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The Blame-X syndrome
Journal of Clinical Epidemiology 54 (2001) 433–439
COMMENTARY
The Blame-X syndrome: Problems and lessons in nosology, spectrum, and etiology Alvan R. Feinstein* Sterling Professor of Medicine and Epidemiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA Received 5 September 2000; received in revised form 20 November 2000; accepted 24 November 2000
Abstract Symptoms of a functional somatic syndrome have been noted in individual persons and groups for more than a century. Often associated with war, the syndrome has received diverse names and many proposed but unproved etiologies, including exposure to trauma, stress, chronic infection, psychosomatic, chemical, or environmental causes. In recent years, when attributed to agent X, the syndrome could be called the Blame-X syndrome. The clinical, legal, and other problems associated with the syndrome are a reflection of nosologic difficulties in identifying and choosing titles for apparently “new” ailments. The difficulties arise from the complex overlap of symptoms, diseases, and laboratory abnormalities found with modern technology, and from the frequent abandonment of pathophysiologic demands for appropriate correlation of symptoms and objective abnormalities. An important principle in naming apparently new ailments is to avoid etiologic titles until the etiologic agent has been suitably demonstrated. A premature causal name can impair a patient’s recovery from the syndrome, and impede research that might find the true cause. © 2001 Elsevier Science Inc. All rights reserved. Keywords: Syndrome; Nosology; Spectrum; Functional Somatic Syndrome; Blame-X
1. Introduction They have been happening for more than a century: outbreaks of symptoms of a functional somatic syndrome occurring in groups of persons exposed to an apparently noxious stimulus. The symptoms, which can vary from one person to another, occur as diverse clusters of the wide array of individual manifestations listed in Table 1, but seldom have a single common pattern. In the absence of concomitant objective abnormalities, the clusters of symptoms have received various names, but they were recently grouped [1,2] under a useful title: Functional Somatic Syndrome (FSS). (The name “syndrome” literally means “running together,” and refers to the group of symptoms or other manifestations associated with a particular condition or disease. In modern medicine, “syndrome” is often used when a characteristic objective abnormality has not been found to identify the condition as a “disease.”) The FSS title is valuable because it is a purely descriptive label, with no etiologic connotations, for symptoms of unknown cause that are not consistently accompanied by objectively demonstrable abnormalities, or by a distinctive pathophysiologic mechanism. The provocative stimuli for FSS have varied extensively, ranging from physical or emotional * Corresponding author. Tel: 203-785-4145; fax: 203 785-5177. E-mail address: [email protected] (A.R. Feinstein)
stress, to chronic infections, to alleged toxins that have been inhaled, ingested, or injected. What the outbreaks or individual episodes have in common is the difficulty of discerning satisfactory mechanisms to explain the symptoms, the controversies about organic causes and components [3,4], the different names chosen for the syndrome, and a new modern fashion in nomenclature. In today’s world, if Stimulus X is suspected or blamed as the cause, it is frequently cited in the title of the outbreak. Stimulus X may then receive wide publicity in the media, legislation intended to provide care and compensation for the victims, and litigation aimed at punishing the producers. Because the offending Stimulus X has often been cited in the name of the ailment, the recent outbreaks might be called the Blame-X syndrome. Before reaching its current nosologic format, however, the syndrome had appeared and re-appeared under many titles, reflecting different modes of discovery and beliefs about etiology. 2. Evolution of the syndrome 2.1. War syndromes The war syndrome [5] seems to have been first noted in the 1850s, when anatomic pathology had been developed well enough to allow “organic” and “non-organic” ailments to be differentiated. During the Crimean battles of 1854–
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Table 1 Symptoms reported in functional somatic syndrome General: Fatigue, exhaustion, apathy, lethargy; Insomnia, other sleep disturbances; Irritability; Excessive sweating Cerebral: Headache; Lightheadedness, fainting; Forgetfulness, impaired memory, difficulty concentrating, confusion Joints and Muscles: Chronic pain in joints, muscles, neck, low back Face and Pharynx: Sore throat, dry mouth, globus, atypical pain Chest: Palpitations, shortness of breath, sharp or burning pain Gut: Nausea, diarrhea, abdominal pain or distress Neurologic: Paresthesias Gynecologic: Chronic pelvic pain, premenstrual syndrome, menorrhalgia Psychic: Anxiety, depression
1856, again in the suppression of an Indian mutiny in 1858, and again during the Boer war in the early 1900s, the syndrome appeared in individual British soldiers and was sometimes regarded as an after-effect of sunstroke [5]. During the U.S. Civil War in the 1860s, however, when DaCosta found the first “outbreak” of the syndrome in 300 referred soldiers, he called it irritable heart, and noted that the syndrome could also appear in civilians [6]. In World War I, the syndrome became a major problem in both British and American soldiers, many of whom were ill enough to be evacuated to England from the continental battleground. Among the nosologic titles used at that time were DaCosta syndrome, soldier’s heart, effort syndrome, shell shock, combat stress, and neurocirculatory asthenia [6]. The latter diagnosis was adapted from the neurasthenia first identified in 1869 by Beard [7]. Adding to the idea of a “War syndrome,” the ailment reappeared—under such names as acute combat stress reaction, battle fatigue, and combat exhaustion—in combat personnel during World War II and later in the Korean War. These names, as well as post-Vietnam syndrome, were also used for occurrences in the Vietnam war, but psychiatrists created an additional title, post-traumatic stress disorder (PTSD), which referred to long-term consequences of the stress [8,9]. PTSD was also retrospectively recognized as having occurred in veterans of both World War II and Korea, as well as in civilians exposed to extreme trauma unrelated to war [6]. The most recent title, Gulf War Syndrome, was used when similar manifestations, including PTSD, appeared in veterans who had returned from the Persian Gulf War of 1991. Analogous health problems were also noted, however, among non-military family members of the affected veterans [10,11].
sis, chronic candidiasis, chronic mononucleosis, or posthepatitis syndrome. In recent years, the condition was called myalgic encephalitis, post-viral infection syndrome, “yuppie flu,” or chronic Lyme disease [12]. The explanatory causal belief was that an infection had been inadequately eradicated or that it had been followed by as-yet-undiscovered inflammatory mechanisms, analogous to the rheumatic fever or glomerulonephritis that could follow a group A streptococcal infection. As the existence of psychosomatic diseases became a popular concept, various psychic mechanisms were invoked and sometimes used as titles. The famous British physician, John Ryle, called the syndrome visceral neuroses [13]; and psychosomatic causes were also invoked for a subset of gastrointestinal symptoms that were variously titled irritable bowel syndrome, functional bowel distress, and non-ulcer dyspepsia. The psychosomatic concepts began to go out of style, however, when alternative causes were invoked or demonstrated, using newer immunologic ideas and infections. Thus, many of the intestinal symptoms became attributed to food allergy or food hypersensitivity [14]; and long-cherished beliefs about a psychosomatic origin for peptic ulcer were demolished with the etiologic discovery of the helicobacter pylori bacillus.
2.2. Post-infectious and psychosomatic syndromes
2.4. Non-disease diseases
In a century that had seem major advances both in the discovery of infectious agents and in revelations about dynamics of the human psyche, it was inevitable that one or both of these causes would be invoked as pathophysiologic mechanisms when the syndrome appeared endemically in the absence of exposure to military stress. Persons with overt evidence of previous (but no longer present) infection were believed to have chronic brucello-
Beginning in the late 1980s, two entities that were long regarded as manifestations of “non-disease” became frequent enough in clinical practice to receive official titles as “diseases”: chronic fatigue syndrome [15] and fibromyalgia [16]. The attempts at pathophysiologic explanation initially consisted of “rounding up the usual suspects” (chronic infection, neurasthenia, physical, social, and emotional stress). New suspects were added, however, on the basis of
2.2. Pathophysiologic “causes” The functional somatic syndrome has also occurred endemically in patients who received (or self-selected) such pathophysiologic designations as hypoglycemia, vascular instability, and hyperventilation syndrome. Common forms of chest pain that could not be attributed to coronary ischemia were called atypical angina or non-cardiac chest pain. This pain was sometimes later, after the advent of echocardiography, attributed to mitral valve prolapse.
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occasional abnormalities found with newer laboratory tests for endocrine imbalances, immunologic dysfunction, enteroviral DNA, and neurotransmitting agents. No consistent mechanism has yet been demonstrated or accepted, however, for either chronic fatigue syndrome or fibromyalgia; and the main clinical challenges have been to help patients cope with the ailment. Both diseases continue to occur endemically and to remain available for inclusion as part of a Blame-X “epidemic” when new provocative stimuli are discovered or accused.
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use of vaccines against plague and anthrax; but more recent studies have suggested a possible role for anti-nerve-gas chemical prophylaxis [23]. Another injected substance, the silicone used in breast implants, has become the latest and most litigiously prominent source of the syndrome. When epidemiologic studies exonerated silicone as a cause of connective tissue diseases, such as scleroderma and rheumatoid arthritis, the unexplained associated functional somatic symptoms were regarded as an atypical connective tissue disease for which a proposed title was Siliconosis Syndrome.
2.5. Chemical and environmental “causes” As major societal concerns developed about environmental pollution by chemical products, worries about the direct effects on humans were inevitable. In some of the persons who had been transiently but accidentally exposed to an overdose of carbon monoxide, the functional somatic syndrome appeared and was called chronic carbon monoxide poisoning. The existence or perception of acute gaseous odors led to occasional epidemics of hysteria [17], and also to a decadelong controversy about adverse health effects in a Canadian community chronically exposed to “sour gas” emanations from a nearby mine. In addition to symptoms of FSS, the suspected adverse effects in that community included increased rates of cancer and of birth defects. The controversy eventually subsided after a heroic epidemiologic study [18] showed that the rates of disease were similar in the exposed community and in two well-chosen control communities, which also had similar rates of objective abnormalities. Analogous complaints (increased rates of cancer and birth defects, and manifestations of FSS) also arose in veterans who were exposed to dioxin (Agent Orange) during the Vietnam war. The rates of disease were later found, however, to be no higher than in unexposed veterans. In another excellent epidemiologic study, led by members of the previously cited Canadian team, carefully chosen comparative groups in South America showed no elevation of diseases attributed to rivers polluted by trace levels of arsenic, mercury, lead and other industrial effluents [19]. After an unequivocal episode of mercury poisoning due to polluted fish in Japan, however, episodes of the functional somatic syndrome elsewhere were attributed to mercury poisoning from dental fillings. Symptoms of FSS have appeared in patients exposed in restaurants and in other public places to perfumes, deodorants, and other scents worn by individual persons. Exposures in the workplace and elsewhere have led to designation of a sick building syndrome [20], a multiple chemical sensitivity syndrome [21], a new ailment called “chemical AIDS,” and the development of a new specialty, called Clinical Ecology [22], for the “medical subculture” of patients who are “environmentally ill” and “allergic to everything.” Because a few vaccinated children have had adverse reactions, the Gulf War Syndrome was at first attributed to the
3. Problems in classification of disease When and if a convincing causal mechanism is found for the functional somatic syndrome, medical historians will probably wonder why the discovery took so long. With the majestic modern advances in molecular biology, biochemistry, and infectious microbiology, why did 20th century medical scientists have so much difficulty in finding the cause? The delayed discovery of causes, of course, is a common event in medical history, as is the custom of forming wrong etiologic beliefs until the correct cause is eventually established. Similar questions about reasons for delay will doubtlessly be asked in the future when etiologic riddles have been solved for such clearly organic diseases as today’s cancers and degenerative ailments. What is more unusual about the Functional Somatic Syndrome, however, is its nosologic meandering. Cancer has been called cancer, and atherosclerosis, atherosclerosis for more than a century, but FSS has gone through the many cited transitions and reincarnations in a large number of different names and causes. The additional designation proposed here as Blame-X syndrome may seem facetious, but is pertinent when X becomes an entity to be shunned and subjected to litigation, worker’s compensation, or protective regulations. 3.1. Challenges in nosology The problems in classifying FSS are not really unusual. They accompany other prominent but often unrecognized contemporary problems in nosology, which refers to the nomenclature and classification of disease. Many clinicians today have never heard of nosology. It is not taught in medical schools; it is seldom discussed in meetings, conferences, or published literature; and probably its only modern manifestation (in the U.S.) occurs when discharge planners seek the most lucrative DRG code number to assign to a patient’s hospitalization. The modern challenges of naming and classifying diseases began early in the 19th century when the increasing use of autopsy led to the development of anatomic pathology, and when experimental and laboratory research later helped demonstrate concepts of physiology and pathophysiology. The morphologic abnormalities of the “internal medicine” revealed at autopsy became the underlying diseases
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that replaced the old clinically named dis-eases [24]. Jaundice became hepatitis; angina pectoris became coronary artery disease; dyspepsia became peptic ulcer. In the first prominent attempt to achieve a systematic and consistent nomenclature for diagnostic terms, William Farr and Marc D’Espine, cited in Pearl [25], in 1853 prepared a list of categories that eventually led to the International Classification of Diseases. Thereafter, during the enormous taxonomic challenges of revising the Classification at 10year intervals, the international committees have been satisfied simply to achieve agreement on the large list of names cited in the taxonomy. The committees have not established rules for distinguishing a syndrome from a disease, for deciding when a “new” disease has been identified, or for offering operational criteria for making diagnoses. In the absence of rules and criteria, diagnostic nomenclature has been formulated with a laissez-faire free-for-all that is often affected more by social, political, or personal customs than by scientific advances. Sometimes the old eponymic titles for diseases have been replaced by new morphologic or pathologic terms. Thus, Bright’s disease became nephritis and Addison’s disease became adrenocortical insufficiency. Certain old names such as diabetes mellitus and rheumatic fever have endured, however, despite the demonstration of underlying causes respectively in hyperglycemia and streptococcal infection. Some of the main problems in nosology today arise from (1) the diverse spectrum of inconsistent inter-relationships of symptoms, diseases, and laboratory abnormalities found with modern technology, and (2) the gradual abandonment of pathophysiologic demands for appropriate correlation of symptoms, lesions, and other abnormalities.
Fig. 1. Overlap of symptoms, objective abnormalities, and diseases to form the spectrum of manifestations of human ailments.
and other abnormalities have been depicted. The “appropriate” entities are those that are clearly explained with mechanisms of pathophysiologic correlation. Thus, the classical symptoms of angina pectoris are appropriately correlated with electrocardiographic evidence of depressed ST segments and with radiographic (or other morphologic) evidence of coronary narrowing or occlusion. When symptoms and lesions are not appropriately correlated, however, the dissociation can lead to errors in diagnosis and subsequent management. For example, angiography may show evidence of occlusive coronary disease in a patient whose substernal chest pain occurs about an hour after
3.2. Problems in spectrum Fig. 1 shows the spectrum of overlap that can occur between symptoms, diseases, and objective abnormalities. In different parts of this complex spectrum, a patient with FSS can have symptoms without demonstrable diseases or abnormalities; and no symptoms may be present in a patient who has angiographically demonstrated coronary disease, with or without electrocardiographic abnormalities. Because of the overlap among different components, clinicians today may be unfamiliar with the diverse entities occurring in different parts of the spectrum, and may either avoid pathophysiologic explanations for the apparent inconsistencies, or may freely offer whatever explanation seems convenient and tenable. A noteworthy example in nomenclature is the term “empty sella syndrome,” which was created to explain an apparent radiographic abnormality in persons who had no corresponding symptoms or neurologic disease. 3.3. Dissociated relationships Fig. 2 shows the source of an important, additional problem. Among the three main sets of Fig. 1, separate subsets of pathophysiologically “appropriate” symptoms, diseases,
Fig. 2. Subsets of Fig. 1 showing pathophysiologic correlations of symptoms and objective abnormalities that can be appropriately attributed to a particular disease. For example, substernal chest pain provoked by exertion and relieved by rest, and ST-T wave abnormalities during an exercise stress test, would be appropriately attributed to coronary artery disease, but not to peptic ulcer. Post-prandial substernal pain relieved by alkali would be appropriate for peptic ulcer (with gastroesophageal acid reflux), but not for coronary artery disease.
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eating and is promptly relieved by milk or antacid therapy. Calling the chest pain “atypical angina” and treating it with cardiac revascularization would not be expected to help the symptoms of gastro-esophageal reflux. Analogously, many patients with irritable bowel syndrome have had unhappy results after it is “treated” with surgery for gall stones that were a “silent” incidental finding during abdominal imaging. A different type of problem arises when wrong diagnoses are made by clinicians who may not realize that a disease’s full spectrum of manifestations, as shown in Fig. 3, contains a complex array of patients complaining of primary and/or secondary symptoms, as well as lanthanic patients [24], who have either no symptoms of that disease, or who do not complain of those that may be present. The lanthanic group of patients will lead to apparently atypical or unusual forms of pathogenesis. For example, the diagnosis of idiopathic splenomegaly was often erroneously given to patients, particularly in tropical countries, who had secondarily developed cirrhosis and portal hypertension after acute episodes of lanthanic anicteric hepatitis. The development of previously anicteric cirrhosis also led to false accusations of alcoholism in patients who had had a silent, unjaundiced bout of hepatitis. Patients whose rheumatic fever occurred with carditis but no arthritis or chorea were later thought to have developed “rheumatic heart disease without a history of rheumatic fever.” A similar type of pathogenesis may lead to chronic glomerulonephritis in patients who lack a history of the primary red-urine manifestation that would have signaled an acute episode. Some of the failures of screening for cancer occur when the cancer first presents with metastases, but no overt evidence of a primary lesion. The current reliance on imaging and other laboratory tests done as part of the diagnostic “workup” to demonstrate diseases has led many clinicians to ignore the old demands for pathophysiologic correlations between symptoms and lesions. Accordingly, entities such as FSS can receive many
Fig. 3. Spectrum of primary and secondary symptoms, and lanthanic patients with a particular disease. The non-lanthanic patients—who are discovered by screening, review of systems, or other routine procedures— have either no symptoms or symptoms about which they do not complain.
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explanations and conjectures about diverse possible causes, because a distinctive pathophysiologic mechanism has not been shown. Furthermore, the proponents of the idiosyncratic explanations can readily justify their claims by pointing to other proposed causes, most recently the bacterial etiology of peptic ulcer, that were initially rejected by the “establishment.” 3.4. Absence of nosologic criteria An equally cogent set of problems arises from the absence of specific rules for nosologic identifications, christenings, and revisions [26]. When should or does the name of a disease or syndrome become altered in changes such as the nosologic sequence from Moynihan’s syndrome, to peptic ulcer, to (the currently not yet used) Marshall’s disease? What are the specifications or authorizations for abandoning such older disease names as dropsy and chlorosis, for revising the glucose boundaries that demarcate diabetes mellitus, for arbitrarily declaring that asymptomatic persons with evidence of HIV infection would be counted as having AIDS, or for introducing names of new entities, such as myalgic encephalitis or sick building syndrome? Because no rules have been promulgated, all of the changes can be made in an ad hoc or ad libitum manner, often proposed in response to cultural, social, or political stimuli, and often accepted without careful attention to cultural, social, and political, as well as scientific, implications. Many of the changes occur after careful deliberation and sponsorship by authoritative committees, but despite careful efforts in nomenclature and criteria, the impact of the changes may not always be fully appreciated. For example, the occurrence rates of AIDS and of diabetes mellitus will rise when the diagnostic criteria are relaxed, but unaware clinical demographers may then be baffled by the otherwise unexplained statistical increases. Infant mortality rates will rise or fall according to whether a baby in precarious condition, who dies soon after birth, is classified as a stillbirth or as a live birth followed by death. A particularly striking example is the long-standing controversy about whether the decline in occurrence rates of tuberculosis during the 20th century was due to public health effects of better housing and nutrition, or to medical interventions, such as isolation in sanitaria and (later) antibiotic therapy. Neither set of proponents in the dispute, however, have considered the role of successive changes in authoritative diagnostic criteria [27], which would lead to fewer formally diagnosed cases as more and better laboratory evidence was increasingly demanded with each change in criteria. The idea of psychosomatic disease was an attractive explanation for functional ailments that had no correlative abnormalities, but the title led to major difficulties in clinical management. Confusing the concepts of psychogenic and psychosomatic, patients who had distressing symptoms were often led (or chose) to believe that their unequivocal
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aches, pains, or fatigue were being dismissed as imaginary or just “in the head.” The result was a loss of confidence in the diagnostic physician, a rejection of therapeutic recommendations, and maintenance of the “sick role” during searches for other forms of explanation and therapy. When specific exposures were cited as titles in the Blame-X syndrome, many patients were pleased to receive an apparent explanation, to regard themselves as victims, and to seek legal redress. The occurrence of “litigation symptoms and diseases,” however, had been noted at least 100 years ago [28]. In some of today’s Blame-X syndromes, the symptoms have persisted despite removal of the offending stimulus—such as replacement of mercury dental fillings, explantation of silicone implants, or transfer of home to a region free of pertinent environmental exposure. In a somewhat analogous syndrome, the symptoms that could follow “whiplash injury” did not regularly occur in countries without associated litigation, and often endured in the U.S. until the lawsuit was resolved [29]. 4. Lessons and recommendaitons Although the cause of FSS remains unknown, certain lessons and recommendations can emerge from this review of historical events and problems. The lessons refer to pathophysiologic correlations, nosologic designations, and clinical management. 4.1. Pathophysiologic correlations The diverse spectrum of symptoms, abnormal tests, and diseases can help physicians remember that concomitant events can occur without being necessarily related. As an era of increased screening and other testing finds many clinically “silent” abnormalities, they will be available for erroneous use as diagnostic explanations for symptoms that they do not really explain. Unless appropriate pathophysiologic explanations are demanded, however, manifestations of functional bowel distress may regularly but erroneously be attributed to gallstones, gastric ulcer, colonic polyps, or localized cervical cancer. Conversely, many ailing veterans of the Gulf War may have developed a functional somatic syndrome, but a few may have distinctly organic ailments, accompanied by appropriate abnormalities, that followed toxic exposures to burning oil or other pertinent agents. Neither the veterans with FSS nor those with organic disease are well served if the complex spectrum of illness and disease is lumped together as a single “Gulf War Syndrome.” The patient’s past history offers another important correlative distinction. With careful history-taking and a check of previous medical records and events, the manifestations of FSS in many patients were found to have occurred before exposure to the “toxic” effects of Agent X. In fact, an existing “medical subculture” may contain persons who bear their suffering quietly and unobtrusively until they begin, after publicity for Agent X, to blame everything on X and to assume the role of “victim.” In this situation, the publicity
and the patient’s adverse expectations may make Agent X act like a “nocebo” [30], which produces a bad effect, in contrast to the good effect often associated with an otherwise inert placebo. 4.2. Nosologic designations In the glare of modern media publicity, a name will be sought for any outbreak or other “new” illness that reaches public attention. The medical personnel and agencies, or the media who provide these names, often do so hurriedly and without suitable attention to consequence. Perhaps the best titles are those that are purely descriptive, without any etiologic implications. For example, during the investigation of apparent epidemics, the U.S. Centers for Disease Control (CDC), will regularly use the descriptive term common source outbreak and will reserve the use of etiologic names, such as food poisoning, until the cause has been clearly established. The Gulf War Syndrome, designated geographically, received a satisfactory descriptive title for an outbreak that seemed to have had a common geographic source. The many subsequent controversies about that syndrome have arisen for reasons other than an initially defective name. Titles such as chronic fatigue syndrome [15] and fibromyalgia syndrome [16] are also reasonably descriptive, without any etiologic implications. (The addition of “syndrome” to the names of the latter two symptoms probably gives them diagnostic respectability, while also conveying the idea that other symptoms may co-exist.) On the other hand, etiologic titles such as irritable heart, neurasthenia, food hypersensitivity, chronic brucellosis, sick building syndrome, and siliconosis are probably the worst way to identify the corresponding maladies. These names imply that a cause is known before a cause has been established; and the label may constrain the search for other etiologic possibilities. The premature etiologic label may also impair successful resolution of the illness by enhancing the patient’s belief and role as a victim [1,2,18]. An interesting comparison can be made with desirable and undesirable nosologic approaches in situations of disease that was definitely organic. Thus, the diagnostic criteria for tuberculosis did not begin to demand evidence of the tubercle bacillus until adequate laboratory methods were available for its identification. Similarly, the Jones diagnostic criteria for rheumatic fever when through several revisions without insisting on demonstration of an antecedent group A streptococcal infection until antibody testing had sufficiently advanced to show evidence of the infection in all cases. On the other hand, the epidemiologic evidence of a causal role for cigarette smoking did not lead to a nosologic conversion from lung cancer to cigarette smoker’s disease. The conversion would have precluded the diagnosis of lung cancer when it occurs in non-smokers. Nevertheless, when babies with the facial and other deformities that are often called FLK (“funny-looking kid”) were born to alcoholic mothers, the malady was designated as fetal alcohol syndrome. The result has led to the diagnos-
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tic peculiarity of giving two different names, FLK and fetal alcohol syndrome, to the same condition according to whether the pregnant mother did or did not consume large amounts of alcohol. (The consequence not only impairs recognition of a distinct pathophysiologic pathway for the disease, but has also terrorized many pregnant women into total abstinence from alcohol during the gestation period.) A valuable guide for nomenclature and diagnosis of unexplained diseases and syndromes is to avoid incorporating a suspected etiologic agent into the name of the disease, or into the demands of proposed diagnostic criteria, until the agent has been demonstrated in all cases of the disease. Another problem produced by a premature etiologic label is that it can impair the optimal management of the functional somatic syndrome. As the clinician and patient form a “therapeutic alliance” [1], various types of physical rehabilitation and cognitive–behavioral therapy can be given in escalating “doses” until the patient begins to resume normal activities. This gradual course of improvement toward normal will be blocked, avoided, or retarded, however, if the patient has focused on etiologic or pathophysiologic beliefs that an infection has been inadequately treated, that multiple sensitivities require occupational and or social isolation, or that legal action is needed to obtain financial compensation from the producers or promoters of the accused agent. The Blame-X syndrome offers an instructive illustration of medical problems that are made possible in an era of extensive anxiety, high technology, and frequent litigation. The syndrome also offers useful lessons, however, about how best to explain, label, and help patients with unknown causes of functional somatic disorders.
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COMMENTARY
The Blame-X syndrome: Problems and lessons in nosology, spectrum, and etiology Alvan R. Feinstein* Sterling Professor of Medicine and Epidemiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA Received 5 September 2000; received in revised form 20 November 2000; accepted 24 November 2000
Abstract Symptoms of a functional somatic syndrome have been noted in individual persons and groups for more than a century. Often associated with war, the syndrome has received diverse names and many proposed but unproved etiologies, including exposure to trauma, stress, chronic infection, psychosomatic, chemical, or environmental causes. In recent years, when attributed to agent X, the syndrome could be called the Blame-X syndrome. The clinical, legal, and other problems associated with the syndrome are a reflection of nosologic difficulties in identifying and choosing titles for apparently “new” ailments. The difficulties arise from the complex overlap of symptoms, diseases, and laboratory abnormalities found with modern technology, and from the frequent abandonment of pathophysiologic demands for appropriate correlation of symptoms and objective abnormalities. An important principle in naming apparently new ailments is to avoid etiologic titles until the etiologic agent has been suitably demonstrated. A premature causal name can impair a patient’s recovery from the syndrome, and impede research that might find the true cause. © 2001 Elsevier Science Inc. All rights reserved. Keywords: Syndrome; Nosology; Spectrum; Functional Somatic Syndrome; Blame-X
1. Introduction They have been happening for more than a century: outbreaks of symptoms of a functional somatic syndrome occurring in groups of persons exposed to an apparently noxious stimulus. The symptoms, which can vary from one person to another, occur as diverse clusters of the wide array of individual manifestations listed in Table 1, but seldom have a single common pattern. In the absence of concomitant objective abnormalities, the clusters of symptoms have received various names, but they were recently grouped [1,2] under a useful title: Functional Somatic Syndrome (FSS). (The name “syndrome” literally means “running together,” and refers to the group of symptoms or other manifestations associated with a particular condition or disease. In modern medicine, “syndrome” is often used when a characteristic objective abnormality has not been found to identify the condition as a “disease.”) The FSS title is valuable because it is a purely descriptive label, with no etiologic connotations, for symptoms of unknown cause that are not consistently accompanied by objectively demonstrable abnormalities, or by a distinctive pathophysiologic mechanism. The provocative stimuli for FSS have varied extensively, ranging from physical or emotional * Corresponding author. Tel: 203-785-4145; fax: 203 785-5177. E-mail address: [email protected] (A.R. Feinstein)
stress, to chronic infections, to alleged toxins that have been inhaled, ingested, or injected. What the outbreaks or individual episodes have in common is the difficulty of discerning satisfactory mechanisms to explain the symptoms, the controversies about organic causes and components [3,4], the different names chosen for the syndrome, and a new modern fashion in nomenclature. In today’s world, if Stimulus X is suspected or blamed as the cause, it is frequently cited in the title of the outbreak. Stimulus X may then receive wide publicity in the media, legislation intended to provide care and compensation for the victims, and litigation aimed at punishing the producers. Because the offending Stimulus X has often been cited in the name of the ailment, the recent outbreaks might be called the Blame-X syndrome. Before reaching its current nosologic format, however, the syndrome had appeared and re-appeared under many titles, reflecting different modes of discovery and beliefs about etiology. 2. Evolution of the syndrome 2.1. War syndromes The war syndrome [5] seems to have been first noted in the 1850s, when anatomic pathology had been developed well enough to allow “organic” and “non-organic” ailments to be differentiated. During the Crimean battles of 1854–
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Table 1 Symptoms reported in functional somatic syndrome General: Fatigue, exhaustion, apathy, lethargy; Insomnia, other sleep disturbances; Irritability; Excessive sweating Cerebral: Headache; Lightheadedness, fainting; Forgetfulness, impaired memory, difficulty concentrating, confusion Joints and Muscles: Chronic pain in joints, muscles, neck, low back Face and Pharynx: Sore throat, dry mouth, globus, atypical pain Chest: Palpitations, shortness of breath, sharp or burning pain Gut: Nausea, diarrhea, abdominal pain or distress Neurologic: Paresthesias Gynecologic: Chronic pelvic pain, premenstrual syndrome, menorrhalgia Psychic: Anxiety, depression
1856, again in the suppression of an Indian mutiny in 1858, and again during the Boer war in the early 1900s, the syndrome appeared in individual British soldiers and was sometimes regarded as an after-effect of sunstroke [5]. During the U.S. Civil War in the 1860s, however, when DaCosta found the first “outbreak” of the syndrome in 300 referred soldiers, he called it irritable heart, and noted that the syndrome could also appear in civilians [6]. In World War I, the syndrome became a major problem in both British and American soldiers, many of whom were ill enough to be evacuated to England from the continental battleground. Among the nosologic titles used at that time were DaCosta syndrome, soldier’s heart, effort syndrome, shell shock, combat stress, and neurocirculatory asthenia [6]. The latter diagnosis was adapted from the neurasthenia first identified in 1869 by Beard [7]. Adding to the idea of a “War syndrome,” the ailment reappeared—under such names as acute combat stress reaction, battle fatigue, and combat exhaustion—in combat personnel during World War II and later in the Korean War. These names, as well as post-Vietnam syndrome, were also used for occurrences in the Vietnam war, but psychiatrists created an additional title, post-traumatic stress disorder (PTSD), which referred to long-term consequences of the stress [8,9]. PTSD was also retrospectively recognized as having occurred in veterans of both World War II and Korea, as well as in civilians exposed to extreme trauma unrelated to war [6]. The most recent title, Gulf War Syndrome, was used when similar manifestations, including PTSD, appeared in veterans who had returned from the Persian Gulf War of 1991. Analogous health problems were also noted, however, among non-military family members of the affected veterans [10,11].
sis, chronic candidiasis, chronic mononucleosis, or posthepatitis syndrome. In recent years, the condition was called myalgic encephalitis, post-viral infection syndrome, “yuppie flu,” or chronic Lyme disease [12]. The explanatory causal belief was that an infection had been inadequately eradicated or that it had been followed by as-yet-undiscovered inflammatory mechanisms, analogous to the rheumatic fever or glomerulonephritis that could follow a group A streptococcal infection. As the existence of psychosomatic diseases became a popular concept, various psychic mechanisms were invoked and sometimes used as titles. The famous British physician, John Ryle, called the syndrome visceral neuroses [13]; and psychosomatic causes were also invoked for a subset of gastrointestinal symptoms that were variously titled irritable bowel syndrome, functional bowel distress, and non-ulcer dyspepsia. The psychosomatic concepts began to go out of style, however, when alternative causes were invoked or demonstrated, using newer immunologic ideas and infections. Thus, many of the intestinal symptoms became attributed to food allergy or food hypersensitivity [14]; and long-cherished beliefs about a psychosomatic origin for peptic ulcer were demolished with the etiologic discovery of the helicobacter pylori bacillus.
2.2. Post-infectious and psychosomatic syndromes
2.4. Non-disease diseases
In a century that had seem major advances both in the discovery of infectious agents and in revelations about dynamics of the human psyche, it was inevitable that one or both of these causes would be invoked as pathophysiologic mechanisms when the syndrome appeared endemically in the absence of exposure to military stress. Persons with overt evidence of previous (but no longer present) infection were believed to have chronic brucello-
Beginning in the late 1980s, two entities that were long regarded as manifestations of “non-disease” became frequent enough in clinical practice to receive official titles as “diseases”: chronic fatigue syndrome [15] and fibromyalgia [16]. The attempts at pathophysiologic explanation initially consisted of “rounding up the usual suspects” (chronic infection, neurasthenia, physical, social, and emotional stress). New suspects were added, however, on the basis of
2.2. Pathophysiologic “causes” The functional somatic syndrome has also occurred endemically in patients who received (or self-selected) such pathophysiologic designations as hypoglycemia, vascular instability, and hyperventilation syndrome. Common forms of chest pain that could not be attributed to coronary ischemia were called atypical angina or non-cardiac chest pain. This pain was sometimes later, after the advent of echocardiography, attributed to mitral valve prolapse.
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occasional abnormalities found with newer laboratory tests for endocrine imbalances, immunologic dysfunction, enteroviral DNA, and neurotransmitting agents. No consistent mechanism has yet been demonstrated or accepted, however, for either chronic fatigue syndrome or fibromyalgia; and the main clinical challenges have been to help patients cope with the ailment. Both diseases continue to occur endemically and to remain available for inclusion as part of a Blame-X “epidemic” when new provocative stimuli are discovered or accused.
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use of vaccines against plague and anthrax; but more recent studies have suggested a possible role for anti-nerve-gas chemical prophylaxis [23]. Another injected substance, the silicone used in breast implants, has become the latest and most litigiously prominent source of the syndrome. When epidemiologic studies exonerated silicone as a cause of connective tissue diseases, such as scleroderma and rheumatoid arthritis, the unexplained associated functional somatic symptoms were regarded as an atypical connective tissue disease for which a proposed title was Siliconosis Syndrome.
2.5. Chemical and environmental “causes” As major societal concerns developed about environmental pollution by chemical products, worries about the direct effects on humans were inevitable. In some of the persons who had been transiently but accidentally exposed to an overdose of carbon monoxide, the functional somatic syndrome appeared and was called chronic carbon monoxide poisoning. The existence or perception of acute gaseous odors led to occasional epidemics of hysteria [17], and also to a decadelong controversy about adverse health effects in a Canadian community chronically exposed to “sour gas” emanations from a nearby mine. In addition to symptoms of FSS, the suspected adverse effects in that community included increased rates of cancer and of birth defects. The controversy eventually subsided after a heroic epidemiologic study [18] showed that the rates of disease were similar in the exposed community and in two well-chosen control communities, which also had similar rates of objective abnormalities. Analogous complaints (increased rates of cancer and birth defects, and manifestations of FSS) also arose in veterans who were exposed to dioxin (Agent Orange) during the Vietnam war. The rates of disease were later found, however, to be no higher than in unexposed veterans. In another excellent epidemiologic study, led by members of the previously cited Canadian team, carefully chosen comparative groups in South America showed no elevation of diseases attributed to rivers polluted by trace levels of arsenic, mercury, lead and other industrial effluents [19]. After an unequivocal episode of mercury poisoning due to polluted fish in Japan, however, episodes of the functional somatic syndrome elsewhere were attributed to mercury poisoning from dental fillings. Symptoms of FSS have appeared in patients exposed in restaurants and in other public places to perfumes, deodorants, and other scents worn by individual persons. Exposures in the workplace and elsewhere have led to designation of a sick building syndrome [20], a multiple chemical sensitivity syndrome [21], a new ailment called “chemical AIDS,” and the development of a new specialty, called Clinical Ecology [22], for the “medical subculture” of patients who are “environmentally ill” and “allergic to everything.” Because a few vaccinated children have had adverse reactions, the Gulf War Syndrome was at first attributed to the
3. Problems in classification of disease When and if a convincing causal mechanism is found for the functional somatic syndrome, medical historians will probably wonder why the discovery took so long. With the majestic modern advances in molecular biology, biochemistry, and infectious microbiology, why did 20th century medical scientists have so much difficulty in finding the cause? The delayed discovery of causes, of course, is a common event in medical history, as is the custom of forming wrong etiologic beliefs until the correct cause is eventually established. Similar questions about reasons for delay will doubtlessly be asked in the future when etiologic riddles have been solved for such clearly organic diseases as today’s cancers and degenerative ailments. What is more unusual about the Functional Somatic Syndrome, however, is its nosologic meandering. Cancer has been called cancer, and atherosclerosis, atherosclerosis for more than a century, but FSS has gone through the many cited transitions and reincarnations in a large number of different names and causes. The additional designation proposed here as Blame-X syndrome may seem facetious, but is pertinent when X becomes an entity to be shunned and subjected to litigation, worker’s compensation, or protective regulations. 3.1. Challenges in nosology The problems in classifying FSS are not really unusual. They accompany other prominent but often unrecognized contemporary problems in nosology, which refers to the nomenclature and classification of disease. Many clinicians today have never heard of nosology. It is not taught in medical schools; it is seldom discussed in meetings, conferences, or published literature; and probably its only modern manifestation (in the U.S.) occurs when discharge planners seek the most lucrative DRG code number to assign to a patient’s hospitalization. The modern challenges of naming and classifying diseases began early in the 19th century when the increasing use of autopsy led to the development of anatomic pathology, and when experimental and laboratory research later helped demonstrate concepts of physiology and pathophysiology. The morphologic abnormalities of the “internal medicine” revealed at autopsy became the underlying diseases
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that replaced the old clinically named dis-eases [24]. Jaundice became hepatitis; angina pectoris became coronary artery disease; dyspepsia became peptic ulcer. In the first prominent attempt to achieve a systematic and consistent nomenclature for diagnostic terms, William Farr and Marc D’Espine, cited in Pearl [25], in 1853 prepared a list of categories that eventually led to the International Classification of Diseases. Thereafter, during the enormous taxonomic challenges of revising the Classification at 10year intervals, the international committees have been satisfied simply to achieve agreement on the large list of names cited in the taxonomy. The committees have not established rules for distinguishing a syndrome from a disease, for deciding when a “new” disease has been identified, or for offering operational criteria for making diagnoses. In the absence of rules and criteria, diagnostic nomenclature has been formulated with a laissez-faire free-for-all that is often affected more by social, political, or personal customs than by scientific advances. Sometimes the old eponymic titles for diseases have been replaced by new morphologic or pathologic terms. Thus, Bright’s disease became nephritis and Addison’s disease became adrenocortical insufficiency. Certain old names such as diabetes mellitus and rheumatic fever have endured, however, despite the demonstration of underlying causes respectively in hyperglycemia and streptococcal infection. Some of the main problems in nosology today arise from (1) the diverse spectrum of inconsistent inter-relationships of symptoms, diseases, and laboratory abnormalities found with modern technology, and (2) the gradual abandonment of pathophysiologic demands for appropriate correlation of symptoms, lesions, and other abnormalities.
Fig. 1. Overlap of symptoms, objective abnormalities, and diseases to form the spectrum of manifestations of human ailments.
and other abnormalities have been depicted. The “appropriate” entities are those that are clearly explained with mechanisms of pathophysiologic correlation. Thus, the classical symptoms of angina pectoris are appropriately correlated with electrocardiographic evidence of depressed ST segments and with radiographic (or other morphologic) evidence of coronary narrowing or occlusion. When symptoms and lesions are not appropriately correlated, however, the dissociation can lead to errors in diagnosis and subsequent management. For example, angiography may show evidence of occlusive coronary disease in a patient whose substernal chest pain occurs about an hour after
3.2. Problems in spectrum Fig. 1 shows the spectrum of overlap that can occur between symptoms, diseases, and objective abnormalities. In different parts of this complex spectrum, a patient with FSS can have symptoms without demonstrable diseases or abnormalities; and no symptoms may be present in a patient who has angiographically demonstrated coronary disease, with or without electrocardiographic abnormalities. Because of the overlap among different components, clinicians today may be unfamiliar with the diverse entities occurring in different parts of the spectrum, and may either avoid pathophysiologic explanations for the apparent inconsistencies, or may freely offer whatever explanation seems convenient and tenable. A noteworthy example in nomenclature is the term “empty sella syndrome,” which was created to explain an apparent radiographic abnormality in persons who had no corresponding symptoms or neurologic disease. 3.3. Dissociated relationships Fig. 2 shows the source of an important, additional problem. Among the three main sets of Fig. 1, separate subsets of pathophysiologically “appropriate” symptoms, diseases,
Fig. 2. Subsets of Fig. 1 showing pathophysiologic correlations of symptoms and objective abnormalities that can be appropriately attributed to a particular disease. For example, substernal chest pain provoked by exertion and relieved by rest, and ST-T wave abnormalities during an exercise stress test, would be appropriately attributed to coronary artery disease, but not to peptic ulcer. Post-prandial substernal pain relieved by alkali would be appropriate for peptic ulcer (with gastroesophageal acid reflux), but not for coronary artery disease.
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eating and is promptly relieved by milk or antacid therapy. Calling the chest pain “atypical angina” and treating it with cardiac revascularization would not be expected to help the symptoms of gastro-esophageal reflux. Analogously, many patients with irritable bowel syndrome have had unhappy results after it is “treated” with surgery for gall stones that were a “silent” incidental finding during abdominal imaging. A different type of problem arises when wrong diagnoses are made by clinicians who may not realize that a disease’s full spectrum of manifestations, as shown in Fig. 3, contains a complex array of patients complaining of primary and/or secondary symptoms, as well as lanthanic patients [24], who have either no symptoms of that disease, or who do not complain of those that may be present. The lanthanic group of patients will lead to apparently atypical or unusual forms of pathogenesis. For example, the diagnosis of idiopathic splenomegaly was often erroneously given to patients, particularly in tropical countries, who had secondarily developed cirrhosis and portal hypertension after acute episodes of lanthanic anicteric hepatitis. The development of previously anicteric cirrhosis also led to false accusations of alcoholism in patients who had had a silent, unjaundiced bout of hepatitis. Patients whose rheumatic fever occurred with carditis but no arthritis or chorea were later thought to have developed “rheumatic heart disease without a history of rheumatic fever.” A similar type of pathogenesis may lead to chronic glomerulonephritis in patients who lack a history of the primary red-urine manifestation that would have signaled an acute episode. Some of the failures of screening for cancer occur when the cancer first presents with metastases, but no overt evidence of a primary lesion. The current reliance on imaging and other laboratory tests done as part of the diagnostic “workup” to demonstrate diseases has led many clinicians to ignore the old demands for pathophysiologic correlations between symptoms and lesions. Accordingly, entities such as FSS can receive many
Fig. 3. Spectrum of primary and secondary symptoms, and lanthanic patients with a particular disease. The non-lanthanic patients—who are discovered by screening, review of systems, or other routine procedures— have either no symptoms or symptoms about which they do not complain.
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explanations and conjectures about diverse possible causes, because a distinctive pathophysiologic mechanism has not been shown. Furthermore, the proponents of the idiosyncratic explanations can readily justify their claims by pointing to other proposed causes, most recently the bacterial etiology of peptic ulcer, that were initially rejected by the “establishment.” 3.4. Absence of nosologic criteria An equally cogent set of problems arises from the absence of specific rules for nosologic identifications, christenings, and revisions [26]. When should or does the name of a disease or syndrome become altered in changes such as the nosologic sequence from Moynihan’s syndrome, to peptic ulcer, to (the currently not yet used) Marshall’s disease? What are the specifications or authorizations for abandoning such older disease names as dropsy and chlorosis, for revising the glucose boundaries that demarcate diabetes mellitus, for arbitrarily declaring that asymptomatic persons with evidence of HIV infection would be counted as having AIDS, or for introducing names of new entities, such as myalgic encephalitis or sick building syndrome? Because no rules have been promulgated, all of the changes can be made in an ad hoc or ad libitum manner, often proposed in response to cultural, social, or political stimuli, and often accepted without careful attention to cultural, social, and political, as well as scientific, implications. Many of the changes occur after careful deliberation and sponsorship by authoritative committees, but despite careful efforts in nomenclature and criteria, the impact of the changes may not always be fully appreciated. For example, the occurrence rates of AIDS and of diabetes mellitus will rise when the diagnostic criteria are relaxed, but unaware clinical demographers may then be baffled by the otherwise unexplained statistical increases. Infant mortality rates will rise or fall according to whether a baby in precarious condition, who dies soon after birth, is classified as a stillbirth or as a live birth followed by death. A particularly striking example is the long-standing controversy about whether the decline in occurrence rates of tuberculosis during the 20th century was due to public health effects of better housing and nutrition, or to medical interventions, such as isolation in sanitaria and (later) antibiotic therapy. Neither set of proponents in the dispute, however, have considered the role of successive changes in authoritative diagnostic criteria [27], which would lead to fewer formally diagnosed cases as more and better laboratory evidence was increasingly demanded with each change in criteria. The idea of psychosomatic disease was an attractive explanation for functional ailments that had no correlative abnormalities, but the title led to major difficulties in clinical management. Confusing the concepts of psychogenic and psychosomatic, patients who had distressing symptoms were often led (or chose) to believe that their unequivocal
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aches, pains, or fatigue were being dismissed as imaginary or just “in the head.” The result was a loss of confidence in the diagnostic physician, a rejection of therapeutic recommendations, and maintenance of the “sick role” during searches for other forms of explanation and therapy. When specific exposures were cited as titles in the Blame-X syndrome, many patients were pleased to receive an apparent explanation, to regard themselves as victims, and to seek legal redress. The occurrence of “litigation symptoms and diseases,” however, had been noted at least 100 years ago [28]. In some of today’s Blame-X syndromes, the symptoms have persisted despite removal of the offending stimulus—such as replacement of mercury dental fillings, explantation of silicone implants, or transfer of home to a region free of pertinent environmental exposure. In a somewhat analogous syndrome, the symptoms that could follow “whiplash injury” did not regularly occur in countries without associated litigation, and often endured in the U.S. until the lawsuit was resolved [29]. 4. Lessons and recommendaitons Although the cause of FSS remains unknown, certain lessons and recommendations can emerge from this review of historical events and problems. The lessons refer to pathophysiologic correlations, nosologic designations, and clinical management. 4.1. Pathophysiologic correlations The diverse spectrum of symptoms, abnormal tests, and diseases can help physicians remember that concomitant events can occur without being necessarily related. As an era of increased screening and other testing finds many clinically “silent” abnormalities, they will be available for erroneous use as diagnostic explanations for symptoms that they do not really explain. Unless appropriate pathophysiologic explanations are demanded, however, manifestations of functional bowel distress may regularly but erroneously be attributed to gallstones, gastric ulcer, colonic polyps, or localized cervical cancer. Conversely, many ailing veterans of the Gulf War may have developed a functional somatic syndrome, but a few may have distinctly organic ailments, accompanied by appropriate abnormalities, that followed toxic exposures to burning oil or other pertinent agents. Neither the veterans with FSS nor those with organic disease are well served if the complex spectrum of illness and disease is lumped together as a single “Gulf War Syndrome.” The patient’s past history offers another important correlative distinction. With careful history-taking and a check of previous medical records and events, the manifestations of FSS in many patients were found to have occurred before exposure to the “toxic” effects of Agent X. In fact, an existing “medical subculture” may contain persons who bear their suffering quietly and unobtrusively until they begin, after publicity for Agent X, to blame everything on X and to assume the role of “victim.” In this situation, the publicity
and the patient’s adverse expectations may make Agent X act like a “nocebo” [30], which produces a bad effect, in contrast to the good effect often associated with an otherwise inert placebo. 4.2. Nosologic designations In the glare of modern media publicity, a name will be sought for any outbreak or other “new” illness that reaches public attention. The medical personnel and agencies, or the media who provide these names, often do so hurriedly and without suitable attention to consequence. Perhaps the best titles are those that are purely descriptive, without any etiologic implications. For example, during the investigation of apparent epidemics, the U.S. Centers for Disease Control (CDC), will regularly use the descriptive term common source outbreak and will reserve the use of etiologic names, such as food poisoning, until the cause has been clearly established. The Gulf War Syndrome, designated geographically, received a satisfactory descriptive title for an outbreak that seemed to have had a common geographic source. The many subsequent controversies about that syndrome have arisen for reasons other than an initially defective name. Titles such as chronic fatigue syndrome [15] and fibromyalgia syndrome [16] are also reasonably descriptive, without any etiologic implications. (The addition of “syndrome” to the names of the latter two symptoms probably gives them diagnostic respectability, while also conveying the idea that other symptoms may co-exist.) On the other hand, etiologic titles such as irritable heart, neurasthenia, food hypersensitivity, chronic brucellosis, sick building syndrome, and siliconosis are probably the worst way to identify the corresponding maladies. These names imply that a cause is known before a cause has been established; and the label may constrain the search for other etiologic possibilities. The premature etiologic label may also impair successful resolution of the illness by enhancing the patient’s belief and role as a victim [1,2,18]. An interesting comparison can be made with desirable and undesirable nosologic approaches in situations of disease that was definitely organic. Thus, the diagnostic criteria for tuberculosis did not begin to demand evidence of the tubercle bacillus until adequate laboratory methods were available for its identification. Similarly, the Jones diagnostic criteria for rheumatic fever when through several revisions without insisting on demonstration of an antecedent group A streptococcal infection until antibody testing had sufficiently advanced to show evidence of the infection in all cases. On the other hand, the epidemiologic evidence of a causal role for cigarette smoking did not lead to a nosologic conversion from lung cancer to cigarette smoker’s disease. The conversion would have precluded the diagnosis of lung cancer when it occurs in non-smokers. Nevertheless, when babies with the facial and other deformities that are often called FLK (“funny-looking kid”) were born to alcoholic mothers, the malady was designated as fetal alcohol syndrome. The result has led to the diagnos-
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tic peculiarity of giving two different names, FLK and fetal alcohol syndrome, to the same condition according to whether the pregnant mother did or did not consume large amounts of alcohol. (The consequence not only impairs recognition of a distinct pathophysiologic pathway for the disease, but has also terrorized many pregnant women into total abstinence from alcohol during the gestation period.) A valuable guide for nomenclature and diagnosis of unexplained diseases and syndromes is to avoid incorporating a suspected etiologic agent into the name of the disease, or into the demands of proposed diagnostic criteria, until the agent has been demonstrated in all cases of the disease. Another problem produced by a premature etiologic label is that it can impair the optimal management of the functional somatic syndrome. As the clinician and patient form a “therapeutic alliance” [1], various types of physical rehabilitation and cognitive–behavioral therapy can be given in escalating “doses” until the patient begins to resume normal activities. This gradual course of improvement toward normal will be blocked, avoided, or retarded, however, if the patient has focused on etiologic or pathophysiologic beliefs that an infection has been inadequately treated, that multiple sensitivities require occupational and or social isolation, or that legal action is needed to obtain financial compensation from the producers or promoters of the accused agent. The Blame-X syndrome offers an instructive illustration of medical problems that are made possible in an era of extensive anxiety, high technology, and frequent litigation. The syndrome also offers useful lessons, however, about how best to explain, label, and help patients with unknown causes of functional somatic disorders.
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