Physicians' Protocol For Using Antibiotics in Rheumatic Disease + My Rheumatoid

November 24, 2008

My Rheumatoid Arthritis Protocol

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(http://articles.mercola.com/sites/articles/archive/2000/08/27/rheumatoid-arthri\

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By Dr. Mercola

The following is a modified version of Dr. Brown's protocol.

Introduction

Rheumatoid arthritis affects about 1 percent of our population and at least

two million Americans have definite or classical rheumatoid arthritis. It is

a much more devastating illness than previously appreciated. Most patients

with rheumatoid arthritis have a progressive disability. More than 50% of

patients who were working at the start of their disease are disabled after five

years of rheumatoid arthritis. The annual cost of this disease in the U.S. is

estimated to be over $1 billion.

There is also an increased mortality rate. The five-year survival rate of

patients with more than thirty joints involved is approximately 50%. This is

similar to severe coronary artery disease or stage IV Hodgkin's disease. Thirty

years ago, one researcher concluded that there was an average loss of

eighteen years of life in patients who developed rheumatoid arthritis before

the

age of 50.

Most authorities believe that remissions rarely occur. Some experts feel

that the term " remission-inducing " should not be used to describe ANY current

rheumatoid arthritis treatment. A review of contemporary treatment methods

shows that medical science has not been able to significantly improve the

long-term outcome of this disease.

My Experience with the Dr. Brown's Protocol

I first became aware of Doctor Brown's protocol in 1989 when I saw him on

20/20 on ABC. This was shortly after the introduction of his first edition of

The Road Back. The newest version is The New Arthritis Breakthrough that is

written by Henry Scammel. Unfortunately, Dr. Brown died from prostate cancer

shortly after the 20/20 program so I never had a chance to meet him. By the

year 2000, I will have treated over 1,500 patients with rheumatic illnesses,

including SLE, scleroderma, polymyositis and dermatomyositis.

My application of Dr. Brown's protocol has changed significantly since I

first started implementing it. Initially, I followed Dr. Brown's work rigidly

with very little modification other than shifting the tetracycline choice to

Minocin. I believe I was one of the first people who recommended the shift to

Minocin, which seems to have been widely adopted at this time.

In the early 90s, I started to integrate the _nutritional model_

(http://www.mercola.com/nutritionplan/) into the program and noticed a

significant

improvement in the treatment response. I cannot emphasize strongly enough the

importance of this aspect of the program. It is absolutely an essential

component of the revised Dr. Brown protocol. One may achieve remission without

it,

but the chances are much improved with its implementation. The additional

benefit of the dietary changes is that they severely reduce the risk of the two

to six month worsening of symptoms that Dr. Brown described in his book.

In the late 80s, the common retort from other physicians was that there was

" no scientific proof " that this treatment works. Well, that is certainly not

true today. If one peeks ahead at the bibliography, one will find over 200

references in the peer-reviewed medical literature that supports the

application of Minocin in the use of rheumatic illnesses.

The definitive scientific support for minocycline in the treatment of

rheumatoid arthritis came with the MIRA trial in the United States. This was a

double blind randomized placebo controlled trial done at six university centers

involving 200 patients for nearly one year. The dosage they used (100 mg

twice daily) was much higher and likely less effective than what most

clinicians

currently use.

They also did not employ any additional antibiotics or nutritional regimens,

yet 55% of the patients improved. This study finally provided the " proof "

that many traditional clinicians demanded before seriously considering this

treatment as an alternative regimen for rheumatoid arthritis.

Dr. Thomas Brown's effort to treat the chronic mycoplasma infections

believed to cause rheumatoid arthritis is the basis for this therapy. Dr. Brown

believed that most rheumatic illnesses respond to this treatment. He and others

used this therapy for SLE, ankylosing spondylitis, scleroderma,

dermatomyositis and polymyositis.

Dr. Osler was also a preeminent figure of his time (1849- 1919). Many regard

him as the consummate physician of modern times. An excerpt from a

commentary on Dr. William Osler provides a useful perspective on application of

alternative medical paradigms:

Osler would be receptive to the cautious exploration of nontraditional

methods of treatment, particularly in situations in which our present science

has

little to offer. From his reading of medical history, he would know that many

pharmacologic agents were originally derived from folk medicine. He would

also remember that in the 19th century physicians no less intelligent than

those in our own day initially ridiculed the unconventional practices of

Semmelweis and Lister.

Osler would caution us against the arrogance of believing that only our

current medical practices can benefit the patient. He would realize that new

scientific insights might emerge from as yet unproved beliefs. Although he

would

fight vigorously to protect the public against frauds and charlatans, he

would encourage critical study of whatever therapeutic approaches were reliably

reported to be beneficial to patients.

Revised Antibiotic-Free Approach

Although the antibiotics frequently worked and the six-month period of

worsening that was part of Dr. Brown's protocol was virtually eliminated, I

always

felt like I had failed because I had to resort to the use of antibiotics.

This has now changed, as I have been able to implement a major change in my

revision of the protocol that allows for a completely drug-free treatment of

RA. The major change seems to be the use of nutritional typing, along with

energy techniques. Since we have integrated nutritional typing with full use of

EFT to address the stressors that seem to be universally present in RA, we

have been able to cause RA to routinely go into remission without the use of

antibiotics.

To say I am excited is a serious understatement.

nutritional typing allows each patient to get a unique diet that is right

for their body. It is very easy to understand how a physician who successfully

treats one patient with a particular diet would come to the conclusion that

the diet that person was on was the " cure " for RA, when in fact nothing could

be further from the truth. Another person with the same disease could quite

possibly need an entirely different diet to receive any benefits, that is how

powerful nutritional typing can be.

If you haven't yet read the book _The nutritional typing Diet_

(http://www.amazon.com/exec/obidos/ASIN/0767905644/optimalwellnessc) , , I

would strongly

encourage you to do so as it reviews these topics extensively (it is

definitely a book that belongs on the shelf of anyone with any interest in

nutrition).

There are some general principles that seem to hold true for all nutritional

types and these include:

Â· Eliminating sugar and grains (you can read more about this below)

Â· Having unprocessed, high-quality foods, organic if possible

Â· Eating your food as close to raw as possible

Â· Having omega-3 fish oil

I am overjoyed beyond belief that after 14 years of treating RA I can

finally offer a drug-free, effective and rapid solution for most of those with

RA

with the aid of nutritional typing. However, it is clear that a perfect diet

alone will rarely cause the RA to go into remission.

This is because RA is an autoimmune illness. It does indeed appear to be

caused by an infection, as Dr. Brown speculated. But the central issue is why

did the person acquire the infection in the first place? It is my experience

that this infection is usually acquired when a person has a stressful event

that causes a disruption in their bioelectrical circuits, which causes an

impairment in their immune system. This impairment predisposes them to

developing

the initial infection and also contributes to their relative inability to

effectively defeat the infection.

The antibiotics clearly seem to help most people fight the infection, but,

as I mention above, there are better ways that address the underlying

foundational cause of the illness.

I am quite convinced that energy techniques are required to resolve this

energetic disruption. Prayer can certainly be one of them. However, in my

experience, most have not utilized prayer in a way that rallies their body's

resources to resolve the problem.

In my experience, energy psychology techniques are very helpful in this area

and can be easily integrated with prayer. I happen to use EFT in my practice

and you can download my free 25-page report

_http://www.mercola.com/forms/eftcourse.htm_

(http://www.mercola.com/forms/eftcourse.htm) to find out more

about this technique

However, the emotional trauma that causes RA is nearly universally quite

severe and is best treated by a professional. Trying to treat this trauma by

yourself is somewhat similar to a general surgeon trying to perform an

appendectomy on him or herself. Although it is possible, it is not generally

recommended (Interesting aside: I read an article in JAMA about 10 years ago in

which

a surgeon in the late 1800s actually did this. Unfortunately, he died from

complications.).

Dr. Partirica Carrington has actually compiled _some guidelines_

(http://www.emofree.com/Practitioners/referralMain.aspx) on how you can find

an EFT

practitioner.

In the following sections I have included information about the antibiotic

therapy for RA for anyone who is interested. However, I now recommend my

drug-free approach for anyone fighting this illness.

Nutritional Considerations

Limiting sugar is a critical element of the treatment program. Sugar has

multiple significant negative influences on a person's biochemistry. Its major

mode of action is through elevation of insulin levels. However, it has a

similarly severe impairment of intestinal microflora. Patients who are unable to

decrease their sugar intake are far less likely improve.

One of the major benefits of implementing the dietary changes is that one

does not seem to develop worsening of symptoms the first three to six months

that is described in Dr. Brown's book. Most of my patients tend to not worsen

once they start the antibiotics. I believe this is due to the beneficial

effects that the diet has on the immune response.

Antibiotic Therapy With Minocin

There are three different tetracyclines available: simple tetracycline,

doxycycline, or Minocin (minocycline). Minocin has a distinct and clear

advantage

over tetracycline and doxycycline in three important areas.

Â· Extended spectrum of activity

Â· Greater tissue penetrability

Â· Higher and more sustained serum levels

Bacterial cell membranes contain a lipid layer. One mechanism of building up

a resistance to an antibiotic is to produce a thicker lipid layer. This

layer makes it difficult for an antibiotic to penetrate. Minocin's chemical

structure makes it the most lipid soluble of all the tetracyclines.

This difference can clearly be demonstrated when one compares the drugs in

the treatment of two common clinical conditions. Minocin gives consistently

superior clinical results in the treatment of chronic prostatitis. In other

studies, Minocin was used to improve between 75-85% of patients whose acne had

become resistant to tetracycline. Strep is also believed to be a contributing

cause to many patients with rheumatoid arthritis. Minocin has shown

significant activity against treatment of this organism.

There are several important factors to consider when using Minocin. Unlike

the other tetracyclines, it tends not to cause yeast infections. Some

infectious disease experts even believe that it even has a mild anti-yeast

activity.

Women can be on this medication for several years and not have any vaginal

yeast infections. Nevertheless, it would be prudent to have patients on

prophylactic oral Lactobacillus acidophilus and bifidus preparations. This will

help to replace the normal intestinal flora that is killed with the Minocin.

Another advantage of Minocin is that it tends not to sensitize patients to

the sun. This minimizes the risk of sunburn and increased risk of skin cancer.

However, one must incorporate several precautions with the use of Minocin.

Like other tetracyclines, food impairs its absorption. However, the absorption

is much less impaired than with other tetracyclines. This is fortunate

because some patients cannot tolerate Minocin on an empty stomach. They must

take

it with a meal to avoid GI side effects. If they need to take it with a meal,

they will still absorb 85% of the medication, whereas tetracycline is only

50% absorbed. In June of 1990, a pelletized version of Minocin became

available. This improved absorption when taken with meals. This form is only

available in the non-generic Lederle brand and is a more than reasonable

justification to not substitute for the generic version. Clinical experience

has shown

that many patients will relapse when they switch from the brand name to the

generic. In February 2006 Wyeth sold manufacturing rights of Minocin to Triax

Pharmaceuticals (866-488-7429).

Clinically it has been documented that it is important to take Lederle brand

Minocin. Most all generic minocycline is clearly not as effective. A large

percentage of patients will not respond at all or not do as well with generic

non-Lederle minocycline.

Traditionally it was recommended to only receive the brand name Lederle

Minocin. However, there is one generic brand that is acceptable and that is the

brand made by Lederle. The only difference between Lederle generic Minocin and

brand name Minocin is the label and the price.

The problem is finding the Lederle brand generic. Some of my patients have

been able to find it at Wal Mart. Since WalMart is one of the largest drug

chains in the US, this should make the treatment more widely available for a

reduced charge.

Many patients are on NSAID's which contribute to microulcerations of the

stomach which cause chronic blood loss. It is certainly possible they can

develop a peptic ulceration contributing to their blood loss. In either event,

patients frequently receive iron supplements to correct their blood counts.

IT IS IMPERATIVE THAT MINOCIN NOT BE GIVEN WITH IRON. Over 85% of the dose

will bind to the iron and pass through the colon unabsorbed. If iron is

taken, it should be at least one hour before the minocin or two hours after.

One

recent uncommon complication of Minocin is a cell-mediated hypersensitivity

pneumonitis.

Most patients can start on Minocin 100 mg. every Monday, Wednesday, and

Friday evening. Doxycycline can be substituted for patients who cannot afford

the

more expensive Minocin. It is important to not give either medication daily,

as this does not seem to provide as great a clinical benefit.

Tetracycline type drugs can cause a permanent yellow- grayish brown

discoloration of the teeth. This can occur in the last half of pregnancy and

in

children up to eight years old. One should not routinely use tetracycline in

children. If patients have severe disease, one can consider increasing the dose

to as high as 200 mg three times a week. Aside from the cost of this approach,

several problems result may result from the higher doses. Minocin can cause

quite severe nausea and vertigo. Taking the dose at night does tend to

decrease this problem considerably.

However, if one takes the dose at bedtime, one must tell the patient to

swallow the medication with TWO glasses of water. This is to insure that the

capsule doesn't get stuck in the throat. If that occurs, a severe chemical

esophagitis can result which can send the patient to the emergency room.

For those physicians who elect to use tetracycline or doxycycline for cost

or sensitivity reasons, several methods may help lessen the inevitable

secondary yeast overgrowth. Lactobacillus acidophilus will help maintain normal

bowel flora and decrease the risk of fungal overgrowth.

Aggressive avoidance of all sugars, especially those found in non-diet sodas

will also decrease the substrate for the yeast's growth. Macrolide

antibiotics like Biaxin or Zithromax may be used if tetracyclines are

contraindicated.

They would also be used in the three pills a week regimen.

Clindamycin

The other drug used to treat rheumatoid arthritis is clindamycin. Dr.

Brown's book discusses the uses of intravenous clindamycin. It is important to

use

the IV form of treatment if the disease is severe. Nearly all scleroderma

patients should take an aggressive stance and use IV treatment. Scleroderma is

a

particularly dangerous form of rheumatic illness that should receive

aggressive intervention.

A major problem with the IV form is the cost. The price ranges from $100 to

$300 per dose if administered by a home health care agency. However, if

purchased directly from Upjohn, significant savings will be appreciated.

For patients with milder illness, the oral form is preferable. If the

patient has a mild rheumatic illness (the minority of cases), it is even

possible

to exclude this from their regimen. Initial starting doses for an adult would

be a 1200 mg dose once a week.

Patients do not seem to tolerate this medication as well as Minocin. The

major complaint seems to be a bitter metallic type taste, which lasts about 24

hours after the dose. Taking the dose after dinner does seem to help modify

this complaint somewhat. If this is a problem, one can lower the dose and

gradually increase the dose over a few weeks.

Concern about the development of C. difficile pseudomembranous enterocolitis

as a result of the clindamycin is appropriate. This complication is quite

rare at this dosage regimen, but it certainly can occur. It is important to

warn all patients about the possibility of developing a severe uncontrollable

diarrhea. Administration of the acidophilus seems to limit this complication by

promoting the growth of the healthy gut flora.

If one encounters a resistant form of rheumatic illness, intravenous

administration should be considered. Generally, weekly doses of 900 mg are

administered until clinical improvement is observed. This generally occurs

within the

first ten doses. At that time, the regimen can be decreased to every two

weeks with the oral form substituted on the weeks where the IV is not taken.

What To Do If Severe Patients Fail To Respond

The most frequent reason for failure to respond to the protocol is lack of

adherence to the dietary guidelines. Most patients will be eating too many

grains and sugars, which disturb insulin physiology. It is important that

patients adhere as strictly as possible to the guidelines. A small minority,

generally under 15%, of patients will fail to respond to the protocol described

above despite rigid adherence to the diet. These individuals should already be

on the IV Clindamycin.

It appears that the hyaluronic acid, which is a potentiating agent commonly

used in the treatment of cancer may be quite useful. It seems that hyaluronic

acid has very little to no direct toxicity but works in a highly synergistic

fashion when administered directly in the IV bag with the Clindamycin.

Hyaluronic acid is also used in orthopedic procedures. The dose is generally

from 2 to 10 cc into the IV bag. Hyaluronic acid is not inexpensive as the

cost may range up to $10 per cc.One does need to exert some caution with its

use as it may precipitate a significant Herxheimer flare reaction.

Patients will frequently have emotional traumas that worsen their illness.

Severe emotional traumas can seriously impair the immune response to this

treatment.

Physicians' Protocol For Using Antibiotics in Rheumatic Disease

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tis2.aspx)

Anti-Inflammatories

The first non-aspirin NSAID, indomethacin was introduced in 1963. Now more

than 30 are available. Relafen is one of the better alternatives as it seems

to cause less of an intestinal dysbiosis. If cost is a concern, generic

ibuprofen can be used. Unfortunately, recent studies suggest this drug is more

damaging to the kidneys. One must be especially careful to monitor renal

function

studies periodically. It is important for the patient to understand and

accept the risks associated with these more toxic drugs.

Unfortunately, these drugs are not benign. Every year, they do enough damage

to the GI tract to kill 2,000 to 4,000 patients with rheumatoid arthritis

alone. That is ten patients EVERY DAY. At any given time patients receiving

NSAID therapy have gastric ulcers in the range of 10-20%. Duodenal ulcers are

lower at 2- 5%. Patients on NSAIDs are at approximately three times greater

relative risk for developing serious gastrointestinal side effects than are

non-users.

Approximately 1.2% of patients taking NSAIDs are hospitalized for upper GI

problems per year of exposure. One study of patients taking NSAIDs showed that

a life-threatening complication was the first sign of ulcer in more than

half of the subjects.

Researchers found that the drugs suppress production of prostacyclin, which

is needed to dilate blood vessels and inhibit clotting. Earlier studies had

found that mice genetically engineered to be unable to use prostacyclin

properly were prone to clotting disorders.

Anyone who is at increased risk of cardiovascular disease should steer clear

of these two new medications. Ulcer complications are certainly potentially

life-threatening, but, heart attacks are a much more common and likely risk,

especially in older individuals.

Risk factor analysis helps to discriminate those that are at increased

danger of developing these complications. Those associated with a higher

frequency

of adverse events are:

Â· Old age

Â· Peptic ulcer history

Â· Alcohol dependency

Â· Cigarette smoking

Â· Concurrent prednisone or corticosteroid use

Â· Disability

Â· High dose of the NSAID

Â· NSAID known to be more toxic

Studies clearly show that the non-acetylated salicylates are the safest

NSAIDs. Celebrex and Vioxx likely cause the least risk for peptic ulcer. But as

mentioned, they pose an increased risk for heart disease. Factoring these

newer medications out would leave the following less toxic NSAIDs: Relafen,

Daypro, Voltaren, Motrin, and Naprosyn. Meclomen, Indocin, Orudis, and Tolectin

are among the most toxic or likely to cause complications.

They are much more dangerous than the antibiotics or non-acetylated

salicylates. One should run an SMA at least once a year on patients who are on

these

medications. One must monitor the serum potassium levels if the patient is on

an ACE inhibitor as these medications can cause hyperkalemia. One should

also monitor their kidney function. The SMA will also show any liver impairment

that the drugs might cause.

These medications can also impair prostaglandin metabolism and cause

papillary necrosis and chronic interstitial nephritis. The kidney needs

vasodilatory

prostaglandins (PGE2 and prostacycline) to counterbalance the effects of

potent vasoconstrictor hormones such as angiotensin II and catecholamines.

NSAIDs decrease prostaglandin synthesis by inhibiting cyclooxygenase, leading

to

unopposed constriction of the renal arterioles supplying the kidney.

One might consider the use of non-acetylated salicylates such as salsalate,

sodium salicylate and magnesium salicylate (i.e., Salflex, Disalcid, or

Trilisate). They are the drugs of choice if there is renal insufficiency. They

have minimal interference with anticyclooxygenase and other prostaglandins.

Additionally, they will not impair platelet inhibition of those patients who

are on every other day aspirin to decrease their risk for stroke or heart

disease. Unlike aspirin, they do not increase the formation of products of

lipoxygenase-mediated metabolism of arachidonic acid. For this reason, they may

be less likely to precipitate hypersensitivity reactions. These drugs have

been safely used in patients with reversible obstructive airway disease and a

history of aspirin sensitivity.

They also are much gentler on the stomach then the other NSAIDs and are the

drug of choice if the patient has problems with peptic ulcer disease.

Unfortunately, all these benefits are balanced by the fact they may not be as

effective as the other agents and are less convenient to take. One needs to

push

them to 1.5-2 grams bid and tinnitus is a frequent complication.

One should warn patients of this complication and explain that if tinnitus

does develop they need to stop the drugs for a day and restart with a dose

that is half a pill per day lower. They repeat this until they find a dose that

relieves their pain and doesn't give them any ringing.

Prednisone

One can give patients with severe disease a prescription for prednisone 5

mg. They can take one of them a day if they develop a severe flare-up as a

result of going on the antibiotics. They can use an additional tablet at night

if

they are in really severe flare.

Explain to all patients that the prednisone is very dangerous and every dose

they take decreases their bone density. However, it is a trade-off. Since

they will only be on it for a matter of months, its use may be justifiable.

This is the first medicine they should try to stop as soon as their symptoms

permit.

Blood levels of cortisol peak between 3 and 9am. It would, therefore, be

safest to administer the prednisone in the morning. This will minimize the

suppression on the hypothalamic-pituitary-adrenal axis. Patients often ask the

dangers of these medications. The most significant one is osteoporosis.

Other side effects that usually occur at higher doses include adrenal

insufficiency, atherosclerosis acceleration, cataract formation, Cushing's

syndrome, diabetes, ulcers, herpes simplex and tuberculosis reactivation,

insomnia,

hypertension, myopathy and renal stones.

One also needs to be concerned about the increased risk of peptic ulcer

disease when using this medicine with conventional non-steroidal

anti-inflammatories. Persons receiving both of these medicines may have a 15

times greater

risk of developing an ulcer.

If a patient is already on prednisone, it is helpful to give them a

prescription for 1 mg tablets so they can wean themselves off of the prednisone

as

soon as possible. Usually one lowers the dose by about 1 mg per week. If a

relapse of the symptoms occurs, than further reduction of the prednisone is not

indicated.

Remission

The following criteria can help establish remission: *A decrease in duration

of morning stiffness to no more than 15 minutes

Â· No pain at rest

Â· Little or no pain or tenderness on motion

Â· Absence of joint swelling

Â· A normal energy level

Â· A decrease in the ESR to no more than 30

Â· A normalization of the patient's CBC. Generally the HGB, HCT, &

MCV will increase to normal and their " pseudo " -iron deficiency will disappear

Â· ANA, RF, & ASO titers returning to normal

The natural course of rheumatoid arthritis is quite remarkable. Less than 1%

of patients who are rheumatoid factor seropositive have a spontaneous

remission. Some disability occurs in 50-70% of patients within five years after

onset of the disease. Half of the patients will stop working within 10 years.

This devastating natural prognosis is what makes the antibiotic therapy so

exciting.

Approximately one third of patients have been lost to follow-up for whatever

reason and have not continued with treatment. The remaining patients seem to

have a 60-90% likelihood of improvement on this treatment regimen. That is

quite a stark contrast to the numbers quoted above.

There are many variables associated with an increased chance of remission or

improvement. The younger the patient is the better they seem to do. The more

closely they follow the diet, the less likely they are to have a severe

flare-up and the more likely they are to improve. Smoking seems to be

negatively

associated with improvement. The longer the patient has had the illness and

the more severe the illness the more difficult it seems to treat.

If patients discontinue their medications before all of the above criteria

are met, there is a greater risk that the disease will recur. If the patient

meets the above criteria, one can have them to try to stop their

anti-inflammatory medication once they start to experience these improvements.

If the

improvements are stable for six months, then discontinue the clindamycin. If

the

improvements are maintained for the next six months, one can then discontinue

their Minocin and monitor for recurrences. If symptoms should recur, it

would be wise to restart the previous antibiotic regimen.

Overall, nearly 80% of the patients do remarkably better with this program.

Approximately 5% of the patients continued to worsen and required

conventional agents, like methotrexate, to relieve their symptoms.

Approximately 15% of

the patients who started the treatment dropped out of the program and were

lost to follow-up. The longer and more severe the illness, the longer it takes

to cure. Smokers tend not to do as well with this program. Age and competency

of the person's immune system are also likely important factors.

Dr. Brown successfully treated over 10,000 patients with this protocol. He

found that significant benefits from the treatment require on the average one

to two years. I have treated nearly over 1,500 patients and find that the

dietary modification I advocate accelerates the response rate to several

months. The length of therapy can vary widely.

In severe cases, it may take up to thirty months for the patients to gain

sustained improvement. One requires patience because remissions may take up to

3 to 5 years. Dr. Brown's pioneering approach represents a safer less toxic

alternative to many conventional regimens and results of the NIH trial have

finally scientifically validated this treatment.

Preliminary Laboratory Evaluation For Non-Rheumatologists

It is important to evaluate patients to determine if indeed they have

rheumatoid arthritis. Most patients will have received evaluations and

treatment by

one or more board certified rheumatologists. If this is the case, the

diagnosis is rarely in question and one only needs to establish some baseline

laboratory data.

However, patients will frequently come in without having any appropriate

workup done by a physician. Arthritic pain can be an early manifestation of

20-30 different clinical problems. These include not only rheumatic disease,

but

also metabolic, infectious and malignant disorders. These patients will

require a more extensive laboratory analysis.

Rheumatoid arthritis is a clinical diagnosis for which there is not a single

test or group of laboratory tests which can be considered confirmatory. When

a patient hasn't been properly diagnosed, then one needs to establish the

diagnosis with the standard Rheumatism Association's criteria found in the

table at the end of the article.

One must also make certain that the first four symptoms listed in the table

are present for six or more weeks. These criteria have a 91-94% sensitivity

and 89% specificity for the diagnosis of rheumatoid arthritis. However, these

criteria were designed for classification and not for diagnosis. One must

make the diagnosis on clinical grounds. It is important to note that many

patients with negative serologic tests can have a strong clinical picture for

rheumatoid arthritis.

The metacarpophalangeal joints, proximal interphalangeal and wrists joints

are the first joints to become symptomatic. In a way, the hands are the

calling card of rheumatoid arthritis. If the patient completely lacks hand and

wrist involvement, even by history, the diagnosis of rheumatoid arthritis is

doubtful. Rheumatoid arthritis rarely affects the hips and ankles early in its

course.

Fatigue may be present before the joint symptoms begin. Morning stiffness is

a sensitive indicator of rheumatoid arthritis. An increase in fluid in and

around the joint probably causes the stiffness. The joints are warm, but the

skin is rarely red. When the joints develop effusions, the patients holds them

flexed at 5 to 20 degrees as it is too painful to extend them fully.

The general initial laboratory evaluation should include a baseline ESR,

CBC, SMA, U/A, and an ASO titer. One can also draw RF and ANA titers to further

objectively document improvement with the therapy. However, they seldom add

much to the assessment.

Follow-up visits can be every two months for patients who live within 50

miles, and every three to four months for those who live farther away. An ESR

at

every visit is an inexpensive and reliable objective parameter of the extent

of the disease. However, one should run this test within several hours of

the blood draw. Otherwise, one cannot obtain reliable and reproducible results.

This is nearly impossible with most clinical labs that pick up your specimen

at the office.

Inexpensive disposable ESR kits are a practical alternative to the

commercial or hospital labs. One can then run them in the office, usually

within one

hour of the blood draw. One must be careful to not run the test on the same

countertop as your centrifuge. This may cause a falsely elevated ESR due to the

agitation of the ESR measuring tube.

Many patients with rheumatoid arthritis have a hypochromic, microcytic CBC.

This is probably due to the inflammation in the rheumatoid arthritis

impairing optimal bone marrow utilization of iron. This type of anemia does NOT

respond to iron. Patients who take iron can actually worsen if they don't need

it

as the iron serves as a potent oxidant stress. Ferritin levels are generally

the most reliable indicator of total iron body stores. Unfortunately it is

also an acute phase reactant protein and will be elevated anytime the ESR is

elevated. This makes ferritin an unreliable test in patients with rheumatoid

arthritis.

Fibromyalgia

One needs to be very sensitive to this clinical problem when treating

patients with rheumatoid arthritis. It is frequently a complicating condition.

Many

times, patients will confuse the pain from it with a flare-up of their

arthritis. One needs to aggressively treat this problem. If this problem is

ignored, the likelihood of successfully treating the arthritis is significantly

diminished.

Fibromyalgia is a very common problem. Some experts believe that 5% of

people are affected with it. Over 12% of the patients at the Mayo Clinic's

Department of Physical Medicine and Rehabilitation have this problem. It is the

third most common diagnosis by rheumatologists in the outpatient setting.

Fibromyalgia affects women five times as frequently as men.

Signs And Symptoms of Fibromyalgia

One of the main features of fibromyalgia is the morning stiffness, fatigue,

and multiple areas of tenderness in typical locations. Most patients with

fibromyalgia complain of pain over many areas of the body, with an average of

six to nine locations. Although the pain is frequently described as being all

over, it is most prominent in the neck, shoulders, elbows, hips, knees, and

back.

Tender points are generally symmetrical and on both sides of the body. The

areas of tenderness are usually small (less than an inch in diameter) and deep

within the muscle. They are often located in sites that are slightly tender

in normal people.

Patients with fibromyalgia, however, differ in having increased tenderness

at these sites than normal persons. Firm palpation with the thumb (just past

the point where the nail turns white) over the outside elbow will typically

cause a vague sensation of discomfort. Patients with fibromyalgia will

experience much more pain and will often withdraw the arm involuntarily.

More than 70% of patients describe their pain as profound aching and

stiffness of the muscles. Often it is relatively constant from moment to

moment, but

certain positions or movements may momentarily worsen the pain. Other terms

used to describe the pain are dull and numb.

Sharp or intermittent pain is relatively uncommon. Patients with

fibromyalgia often complain that sudden loud noises worsen their pain. The

generalized

stiffness of fibromyalgia does not diminish with activity, unlike the

stiffness of rheumatoid arthritis, which lessens as the day progresses.

Despite the lack of abnormal lab tests, patients can suffer considerable

discomfort. The fatigue is often severe enough to impair activities of work and

recreation. Patients commonly experience fatigue on arising and complain of

being more fatigued when they wake up then when they went to bed. Over 90% of

patients believe the pain, stiffness, and fatigue are made worse by cold,

damp weather. Overexertion, anxiety and stress are also factors. Many people

find that localized heat, such as hot baths, showers, or heating pads, give

them

some relief. There is also a tendency for pain to improve in the summer with

mild activity or with rest.

Some patients will date the onset of their symptoms to some initiating

event. This is often an injury, such as a fall, a motor vehicle accident, or a

vocational or sports injury. Others find that their symptoms began with a

stressful or emotional event, such as a death in the family, a divorce, a job

loss,

or similar occurrence.

Pain Location

Patients with fibromyalgia have pain in at least 11 of the following 18

tender point sites (one on each side of the body):

1. Base of the skull where the suboccipital muscle inserts.

2. Back of the low neck (anterior intertransverse spaces of C5-C7).

3. Midpoint of the upper shoulders (trapezius).

4. On the back in the middle of the scapula.

5. On the chest where the second rib attaches to the breastbone

(sternum).

6. One inch below the outside of each elbow (lateral epicondyle).

7. Upper outer quadrant of buttocks.

8. Just behind the swelling on the upper leg bone below the hip

(trochanteric prominence).

9. The inside of both knees (medial fat pads proximal to the joint

line).

Treatment Of Fibromyalgia

There is a persuasive body of emerging evidence that indicates that patients

with fibromyalgia are physically unfit in terms of sustained endurance. Some

studies show that cardiovascular fitness training programs can decrease

fibromyalgia pain by 75%. Sleep is critical to the improvement. Many times,

improved fitness will correct the sleep disturbance.

My favorite, and most profoundly beneficial treatment for fibromyalgia is

NST.

Allergies, especially to mold, seem to be another common cause of

fibromyalgia. There are some simple interventions using techniques called Total

Body

Modification (TBM) 800-243-4826.

Exercise For Rheumatoid Arthritis

It is very important to exercise or increase muscle tone of the non-weight

bearing joints. Experts tell us that disuse results in muscle atrophy and

weakness. Additionally, immobility may result in joint contractures and loss of

range of motion (ROM). Active ROM exercises are preferred to passive.

There is some evidence that passive ROM exercises increase the number of

WBCs in the joint. If the joints are stiff, one should stretch and apply heat

before exercising. If the joints are swollen, application of ten minutes of ice

before exercise would be helpful.

The inflamed joint is very vulnerable to damage from improper exercise, so

one must be cautious. People with arthritis must strike a delicate balance

between rest and activity. They must avoid activities that aggravate joint

pain.

Patients should avoid any exercise that strains a significantly unstable

joint.

A good rule of thumb is that if the pain lasts longer than one hour after

stopping exercise, the patient should slow down or choose another form of

exercise. Assistive devices are also helpful to decrease the pressure on

affected

joints. Many patients need to be urged to take advantage of these. The

Arthritis Foundation has a book, Guide to Independent Living, which instructs

patients about how to obtain them.

Of course, it is important to maintain good cardiovascular fitness. Walking

with appropriate supportive shoes is also another important consideration.

The Infectious Cause Of Rheumatoid Arthritis

It is quite clear that autoimmunity plays a major role in the progression of

rheumatoid arthritis. Most rheumatology investigators believe that an

infectious agent causes rheumatoid arthritis. There is little agreement as to

the

involved organism. Investigators have proposed the following infectious

agents: Human T-cell lymphotropic virus Type I, rubella virus, cytomegalovirus,

herpesvirus, and mycoplasma. This review will focus on the evidence supporting

the hypothesis that mycoplasma is a common etiologic agent of rheumatoid

arthritis.

Mycoplasmas are the smallest self-replicating prokaryotes. They differ from

classical bacteria by lacking rigid cell wall structures and are the smallest

known organisms capable of extracellular existence. They are considered to

be parasites of humans, animals, and plants.

In 1939, Dr. Sabin, the discoverer of the polio vaccine, first reported a

chronic arthritis in mice caused by a mycoplasma. He suggested this agent might

cause that human rheumatoid arthritis. Dr. Thomas Brown was a rheumatologist

who worked with Dr. Sabin at the Rockefeller Institute. Dr. Brown trained at

John Hopkins Hospital and then served as chief of medicine at George

Washington Medical School before serving as chairman of the Arthritis Institute

in

Arlington, Virginia. He was a strong advocate of the mycoplasma infectious

theory for over fifty years of his life.

Culturing Mycoplasmas From Joints

Mycoplasmas have limited biosynthetic capabilities and are very difficult to

culture and grow from synovial tissues. They require complex growth media or

a close parasitic relation with animal cells. This contributed to many

investigators failure to isolate them from arthritic tissue. In reactive

arthritis

immune complexes rather than viable organisms localize in the joints. The

infectious agent is actually present at another site. Some investigators

believe that the organism binding in the immune complex contributes to the

difficulty in obtaining positive mycoplasma cultures.

Despite this difficulty some researchers have successfully isolated

mycoplasma from synovial tissues of patients with rheumatoid arthritis. A

British

group used a leucocyte-migration inhibition test and found two-thirds of their

rheumatoid arthritis patients to be infected with Mycoplasma fermentens. These

results are impressive since they did not include more prevalent Mycoplasma

strains like M salivarium, M ovale, M hominis, and M pneumonia.

One Finnish investigator reported a 100% incidence of isolation of

mycoplasma from 27 rheumatoid synovia using a modified culture technique. None

of the

non- rheumatoid tissue yielded any mycoplasmas. The same investigator used an

indirect hemagglutination technique and reported mycoplasma antibodies in

53% of patients with definite rheumatoid arthritis. Using similar techniques

other investigators have cultured mycoplasma in 80- 100% of their rheumatoid

arthritis test population.

Rheumatoid arthritis follows some mycoplasma respiratory infections. One

study of over 1000 patients was able to identify arthritis in nearly 1% of the

patients. These infections can be associated with a positive rheumatoid

factor. This provides additional support for mycoplasma as an etiologic agent

for

rheumatoid arthritis. Human genital mycoplasma infections have also caused

septic arthritis.

Harvard investigators were able to culture mycoplasma or a similar organism,

ureaplasma urealyticum, from 63% of female patients with SLE and only 4% of

patients with CFS. The researchers chose CFS as these patients shared similar

symptoms as those with SLE, such as fatigue, arthralgias, and myalgias.

Animal Evidence for The Protocol

The full spectrum of human rheumatoid arthritis immune responses (lymphokine

production, altered lymphocyte reactivity, immune complex deposition,

cell-mediated immunity and development of autoimmune reactions) occurs in

mycoplasma induced animal arthritis. Investigators have implicated at least 31

different mycoplasma species. Mycoplasma can produce experimental arthritis in

animals from three days to months later. The time seems to depend on the dose

given and the virulence of the organism.

There is a close degree of similarity between these infections and those of

human rheumatoid arthritis. Mycoplasmas cause arthritis in animals by several

mechanisms. They either directly multiply within the joint or initiate an

intense local immune response. Mycoplasma produces a chronic arthritis in

animals that is remarkably similar to rheumatoid arthritis in humans.

Arthritogenic mycoplasmas cause joint inflammation in animals by many

mechanisms. They

induce nonspecific lymphocyte cytotoxicity and antilymphocyte antibodies as

well as rheumatoid factor. Mycoplasma clearly causes chronic arthritis in mice,

rats, fowl, swine, sheep, goats, cattle and rabbits. The arthritis appears

to be the direct result of joint infection with culturable mycoplasma

organisms.

Gorillas have tissue reactions closer to man than any other animal.

Investigators have shown that mycoplasma can precipitate a rheumatic illness in

gorillas. One study demonstrated mycoplasma antigens occur in immune complexes

in

great apes. The human and gorilla IgG are very similar and express nearly

identical rheumatoid factors (IgM anti-IgG antibodies). The study showed that

when mycoplasma binds to IgG it can cause a conformational change. This

conformational change results in an anti-IgG antibody, which can then stimulate

an

autoimmune response.

The Science of Why Minocycline Is Used

If mycoplasma were a causative factor in rheumatoid arthritis, one would

expect tetracycline type drugs to provide some sort of improvement in the

disease. Collagenase activity increases in rheumatoid arthritis and probably

has a

role in its cause. Investigators demonstrated that tetracycline and

minocycline inhibit leukocyte, macrophage, and synovial collagenase.

There are several other aspects of tetracyclines that may play a role in

rheumatoid arthritis. Investigators have shown minocycline and tetracycline to

retard excessive connective tissue breakdown and bone resorption while

doxycycline inhibits digestion of human cartilage. It is also possible that

tetracycline treatment improves rheumatic illness by reducing delayed-type

hypersensitivity response. Minocycline and doxycycline both inhibit

phosolipases which

are considered proinflammatory and capable of inducing synovitis.

Minocycline is a more potent antibiotic than tetracycline and penetrates

tissues better. These characteristics shifted the treatment of rheumatic

illness

away from tetracycline to minocycline. Minocycline may benefit rheumatoid

arthritis patients through its immunomodulating and immunosuppressive

properties. In vitro studies demonstrated a decreased neutrophil production of

reactive oxygen intermediates along with diminished neutrophil chemotaxis and

phagocytosis.

Investigators showed that minocycline reduced the incidence of severity of

synovitis in animal models of arthritis. The improvement was independent of

minocycline's effect on collagenase. Minocycline has also been shown to

increase intracellular calcium concentrations that inhibit T-cells.

Individuals with the Class II major histocompatibility complex (MHC) DR4

allele seem to be predisposed to developing rheumatoid arthritis. The

infectious

agent probably interacts with this specific antigen in some way to

precipitate rheumatoid arthritis. There is strong support for the role of T

cells in

this interaction.

Minocycline may suppress rheumatoid arthritis by altering T cell calcium

flux and the expression of T cell derived from collagen binding protein.

Minocycline produced a suppression of the delayed hypersensitivity in patients

with

Reiter's syndrome. Investigators also successfully used minocycline to treat

the arthritis and early morning stiffness of Reiter's syndrome.

Clinical Studies

In 1970 investigators at Boston University conducted a small, randomized

placebo-controlled trial to determine if tetracycline would treat rheumatoid

arthritis. They used 250 mg of tetracycline a day. Their study showed no

improvement after one year of tetracycline treatment. Several factors could

explain

their inability to demonstrate any benefits.

Their study used only 27 patients for a one-year trial, and only 12 received

tetracycline. Noncompliance could have been a factor. Additionally, none of

the patients had severe arthritis. Patients were excluded from the trial if

they were on any anti-remittive therapy.

Finnish investigators used lymecycline to treat the reactive arthritis in

Chlamydia trachomatous infections. The study compared the effect of the

medication in patients with two other reactive arthritis infections Yersinia

and

Campylobacter.

Lymecyline produced a shorter course of illness in the Chlamydia induced

arthritis patients, but did not affect the other enteric infections-associated

reactive arthritis. The investigators later published findings that suggested

lymecycline achieved its effect through non-antimicrobial actions. They

speculated it worked by preventing the oxidative activation of collagenase.

Breedveld published the first trial of minocycline for the treatment of

animal and human rheumatoid arthritis. In the first published human trial,

Breedveld treated ten patients in an open study for 16 weeks. He used a very

high

dose of 400 mg per day. Most patients had vestibular side effects resulting

from this dose.

However, all patients showed benefit from the treatment. All variables of

efficacy were significantly improved at the end of the trial. Breedveld

concluded an expansion of his initial study and observed similar impressive

results.

This was a 26-week double-blind placebo-controlled randomized trial with

minocycline for 80 patients. They were given 200 mg twice a day. The Ritchie

articular index and the number of swollen joints significantly improved (p <

0.05) more in the minocyline group than in the placebo group.

Investigators in Israel studied 18 patients with severe rheumatoid arthritis

for 48 weeks. These patients had failed two other DMARD. They were taken off

all DMARD agents and given minocycline 100 mg twice a day. Six patients did

not complete the study, three withdrew because of lack of improvement, and

three had side effects of vertigo or leukopenia. All patients completing the

study improved. Three had complete remission, three had substantial improvement

of greater than 50% and six had moderate improvement of 25% in the number of

active joints and morning stiffness.

Criteria For Classification Of Rheumatoid Arthritis

Â· Morning Stiffness - Morning stiffness in and around joints

lasting at least one hour before maximal improvement is noted.

Â· Arthritis of three or more joint areas - At least three joint

areas have simultaneously had soft-tissue swelling or fluid (not bony

overgrowth) observed by a physician. There are 14 possible joints: right or

left PIP,

MCP, wrist, elbow, knee, ankle, and MTP joints.

Â· Arthritis of hand joints - At least one joint area swollen as

above in a wrist, MCP, or PIP joint

Â· Symmetric arthritis - Simultaneous involvement of the same joint

areas (as in criterion 2) on both sides of the body (bilateral involvement of

PIPs, MCPs, or MTPs) is acceptable without absolute symmetry. Lack of

symmetry is not sufficient to rule out the diagnosis of rheumatoid arthritis.

Â· Rheumatoid Nodules - Subcutaneous nodules over bony prominences,

or extensor surfaces, or in juxta-articular regions, observed by a physician.

Only about 25% of patients with rheumatoid arthritis develop nodules, and

usually as a later manifestation.

Â· Serum Rheumatoid Factor - Demonstration of abnormal amounts of

serum rheumatoid factor by any method that has been positive in less than 5% of

normal control subjects. This test is positive only 30-40% of the time in

the early months of rheumatoid arthritis.

Radiological Changes

Radiological changes typical of rheumatoid arthritis on PA hand and wrist

X-rays, which must include erosions or unequivocal bony decalcification

localized to or most marked adjacent to the involved joints (osteoarthritic

changes

alone do not count).

Note: Patients must satisfy at least four of the seven criteria listed. Any

of criteria 1-4 must have been present for at least 6 weeks. Patients with

two clinical diagnoses are not excluded. Designations as classic, definite, or

probable rheumatoid arthritis is not to be made.

Presented at the 32nd International Congress of the Great Lakes College of

Clinical Medicine. Baltimore, Maryland, September 25, 1999

Dr. Joseph M. Mercola

Using Antibiotics in Rheumatic Diseases - Bibliography

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Presented at the 32nd International Congress of the Great Lakes College of

Clinical Medicine. Baltimore, Maryland, September 25, 1999

Dr. Joseph M. Mercola

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