SOURCE:  Ann Intern Med 1980 Jul;93(1):1-8
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6967272&form=6&db=m&Dopt=b

TITLE: 
Elevated levels of collagenase and prostaglandin E2 from synovium
associated with erosion of cartilage and bone in a patient with
chronic Lyme arthritis.
AUTHORS: Steere AC; Brinckerhoff CE; Miller DJ; Drinker H
Harris ED Jr; Malawista SE
ABSTRACT:
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.
NLM PUBMED CIT. ID: 6246904 NLM CIT. ID: 80197837
SOURCE:  Arthritis Rheum 1980 May;23(5):591-9
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6246904&form=6&db=m&Dopt=b

TITLE: 
Cases of Lyme disease in the United States: locations correlated with
distribution of Ixodes dammini.
AUTHORS: Steere AC; Malawista SE
ABSTRACT:
Lyme disease, defined by erythema chronicum migrans and sometimes
followed by neurologic, cardiac, or joint involvement, is known to
have affected 512 patients in the United States. The disease seems to
occur in three distinct foci: along the northeastern coast, in
Wisconsin, and in California and Oregon, a distribution that
correlates closely with that of Ixodes dammini in the first two areas
and with Ixodes pacificus in the last. The implicated tick, saved by
six patients in the Northeast, was identified as nymphal I. dammini.
Residence in or travel to endemic areas and history of tick bite may
be important clues to diagnosis.
NLM PUBMED CIT. ID: 496106 NLM CIT. ID: 80040599
SOURCE:  Ann Intern Med 1979 Nov;91(5):730-3
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=496106&form=6&db=m&Dopt=b

TITLE: 
Chronic Lyme arthritis. Clinical and immunogenetic differentiation
from rheumatoid arthritis.
AUTHORS: Steere AC; Gibofsky A; Patarroyo ME; Winchester RJ
Hardin JA; Malawista SE
ABSTRACT:
Ten patients with Lyme arthritis have developed chronic involvement of
one or both knees. Lyme arthritis was diagnosed by onset with
erythema chronicum migrans (six patients); residence in Lyme,
Connecticut (eight); seasonal onset in summer and early fall (nine);
early periods of short recurrent attacks (nine); absence of
rheumatoid factor (nine); and absence of symmetrical polyarthritis,
morning stiffness, subcutaneous nodules, or antinuclear antibodies
(in all). Five patients had synovectomies; pannus formation and
underlying cartilage erosion were present in all. Seven of the 10
patients had the same B-cell alloantigen, DRw2 (frequency in normal
control subjects, 22% [P less than 0.005]), but did not have an
increased frequency of the alloantigens associated with rheumatoid
arthritis. Chronic Lyme arthritis, the result of an apparent
tick-transmitted infection, resembles rheumatoid arthritis
pathologically but generally differs from it in both prearticular and
immunogenetic characteristics.
NLM PUBMED CIT. ID: 312615 NLM CIT. ID: 79185855
SOURCE:  Ann Intern Med 1979 Jun;90(6):896-901
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=312615&form=6&db=m&Dopt=b

TITLE: Lyme arthritis: correlation of serum and cryoglobulin IgM with
activity, and serum IgG with remission.
AUTHORS: Steere AC; Hardin JA; Ruddy S; Mummaw JG
Malawista SE
ABSTRACT:
Forty-eight patients with erythema chronicum migrans (ECM) were
studied prospectively for 6 to 18 months. Twenty-six patients had no
later symptoms, but 22 subsequently developed Lyme arthritis and 9 of
them also experienced neurologic abnormalities. Eighty-seven percent
of patients with active ECM followed by subsequent involvement had
cryoglobulins containing IgM compared to only 13% of those with
active ECM and no later symptoms. The former group also had
significantly lower IgG, C3 and C4 levels. Sixty-seven percent of
patients still had serum cryoglobulins when neurologic disease was
most active, and 45% had them when joint symptoms were most severe,
but only 11% continued to have small amounts in remission. The number
of patients who continued to have serum cryoglobulins with recurrent
attacks of arthritis decreased with time. In contrast, patients
always had cryoglobulins in joint fluid, a finding Lyme arthritis
shares with rheumatoid arthritis. The cryoprecipitates from 2 of 10
patients contained particles with internal structure, but their viral
nature is problematic. All components of antisera obtained from goats
and rabbits immunized with cryoglobulins were absorbed by normal
human sera. The amount of IgM in cryoglobulins correlated directly
with serum IgM, which generally rose during exacerbations and fell
during remissions; serum IgG and IgA moved conversely. Thus, IgM was
an important correlate of clinical disease activity and IgG or
remission.
NLM PUBMED CIT. ID: 109097 NLM CIT. ID: 79187358
SOURCE:  Arthritis Rheum 1979 May;22(5):471-83
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=109097&form=6&db=m&Dopt=b

TITLE: 
Erythema chronicum migrans and Lyme arthritis: epidemiologic evidence
for a tick vector.
AUTHORS: Steere AC; Broderick TF; Malawista SE
ABSTRACT:
Forty-three residents of 12 contiguous Connecticut communities were
identified who had the onset of erythema chronicum migrans, Lyme
arthritis, or both during the summer and fall of 1977. Nine of them
(21%) remembered having been bitten by a tick at the site of the
initial skin lesion a median of 12 days (range 3-20) before onset;
one patient brought in the tick for identification (Ixodes
scapularis). Compared to 64 of their neighbors, significantly more
patients had cats and farm animals, and had noted ticks on their pets
and tick bites on themselves. The incidence of the illness during
1977 was 2.8 cases per 1000 residents in the three communities on the
east side of the Connecticut River, compared to 0.1 cases per 1000
residents in the nine communities on the west side, a difference of
almost 30-fold. Taken with the results of a concomitant acarological
study on both sides of the river, these findings support the
hypothesis that erythema chronicum migrans and Lyme arthritis are
tick-transmitted, specifically by I. scapularis.
NLM PUBMED CIT. ID: 727200 NLM CIT. ID: 79080217
SOURCE:  Am J Epidemiol 1978 Oct;108(4):312-21
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=727200&form=6&db=m&Dopt=b

TITLE: Erythema chronicum migrans and Lyme arthritis: related problems
recently recognized in Connecticut.
AUTHORS: Steere AC; Hardin JA; Malawista SE
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 657796 NLM CIT. ID: 78189918
SOURCE:  Conn Med 1978 Jun;42(6):353-7
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=657796&form=6&db=m&Dopt=b

TITLE: Lyme arthritis: a new clinical entity.
AUTHORS: Steere AC; Hardin JA; Malawista SE
ABSTRACT:
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.
NLM PUBMED CIT. ID: 658948 NLM CIT. ID: 78192800
SOURCE:  Hosp Pract 1978 Apr;13(4):143-58
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=658948&form=6&db=m&Dopt=b

TITLE: 
Erythema chronicum migrans and Lyme arthritis: cryoimmunoglobulins and
clinical activity of skin and joints.
AUTHORS: Steere AC; Hardin JA; Malawista SE
ABSTRACT:
We report the presence of serum cryoimmunoglobulins in patients with
attacks of a newly described epidemic arthritis--Lyme arthritis--and
in some patients with a characteristic skin lesion--erythema
chronicum migrans--that sometimes precedes the onset of the
arthritis. Seven patients who had cryoimmunoglobulins at the time of
the skin lesion have developed arthritis; four patients without them
have not. The cryoglobulins in patients with the skin lesion
consisted primarily of immunoglobulin M (IgM); those in patients with
arthritis often included both IgM and IgG. These findings support the
hypothesis that a common origin exists for the skin and joint lesions
and suggest that circulating immune complexes may have a pathogenetic
role in Lyme arthritis.
NLM PUBMED CIT. ID: 870973 NLM CIT. ID: 77174694
SOURCE:  Science 1977 Jun 3;196(4294):1121-2
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=870973&form=6&db=m&Dopt=b

TITLE: 
Erythema chronicum migrans and Lyme arthritis. The enlarging clinical
spectrum.
AUTHORS: Steere AC; Malawista SE; Hardin JA; Ruddy S
Askenase W; Andiman WA
ABSTRACT:
Thirty-two patients with the onset of erythema chronicum migrans, Lyme
arthritis, or both in mid-1976 were studied prospectively. The skin
lesion (24 patients) typically lasted about 3 weeks, beginning as a
red macule or papule that expanded to form a large ring with central
clearing. Associated symptoms ranged from none to malaise, fatigue,
chills and fever, headache, stiff neck, backache, myalgias, nausea,
vomiting, and sore throat. Three patients had been bitten by ticks at
the site of the initial lesion 4 to 20 days before its onset.
Nineteen patients suddenly developed a monoarticular or
oligoarticular arthritis 4 days to 22 weeks (median, 4 weeks) after
onset of the skin lesion; eight developed arthritis without a
preceding skin lesion. Seven of these 27 experienced migratory joint
pains. Arthritis attacks, most commonly in the knee, were typically
short (median, 8 days) but sometimes persisted for months. Other
manifestations included neurologic abnormalties, myocardial
conduction abnormalities, serum cryoprecipitates, elevated serum IgM
levels, and elevated erythrocyte sedimentation rates. The diagnostic
marker is the skin lesion; without it, geographic clustering is the
most important clue.
NLM PUBMED CIT. ID: 869348 NLM CIT. ID: 77200064
SOURCE:  Ann Intern Med 1977 Jun;86(6):685-98
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=869348&form=6&db=m&Dopt=b

TITLE: 
Lyme arthritis: an epidemic of oligoarticular arthritis in children
and adults in three connecticut communities.
AUTHORS: Steere AC; Malawista SE; Snydman DR; Shope RE
Andiman WA; Ross MR; Steele FM
ABSTRACT:
An epidemic form of arthritis has been occurring in eastern
Connecticut at least since 1972, with the peak incidence of new cases
in the summer and early fall. Its identification has been possible
because of tight geographic clustering in some areas, and because of
a characteristic preceding skin lesion in some patients. The authors
studied 51 residents of three contiguous Connecticut communities --
39 children and 12 adults -- who developed an illness characterized
by recurrent attacks of asymmetric swelling and pain in a few large
joints, especially the knee. Attacks were usually short (median: 1
week) with much longer intervening periods of complete remission
(median: 2.5 months), but some attacks lasted for months. To date the
typical patient has had three recurrences, but 16 patients have had
none. A median of 4 weeks (range: 1-24) before the onset of
arthritis, 13 patients (25%) noted an erythematous papule that
developed into an expanding, red, annular lesion, as much as 50 cm in
diameter. Only 2 of 159 family members of patients had such a lesion
and did not develop arthritis (P less than 0.000001). The overalll
prevalence of the arthritis was 4.3 cases per 1,000 residents, but
the prevalence among children living on four roads was 1 in 10. Six
families had more than 1 affected member. Nine of 20 symptomatic
patients had low serum C3 levels, compared to none of 31 asymptomatic
patients (P less than 0.005); no patient had iridocyclitis or a
positive test for antinuclear antibodies. Neither cultures of
synovium and synovial fluid nor serologic tests were positive for
agents known to cause arthritis. "Lynne arthritis" is thought to be a
previously unrecognized clinical entity, the epidemiology of which
suggests transmission by an arthropod vector.
NLM PUBMED CIT. ID: 836338 NLM CIT. ID: 77112064
SOURCE:  Arthritis Rheum 1977 Jan-Feb;20(1):7-17
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=836338&form=6&db=m&Dopt=b

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Compiled by
Art Doherty
Lompoc, California
doherty@utech.net