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12th International Conference on Lyme Disease and Other Spirochetal and

Tick-Borne Disorders

Day 2 - April 10, 1999

Differential Diagnosis in Lyme Disease

A. Fallon, MD

Two presentations today addressed the overlap that exists between similar

disorders — one talk focused on

diagnostic distinctions between fibromyalgia, Lyme disease, and Gulf War

syndrome; the other was devoted to

Chronic Fatigue Syndrome and Post-Lyme Disease.

Dr. Sam T. Donta of the Boston University Medical Center discussed

fibromyalgia and Lyme disease, noting the

increasing awareness of the similarities and differences between chronic

Lyme disease and other chronic

multi-symptom disorders (CMSDs) such as fibromyalgia, chronic fatigue, and

Persian Gulf War illness.[1] Still,

since all are characterized by fatigue, musculoskeletal pain, and

neurocognitive dysfunction, discriminating one

from the others is often difficult.

Historical Perspectives

In the early 1900s, fibromyalgia was referred to as " fibrositis " . By the

early 1990s, the term " fibromyalgia " began

to be used more widely. Current epidemiologic studies indicate

approximately a 0.1% to 0.2% incidence of

fibromyalgia.

Descriptions of patients plagued by prominent fatigue states first appear

in the 1850s, Dr. Donta said. These early

references describe patients' symptoms as " bed cases " or " sofa cases, " and

physicians characterized such cases as

neuromyasthenia. Following both World War I and World War II, epidemics of

fatigue were reported and in

1988, the term " chronic fatigue syndrome " was first used. In Europe, the

term " myalgic encephalomyelitis " is more

commonly used than " chronic fatigue. "

It is estimated that the incidence of chronic fatigue is approximately 0.1%

-0.2% in the overall population, while in

primary care settings the incidence is higher. A recent study indicated an

incidence of 11.3% in a primary care

sample of 2,376 patients. Following flu-like illness, 15% of patients

developed post-infection chronic fatigue. A

recent study from England demonstrated that after Q-fever, 42% of patients

developed chronic fatigue.

Dr. Donta pointed out that Chronic Fatigue Syndrome shares a number of

symptoms with Lyme disease.

Symptoms of Lyme disease include fatigue, arthalgias, myalgias, headaches,

cognitive problems, mood swings,

and paresthesias.[2] Similarly, Chronic Fatigue Syndrome is characterized

by a fatigue for 6 months, associated

with at least 4 of 8 associated symptoms such as impaired memory, sore

throat, tender or swollen lymph nodes,

muscle pain, multi-joint pain, unrefreshing sleep, new onset headaches, and

post-exertion malaise.

Chronic Lyme disease etiology may be multifactorial, Dr. Donta said. It may

stem from a persistent relapsing

infection, be an autoimmune-triggered disorder, or result from release of

toxin during reactivation of infection.

The persistent infection hypothesis has also been applied to some of the

other CMSDs. In recent studies of

chronic fatigue syndrome, tests showed evidence of mycoplasma DNA in the

WBC buffy coat in 50% of

subjects. In another study -- this one of patients with Gulf War Syndrome

-- similar findings were seen:

mycoplasma fermentens in the blood of half the subjects.

Challenges in Differential Diagnosis

The diagnosis of these CMSDs relies largely on clinical criteria. Problems

emerge given the non-specific nature of

many of these symptoms; even in fibromyalgia, elucidation of tender points

is not always reliable. Laboratory

testing is of primary use as an adjunctive tool in clinical assessment.

In Lyme disease, Western blot testing appears superior to the ELISA in

detecting the illness, Dr. Donta said. In

one of Dr. Donta's studies, conducted in a large cohort of patients with

Western blot-positive serum results, only

35% (72/205) of the cohort had correspondingly positive ELISA results.

These findings, Dr. Donta pointed out,

are contrary to the recommendations of the CDC for a two-tiered approach to

the serologic testing. The CDC

recommendations say patients should not be tested by Western blot unless

their screening ELISA results are

either positive or equivocal.

Dr. Donta said that in formulating the standardized criteria for the

interpretation of a Western blot, the CDC relied

upon the number of bands that were most frequently seen rather than the

specificity of the bands themselves. For

this reason, he says, some of the most specific bands for Lyme disease (eg,

the 31 and 34Kd bands) were

excluded. Dr. Donta emphasized that a new set of criteria needs to be

established for the interpretation of

Western blot results, and that those criteria should include the

specificity of the bands for Lyme disease.

Further, he said, the CDC case criteria for the diagnosis of Lyme disease

do not include one of the more common

late manifestations of neurologic Lyme disease: encephalopathy. SPECT

imaging can be helpful in the differential

diagnosis, demonstrating a pattern of heterogeneity, he said. DNA PCR

studies may also be helpful, but Dr.

Donta says that in his experience fewer than 5% of patients with chronic

Lyme disease have positive PCR results.

Dr. Donta stressed that spinal fluid analysis is an important tool in the

differential diagnosis of Lyme disease --

ruling out other disorders before the diagnosis of Lyme disease is firmly

established.

Post-Lyme Disease and Chronic Fatigue Syndrome lOOK HERE

The other presentation that highlighted how other clinical syndromes share

symptomology with Lyme disease was

delivered by Dr. Krupp, of the State University of New York at Stony

Brook and principal investigator of

the Stop Lyme Disease NIH-funded research study.[3] She described her work

comparing Post-Lyme Syndrome

with Chronic Fatigue Syndrome. She said her studies are based on

observations that a small percentage of

patients (5-16%) experience a constellation of symptoms following early

disease treatment: headache, myalgia,

fatigue, paresthesias, arthralgias, and mood disturbance.

Prior studies have demonstrated that risk factors for the development of

sequelae from Lyme disease include

lengthy duration of disease (>1 year) prior to treatment, high specific IgG

antibody titers, and multiple bands on

the Western blot (which have been correlated with poor verbal memory

performance).

The term " Post-Lyme Syndrome " encompasses chronic or intermittent problems

that begin at the time of clinical

Lyme disease and persist for months to years despite adequate antibiotic

therapy. Synonymous terms include

" post treatment Lyme disease " and " chronic Lyme disease " . Similar in

symptomology to other disorders,

Post-Lyme Syndrome (PLS) may produce cognitive disturbances

(encephalopathy), fatigue/malaise (Chronic

Fatigue Syndrome), joint and muscle pain (fibromyalgia), headache, and

other features such as hearing loss,

vertigo, mood disturbances, paresthesias, sleep disturbances, and stiff

neck.

Dr. Krupp said estimates of the frequency of PLS range from 13% (in a 1993

study of 788 patients), to 53% (in

a 1993 study of 215 patients). In a population-based study by Shadick in

1994 comparing Lyme disease patients

to community controls, the significantly more common and distinguishing

clinical symptoms between the two

groups respectively were severe fatigue (26% vs 9%), concentration problems

(47% vs 16%), emotional lability

(18% vs 5%), difficulty sleeping (47% vs 16%), and objective cognitive

impairment (12% vs 5%).[4]

Dr. Krupp said that in addition to persistent infection, reinfection, or a

post-infectious immune or inflammatory

process, other causes of Post-Lyme Syndrome need to be considered. These

include incorrect diagnosis, slow

resolution of symptoms, residual damage, and unmasked prior pathology.

In one post-treatment Lyme disease study, Dr. Krupp compared patients with

PLS to patients with Chronic

Fatigue Syndrome (CFS). The PLS patients had a history of seropositivity, a

compatible clinical syndrome, severe

fatigue persisting for 6 months or more, and no other explanation for

fatigue. The CFS patients had no history of

Lyme disease. Although all of the CFS patients met the 1994 CFS criteria,

as many as 84% of the PLS patients

also met the same criteria. The clinical symptoms that significantly

distinguished the two groups, comparing CFS

and PLS respectively, were: fever (72% vs 28%), sore throat (76% vs 28%),

unrefreshing sleep (96% vs 36%)

and tender cervical or axillary lymph nodes (60% vs 26%). In the CSF

analyses of these two patient groups,

21-40% of the PLS patients were Borrelia antigen positive vs 0% of the CFS

patients. In regards to cognitive

performance, both groups had more deficits than the controls, with the PLS

patients having more deficits on

verbal fluency, verbal memory, and digit span than the CFS patients.

Determining Efficacy of Therapy

In the Stop Lyme Disease Study, which is ongoing, the goal has been to

characterize the clinical and laboratory

findings of patients with PLS and to determine the efficacy of one month of

parenteral ceftriaxone therapy.

All patients met the CDC case definition of Lyme disease. This

placebo-controlled study has 3 primary endpoints:

fatigue, cognitive speed, and CSF infection markers. Neurologic, CSF,

psychiatric, fatigue, and cognitive

measures were applied at baseline and at 6 month follow-up. Of 45 enrolled

subjects, 27 have completed

treatment and the 6-month follow-up, 13 are in phase, 3 had allergic

reactions and 2 have dropped out of the

study. Most patients are working full time (77%) and there are slightly

more women (55%) than men (45%).

About 25% of the patients had only an initial EM rash on presentation,

while 55% had an EM and late

manifestations, and 20% had only late manifestations (such as arthritis).

At baseline, 100% of the PLS patients had severe fatigue, 63% had objective

cognitive impairment, 22% were

OspA CSF-antigen postive, and 32% had a current psychiatric disorder. Dr.

Krupp said the treatment results

thus far from the study could not be divulged because the trial is ongoing.

Dr. Krupp noted that there is considerable overlap between PLS and CFS and

that cognitive deficits and

psychiatric comorbidity are common.

References

1.Donta ST: Fibromyalgia, Lyme disease, and Gulf War Syndrome. 12th

International Conference on Lyme

Disease and Other Spirochetal and Tick-Borne Disorders, New York, NY,

1999.

2.Donta ST. Tetracycline therapy for chronic Lyme Disease. Clin Infect

Dis 1997 25(Suppl 1): 52-6, 1997

Jul.

3.Krupp L: Chronic Fatigue Syndrome and Post-Lyme Disease. 12th

International Conference on Lyme

Disease and Other Spirochetal and Tick-Borne Disorders, New York, NY,

1999.

4.Shaddick NA, CB, Logigian EL, et al: The long-term clinical

outcomes of Lyme disease. Ann

Intern Med 1221: 560-67, 1994.

Return To Day 2 Stories

All material on this website is protected by copyright. Copyright © 1994-1999 by

Medscape Inc. All rights reserved. This website also

contains material copyrighted by 3rd parties. CME means Continuing Medical

Education credit is available. Medscape requires 3.x

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" C.Tab. " wrote:

> From: " C.Tab. " <tab@...>

>

> Dear Stania,

>

> Merry CHristmas to you! And thank you for being here for us!!

>

> Take care,

>

> Christie

>

> > Hi List, I wish you Merry Christmas and a Happy New Year Thank you

> >all very much for being there. Thank you for your help, knowledge and

> >support. It meant so much not only for me but also for many other people

> >in my country. Stania

>

> > This list is intended for patients to share personal experiences with each

other, not to give medical advice. If you are interested in any treatment

discussed here, please consult your doctor.

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