Dr Brown's scleroderma protocol

Physicians' Protocol For Using Antibiotics in Rheumatic Disease (SCLERODERMA)
By Dr. Joseph Mercola

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:

Old age
Peptic ulcer history
Alcohol dependency
Cigarette smoking
Concurrent prednisone or corticosteroid use
Disability
High dose of the NSAID
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.

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.

The following criteria can help establish remission: *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 the ESR to no more than 30
A normalization of the patient's CBC. Generally the HGB, HCT, & MCV will increase to normal and their "pseudo"-iron deficiency will disappear
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.

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.

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.