Below is his guide to treating patients with ME/CFS using antimicrobial agents. He also includes the roster of tests he uses for diagnosis, and a section on patient care.
Dr. Lerner makes the disclaimer that his guide has not been peer-reviewed, but that does not make it any less valid. The guide is a summary of decades of clinical experience and, as such, stands on its own.
You can read the original document here:
http://www.treatmentcenterforcfs.com/documents/MECFSTreatmentResourceGuideforPractitioners.pdf
____________________
DISCLAIMER: The information contained in this document is
meant for informational purposes only. The management of ME/CFS in any given
patient must be approached on an individual basis using an Infectious Diseases’
specialist’s best judgment. This document is a culmination of over 20 years of ME/CFS
practice and peer reviewed articles. This document is not a peer reviewed
publication.
ME/CFS Treatment Resource Guide for Practitioners
By A. Martin Lerner, M.D., M.A.C.P.
Beaumont Health System Treatment Center for Chronic Fatigue
Syndrome
Diagnostic Methodology
Initial patient visit:
Complete history, physical examination, chest X-ray,
electrocardiogram, complete blood count, urinalysis, serum aspartate and
aminotransferases (AST, ALT), glucose, thyroid stimulating hormone, sodium,
potassium, uric acid, alkaline phosphatase and creatinine measurements
performed.
ME/CFS analysis:
Energy Index Point Score® assessing physical functional
capacity in activities of daily life documenting limitations. The EIPS® system
defines the severity of patient fatigue, 0-10, through measurement of real-life
situations including one’s ability to sit, stand, be out of bed, work, perform
housework, socialize, exercise. The EIPS® level is determined through
discussion between the physician and patient. A change in EIPS® level of one is
a significant change in health and lifestyle for the patient, as ME/CFS
symptoms decrease when the EIPS® increases.
Cardiac testing:
–24-hour Holter monitor - symptoms recorded (syncope, chest
pain, palpitations, muscle aches)
–Standard 12-lead resting electrocardiogram – if original
ECG abnormal
–Rest/stress myocardial perfusion study – if original ECG
abnormal
–Multigated (radionuclide) MUGA rest/stress
ventriculographic examination – if original ECG abnormal
–Monitor Blood Pressure (laying, sitting, standing)
–Monitor Heart Rate (laying, sitting, standing)
Viral testing for EBV, HCMV, HHV6:
–EBV serum IgM viral capsid antibodies (VCA) - Diasorin,
Inc., Stillwater, MN
–EBV early antigen diffuse (EA) - Diasorin, Inc.,
Stillwater, MN
–ELISA HCMV(V) IgG and IgM serum antibodies to viral capsid,
strain 169 HCMV - Diasorin, Inc., Stillwater, MN
–HHV6 IgM and IgG serum - Lab Corp, Dublin, OH
Co-infection testing:
–Western blot and ELISA to Borrelia burgdorferi (IgM and
IgG) - Lab Corp, Dublin, OH
–IgM and IgG of Babesia microti - Lab Corp, Dublin, OH
–IgM and IgG of Anaplasma phagocytophila - Lab Corp, Dublin,
OH
–IgM and IgG of Mycoplasma pneumoniae - Lab Corp, Dublin, OH
–Anti-streptolysin O (ASO) titer ≥400 units - Lab Corp,
Dublin, OH
Note Lyme and Lyme co-infections can be elusive. Lyme
disease can present clinically as ME/CFS. A significant portion of Lyme disease
cases have negative Lyme serologic tests. We prefer Lab Corp for Lyme testing
and use all 4 tests. The antigens used are those used by the CDC. An
appropriate rural exposure, a tick bite, a bull’s eye rash, can all add to the
likelihood of Lyme disease. Due to the need for both clinical and diagnostic
evaluation in Lyme disease, it is recommended to consider an Equivocal (not
negative or positive) lab result, as positive and begin Lyme treatment.
Follow-up:
–Every 4-6 weeks - Complete blood counts, sodium, potassium,
AST, ALT, alkaline phosphatase, creatinine and urinalysis.
–Every 3 months – Serum assays for EBV VCA IgM, EBV EA,
HCMV(V) IgM and IgG, HHV6 IgM and IgG and all co-infections which are positive originally
EIPS® - A Functional Capacity Measurement Tool For Chronic
Fatigue Syndrome (CFS) Patients
To Physicians Caring for Patients with CFS
The Energy Index Point Score (EIPS) chart provides the
severity of patient fatigue. A change in EIPS level of one is a large
significant change. The EIPS level is determined by agreement of physician and
patient with the EIPS chart easily available for viewing at out-patient visits.
As the EIPS level increases, CFS symptoms lessen and disappear.
How to use the EIPS system in four easy steps:
1) Post the EIPS chart in examining room
2) Ask patient to evaluate their level of activity based
upon the prior two weeks
3) Question the patient’s EIPS evaluation
4) Record and track the EIPS level. Report every 6-12
weeks.*
* The EIPS is not assessed if the patient has an
intercurrent infection (respiratory, gastroenteral, ...). At the same visit the
following 4 symptoms are regularly categorized: 1) chest pain 2) palpitations
3) muscle aches 4) lightheadedness - noting whether absent or present. If
present, when (beginning or end of day, how frequent), where, severity, etc.
All of these factors are included in the EIPS assessment.
Antiviral Treatment of EBV
General Information
A diagnosis of Epstein-Barr virus(EBV) infection is made
with a positive EBV EA antibody diffuse and/or a positive VCA IgM antibody.
Treatment
Valacyclovir (Valtrex) is remarkably effective and safe. The
one concern is that valacyclovir is excreted by the glomerulus and secreted by
the tubules and can cause acyclovir stones and obstructive uropathy. This will
not occur if the patient drinks at least six 8-ounce glasses of water daily.
Occasionally diarrhea may be caused by the valacyclovir. If the patient weighs
70 kg, the dosage is 1 gram four times daily, ideally every six hours; however
safe to take four hours after the last dosage (it is not necessary to awake in
the middle of the night for a dose). It is important that the patient take four
doses for treatment. A higher dose of Valtrex may be necessary with patients
who weigh more than 175 pounds and this must be done carefully. A patient who
weighs more than 175 pounds may require 1.5 grams of Valtrex, valacyclovir four
times daily. Please note valacyclovir is now available in generic form. While I
have not had experience with all distributors of generic forms yet, I have had
patients move to the generic form of valacyclovir by Teva and Mylan with no
issue.
Famvir at the same dosage can be substituted and although
there is not the strong evidence that we have for valacyclovir, it likely is
equally effective. One does not have the worries concerning renal calculi with
Famvir and it has also been extraordinarily safe. It does not cause diarrhea.
An initial worsening of symptoms with normal laboratory at a
two-week special visit with worsening symptoms is a Jarisch Herxheimer reaction
and predicts a good response. Initial benefit is usually not noted for the
first six weeks’ of therapy and then occurs thereafter. A minimum period of
therapy is one year. Usually benefit is not apparent until after 3.5 months of
therapy.
We have not seen thrombocytopenia with Valtrex,
valacyclovir. However, an elevated mean corpuscular volume is seen. This is not
a toxicity, and does not require one to stop medicines.
Antiviral Treatment of HCMV & HHV6
General Information
A diagnosis of cytomegalovirus(CMV) infection is made with
an elevated CMV IgG titer. The IgM titer for CMV is inaccurate and insensitive.
The higher the CMV IgG titer, the greater the viral load. Human herpes virus 6
infection is made with an elevated titer at least twice normal. The diagnosis
of EBV, CMV, or HHV6 ME/CFS meets the Canadian consensus and Fukuda CFS
criteria.
Treatment
The usual treatment for either/both is valganciclovir (Valcyte)
one 450-mg capsule daily for three days, followed by two 450-mg capsules in the
morning daily. Liver function tests are studied very carefully. If there is any
abnormality, one alters the dosage. Given the patient’s ability to safely
tolerate two 450-mg capsules, dosing can be increased to two, 450-mg capsules
in the morning and a one additional 450-mg capsule twelve hours later. Liver
function tests, again, must be studied carefully and frequently.
Both valacyclovir and valganciclovir are absorbed with a 20%
increment if there is food in the stomach. The most common side effect of
valganciclovir is hepatotoxicity. If this occurs, the drug is stopped, the
dosage is decreased, and is again restarted. When monitoring reveals AST and
ALT are normal, the monitoring can continue every four to six weeks, but more
frequent with hepatotoxicity. The rule is no valganciclovir at all if there is
any abnormality in liver function.
The duration of valganciclovir and therapy for CMV and/or
HHV6 is aimed at one year to start with no improvement expected for the first
four to six months. It is a general rule that the shorter the duration of
ME/CFS, and the earlier appropriate therapy is started, the earlier recovery
will occur. Recovery is a continuing, gradual process.
We have not seen thrombocytopenia with Valcyte,
valganciclovir. An elevated mean corpuscular volume is seen. This is not a
toxicity to stop medicines.
Antibiotic Treatment of Co-infections
Background
If the diagnosis of ME/CFS is made by the accepted criteria
and there is no coinfection, one begins antiviral therapy promptly. However, if
there is coinfection with a diagnosis of Lyme disease, Babesiosis,
Ehrlichiosis, Mycoplasma pneumoniae, or adult rheumatic fever, these conditions
are addressed first. After these conditions are addressed, ME/CFS is treated
with antiviral therapy. Should one or more of these co-infections occur mid-
antiviral treatment, do not stop but treat in parallel.
Treatment of Lyme Disease
The protocol for Lyme disease, serologically positive or
epidemiologically positive and serologically negative, that I use is a
six-week’s course of intravenous therapy. Ceftriaxone is preferred. If there is
a history of allergy to penicillins and it is not an immediate allergy, I
routinely refer the patient to an allergist for cephalosporin testing. Under
ordinary circumstances if this is negative, ceftriaxone is given; depending on
the size of the individual 1-1.5 grams intravenously every 12 hours. The
patient is seen weekly. They are asked not to travel further than 45 minutes
from this office, because a PICC lines has been placed and infection of the
PICC line site or side effects to the cephalosporin can occur; particularly
biliary dyskinesia or abnormal liver function tests with ceftriaxone.
Cefotaxime may be substituted for ceftriaxone in the case of biliary
dyskinesia. If there is biliary dyskinesia, Unasyn, or ertapenem may be used.
If diagnosis of Lyme occurs after antiviral treatment has commenced, and
patient shows liver sensitivities with Valcyte dosing, Unasyn is recommended.
Unasyn is given 2 grams IV piggyback every 12 hours. Ertapenem is given 2 grams
IV piggyback every 24 hours. The same dosage of cefotaxime (as ceftriaxone) of
1-1.5 grams is used, but the administration of cefotaxime IV is every 8 hours,
rather than every 12 hours, for ceftriaxone. Cefotaxime has no hepatotoxicity.
Cefotaxime is excreted by the kidneys.
The goal of Lyme therapy, of course, is a well patient, but
particularly a negative serology. Oral suppressive therapy is continued for at
least three months or until the Lyme serology is negative. Typical medicines
used for Lyme suppression after the original six weeks are amoxicillin; in a 70-kg
individual 750 mg before every meal and at bedtime. Doxycycline 100-150 mg
twice daily after meals and with a full glass of water may be given in the
place of amoxicillin for suppression.
Treatment of Mycoplasma Pneumonia
We use LabCorp less than 300 as a normal level. The patient
is not considered to have persistent Mycoplasma pneumoniae infection unless the
initial titer is 600 or more. Mycoplasma pneumoniae is treated intravenously
with doxycycline 150 mg IV piggyback for six weeks followed by oral suppression
with doxycycline 100-150 mg twice daily or moxifloxacin 400 mg once daily for
three months. The goal of this therapy is a serum level which is less than
twice the normal. The duration of time again is six weeks intravenously plus a
minimum of three months oral suppression.
Treatment of Adult Rheumatic Fever
The diagnosis of adult rheumatic fever is made with an ASO
titer of over 400. Echocardiograms are done in all patients with ME/CFS
originally and any changes in the mitral valve, either thickening or mitral
valve prolapse are additional supports for the diagnosis of adult rheumatic
fever. A patient who meets the criteria for ME/CFS with an ASO titer of 400 or
more is considered to have adult rheumatic fever and treated accordingly.
Chest pain, joint pain, rash, life-altering fatigue are all
common to ME/CFS and adult rheumatic fever. Patients are diagnosed with adult
rheumatic fever with the following criteria:
(1) EIPS <5
(2) Diffuse, multi-joint pain
(3) Antistreptolysin O titer ≥ 400 (critical to diagnosis)
(4) Abnormal 24 hour Holter monitor with tachycardia and
oscillating T-wave flattening, with or without T-wave inversions
(5) A thickened mitral valve at echocardiogram.
If there are symptoms of sinus disease, a CT of the sinuses
is done to make certain there is no obstructive sinusitis which may need sinus
surgery.
Patients are treated with intravenous Unasyn 3grams IV
piggyback every 12 hours for 4-6 weeks, followed by 2.4 million units IM (1.2
million units each hip every 30 days) until ASO titer is ≤200.
Patient Management
Patient Visits and Testing
Check-ups with labwork should occur every 6 weeks in-person.
Diet and Exercise
A healthy, well balanced diet is a must. Minimize sugar
intake. Minimize caffeine intake. Absolutely no alcohol allowed, as it may be a
cardiac toxin for ME/CFS patients.
No physical exertion or exercise until above a 7 Energy
Index Point Score. Stretching regularly is recommended. Once the EIPS is 7,
modest exercise can and should begin. The ultimate test is - Are you tired the
next day after exercise? If you are, then the exercise that you have done is
too much. Start out very slow. Just a few minutes, allowing for breaks and recovery
time.
Lifestyle
10-12+ hours of sleep per day and daily naps until the EIPS
is at least a 6. Avoid germs (think airplanes, libraries, churches). Stretch
daily, minimize exertion, seek assistance with housework/chores/errands. Keep
feet elevated, promote a network for assistance and ask for help.
Daily energy
envelope management is a must. Do not push until a crash. This is not
productive. As much as possible, do not allow yourself to get overly tired.
Healing is a slow process.
Publication Resources
•Lerner, A.M., Lawrie, C., Dworkin, H.S., and Fitzgerald,
J.T.: Repetitively Negative Changing T-Waves at 24-Hour ElectrocardiographicMonitors In Patients With The Chronic Fatigue Syndrome: Left VentricularDysfunction In A Cohort. CHEST 104:1417-1421, 1993
•Dworkin, H.J., Lawrie, C., Bohdiewicz, P., and Lerner,
A.M.: Abnormal Left Ventricular Myocardial Dynamics in Eleven Patients With TheChronic Fatigue Syndrome. Clinical Nuclear Medicine 19:675-677, 1994
•Lerner, A.M., Zervos, M., Dworkin, H., Chang, C.H.,
Fitzgerald, J.T., Goldstein, J., Lawrie-Hoppen, C., Franklin, B., Korotkin, S.,
Brodsky, M., Walsh, D., O’Neill, W.: New Cardiomyopathy: Pilot Study ofIntravenous Ganciclovir in a Subset of the Chronic Fatigue Syndrome. Infectious
Diseases in Clinical Practice 6:110-117, 1997
•Lerner, A.M., Zervos, M., Dworkin, M., Chang, C.H.,
O’Neill, W.: A Unified Theory of the Cause of Chronic Fatigue Syndrome.
Infectious Disease in Clinical Practice 6:239-243, 1997
•Lerner, A.M., Goldstein, J., Chang, C., Zervos, M.,
Fitzgerald, J., Dworkin, H., Lawrie-Hoppen, C., Korotkin, S., Brodsky, M.,
O’Neill, W.: Cardiac Involvement in Patients with Chronic Fatigue Syndrome asDocumented with Holter and Biopsy Data in Birmingham, Michigan, 1991-1993.
Infectious Diseases in Clinical Practice 6:327-333, 1997
•Lerner, A M. Recurrent Herpes Simplex Virus Cellulitis ofthe Right Forearm with Early Elephantiasis Responsive to Both Treatment andProphylaxis by Valacyclovir. Infectious Diseases in Clinical Practice
8:260-262,1999
•Lerner, A.M., Beqaj, S.H., Deeter, R.G.: IgM antibodies tohuman cytomegalovirus nonstructural gene products p52 and CM2 (UL44 and UL57)are uniquely present in a subset of patients with chronic fatigue syndrome. In
Vivo 16:153-160, 2002
•Lerner, A.M., Beqaj, S.H., Deeter, R.G., Dworkin, H.J.,
Zervos, M., Chang, C.H., Fitzgerald, J.T., Goldstein, J., and ONeil, W. Asix-month trial of valacyclovir in the Epstein-Barr virus subset of chronicfatigue syndrome improvement in left ventricular function. Drugs of Today 38
8:249-561, 2002
•Carruthers BM, Jain AK, DeMeirleir KL, Peterson DL, Klimas
NG, Lerner AM, Bested AC, Flor-Henry P, Joshi P, Powles AC, Sherkey JA, van de
Sande, MI. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical WorkingCase Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue
Syndrome 11 1:7-115, 2003
•Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT: IgM SerumAntibodies to Epstein-Barr Virus are Uniquely Present in a Subset of Patientswith the Chronic Fatigue Syndrome. In Vivo 18:101-106, 2004
• LernerAM, Dworkin HJ, Sayyed T, Chang CH, Fitzgerald JT,
Beqaj S, Deeter RG, Goldstein J, Gottipolu P, O'Neill W: Prevalence of AbnormalCardiac Wall Motion in the Cardiomyopathy Associated with IncompleteMultiplication of Epstein-Barr Virus and/or Cytomegalovirus in Patients withChronic Fatigue Syndrome. In Vivo 18:417-424, 2004
Beqaj SH, Lerner AM, Fitzgerald JT: Immunoassay withcytomegalovirus early antigens from gene products p52 and CM2 (UL44 and UL57)detects active infection in patients with chronic fatigue syndrome. J Clin
Pathology 61:623-626, 2008
•Lerner, Beqaj, Deeter, Fitzgerald. Valacyclovir treatmentin Epstein-Barr virus subset chronic fatigue syndrome: thirty-six monthsfollow-up. In Vivo 21(5): 707-713, 2007
•Lerner AM, Beqaj SH, Fitzgerald JT. Validation of theEnergy Index Point Score to Serially Measure the Degree of Disability inPatients with Chronic Fatigue Syndrome. In Vivo 22: 799-802, 2008
•Lerner AM, Beqaj SH, Fitzgerald JT, Gill K, Gill C,
Edington J: Subset-directed antiviral treatment of 142 herpesvirus patientswith chronic fatigue syndrome. Virus Adaptation and Treatment 2010:2 47-57
•Lerner AM, Beqaj SH, Gill K, Edington J, Fitzgerald JT,
Deeter RG: An Update on the management of glandular fever (infectiousmononucleosis) and its sequelae caused by Epstein-Barr virus (HHV-4): new andemerging treatment strategies. Virus Adaptation and Treatment 2010:2 135-145
•Lerner AM, Beqaj SH: A paradigm linking herpesvirusimmediate early gene expression apoptosis and myalgic encephalomyelitis/chronicfatigue syndrome. Virus Adaptation and Treatment 2011:3 19-24
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Patent Information
•A US patent (CFS LLC and The Ohio State University) is
underway to be filed, February 2012, describing serum antibody to molecular
markers EBV EA(D), EBV dUTPase and EBV DNA polymerase for diagnoses of EBV
subset ME/CFS.
•CFS LLC has a US patent application pending entitled
Methods for Diagnosis and Treatment of Chronic Fatigue Syndrome. Inventor
Lerner, Albert Martin. Agents Barry, Thomas F. et al: Venable LLP, P.O. Box
3485 Washington, DC 20043-9998 (US). This patent differentiates Group A and
Group B CFS.
Further information concerning patents owned by CFS LLC can
be found in US Pat Nos 5,872,123; 6,258,818; 6,399,622; 6,537,997 and
6,894,056.
© 1998 - 2008 Dr. A. Martin Lerner CFS Treatment Center ;
Last revised: February 2011
EIPS® and Energy Index Point Score ® are trademarks of the
Dr. A. Martin Lerner CFS Treatment Center. All rights reserved. This document
may be copied for use by physicians and patients, but may not be modified,
sold, or distributed promotionally in any form without express written
permission.
For more information visit: treatmentcenterforcfs.com
For more information visit: treatmentcenterforcfs.com
