Early Studies (pre-spirochete discovery)

[itsybitsyone]

Steere AC; Malawista SE; Hardin JA; Ruddy S; Askenase PW; Andiman WA
1977 Erythema chronicum migrans and Lyme arthritis. The enlarging clinical spectrum. Annals of Internal Medicine, 86:685-698
"We remain skeptical that antibiotic therapy helps... Eight of our patients received penicillin, erythromycin, or cephalexin before entering the study because of the
skin lesion. In one of them, the lesion persisted for 2 months despite therapy, longer than in any of the other study patients, and seven of the eight patients still
. developed joint, neurologic, or cardiac abnormalities..
“Particularly puzzling has been the observation that organisms are extremely
difficult to find in infected tissue, using either microbiologic or morphologic
techniques. However, in many instances continued infection appears to be
essential for symptoms to persist, no matter how small the number of
organisms, as antimicrobial therapy is generally followed by clinical
improvement.”





Arthritis Rheum. 1979 May;22(5):471-83.
Lyme arthritis: correlation of serum and cryoglobulin IgM with activity, and serum IgG with remission.
Steere AC, Hardin JA, Ruddy S, Mummaw JG, Malawista SE.
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.

[itsybitsyone]

Arthritis Rheum. 1977 Jan-Feb;20(1):7-17.
Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities.
Steere AC, Malawista SE, Snydman DR, Shope RE, Andiman WA, Ross MR, Steele FM.
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.


Ann Intern Med. 1977 Jun;86(6):685-98.
Erythema chronicum migrans and Lyme arthritis. The enlarging clinical spectrum.
Steere AC, Malawista SE, Hardin JA, Ruddy S, Askenase W, Andiman WA.
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.

[itsybitsyone]

Steere AC. Schoen RT. Taylor E.
Department of Internal Medicine, Yale University School of Medicine, New
Haven, Connecticut.
The clinical evolution of Lyme arthritis.
Annals of Internal Medicine. 107(5):725-31, 1987 Nov.
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 intermit
tent attacks of arthritis, to chronic erosive disease.





Steere AC. Malawista SE. Newman JH. Spieler PN. Bartenhagen NH.
Antibiotic therapy in Lyme disease.
Annals of Internal Medicine. 93(1):1-8, 1980 Jul.

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.