Interpret Steere's Comments With Great Caution

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I. LYMENET: Interpret Steere's Comments With Great Caution ------------------------------------------------------------- Sender: Peter McFadden

I am writing this contribution to the LymeNet Newsletter in response to the recent 10/13/95 Science article [1] reporting the National Institutes' of Health (NIH) plans to study the possible existence of chronic Lyme disease. The main focus of the article was the controversy between patient advocacy groups and treating physicians on one side, and university based researchers (who frequently dispute the existence of chronic Lyme disease) on the other. The article reported that the patient groups' tactics to encourage the study of chronic Lyme disease "have angered research leaders such as Allen Steere of Tufts University." Is patient inspired research really so bad? What if this is an important research area university based physicians have chosen not to study?

Dr. Steere has been one of the most outspoken critics of the existence of chronic Lyme disease [2], and one of the most outspoken proponents of the success of modest (10 - 30 day) courses of antibiotics [2]. In a 1993 paper [3], Dr. Steere writes that in Lyme disease "Standard antibiotic treatment probably fails less often than one might think. Most apparent treatment failures actually reflect misdiagnosis."

However evidence is mounting that the Lyme disease spirochete, Borrelia burgdorferi, can persist in some patients despite antibiotic therapy. The spirochete has been isolated from the skin [4,5], spinal fluid [5,6], synovial fluid [7], blood [8], ligamentious tissue [9], muscle tissue [39] and iris tissue [10] of patients after antibiotic therapy, including intravenous (IV) and/or long courses of supposedly curative antibiotics. In one large European study of late Lyme disease treatment [11], 2 weeks of IV Rocephin resulted in a cure rate of 31% (4 of 13 patients). When 2 weeks of IV Rocephin were followed with 100 days of oral antibiotics, the cure rate went up to 87% (69 of 79 patients).

A second European study of Lyme disease [12] showed a 50% cure rate with 3 weeks of antibiotics, and a 78% cure rate with 8 weeks of antibiotics.

Perhaps examining some of Dr. Steere's earlier beliefs can add insight to his belief that chronic Lyme disease is extremely rare or does not exist. It may surprise some to learn that in the first few years he was associated with Lyme disease, Dr. Steere believed antibiotics were ineffective. In a 1977 Lyme disease paper [13], Dr. Steere and his colleagues state "We remain skeptical that antibiotic therapy helps." In a 1978 paper [14], Dr. Steere and his colleagues wrote "To sum up the therapy of Lyme arthritis (Lyme disease), it appears that at this point only symptomatic treatment is feasible." In a 1979 paper [15] on the neurological abnormalities of Lyme disease, Dr. Steere and his colleagues reported that they "have noted no benefit from antibiotic treatment."

In an article in The New Yorker [16], a physician from Shelter Island, New York, who was treating Lyme disease with antibiotics as early as 1976, stated that"When Steere assured me that the disease was self-limiting, I stopped using antibiotics."

Dr. Steere's early beliefs about antibiotics are surprising, considering the literature that existed at the time. A literature search revealed 18 papers [18-35] reporting the efficacy of antibiotics in treating Lyme disease (then called ECM disease) before 1979. Only one paper could be found (besides Dr. Steere's) that reported no benefit [36]. In fact in all 4 case report papers [20-23] on Lyme disease (ECM disease) where the patient(s) acquired the disease in the United States, published before Dr. Steere's first Lyme disease paper [37], all patients received antibiotics.

It is ironic that Dr. Steere, currently an outspoken proponent of the near universal efficacy of 10 - 30 days of antibiotics in the treatment of Lyme disease, was, with his colleagues, one of the lone voices in the late 1970's insisting that antibiotics did not help.

Dr. Steere apparently turned his beliefs into action, or inaction as the case may be. In a 1987 paper [17] co-authored with Dr. Robert T. Schoen, Dr. Steere reported: "To determine the clinical evolution of Lyme arthritis, 55 patients who did not receive antibiotic therapy for erythema chronicum migrans (ECM, the rash) were followed longitudinally for a mean duration of 6 years [up until 1981]." This paper goes on to describe the ailments of many of these unfortunate individuals, including frank arthritis, chronic synovitis, joint erosions, and permanent joint disability.

Dr. Steere eventually conducted his own studies of antibiotics, and discovered what many physicians already knew; antibiotics frequently worked. In a 1985 paper [38] describing the efficacy of antibiotics in treating arthritic manifestations of Lyme disease, Steere wrote that in the period 1980-1982, "We found that neurological abnormalities of Lyme disease responded to high dose intravenous penicillin."In a 1958 paper [28], 58 of 65 patients responded to treatment with penicillin. One wonders why Dr. Steere had to reinvent the wheel considering the 18 prior papers spanning 3 decades, from both the US [18-24], and Europe [25-35], describing the efficacy of antibiotics in treating this illness. These studies report exactly what Dr. Steere later found [38]; though not universally effective, most patients treated with penicillin fared much better.

It is interesting that the only controlled studies [11,12] of longer term antibiotics in helping to prevent chronic or relapsing Lyme disease (both successful) were performed in Europe. But then Dr. Steere himself stated [1] that the proposed NIH study of chronic Lymedisease "would never have been funded" through the "normal mechanisms" of investigator-initiated research. Unfortunately, I'm afraid I agree with Dr. Steere on this point.

Dr. Steere's early insistence that antibiotics played no role in the treatment of Lyme disease indicates that his current statements and beliefs should be interpreted with great caution.

Peter McFadden, M.S. 4611 Governor's Drive Apartment 1001 Huntsville, AL 35805 (205) 722-0474

REFERENCES:

[1] Marshall, E: Science 270, 228 (1995)

[2] Steere AC et al: "The Overdiagnosis of Lyme Disease" JAMA 269, 1812 (1993)

[3] Steere AC: Hospital Practice, pg 37 (April, 1993)

[4] Hassler D et al: The Lancet 338, 193 (1991)

[5] Preac-Mursic V et al: Infection 17, 355 (1989)

[6] Pfister H et al: The J of Infectious Disease 163, 311 (1991)

[7] Schmidli J., et al; Cultivation of B. burgdorferi from Joint Fluid Three Months After Treatment of Facial Palsey Due to Lyme Borreliosis; J. of Infectious Disease 158: 4, pg 905-906 (1988)

[8] Masters E et al: "Spirochetemia Two Weeks post cessation of six months of continuous p.o. Amoxicillin Therapy" (Abstr. 65, Fifth Int'l Conf on Lyme Borreliosis, Arlington, VA; 1992)

[9] Haupl T et al: Arthritis & Rheumatism 36, 1621 (1993)

[10] Preac-Mursic V et al: J of Neuroloophthalmology 13, 155 (1993)

[11] Wahlberg P et al: J of Infection 29, 255 (1994)

[12] Bojic I et al: Glas Srp Akad Nauka 43 (Yugoslavia), 257 (1993)

[13] Steere AC et al: Annals of Internal Medicine 86, 685 (1977)

[14] Steere AC et al: Hospital Practice, 143 (April, 1978)

[15] Reik L, Steere AC et al: Medicine 58, 281 (1979)

[16] Roueche B: The New Yorker, 83 (Sept. 12, 1988)

[17] Steere AC et al: Annals of Internal Medicine 107, 725 (1987)

[18] Hellerstrom S: Erythema chronicum migrans afzelius with meningitis. Southern Med J 43:330, 1950.

[19] Flanagan BP: Erythema chronicum migrans Afzelius in Americans. Arch Dermatol 86:410-411, 1962.

[20] Scrimenti RJ: Erythema chronicum migrans. Arch Dermatol 102:104-105, 1970.

[21] Mast WE, Burrows WM Jr: Erythema chronicum migrans in the United States: JAMA 236:859-860, 1976.

[22] Wagner L, Susens G, Heiss L, et al: Erythema chronicum migrans: a possibly infectious disease imported from Northern Europe. West J Med 124:503-505, 1976.

[23] Smith RL et al: Cutis 17, 962 (1976)

[24] Naversen DN, et al; Erythema Chronicum Migrans in America; Archives of Dermatology 114, pg 253-254 (1978)

[25] Lennhoff C: Spirochaetes in aetiologically obscure diseases. Aca Derm Venereol (Stockh) 28:295-324, 1948.

[26] Hollstrom E: Successful treatment of erythema migrans Afzelius. Acta Derm Venereol (Stockh) 31:235-243, 1951.

[27] Hellerstrom S: Erythema chronicum migrans Afzelius with meningitis. Acta Derm Venereol 31:227-234, 1951.

[28] Janson P: Haufigkeit, klinisches Bild, Therapie und Aetiologie des Erythema chronicum migrans. Med Kiin 48:1139-1141, 1953.

[29] Degos R, Touraine R, Aroutte J: Erythema chronicum migrans: Discussion of rickettsial origin. Ann Derm Syph 89:247-260, 1962.

[30] Hollstrom E: Penicillin Treatment of erythema chronicum migrans afzelius. Acta Derm 38:285-289, 1958.

[31] Binder E, Doepfmer R, Horstein O: Experimentelle ubertragung des erythema chronicum migrans von Mensch zu Mensch. Hautarzt 6:494-496, 1955. Abstracted, Excerpta Med 10:453, 1956.

[32] Sonck CE: Erythema chronicum migrans with multiple lesions. Acta Derm Venereol (Stockh) 45:34-36, 1965.

[33] Andermann I: Beitrag zur Begandkung des Erythema chronicum migrans. Dermatol Wochenschur 149:441-443, 1964.

[34] Sonck CE: Griseofulvin: Unwirksam bei erythema chronicum migrans.Hautarzt 21:514-516, 1970. Abstracted, Exerpta Med 26:149, 1972.

[35] Weber K: Erythema chronicum migrans meningitis eine bakterielle Infektionskrankheit? Munch Med Wochenschr 116:1993-1998, 1974.

[36] Horstrup P, Ackermann R: Durch zecken ubertragene Meningopolyneuritis (Garin-Bujadoux, Bannwarth). Fortschr Neurol Psychiatr 41:583-606, 1973.

[37] Steere AC et al: Arthritis Rheum 20, 7 (1977)

[38] Steere AC et al: NEJM 312, 869 (1985)

[39] Hoffmann JC et al: Lyme disease in a 74 year old forest owner with symptoms of dermatomyositis. Arthritis Rheum 38, 8: 1157-1160 (1995)