By Prof. Garth L. Nicolson
The Institute for Molecular Medicine
15162 Triton Lane, Huntington Beach, CA 92649-1401
In addition to muscle pain and tenderness at specific sites, Fibromyalgia Syndrome (FMS) is often characterized by a number of other less specific chronic signs and symptoms. Among these are disabling fatigue that does not resolve with rest, intermittent low-grade fevers, joint pain and loss of joint mobility, impairments in short-term memory, headaches, gastrointestinal and vision problems and other signs and symptoms.
In many patients the diagnosis of FMS is accompanied by other secondary diagnoses, such as Chronic Fatigue Syndrome (CFS), Rheumatoid Arthritis (RA), Inflammatory Bowel Diseases, and other syndromes, which can also present with many of the same signs and symptoms. This suggests that there may be some overlap in the underlying causes of all of these conditions or at least in the factors or cofactors that may result in sickness (morbidity) or in progression of the illness.
There are a variety of different theories about possible causes and progression of chronic illnesses like FMS. We have been interested in the potential role that chronic infections may play in FMS. Although the causes of chronic illnesses are for the most part unknown, the complex signs and symptoms that evolve in many FMS, CFS, GWI and RA patients may be due, in part, to systemic chronic infections (bacteria, viruses, fungi). Such infections can follow acute or chronic chemical, environmental or other insults (trauma, acute viral illness, etc.) that have the potential to suppress the immune system and cause metabolic imbalances [1, 2].
It is thought that illnesses like FMS probably evolve over time in a multistep process that may require multiple toxic exposures, including infections that can be causative for the illness in a few patients, cofactors for the illness (not causative but important in patient morbidity) in others, or more likely in many patients, opportunistic infections. Such infections need not be present at the onset of illness to be important in patient morbidity. Because of their dysfunctional metabolic and immune systems, many FMS patients may be particularly susceptible to chronic infections that worsen their illness. Of course, illness progression in FMS patients could also be caused by other factors, psychological stress, physical trauma, other illnesses and many other factors, but my remarks will be limited to the potential role of chronic bacterial infections in the progression of FMS.
Chronic infections are usually held in check by our immune systems, but they can take hold if they can avoid immune surveillance and penetrate and hide in various tissues and organs, including cells of the Central and Peripheral Nervous Systems . When such "stealth" viral and bacterial infections occur, they can cause many of the complex signs and symptoms seen in FMS, CFS, RA and GWI, including enhanced immune dysfunction and metabolic imbalances . Changes in environmental responses as well as increased titers to various endogenous viruses that are commonly found to be expressed in these patients have been seen in FMS, CFS and GWI patients. If infectious agents are involved, few can produce the complex chronic signs and symptoms found in these patients.
One type of airborne infection that has received renewed interest of late as an possible cause, cofactor or opportunistic infection in various chronic disorders is represented by some small, primitive classes of bacteria . These microorganisms, principally Mycoplasmas and other bacteria (Chlamydia, Coxiella, Brucella, Borellia, etc.), although not as well known as other agents in causing various diseases, are now considered important emerging pathogens in various chronic illnesses. They may also be important cofactors in some illnesses, including HIV-AIDS and other immunodeficiency disorders, skin diseases and some autoimmune diseases .
As chronic illnesses such as FMS, CFS, GWI and RA progress, there are a number of accompanying clinical problems, and in some patients increases in autoimmune signs and symptoms are seen. These increases in autoimmune signs and symptoms usually mean that some patients acquire many but usually not all of the classical signs and symptoms that define Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS or Lew Gehrig’s Disease), Lupus, Graves’ Disease, RA and other complex autoimmune diseases. This suggests that they do not have classical autoimmune diseases. Although it is certainly not proven, such usually rare autoimmune responses and incomplete diagnoses for autoimmune disorders are at least consistent with certain chronic infections, such as mycoplasmal infections, that penetrate into nerve cells, synovial cells in joints and other cell types. We have proposed that in certain patients these autoimmune signs and symptoms are caused when intracellular pathogens, such as mycoplasmas and other bacteria, escape from cellular compartments and stimulate autoimmune responses.
Microorganisms like mycoplasmas can incorporate into their own surface structures pieces of host cell membranes that contain important host membrane antigens that can trigger autoimmune responses , and they can also mimic host cell antigen structures . Thus patients with such infections may respond immunologically to microorganism antigens as well as their own membrane antigens, producing unusual autoimmune signs and symptoms. This could explain why such patients do not have all of the clinical characteristics expected in these usually rare autoimmune diseases.
Microorganisms Can Cause Morbidity in Many FMS, CFS, GWI and RA Patients
Microorganisms like Mycoplasmas are not considered as important human pathogens when they are found at superficial sites, such as the oral cavity or gut, but some species, such as M. fermentans, M. penetrans, M. pneumoniae, M. genitalium, M. pirum and M. hominis, among others, have the capacity to penetrate into the blood circulation and colonize various tissues, and these cell-penetrating microorganisms have been closely associated with various human diseases . Do such infectious agents actually cause FMS, CFS, GWI or RA? Probably not on their own, but pathogenic microorganisms like Mycoplasma, Chlamydia, Brucella, Coxiella and other bacteria and some viruses appear to be an important element in causing chronic illness progression, patient morbidity, or exacerbating the major signs and symptoms seen in patients with chronic illnesses.
If certain microorganisms are associated with chronic illnesses, is there any evidence for microorganism infections in FMS, CFS, GWI or RA patients? The answer is obviously yes. In ~70% of FMS, ~60% of CFS, and ~50% of GWI and RA patients examined we and others, principally Dr. Daryl See, formally of the University of California College of Medicine, Irvine, and Eli Mortechai of Medical Diagnostics of New Jersey, are finding strong evidence for mycoplasmal blood infections that can explain many of the chronic signs and symptoms found in these patients. In our studies on GWI, a CFS-, FMS-like illness , we have found mycoplasmal infections in the blood of about one-half of over 200 patients, and these patients were found to have principally one infectious species of mycoplasma, M. fermentans [4-6].
However, in ~60% of the >200 civilians with FMS or CFS that we have examined we have found a variety of pathogenic mycoplasma species, such as M. fermentans, M. penetrans, M. pneumoniae, M. genitalium, M. pirum and M. hominis, in their white blood cells but these infections are only found in 0-9% of controls [1, 6]. Interestingly, the majority of CFS and FMS patients had multiple mycoplasmal infections but none were found in controls ; however, single infections are found in some nonsymptomatic subjects (0-9%). The tests that we use to identify mycoplasmal infections, Forensic Polymerase Chain Reaction and Nucleoprotein Gene Tracking, are very sensitive and highly specific. These tests are a dramatic improvement over the relatively insensitive serum antibody and other tests that are currently being used to assay for systemic infections.
Antibiotic Treatments for Chronic Illnesses Like FMS
When microorganism infections are identified in blood fractions of subsets of patients with FMS, CFS, GWI or RA, these patients can be treated as medical not psychological or psychiatric patients, just like any other patients with blood infections. This does not mean that psychological or psychiatric problems are not important in chronic illness patients. But if such infections are important in these disorders, then appropriate treatments with antibiotics or other medications that suppress chronic infections should result in improvement and even recovery. This is exactly what has been found [7, 8]. The majority of patients with confirmed pathogenic mycoplasmal infections eventually recover from 50-100% of their premorbid health on therapies that are directed specifically against their chronic infections not against possible psychological problems.
The recommended treatment for confirmed mycoplasmal blood infections is long-term antibiotic therapy, usually multiple 6-week cycles of doxycycline (200-300 mg/day), ciprofloxacin or Cipro (1,500 mg/day), azithromycin or Zithromax (500 mg/day) or clarithromycin or Biaxin (750-1,000 mg/day). Multiple cycles are required, because few patients recover after only a few cycles [4-6], possibly because of the intracellular locations of the infections, the slow-growing nature of these microorganisms and their inherent insensitivity to antibiotics. We now recommend that patients who have been diagnosed with blood infections receive continuous oral antibiotics for at least 6 months before using the 6-week cycles of treatment.
Although patients starting such therapy usually have Herxheimer reactions and feel initially worse due to die-off or release of toxic materials from damaged microorganisms, they eventually stabilize within days to a few weeks and then slowly begin to recover. Unfortunately, the treatment requires long-term therapy, and recovery is usually very slow. Patients that have been sick for many years are unlikely to recover within a year of therapy.
The clinical responses that are seen are not due to placebo effects, because administration of some antibiotics, such as penicillins, resulted in patients becoming more not less symptomatic. In addition, they are not due to immunosuppressive effects of some of the antibiotics, because other antibiotics that do not cause immune suppression are also effective but only if they suppress the chronic infections. If they don’t have these infections, then antibiotics do not work.
Some patients recover to a certain point and then fail to continue to respond to the recommended antibiotics, suggesting that other problems, such as viral infections, environmental exposures and other toxic events, and even stress, also play an important role in these illnesses, and may even play a predominant role in some patients.
What results have been obtained with antibiotics for chronic illnesses like FMS? Although a majority of patients diagnosed with chronic blood infections appear to benefit from antibiotic therapy, many patients respond and have some alleviation of most signs and symptoms but do not fully recover. A 3-year follow-up of antibiotic therapy in Northern California is instructive.
According to Sharon Briggs, R.N., a majority (~80%) of chronic illness (FMS, CFS) patients from the Shasta County that were confirmed with mycoplasmal infections recovered from 50-100% of their pre-illness health within this time period, and even some patients who did not test positive showed benefit from antibiotics, suggesting other bacterial infections. Similar to other therapies for chronic illnesses, not every patient benefited from antibiotic therapy, and the time required for recovery was quite variable in different patients.
Do chronic infections explain illnesses like FMS? It is unlikely that there is only one or even a few explanations for complex chronic illnesses like FMS or CFS. Rather, these illnesses are probably due to a combination of multiple toxic exposures, chemical and biological, in combination with genetic susceptibility (immune systems and/or detoxification systems, cellular metabolism) that determines whether a person becomes chronically ill. These considerations probably also play an important role in determining who will recover to various extents on different types of therapy.
In addition, recovery can be complicated by patients’ over-dependence on drugs, such as certain antidepressants or other drugs that can suppress portions of the immune system. Interestingly, those patients that slowly recover after several cycles of antibiotics are generally less environmentally sensitive, suggesting that their immune systems may be returning to pre-illness states. If such patients had illnesses that were solely caused by psychological or psychiatric problems or by environmental or chemical exposures, they should not respond to the recommended antibiotics and recover their health. In addition, if such treatments were just reducing the autoimmune responses, then patients should not maintain recovery after the treatments are discontinued.
Complex Role of Toxic Exposures in Chronic Illnesses
The treatments of chronic illnesses that are due to toxic exposures from chemical or radiological agents are quite different from the treatment of chronic infections . The treatment of chemically exposed patients usually involves removal of offending chemicals from the patient's environment, depletion of chemicals from the patient's system and treatment of the signs and symptoms caused by chemical exposure(s). Chemically exposed patients are often extremely sensitive to a variety of commonly encountered chemicals, including perfumes and air freshners, petrochemical fumes, chlorine, cleaning solutions and solvents, among others. They are also very sensitive to certain foods, and special diets are often necessary, and in some cases direct skin contact with certain substances can cause strong cutaneous reactions.
Therefore, an important part of treatment for chemical exposures requires limiting exposures to a variety of common chemicals and gradual removal of the toxic chemicals [9, 10].
To be successful a comprehensive approach to the therapy of chronic illnesses must be undertaken with each patient . In addition to treatments like antibiotics or removal of toxic agents and treatment of metabolic disorders, these patients often have nutritional and other deficiencies that must be corrected. For example, these patients are often depleted in vitamins B, C and E, among others, and certain minerals. Unfortunately, patients with chronic illnesses often have poor absorption.
Therefore, high doses of some vitamins must be used, and others, such as vitamin B complex, cannot be easily absorbed by the gut, so sublingual natural B-complex vitamins in small capsules or liquids should be used instead of oral capsules that are swallowed. General vitamins plus extra C, E, CoQ-10, beta-carotene, folic acid, bioflavoids and biotin are best. L- cysteine, L-tyrosine, L-carnitine, malic acid and especially flaxseed oil are reported by some to be useful. Certain minerals are also often depleted in these patients, such as zinc, magnesium, chromium and selenium, and these should be supplemented as well.
One problem with taking these supplements is that they cannot be taken at the same time as antibiotics because they may inhibit antibiotic uptake. Antibiotics deplete normal gut bacteria which can result in over-growth of less desirable bacteria. To supplement bacteria in the gastrointestinal system Lactobacillus acidophillus tablets are recommended. One product is a mixture of Lactobacillus acidophillus, Lactobacillus bifidus and other bacteria with FOS (fructoologosaccharides) to promote growth of these "friendly" bacteria in the gut .
A number of natural remedies that boost the immune system can be useful in the therapy of chronic illnesses. Among these are whole lemon/olive extract drink or an extract of olive leaves with antioxidants, plant extracts or purified plant products and milk proteins such as whey. These products are marketed under a variety of brand names and can be especially useful during or especially after antibiotic therapy has been completed. Although these products appear to help some patients, their clinical effectiveness in various chronic illness patients has not been carefully evaluated. They should be used during therapy to boost the immune system or especially after antibiotic therapy in a maintenance program to prevent relapse of illness .
Another useful therapy for some patients is oxygen therapy. This can be administered as hyperbaric oxygen, ozone therapy or even oxygen-releasing products, such as Dioxyclor® by American Biologics. The reason that these products are often useful in patients with "stealth" infections is that these infections grow better under low oxygen conditions. This probably explains why some patients relapse after flying long distances or after moving to high altitude locations.
For Further Information
The Institute for Molecular Medicine can test patients for evidence of mycoplasmal and other infections of the types that worsen human diseases like FMS, CFS, GWI and RA. Blood samples can be sent to our new certified reference lab, International Molecular Diagnostics, Inc. (Tel: 714-799-7177) for mycoplasma and other testing. The website for further information is: www.immed.org.
Prof. Garth L. Nicolson
The Institute for Molecular Medicine
15162 Triton Lane
Huntington Beach, CA 92649-1401
Tel: 714-903-2900 Fax: 714-379-2082
1. Nicolson, G.L., Nasralla, M, Hier, J., Erwin, R., Nicolson, N.L. and Ngwenya, R. Mycoplasmal infections in chronic illnesses: Fibromyalgia and Chronic Fatigue Syndromes, Gulf War Illness, HIV-AIDS and Rheumatoid Arthritis. Med. Sentinel 1999; 4: 172-176.
2. Nicolson, G.L. and Nicolson, N.L. Chronic fatigue illness and Operation Desert Storm. J. Occup. Environ. Med. 1996; 38: 14-16.
3. Baseman, J.B. and Tully, J.G. Mycoplasmas: Sophisticated, reemerging, and burdened by their notoriety. Emerg. Infect. Dis. 1997; 3: 21-32.
4. Nicolson, G.L. and Nicolson, N.L. Diagnosis and treatment of mycoplasmal infections in PersianGulf War Illness-CFIDS patients. Intern. J. Occup. Med. Immunol. Tox. 1996; 5: 69-78.
5. Nicolson, G.L., Nicolson, N.L. and Nasralla, M. Mycoplasmal infections and Chronic FatigueIllness (Gulf War Illness) associated with deployment to Operation Desert Storm. Intern. J. Med. 1998; 1: 80-92.
6. Nicolson, G.L., Nasralla, M, Hier, J. and Nicolson, N.L. Diagnosis and treatment of chronic mycoplasmal infections in Fibromyalgia Syndrome and Chronic Fatigue Syndrome: relationship to Gulf War Illness. Biomed. Therapy 1998; 16: 266-271.
7. Nicolson, G.L. and Nicolson, N.L. Doxycycline treatment and Desert Storm. JAMA 1995; 273: 618-619.
8. Nicolson, G.L. Considerations when undergoing treatment for chronic infections found in Chronic Fatigue Syndrome, Fibromyalgia Syndrome and Gulf War Illnesses. (Part 1). Antibiotics Recommended when indicated for treatment of Gulf War Illness/CFIDS/FMS (Part 2). Intern. J. Med. 1998; 1: 115-117, 123-128.
9. Ziem GE. Multiple chemical sensitivity: treatment and followup with avoidance and control of chemical exposures. Toxicol. Ind. Health 1992; 8: 73-86.
10. Rea WJ, Pan Y, Johnson AR, Ross GH, Suyama H, Fenyves EJ. Reduction of chemical sensitivity by means of heat depuration, physical therapy and nutritional supplementation in a controlled environment. J. Nutrit. Environ. Med. 1996; 6: 141-148.
Source: www.immed.org. Originally published in Fibromyalgia Newsletter 1999. © 2002 Institute for Molecular Medicine. All Rights Reserved.