Chronic Fatigue Syndrome - A Homotoxicological View

Chronic Fatigue Syndrome -- A Homotoxicological View

Keywords: Chronic fatigue syndrome, homotoxicology

Summary

Chronic fatigue syndrome, now recognized by the World Health Organization as a "debilitating and distressing condition," has a complex symptomatology. The syndrome has also become the subject of intense research and debate in the medical world.

However, if we consider chronic fatigue syndrome from the viewpoint of homotoxicology, we see a syndrome that can be explained by the theory of Reckeweg's principles of disease and that can be treated accordingly to invoke regressive vicariation toward the left of the "six phase table," often bringing about a complete cure.

Nomenclature

Let's first consider this syndrome as academic medicine presents it. Chronic fatigue syndrome has quite legitimately been called "the illness with a thousand names," because it has been given a new name at each new outbreak [ 22].

As early as 1750, Sir Richard Manning observed a post-infection disorder he called "febricula." It was later known as atypical polio, royal free disease (Great Britain), endemic neuromyasthenia (USA), and Tapanui flu (New Zealand).

Later the disease was called myalgic encephalomyelitis or ME (Great Britain) and chronic Epstein-Barr (USA). The media term "yuppie flu" has negative connotations and should be avoided [ 35].

At present, the disease is known as post-viral fatigue syndrome (PVFS) in Great Britain and as chronic fatigue and immune dysfunction syndrome in the United States.

At an international conference in 1994 the international designation "chronic fatigue syndrome" (CFS) was introduced. This is the term that will be used here.

Patients who clearly suffer from unexplained fatigue but fail to meet the diagnostic criteria for CFS are classified as suffering from "idiopathic or chronic" fatigue [ 17, 35].

Prevalence of the disease

Since many patients are still being incorrectly included because of inadequate diagnostic procedures, it is difficult to provide correct figures for chronic fatigue syndrome.

In Great Britain, an incidence of 1 in a population of 1000 is assumed. More recent American studies have yielded incidence figures of 37.1 in 100,000 [ 35] and 98 to 267 in 100,000 [ 8]. In the same study the incidence of chronic fatigue was set at 2414 to 6588 in 100,000. Although the disease can strike both very young and very old people, it appears most frequently among 20 to 40-year-olds and is somewhat more frequent in women. Teachers and health care personnel are affected more often than members of other professions.

Diagnosis

Criteria

For many years researchers have been looking for a laboratory standard for distinguishing chronic fatigue syndrome from other diseases. However, such a standard is difficult to find, so in 1988 the Center for DiseAse Control and Prevention in Atlanta asked Holmes [ 21] to develop criteria for identifying patients for research purposes. Recently, these criteria were reviewed by Fukuda et al, who suggested the comprehensive system for diagnosing CFS that is presented in Tables 1 and 2 [ 17].

In addition to these criteria, there are other symptoms observed in practice that support a diagnosis of chronic fatigue syndrome:

- autonomic imbalances such as hypotension, frequent need to urinate, and palpitations

- frequent appearance of IBS symptoms

- hypersensitivity to toxins such as alcohol, allopathic drugs, and environmental toxins

- prior history of allergies and frequent infections before the actual onset of the illness (of course this is a concomitant of frequent use of antibiotics, antihistamines, and cortisone)

- symptoms related to connective tissue abnormalities, such as joint pain and edema; low ANA titer

- symptoms related to the hypothalamus/hypophysis axis, such as menstrual disorders and poor thermoregulation.

Laboratory tests

Complete blood chemistry profile tests should always be performed and the following values should be checked: ESR, SGPT, alkaline leukocyte phosphatase, all proteins, albumin, calcium, phosphate, glucose, urea, electrolytes, creatinine, and TSH. A urinalysis should also be performed.

Additional tests are advisable if they seem medically necessary or if the patient's prior history is suspicious. At present, immune system analyses are being performed only on an experimental basis -- for instance, in viral studies (see below).

Differential diagnosis of chronic fatigue syndrome involves a wide range of symptoms but can be dispensed with if all criteria are met and a thorough homotoxicological anamnesis has been conducted. Infectious, rheumatic, metabolic, endocrine, and neoplastic causes must be ruled out first.

Pathogenesis

On the basis of immunological, metabolic, viral, and environmental studies, most allopathic physicians agree that the cause of chronic fatigue syndrome is multifactorial.

Evidence of immune dysfunction

Numerous subtle anomalies have been detected in patients with chronic fatigue syndrome. However, since the study in question did not document the severity and duration of the illness, it is difficult to draw definitive conclusions [ 10].

The most frequently detected anomaly was weakened natural killer cell functioning. An increasing number of studies suggest a state of immune system activation that seems to be a reaction to a viral infection. It is not clear whether an initial or a reactivated virus is involved. The most frequently detected anomalies are a decrease in CD8 cells with the marker CD11b, i.e. T-suppressor cells. An increase in the activation markers CD38 and HLA-DR suggests that a series of cytotoxic cells has been activated. This pattern seems typical of CFS patients but is not detected either in healthy members of their families or in depressive patients. A similar pattern of cell activation is detected in acute viral infections but returns to normal within two weeks after the infection is over. In acute viral infections CD11b populations and the activity of the natural killer cells increase, but in chronic fatigue syndrome they decrease [ 3, 26].

A different study detected a pattern of immune activation in which 80% of patients with chronic fatigue syndrome had elevated levels of transforming growth factor, in comparison to 9.4% of unaffected control subjects [ 25].

The elevated cytokine levels (II-1, II-6, and TNF) reported in different groups of patients have been postulated as the mechanism responsible for CFS symptoms [ 28, 30]. When they cross the blood/brain barrier, certain cytokines function as neurotransmitters and can cause mood swings and influence perceptive ability. Some of them (II-1 and II-6) influence the hypothalamus-hypophysis axis [ 32].

Some patients develop low-grade autoimmunity, and there is an overlap between CFS and certain well-known autoimmune diseases such as Sjögren's syndrome [ 11]. The significance of these phenomena is unknown, although two possible mechanisms have been presented. The population of T-suppressor cells plays an important role in the immune system's self-tolerance [ 39]. In addition, because of toxin damage to cell membranes, the immune system may be subjected to large amounts of endogenous proteins before they can be eliminated by phagocytes. Tolerance breaks down as a result.

Viral studies

The role of various viruses in chronic fatigue syndrome is the subject of intensive research. Herpes viruses, enteroviruses, and retroviruses have all been investigated [ 14, 15, 23, 26, 29].

Although titers of both Epstein-Barr virus and herpes simplex virus 6 are elevated, it is often assumed that this results from viral reactivation due to a compromised immune system.

The role of Coxsackie-B virus is emphasized in Great Britain [ 18]. Patients have been found to have antibodies against it, and its RNA has been found in the muscles of certain patients. However, these virus particles have also been detected in the muscles of patients with other neuromuscular diseases, which leads to the conclusion that enteroviruses do not contribute to muscular pathologies as such. Rather, the theory is that the Coxsackie virus implants in damaged muscles. This cannot be excluded as a possible trigger event for chronic fatigue syndrome [ 19].

Retroviruses have been investigated; however, as has generally been assumed, they seem to play no role in the pathogenesis of CFS [ 15, 20, 26].

Some researchers have postulated the theory of a "hit and run" viral infection that triggers a process that is then eliminated but leaves the immune system in a state of activation. This is supported by the detection of an up-regulation of the 2-5-A synthetase RNAse antiviral pathway in patients with chronic fatigue syndrome.

Neuroendocrine and neurotransmitter studies

In recent years, the new discipline of neuroendocrine immunology has become a favorite area of research. In chronic fatigue syndrome, the connection between the various systems is apparent.

Studies of the hypothalamus/hypophysis axis point to an up-regulation of serotonergic pathways in CFS. In addition, plasma levels of mono-amine metabolites are reduced, indicating a possible deficiency.

Abnormal suppression of arginine and vasopression secretion and abnormal water metabolism have been observed [ 2]. Various studies in Great Britain and Italy have shown abnormal basal cortisol secretion and low growth hormone levels in CFS patients. This may also be due to a decreased response to CRH (corticotropin releasing hormone) and may contribute to immune system activation as well as to the obesity and hypoglycemia observed in a large group of patients suffering from this syndrome [ 16, 31].

Metabolic anomalies

Several anomalies in mitochondrial function have been demonstrated, in particular a deficiency of acylcarnitine, a substance that plays a role in energy production and in the modulation of coenzyme A [ 24]. The mitochondria themselves are pleomorphic with prolific cristae [ 7]. Deficiencies in oxidative metabolism have been detected in CFS patients with reduced cell concentrations of ATP [ 4].

Studies of environmental factors

More direct connections have been determined between chronic fatigue syndrome and exposure to toxins such as organophosphates [ 36] or those involved in so-called "sick building syndrome." Many other toxins that provoke symptoms similar to those of chronic fatigue syndrome have been documented [ 6].

The consequences of overburdening the liver's detoxification system have been described in detail by Dr. Sherry Rogers in her book Tired or Toxic [ 34]. The metabolic pathway of aldehyde is an example that can illustrate this. All alcohols, including formaldehyde and the hydrocarbons, are detoxified via this pathway. The process is made easier by a series of enzymes that work at specific speeds and are dependent on specific co-factors (e.g. zinc, molybdenum, and selenium) for their functioning. Some of the transitional substances, such as acetaldehyde, are highly toxic. When the system is overburdened, homotoxins can be shifted onto different pathways where they produce toxic by-products. Alcohol, for example, can be converted into chloral hydrate, which has a sedative effect; it is used to sedate children and causes fatigue in adults. If the system is overburdened and the co-factors for the detoxifying enzymes are not present, surplus toxins are funneled into the blood, where they cross the blood/brain barrier, causing symptoms like fatigue, depression, and cognitive dysfunction. Some of these substances can form highly reactive free radicals that damage cell membranes, proteins, etc. This process is intensified if there is a deficiency of antioxidants such as beta-carotene, vitamin C, vitamin E, and glutathione or selenium. (See Figure 1.)

This can be intensified still further in CFS patients because of abnormal intestinal permeability, a condition in which the tight connections between cells of the gastrointestinal mucosa loosen, permitting absorption of macromolecular toxins (such as proteins and sugars) that would otherwise have remained in the lumen. These toxins reach the liver by way of the portal veins and constitute an additional burden on the detoxification system [ 33].

Structural and functional anomalies of the brain

In 78% of the patients examined, NMR tomography of the brain detected areas of high signal intensity in the subcortical regions and a corresponding demyelinization or edema [ 10].

Most recently, brain perfusion tests using 99 mTc HMPAO tomography or SPECT (single photon emission computer tomography) have aroused much attention, because they indicated hypoperfusion in some areas of the brain, especially the hypothalamus and brain stem. This pattern is induced through bodily movement and is distinct from the one observed in depressive patients [ 13].

A homotoxicological view of chronic fatigue syndrome

According to Reckeweg, illness is the body's attempt to free itself of toxins. It is an expression of the body's defense mechanisms that are attempting to eliminate or compensate for the damage caused by exogenous and endogenous homotoxins. In order to achieve this, the unspecific defense system consisting of the reticuloendothelial system and its components (liver, hypothalamus/hypophysis axis, nerve reflexes, and connective tissue) is activated. If the body is unsuccessful, the toxins are driven deeper into the body or, according to the six-phase table, toward the right, eventually crossing the biological division and entering the cellular phases.

In recent years, allopathic medicine has acknowledged the interactions of all these systems by establishing the discipline of neuroendocrine immunology [ 32].

As we can see from the results of the most recent research, we are dealing with a syndrome in which the body attempts unsuccessfully to free itself of toxins, regardless of whether these are viral or environmental in origin. We detect a disturbed and activated immune system that is producing neurohumoral substances and causing inflammation. We also detect an overburdened liver that cannot cope with the amount of toxins it is supposed to eliminate and therefore funnels them into the blood and ultimately into connective and fatty tissues (deposition phase) and into the brain, where inflammation may occur.

Patients with chronic fatigue syndrome offer clear evidence of autonomic dysfunction-low blood pressure, palpitations, etc. In our practices we often find that these patients develop neurodermatitis in an additional attempt by the autonomic nervous system to free the body of toxins (reaction phase).

Joint and muscle pain points to the fact that connective tissues have become the battlefield where the war between the toxins and the immune system is waged. This clearly indicates a disturbance of the hypothalamus/hypophysis axis. We detect an interruption in oxidative metabolism; this system shifts to the right side of the biological division in the impregnation phase.

Newer studies conclude that there has been an increased incidence of brain tumors in patients who contracted chronic fatigue syndrome in the Lake Tahoe area. If this is indeed the case, what we are seeing is the ultimate shift on the six-phase table, the shift to the neoplasm phase.

Possible etiology

Holistic model

As in any other illness, three factors are needed for someone to contract chronic fatigue syndrome: genetic predisposition, an environment that supports or aggravates this predisposition, and a triggering agent.

Genetic predisposition

More recent studies indicate that certain HLA alleles may constitute risk factors for the development of chronic fatigue syndrome. It is known that the performance of detoxifying enzymes in the liver (fast or slow acetylation), and probably that of our immune system as well, is inherited.

Family studies of CFS patients point to an above-average incidence of autoimmune diseases, allergies, and cancer.

Environment

Undeniably, our modern environment constitutes an ever greater threat to the human body. We are exposed to toxic substances in our food, our houses, and the air we breathe. With regard to nutrients, the quality of the food and groundwater we consume is extremely poor. Our bodies are overburdened, and when our detoxifying and energy-producing enzymes lack vital cofactors such as vitamins and minerals, disaster is inevitable.

Let's take the example of a CFS patient who already suffered from allergies as a child. These allergies were probably suppressed with antihistamines and cortisone, and the patient then developed chronic sinusitis and asthma, which were treated with frequent doses of antibiotics and more cortisone. The next step is intestinal dysbiosis with yeast overgrowth. Then food allergies become a problem because the good bacteria no longer present a barrier to toxins. The liver is overburdened and funnels toxins such as acetaldehyde or its still more lethal by-products into the bloodstream, where they destroy protein structures and cell membranes. The patient's delicate immune system is damaged.

Triggering agents

Anything from a flu-like illness to a stressful situation to chemical exposure (such as dusting the dog with flea powder or moving into a "sick" building) can be the final trigger, which is more of a straw that breaks the camel's back than an actual triggering event. We now have a patient who cannot work, sleep, or play. Most patients with chronic fatigue syndrome report that they had not been feeling well for years before the incident that finally made them really sick.

Care of patients with chronic fatigue syndrome

Patients with chronic fatigue syndrome are a heterogenous group; each one may be in a different stage of the illness and may have been ill for a different length of time. While allopathic medicine has no means of classifying these patients at present, homotoxicology -- with the help of the six-phase table -- can work out a comprehensive treatment program for each individual patient.

Medical history

A thorough homotoxicological anamnesis should be conducted. We must keep in mind that this problem is the sum of many environmental attacks over a period of many years, including incidents that may constitute the starting point and which will delay healing or allow the problem to persist until they have been dealt with.

Diagnosis

Apart from arriving at a diagnosis on the basis of symptoms and thorough laboratory testing as has already been described, the homotoxicologist should attempt to determine the patient's position on the six-phase table.

This can involve procedures such as NMR tomography of the brain to determine whether demyelinization is present, to exclude multiple sclerosis (which has similar symptoms), or to look for neoplasms.

In this syndrome, other biological methods such as electroacupuncture are of inestimable value in. documenting organic involvement or heavy metal toxicity or in explaining trigger agents and foci.

Treatment

Chronic fatigue syndrome is to be treated holistically. It is a syndrome with a plethora of symptoms, and if we treat each symptom with its own "anti" medication, we will make the sick person even sicker!

There are various allopathic approaches to treatment that are primarily symptom-oriented and will not be discussed here. Interested readers can find descriptions of them in Charles Shepherd's Guidelines for the Care of Patients [ 35].

General

For the reasons mentioned above, it is clear that we are dealing with patients whose greater defense system is exhausted and whose immune system is overactive and waging its own war within the brain and connective tissues. We see a body that does not respond and may be heading toward neoplastic proliferation. The main principles of homotoxicology apply here -- namely to induce regressive vicariation by triggering a reaction and to support the organs of detoxification.

The patient's environment should be as toxin-free as possible. Treatment of intestinal dysbiosis should begin with diet and restoring beneficial intestinal flora. Many methods of treatment have been described. A complete multivitamin, mineral, and antioxidant supplement should be taken to support the enzymes of detoxification and phosphorylation.

Stressful situations should be avoided, and if the patient feels very unwell he or she should be allowed to take sick leave. To have his or her situation properly explained is of great value to a patient who has been shunted from one doctor to the next and eventually ended up in the psychiatrist's office.

Specific treatment

The goals of therapy can be defined as follows:

to stimulate oxidative metabolism

to open detoxification pathways via the liver, kidneys, and connective tissue

to regulate and cleanse the disturbed immune system

to regenerate affected organs and systems

to find and treat foci and old toxins (which prevent healing) by using nosodes

to provide supportive treatment for symptoms until the above measures take effect.

The successive stages of auto-sanguis therapy offer a quick and elegant method of treatment (see Table 3). I often begin treatment with Coenzyme compositum and Ubichinon compositum on a daily basis, then continue them three times weekly, along with 500 mg of carnitine three times a day to restore oxidative metabolism. Nux vomica Homaccord is added to support the treatment of dysbiosis. The patient takes these remedies by mouth at home.

Other measures

Own-blood therapy

Oral own-blood therapy is useful in stimulating the immune system in the intestinal walls. Additionally, it supplies a patient-specific nosode. Treatment should begin with a higher dilution since we are dealing with an overactive immune system.

Acupuncture

This method is invaluable in restoring the flow of energy and in controlling pain.

Ozone and oxygen therapy

Such therapy is also helpful in modulating the immune system and supporting cellular respiration; however, we must first make sure that the patient is not suffering from antioxidant deficiencies.

Supportive psychotherapy

This is valuable for helping patients learn to pace themselves and in supporting family relationships strained by chronic illness. The concept of "illness burden" has recently been acknowledged, and patients seem to respond to behavior modification [ 1].

Bach flower remedies

An important complement to therapy.

Conclusions

Chronic fatigue syndrome is a many-sided illness of high morbidity. It causes the loss of many hours of productive work and lasting disruptions in family dynamics.

However, if we look at CFS in a homotoxicological context, it is revealed as a syndrome that can be explained on the basis of Reckeweg's theory of disease and that can be treated to bring about regressive vicariation toward the left side of the six-phase table, often ringing about a complete cure.

References
(1) Antoni MH et al. Psychosocial Correlates of Illness Burden in Chronic Fatigue Syndrome. Clin Infect Dis 1994; 18 (supp 1): 73-8.

(2) Bakheit AMO et al. Abnormal argininevasopressin secretion and water metabolism in patients with post-viral fatigue syndrome. Acta Neurol Scand 1990; 82: 209-16.

(3) Baker E et al. Immunologic abnormalities associated with chronic fatigue syndrome. Clin Infect Dis 1994; 18 (supp 1): 136-41.

(4) Barnes PRJ et al. Skeletal muscle bioenergetics in chronic fatigue syndrome. Neurosurgery and Psychiatry 1993; 56: 679-83.

(5) Bates DW et al. A comparison of case definitions of chronic fatigue syndrome. Clin Infect Dis 1994; 18 (supp 1): 11-4.

(6) Behan PO, Hannifah BAG. Chronic fatigue syndrome: a possible delayed hazard of pesticide exposure. Clin Infect Dis 1994; 18 (supp 1): 54.

(7) Behan WMH et al. Mitochondrial findings in the chronic fatigue syndrome. Paper delivered at the International Meeting on Chronic Fatigue Syndrome. Dublin (Ireland), May 1994.

(8) Buchwald D. Prevalence of Chronic Fatigue and Chronic Fatigue Syndrome in the Community. Paper delivered at the International Meeting on CFS. Dublin (Ireland), May 1994.

(9) Buchwald D. Laboratory abnormalities associated with chronic fatigue syndrome. In: Jenkins R (ed). Post-Vital Fatigue Syndrome. Sussex: Wiley 1992; 117-36.

(10) Buchwald D et al. A chronic illness characterized by fatigue, neurologic and immune disorders and active HHV 6 infection. Ann Intern Med 1992; 116: 103-13.

(11) Calabrese LH et al. Chronic fatigue and a disorder resembling Sjögren's syndrome: preliminary report. Clin Infect Dis 1994; 18 (supp 1): 28-31.

(12) Chester CC, Levine PH. Concurrent Sick Building Syndrome and CFS. Epidemic Neurasthenia revisisted. Clin Infect Dis 1994; 18 (supp 1): 43-9.

(13) Costa DC et al. Brain Stem and SPECT studies in normals, ME/CFS and depression. Nucl Med Commun 1992; 304: 1567.

(14) De Freitas E. Possible CFIDS-associated retrovirus. In: Review of Mainstream CFIDS Research in the USA. Rochester (NY): Dayger 1990-1992.

(15) Dharam V, Ablashi et al. Viruses and Chronic Fatigue Syndrome: Current status. J Chronic Fatigue Syndrome 1995; 1(2): 3-22.

(16) Dinan TG, Majeed T, Behan E Chronic fatigue syndrome: a perspective. Paper delivered at the International Meeting on Chronic Fatigue Syndrome. Dublin (Ireland), May 1994.

(17) Fukuda K et al. The Chronic Fatigue Syndrome: A comprehensive approach to its definition and study. Ann Int Med 1994; 121(12): 953-9.

(18) Gow JW et al. Studies on enterovirus in patients with CFS. Clin Infect Dis 1994; 18 (supp 1): 126-33.

(19) Gow JW. Enteroviral replication and CFIDS. Paper delivered at the International Meeting on Chronic Fatigue Syndrome. Dublin (Ireland), May 1994.

(20) Heneine W et al. Lack of evidence for infection with known retroviruses in patients with CFS. Clin Infect Dis 1994; 18 (supp 1): 121-5.

(21) Holmes GP et al. Chronic fatigue syndrome -- a working case definition. Ann Intern Med 1988; 108:387-9

(22) Jenkins R. History, Epidemiology and Aetiology. In: Jenkins R (ed). Post-viral Fatigue Syndrome. Sussex: Wiley 1992.

(23) Komaroff AL. The possible role of HHV 6 in CFIDS. In: Review of the Mainstream CFIDS Research in the USA 1990-1992. Rochester (NY): Dayger 1992.

(24) Kuratsane H et al. Acylcarnitine deficiency in chronic fatigue syndrome. Clin Infect Dis 1994; 18 (supp 1): 62-7.

(25) Liebermann J, Bell DS. Serum angiotensin converting enzyme as a marker for CFIDS. A comparison to serum angiotensin converting enzyme in sarcoidosis. Am J Med 1993; 95: 407-12.

(26) Levy JA. Viral studies of chronic fatigue syndrome -- introduction. Clin Infect Dis 1994; 18 (supp 1): 117-20.

(27) Lloyd A. First published epidemiological study on CFIDS. In: Review of Themainstream CFIDS Research in the USA 1990-1992. Rochester (NY): Dayger 1992.

(28) Lloyd A et al. Cytokine production and fatigue in patients with CFS and healthy control subjects in response to exercise. Clin Infect Dis 1994; 18 (supp 1): 142-6.

(29) Martin WJ. Spumavirus in CFIDS and other neurological disease. In: Review of the Mainstream FID Research in the USA 1990-1992. Rochester (NY): Dayger 1992.

(30) Patarca R et al. Dysregulated expression of tumor necrosis factor in CFS: interrelations with cellular sources and patterns of soluble mediator expression. Clin Infect Dis 1994; 18 (supp 1): 147-53.

(31) Pizigallo E et al. Neuroendocrine studies of the HPA-axis in patients with CFS: preliminary results. Paper delivered at the International Meeting for Chronic Fatigue Syndrome. Dublin (Ireland), May 1994.

(32) Reichlin SI. Neuroendocrine-immune interactions. N Engl J Med 1993; 21: 1246-52.

(33) Ridgen D. Entero-heparic resuscitation program for CFIDS. CFIDS Chronicle 1995; 46-8.

(34) Rogers SA. Tired or Toxic. Syracuse (NY): Prestige 1990.

(35) Shepherd CB. Myalgic Encephalomyelitis: Post-viral Fatigue Syndrome. Guidelines for the care of patients. London: Thornton and Pearson 1994.

(36) Shepherd CB. Organophosphate pesticides -- a cause for concern. Practitioner 1993; 273: 212-4.

(37) Steinbach T et al. Subjective reduction in symptoms of CFS following long-term treatment with a porcine liver extract. A phase I trial. Clin Infect Dis 1994; 18 (supp 1): 114-5.

(38) Suhaldonik RJ et al. Upregulation of the 2-5A synthetase RNAse antiviral pathway associated with CFS. Clin Infect Dis 1994; 18 (supp 1): 96-104.

(39) Yoshida S, Getswin ME. Autoimmunity and selected environmental factors of disease induction. Semin Arthritis Rheum 1993; 22 (6): 399-419.

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