The next three posts will be on the phenomenon of Chronic Lyme disease with specific attention to those patients who test negative in validated laboratory tests. Please wait until these Chronic Lyme posts are complete to engage in discussion with me about this. There is a lot of information to present and this makes it easier for me to present it in a way that is understandable for people who are not familiar with Lyme disease. Thanks!
“Chronic Lyme disease” is a term applied to multiple patient populations of different characteristics. It is sometimes used to refer to “Post treatment Lyme disease syndrome,” a condition affecting up to 1/3 of Lyme diagnosed patients that causes persistent symptoms for some time following the completion of antibiotics. It sometimes refers to untreated, disseminated, late-stage Lyme diseases, particularly those with Lyme arthritis or neuroborreliosis. It sometimes refers to a patient group with various ongoing symptoms who demonstrate no objective evidence of previous or current Lyme infection.
Right now, I am going to address PTLDS and what I call “negative serology Lyme,” which I am defining as follows:
PTLDS: patients with well documented laboratory evidence of Lyme disease who continue to have persistent symptoms for many months after antibiotic therapy is discontinued.
“Negative serology Lyme”: patients who demonstrate no laboratory evidence of current or previous Lyme infection, but who have ongoing, serious symptoms attributable to Lyme disease. Importantly, doctors who diagnose this condition believe that these people are continuously infected with Borrelia. They do not believe that symptoms are from a previous infection, but from an active one.
I want to be clear about the fact that my naming this group “negative serology Lyme” rather than “chronic Lyme” does NOT mean that I don’t believe that they have Lyme derived health problems. I am going to review the available data with you guys and give you my thoughts on what causes each distinct pathology. I am simply differentiating between them since both are called chronic Lyme in literature and it can be really confusing.
Both of these patient groups report a variety of symptoms, including fatigue, night sweats, sore throat, swollen glands, stiff neck, joint and muscle pain, palpitations, abdominal pain, nausea, diarrhea, sleep disturbance, poor concentration, irritability, depression, back pain, headache and dizziness. Some report a severe level of disability.
One paper (Klempner 2001) reported on two trials done by the same group, one on 78 PTLDS patients and one on 51 negative serology patients. These trials were double blind, randomized, placebo controlled trials, the gold standard. All patients in both groups were required to have a history of acute Lyme contracted in the US, with at least one of the following: history of at least one bull’s eye rash; early neurologic or cardiac symptoms attributed to Lyme disease, radiculoneuropathy or Lyme arthritis. Documented previous treatment of Lyme with recommended antibiotic regimen by a knowledgable doctor was also required. All patients in both groups had at least one of the following: widespread musculoskeletal pain, cognitive impairment, radicular pain, paresthesias or dysesthesias. Profound fatigue was a noted symptom in some, but not all, patients. These symptoms started within six months of contracting Lyme disease and persisted for some time between 6 months and 12 years. Patients in the PTLDS group were blot positive for Borrelia IgG.
Enrollees could not have previously received IV antibiotic therapy for 60 days or more for current symptoms, have active inflammatory synovitis, had a coincident diagnosis that could explain some or all symptoms, or could not discontinue medications that could affect treatment response, like pain medications or steroids. They were also excluded if they had a positive PCR test for B. burgdorferi in plasma or cerebrospinal fluid. (Remember this – I’m coming back to it later.)
In each group, half received antibiotics, while half received placebo. The antibiotic treatment selected was 30 days of IV ceftriaxone, 2 gm/day, followed by 60 days of oral doxycycline, 100 mg twice daily. The placebo group received an IV dextrose solution the same color as the IV ceftriaxone, and placebo capsules identical looking to the doxycycline.
The objective of the study was to determine if the patients’ health related quality of life improved, which was determined by a self reported survey called the SF-36. This survey assesses physical functioning, vitality, bodily pain, general health perceptions, social functioning, emotional limitations on typical daily activities, social functioning, and mental health. Additional questionnaires measured pain, cognition, and how well patients could execute basic daily activities.
55% of patients in the antibiotic group had improved health status, as well as 42% of the placebo group. 14% in the antibiotic group had worsened health status, as well as 19% in the placebo group. There was no statistically significant difference between the two groups. Statistically, the antibiotic group and the placebo group had similar outcomes. During the six month period encompassing the treatment and three months after, 36% in the placebo group reported an improved health status, 39% had worsened health status and 25% had no significant change. So without any treatment, 36% improved. Two major adverse events occurred, both in the antibiotic group: one had a life threatening pulmonary embolism, and the other had fever, anemia and GI bleeding.
Another study (Krupp 2003) with 55 PTLDS patients with severe fatigue received either ceftriaxone or placebo for 28 days. 22% of patients receiving ceftriaxone saw an improvement in fatigue, compared to 9% placebo group, in a self reported survey. There was no significant difference in cognitive improvement or reported health status when surveyed. However, patients in the ceftriaxone group were much more able to correctly identify their treatment protocol than placebo patients, meaning the study may have been compromised and that the improvements in fatigue may have been due to the placebo effect.
A variety of other studies have been done on both PTLDS and negative serology patient groups. Some of them report improvement with long term antibiotic treatment of negative serology patients. However, as these studies were uncontrolled, the findings cannot be considered reliable. Additionally, criteria for acceptance to these studies were very broad, and unvalidated tests have been used to interpret findings. As a researcher, these particular aspects are very troubling.
(Continued in the next post)
Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345:85-92
Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology 2003;60:1923-1930
Donta ST. Macrolide therapy of chronic Lyme disease. Med Sci Monit 2003;9:I-136.
Stricker RB, et al. Benefit of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Int J Gen Med. 2011; 4:639-46.
Fallon BA, Tager F, Fein L, et al. Repeated antibiotic treatment in chronic Lyme disease. J Spirochetal Tickborne Dis 1999;5:94-102.
Stricker RB, et al. Counterpoint: long-term antibiotic therapy improves persistent symptoms associated with Lyme disease. Clin Infect Dis. 2007; Jul 15; 45(2):149-57.