Anti-Aging Medical News (2000)

Identification and Treatment of Chronic Infections in Fatigue Illnesses, Autoimmune Diseases and other Chronic Conditions

Garth L. Nicolson, PhD and Paul A. Berns, MD

The Institute for Molecular Medicine, www.immed.org
Huntington Beach, CA 92647

Various chronic illnesses are associated with aging, including the fatigue and autoimmune illnesses. The most common complaint of new patients in the United States is fatigue that does not resolve with rest.  This illness is often diagnosed as Chronic Fatigue Syndrome (CFS), and it is characterized by a number of chronic (>6 months duration) signs and symptoms that do not resolve with rest.  Among these are disabling fatigue, intermittent fevers, joint and muscle pain and loss of joint mobility, impairments in short-term memory, headaches, skin rashes, diarrhea, coughing, nausea and gastrointestinal and breathing problems, diminished vision and other signs and symptoms.  Other chronic illnesses, such as Fibromyalgia Syndrome (FMS), Rheumatoid Arthritis (RA), Inflammatory Bowel Diseases, among others, also show fatigue and many of these same additional signs and symptoms, suggesting that there may be some overlap in the underlying causes of these illnesses or at least in the factors that result in sickness (morbidity) or illness progression (worsening of illness).  Illnesses such as Rheumatoid Arthritis (RA) also have fatigue as a major symptom but they are typically characterized by joint pain, swelling and tenderness, loss of joint mobility and joint destruction due to autoimmune inflammation. RA patients also present with a number of other less specific chronic signs and symptoms.  Among these are fatigue, muscle pain and tenderness, headaches, gastrointestinal and heart problems and sometimes intermittent low-grade fevers and other signs and symptoms. In many patients the diagnosis of fatigue or autoimmune illnesses is accompanied by other secondary diagnoses, such as Inflammatory Bowel Diseases, osteoporosis and other conditions, which are commonly found in aging patients.  Thus although the exact causes of these illnesses are not known and may be different in each patient, there are similarities in these conditions that may be important in causing patient morbidity (sickness) or in illness progression [1].  
Instead of concentrating on possible initial causes of chronic illnesses, we have been interested in the progression of fatigue illnesses and autoimmune diseases and in the potential role that chronic infections may play in patient morbidity.  The complex signs and symptoms that evolve in many FMS, CFS and RA and other chronic illness patients may be due, in part, to systemic chronic infections (bacteria, viruses, fungi), and this is why many of these patients can respond to antibiotics [2].  Such infections can follow acute or chronic chemical, environmental or other insults (trauma, chemical exposures, acute viral illness, etc.) that have the potential to suppress the immune system and cause metabolic imbalances [1].  Alternatively, they could occur in patients that have genetic, hormonal or nutritional deficiencies, or they could occur as a natural result of the aging process and gradual decline of the immune and hormonal systems. 

Progression of Chronic Illnesses in Aging Patients

 Fatigue and autoimmune illnesses evolve over time, probably in a multistep process that may require multiple exposures, including infections that could be causative for the illness in some patients, cofactors for the illness (not causative but important in patient morbidity) in others, or opportunistic infections that cause morbidity and eventually become the major source of sickness.  Thus infections need not be the actual trigger or cause of illness or be present at the onset of illness to be important.  Because of their dysfunctional metabolic and immune systems, many aging patients may be particularly susceptible to secondary chronic infections that can worsen their illness.  Of course, illness progression in these patients could also be caused by other factors, psychological stress, physical trauma, other illnesses and many other factors that impair the immune system and stimulate autoimmunity [2].
Chronic infections are usually held in check by our immune systems, but they can take hold and cause problems if they can avoid immune surveillance and penetrate and hide in various tissues and organs, including synovial cells in joints and nerve cells.  When such “stealth” viral and bacterial infections occur, they can cause many of the complex signs and symptoms seen in FMS, CFS and RA, including enhanced immune dysfunction and metabolic imbalances [1, 2].  Changes in environmental responses as well as increased titers to various endogenous viruses (some are commonly found in these patients) have been seen in RA, FMS and CFS patients.  If infectious agents are involved, few can produce the complex chronic signs and symptoms found in these patients.  One that can is represented by a small, primitive class of bacteria called mycoplasmas [3]. Mycoplasmas and other bacteria (Chlamydia, Coxiella, Brucella, Borrelia, etc.), although not as well known as other agents in causing various chronic diseases, are now considered important emerging pathogens in fatigue and autoimmune illnesses, including RA.  For example, Borrelia species (Lyme Disease) infections can result in RA signs and symptoms.
As chronic illnesses, such as RA, FMS and CFS, progress there are a number of accompanying clinical problems as well as increases in multi-organ autoimmune signs and symptoms.  This may occur when cell wall-less microorganisms like mycoplasmas bleb from cells and are released while carrying host cell antigens on their membrane surface [1].  This can set up what is termed a concomitant host immune response, which are immune responses against the microorganism antigens as well as the host cell antigens carried by the microorganism.  Mycoplasmas and other microorganisms can also express antigens that mimic host cell antigens [3], and these may directly stimulate autoimmune responses.  Although it is certainly not proven, this pattern is consistent with certain chronic infections, such as mycoplasmal infections, that penetrate into nerve cells, synovial cells in joints, muscle cells and other cell types.  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 often do not have all of the clinical characteristics expected for their autoimmune disease.

Microorganisms Cause Significant Patient Morbidity

Microorganisms like Mycoplasmas are not considered 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 [1, 3].  Do such infectious agents actually cause FMS, CFS or RA?  Probably not on their own, but some bacteria and 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.  
We have found that ~70% of FMS, ~60% of CFS [4] and ~50% of RA [5] and Gulf War Illness [6] patients have mycoplasmal blood infections that can explain many of the chronic signs and symptoms found in these patients.  In the majority of RA, FMS and CFS patients we have found multiple pathogenic mycoplasmas in their white blood cells but these infections are only found in 0-9% of controls [1, 4, 5].  Interestingly, the majority of RA, CFS and FMS patients had multiple mycoplasmal infections but none were found in controls [4, 5]; however, single infections are found in some nonsymptomatic subjects (0-9%).  Other laboratories have replicated our tests and have found and published similar findings [7].

New Treatments for RA, CFS, FMS and other Chronic Illnesses

Many patients with chronic illnesses are treated as psychiatric patients.  However, when microorganism infections are identified in the blood, these patients should be treated as medical not psychiatric patients, just like any other patients with blood infections.  This does not mean that psychological or psychiatric problems are not important in chronic illnesses.  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 [1, 2, 6].  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 [2].
The recommended treatment for confirmed mycoplasmal blood infections is long-term antibiotic therapy.  Some physicians treat every other day with antibiotics.  Multiple cycles are required, because few patients recover after only a few cycles, possibly because of the intracellular locations of the infections, the slow-growing nature of these microorganisms and their inherent insensitivity to antibiotics [8, 9].  We now recommend that patients who have been diagnosed with blood infections receive 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 [8, 9].
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 should  not work [2].  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.  Other considerations include the removal of refined sugars, alcohol, certain fats and allergy-prone foods from your diet and the appropriate support for your endocrine and immune systems [8, 9].
What results have been obtained with antibiotics for chronic illnesses like RA, CFS and 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 indicates that a majority (~80%) of FMS/CFS patients from 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 [3].  In RA patients blinded clinical trials have shown the effectiveness of antibiotic therapy with minocycline [10, 11]. 
In addition to antibiotics, patients must take vitamins, minerals, immune enhancement and other supplements to help boost immunity.  For example, these patients are often depleted in vitamins B complex, C and E, among others, and certain minerals [8, 9].  Amino acids, fish oils, probiotic bacteria (Lactobacillus acidophillus) and a number of natural remedies have proven useful during therapy [8, 9]. 
In some patients oxygen therapy has proved very useful.  Oxygen suppresses the borderline anaerobic chronic infections like Mycoplasmas and Chlamydias [9].  We are beginning to employ hyperbaric oxygen therapy (HBOT) in clinical trials to treat borderline anaerobic chronic infections and as an anti-aging therapy that delivers oxygen to cells. Clinical trials using HBOT for Multiple Sclerosis, Cerebral Edema, migraine headaches, wounds, CFS, FMS, RA, and other illness are being undertaken.  During the aging process many patients have reduced capacity to deliver oxygen to critical tissues, such as the Central Nervous System.  HBOT is being investigated as an excellent anti-aging modality to treat various conditions related to the aging process.

For Further Information

The Institute for Molecular Medicine (website: www.immed.org, also the source of the references below) can test patients for evidence of Mycoplasma, Chamydia, Borrelia and other infections, including viruses (HHV-6A, CMV, EBV, etc.), of the types that worsen human diseases like RA, FMS, CFS and Gulf War Illness.  Blood samples can be sent to the Institute for Molecular Medicine’s new full-service, certified reference laboratory, International Molecular Diagnostics, Inc. for testing (Tel: 714-799-7177; website: www.imd-lab.com).  Molecular Hyperbaric Medicine (Tel: 714-846-6360; website: www.o2med.com) can be contacted for information on HBOT.
 
Contact:
Prof. Garth L. Nicolson
The Institute for Molecular Medicine
Huntington Beach, CA 92647
Tel: 949-715-5978 Fax: 714-596-3792
Website: www.immed.org
email: gnicolson@immed.org

References

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. Medical Sentinel 1999; 4: 172-176. 

2. Nicolson, G.L. The role of microorganism infections in chronic illnesses: support for antibiotic regimens. CFIDS Chronicle  1999; 12(3): 19-21.

3. Baseman, J.B. and Tully, J.G. Mycoplasmas: Sophisticated, reemerging, and burdened by their notoriety.  Emerging Infectious Diseases  1997; 3: 21-32.

4. Nasralla, M., Haier, J. and Nicolson, G.L.  Multiple mycoplasmal infections detected in blood of Chronic Fatigue and Fibromyalgia Syndrome patients. European  Journal of  Clinical Microbiology & Infectious Disease  1999; 18: 859-865.

5. Haier, J., Nasralla, M., Franco, A.R., Nicolson, G.L.  Detection of mycoplasmal infections in blood of patients with Rheumatoid Arthritis. Rheumatology 1999; 38: 504-509.

6. Nicolson, G.L., Nasralla, M., Haier, J., Nicolson, G.L. Diagnosis and treatment of chronic mycoplasmal infections in Fibromyalgia Syndrome and Chronic Fatigue Syndrome: Relationship to Gulf War Illness. Biomedical Therapy 1998; 16: 266-271

7. Vojdani, A. and Franco, A.R.  Multiplex PCR for the detection of Mycoplasma fermentans, M. hominis and M. penetrans in patients with Chronic Fatigue Syndrome, Fibromyalgia, Rheumatoid Arthritis and Gulf War Illness.  Journal of Chronic Fatigue Syndrome  1999; 5: 187-197.

8. Nicolson, G.L. Considerations when undergoing treatment for chronic infections found in Chronic Fatigue Syndrome, Fibromyalgia Syndrome, Rheumatoid Arthritis and Gulf War Illnesses. (Part 1). Antibiotics Recommended when indicated for treatment of Gulf War Illness/CFIDS/FMS/RA (Part 2). International  Journal of Medicine  1998; 1: 115-117, 123-128.

9. Nicolson G.L., Nasralla, M., Franco, A.R., Erwin, R., Nicolson, N.L., Ngwenya, R., Berns, P. Diagnosis and Integrative Treatment of Intracellular Bacterial Infections in Chronic Fatigue and Fibromyalgia Syndromes, Gulf War Illness, Rheumatoid Arthritis and other Chronic Illnesses. Clinical Practice of Alternative Medicine 2000; 1(2): 92-101.

10. Tilley, B.C., Alarcon, G.S., Heyse, S.P. et al. Minocycline in rheumatoid arthritis.  A 48-week, double-blind, placebo-controlled  trial.  Annuals of Internal Medicine  1995: 122: 81-89.

11. O’Dell, J.R., Paulsen, G. Haire, C.E. et al.  Treatment of early seropositive rheumatoid arthritis with minocycline: four-year follow-up of a double-blind, placebo-controlled trial. Arthritis and Rheumatology  1999; 42: 1691-1695.