Unraveling The Mystery of Rheumatoid Arthritis, Part Two

[Mrs. Sharon B. Hodge]

Painful Debilitating Disease More Devastating than Previously Recognized Part Two

Posted By Dr. Mercola
August 16 2010

How Do You Know When to Stop the Drugs?

Unlike conventional approaches to RA, my protocol is designed to treat the underlying cause of the problem. So eventually the drugs that you are going to use during the program will be weaned off.

The following criteria can help determine when you are in remission and can consider weaning off your medications: *

* A decrease in duration of morning stiffness to no more than 15 minutes
* No pain at rest
* Little or no pain or tenderness on motion
* Absence of joint swelling
* A normal energy level
* A decrease in your ESR to no more than 30
* A normalization of your CBC. Generally your HGB, HCT, & MCV will increase to normal and your "pseudo"-iron deficiency will disappear
* ANA, RF, & ASO titers returning to normal

If you discontinue your medications before all of the above criteria are met, there is a greater risk that the disease will recur.

If you meet the above criteria, you can try to wean off your anti-inflammatory medication and monitor for flare-ups. If no flare-ups occur for six months, then discontinue the clindamycin.

If the improvements are maintained for the next six months, you can then discontinue your Minocin and monitor for recurrences. If symptoms should recur, it would be wise to restart the previous antibiotic regimen.

Evaluation to Determine and Follow RA

If you have received evaluations and treatment by one or more board certified rheumatologists, you can be very confident that the appropriate evaluation was done. Although conventional treatments fail miserably in the long run, the conventional diagnostic approach is typically excellent, and you can start the treatment program discussed above.

If you have not been evaluated by a specialist then it will be important to be properly evaluated to determine if indeed you have rheumatoid arthritis.

Please be sure and carefully review Appendix Two, as you will want to confirm that fibromyalgia is not present.

Beware that 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. Rheumatoid arthritis is a clinical diagnosis for which there is not a single test or group of laboratory tests which can be considered confirmatory.

Criteria for Classification of Rheumatoid Arthritis

* Morning Stiffness - Morning stiffness in and around joints lasting at least one hour before maximal improvement is noted.
* 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.
* Arthritis of hand joints - At least one joint area swollen as above in a wrist, MCP, or PIP joint.
* Symmetric arthritis - Simultaneous involvement of the same joint areas (as in criterion 2) on both sides of your 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.
* Rheumatoid Nodules - Subcutaneous nodules over bony prominences, or extensor surfaces, or in juxta-articular regions, observed by a physician. Only about 25 percent of patients with rheumatoid arthritis develop nodules, and usually as a later manifestation.
* Serum Rheumatoid Factor - Demonstration of abnormal amounts of serum rheumatoid factor by any method that has been positive in less than 5 percent of normal control subjects. This test is positive only 30-40 percent of the time in the early months of rheumatoid arthritis.

You must also make certain that the first four symptoms listed in the table above are present for six or more weeks. These criteria have a 91-94 percent sensitivity and 89 percent specificity for the diagnosis of rheumatoid arthritis.

However, these criteria were designed for classification and not for diagnosis. The diagnosis must be made on clinical grounds. It is important to note that many patients with negative serologic tests can have a strong clinical picture for rheumatoid arthritis.

Your Hands are the KEY to the Diagnosis of RA

In a way, the hands are the calling card of rheumatoid arthritis. If you completely lack hand and wrist involvement, even by history, the diagnosis of rheumatoid arthritis is doubtful. Rheumatoid arthritis rarely affects your hips and ankles early in its course.

The metacarpophalangeal joints, proximal interphalangeal and wrist joints are the first joints to become symptomatic. Osteoarthritis typically affects the joints that are closest to your fingertips (DIP joints) while RA typically affects the joints closest to your wrist (PIP), like your knuckles.

Fatigue may be present before your joint symptoms begin, and morning stiffness is a sensitive indicator of rheumatoid arthritis. An increase in fluid in and around your joint probably causes the stiffness. Your joints are warm, but your skin is rarely red.

When your joints develop effusions, hold them flexed at 5 to 20 degrees as it is likely going to be too painful to extend them fully.

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: You 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, are not to be made.

Laboratory Evaluation

The general initial laboratory evaluation should include a baseline ESR, CBC, SMA, U/A, 25 hydroxy D level and an ASO titer. You 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 to four months depending on the extent of the disease and ease of testing.

The exception here would be vitamin D testing which should be done every two weeks until your 25 hydroxy D level is between 65 and 80 ng/ml.

Many patients with rheumatoid arthritis have a hypochromic, microcytic CBC that appears very similar to iron deficiency, but it is not at all related. This is probably due to the inflammation in the rheumatoid arthritis impairing optimal bone marrow utilization of iron.

It is important to note that this type of anemia does NOT respond to iron and if you are put on iron you will get worse, as the iron is a very potent oxidative 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.

APPENDIX ONE: 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, however.

Investigators have proposed the following infectious agents:

* Human T-cell lymphotropic virus Type I
* Rubella virus
* Cytomegalovirus
* Herpesvirus
* 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.

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 your 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 percent 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 percent of patients with definite rheumatoid arthritis. Using similar techniques other investigators have cultured mycoplasma in 80-100 percent of their rheumatoid arthritis test population.

Rheumatoid arthritis can also follow some mycoplasma respiratory infections.

One study of over 1000 patients was able to identify arthritis in nearly 1 percent 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 percent of female patients with SLE and only 4 percent 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.

Arthritogenic mycoplasmas also cause joint inflammation in animals by several 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, and investigators have shown that mycoplasma can precipitate a rheumatic illness in gorillas. One study demonstrated that mycoplasma antigens do 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 have 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 have demonstrated a decreased neutrophil production of reactive oxygen intermediates along with diminished neutrophil chemotaxis and phagocytosis.

Minocycline has also been shown to reduce the incidence and 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.

So 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, and 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, so noncompliance may 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. Their 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.

The first trial of minocycline for the treatment of animal and human rheumatoid arthritis was published by Breedveld. 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, and all variables of efficacy were significantly improved at the end of the trial.

Breedveld expanded on his initial study and later 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 percent, and six had moderate improvement of 25 percent in the number of active joints and morning stiffness.

APPENDIX TWO: Make Certain You are Assessed for Fibromyalgia

You need to be very sensitive to this condition when you have rheumatoid arthritis as it is frequently a complicating condition. Many times, the pain will be confused with a flare-up of the RA.

You need to aggressively treat this problem. If it is ignored, the likelihood of successfully treating the arthritis is significantly diminished.

Fibromyalgia is a very common problem. Some experts believe that 5 percent of people are affected with it. Over 12 percent of the patients at the Mayo Clinic's Department of Physical Medicine and Rehabilitation have this problem, and 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 morning stiffness, fatigue, and multiple areas of tenderness in typical locations. Most people with fibromyalgia complain of pain over many areas of their 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.

People with fibromyalgia, however, differ in having increased tenderness at these sites than the average person. 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 percent of patients describe their pain as profound aching and stiffness of 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 also 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 than when they went to bed.

Over 90 percent of patients believe the pain, stiffness, and fatigue are made worse by cold, damp weather. Overexertion, anxiety and stress are also factors.

Many 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).

Fibromyalgia pain sites
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 exercise can decrease fibromyalgia pain by 75 percent.

Sleep is also critical to improvement, and many times, improved fitness will also correct the sleep disturbance.

Normalizing vitamin D levels has also been shown to be helpful to decrease pain as has topical magnesium oil supplementation.

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.

APPENDIX THREE: 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:

1. Extended spectrum of activity
2. Greater tissue penetrability
3. 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 you compare 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 percent 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.

Important Factors to Consider When Using Minocin

Unlike the other tetracyclines, Minocin tends not to cause yeast infections. Some infectious disease experts even believe that it 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 take 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 you to the sun. This minimizes your risk of sunburn and increased risk of skin cancer.

However, you 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 people cannot tolerate Minocin on an empty stomach and have to take it with a meal to avoid GI side effects.

If you need to take it with a meal, you will still absorb 85 percent of the medication, whereas tetracycline is only 50 percent absorbed. In June of 1990, a pelletized version of Minocin also became available, which 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 as most all generic minocycline are clearly less 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 Wal Mart 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 that contribute to microulcerations of the stomach, which cause chronic blood loss. It is certainly possible to develop a peptic ulcer contributing to this blood loss. In either event, patients are frequently receiving iron supplements to correct their blood counts.

IT IS IMPERATIVE THAT MINOCIN NOT BE GIVEN WITH IRON!

Over 85 percent of the dose will bind to the iron and pass through your colon unabsorbed.

If iron is taken, it should be at least one hour before Minocin, or two hours after.

A recent, uncommon, complication of Minocin is a cell-mediated hypersensitivity pneumonitis.

Most patients can start on 100 mg of Minocin 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.

WARNING: Tetracycline type drugs can cause a permanent yellow- grayish brown discoloration of your teeth.

This can occur in the last half of pregnancy, and in children up to eight years old. You should not routinely use tetracycline in children.

If you have severe disease, you can consider increasing the dose to as high as 200 mg three times a week. Aside from the cost of this approach, several problems may result from the higher doses.

Minocin can cause quite severe nausea and vertigo, but taking the dose at night tends to decrease this problem considerably.

However, if you take the dose at bedtime, you must swallow the medication with TWO glasses of water. This is to insure that the capsule doesn't get stuck in your throat. If that occurs, a severe chemical esophagitis can result, which can send you 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, and it is important to use the IV form of treatment if the disease is severe.

In my experience nearly all scleroderma patients require a more 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 can be had.

If you have a milder illness, the oral form of clindamycin is preferable.

With a mild rheumatic illness (the minority of cases), it is even possible to exclude this from your regimen. Initial starting doses for an adult would be a 1200 mg dose once a week.

Please note that many people 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, you 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 also important to be aware of the possibility of developing a severe and uncontrollable bout of diarrhea. Administration of acidophilus seems to limit this complication by promoting the growth of the healthy gut flora.

If you have 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 10 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 You Fail to Respond

The most frequent reason for failure to respond to the protocol is lack of adherence to the dietary guidelines.

Most people eat too many grains and sugars, which disturbs insulin physiology. It is important that you adhere as strictly as possible to the guidelines.

A small minority, generally under 15 percent 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 hyaluronic acid, which is a potentiating agent commonly used in the treatment of cancer, may be quite useful in these cases. 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, however, as the cost may range up to $10 per cc. You also need to use some caution, as it may precipitate a significant Herxheimer flare reaction.