- Email: [email protected]
The problem of Gulf War syndrome
Medical Hypotheses (2001) 56(6), 697–701 © 2001 Harcourt Publishers Ltd doi: 10.1054/mehy.2001.1311, available online at http://www.idealibrary.com on
The problem of Gulf War syndrome R. Ferrari,1 A. S. Russell2 1
Edmonton, Alberta, Canada Department of Rheumatic Diseases, University of Alberta, Edmonton, Alberta, Canada
2
Summary Following a war with widespread attention to and concern over the potential for numerous biological and chemical warfare exposures, some Gulf War veterans returned home and developed various illnesses. Although some of these illnesses are readily diagnosable, the so-called Gulf War syndrome has remained a controversial and nebulous diagnosis. It is characterized by multiple, subjective symptoms, and by a lack of objective pathology. To date, the search for a single disease entity and a biological model to explain this illness has been unsuccessful. Wars have long affected the health of veterans in multiple ways, and a single disease entity is not likely as a viable explanation for these outcomes. Given the nature of the illness, and its overlap with many other controversial chronic illnesses, we suggest that the biopsychosocial model may provide a better solution to this diagnostic conundrum. © 2001 Harcourt Publishers Ltd
INTRODUCTION The difficulty with Gulf War syndrome is that the medical community is searching for a unique syndrome without knowing what it looks like. There are no formal case definitions or diagnostic criteria for Gulf War syndrome as the syndrome did not evolve from identifying specific diseases or pathology in patients, but rather from the appearance of patients with common, non-specific and widely varying subjective symptoms, and the expectation that there should be an underlying ‘Gulf War disease’ to explain it all. Throughout preparations for the Gulf War and during the war itself, the soldiers and their families were made aware of the very real potential for toxic exposures and the soldiers even took drugs and other agents to prevent such toxicity. Inevitably, as we shall discuss later, wars always affect the health of soldiers in some way (often via multiple factors). Over several months or years some soldiers returning from the Persian Gulf developed symptoms noted by their families and their physicians. Of
course, many out of the 750 000 returning troops were bound to develop symptoms/illnesses anyway; this being normal part of civilian/veteran life. Obviously, given the discussions that had already taken place before the Gulf War about toxic exposures, the tremendous media attention and the current trends in Western society regarding environmental illnesses, their exposure in the Gulf was blamed. As there is also an understandable paranoia that the government and the military are capable of conspiracy, covering up and denying any serious threat to the soldiers’ health, their conclusion (and that of some physicians) that Gulf War was to blame was a natural one. It is suggested that upon review of the efforts thus far, no unique Gulf War syndrome exists. What has happened is a failure to recognize: a) the pattern of normal symptoms in the community and how common they are; b) that war causes ill health in a variety of ways, and there is nothing unique about that; and c) that the media, the government and the medical community by their behaviour can engender an environment that makes it difficult for soldiers to see that their symptoms better fit a benign explanation than some ominous new syndrome.
Received 7 July 2000 Accepted 7 July 2000
SYMPTOMS BEING REPORTED
Correspondence to: Dr R. Ferrari, 12779-50 Street, Edmonton, Alberta, Canada T5A 4L8. Phone: 780-990-8310; Fax: 780-473-3529; E-mail: [email protected]
There are neither specific symptoms that identify Gulf War syndrome nor any overall specific pattern of symptoms that Gulf War veterans report. Of those veterans 697
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who are believed to possibly be ill with the toxic exposures in the Gulf War, various surveys of samples ranging from small groups (tens) to over 70 000 give a prevalence of symptoms ranging from 5–50% (1–15). The most common symptoms seem to be fatigue, followed by depressed mood or anxiety, and then pain. The symptoms are not only non-specific, but the relative prevalence pattern (in terms of distribution of symptoms) is very similar to that reported in general population surveys (16–19). It is true that the Gulf War veterans and the general population samples have some demographic differences, but it is equally true that the Gulf War veterans are likely to carry the background population risk of having such symptoms (at least 5–10%) even if they were not victims of toxic exposure. Gulf War veterans do not report a more selective or specific pattern of symptoms when compared, for example, to Bosnia veterans, but do report them more frequently (8). Haley et al. attempted to find a symptom pattern, and thought they did (1), but their study is severely hampered by selection bias: it was not population-based, but rather focused on a very small group of soldiers (249) from one unit, and had only 41% of the available members of the battalion unit participate. In addition, there were no controls from any source and all information regarding symptoms and toxic exposures was self-reported with no attempt to verify the exposures described (20). Indeed, larger and better designed studies failed to uphold Haley’s suggestion of specific symptom groupings that could separate these symptoms from the ‘normal’ ones found in the general population or in subjects with other well-recognized illnesses (4,7,8,17,21). Further complicating the difficulty of specificity is the lack of a specific onset of symptoms. Kroenke et al. found, in a study of 18 000 veterans, that about 40% of the symptoms being reported did not being until more than one year after the return from the war, and they found no correlation between symptoms and self-reported exposures in this large population (3). This study was much larger (over 18 000 subjects) and more thorough than those of Haley and others (5). PSYCHOLOGICAL DISORDERS AND FACTORS Among the more common symptoms being reported are anxiety or depressed mood. Depression and anxiety may have somatic symptoms that accompany the psychological distress, but it could also be that the effect of stress is to amplify various common, even normal, symptoms that have benign origins and are frequent in the general population. When one is expecting symptoms, especially with the possibility of an ominous new disease, one is in a state of hypervigilance, the result of which is to register Medical Hypotheses (2001) 56(6), 697–701
normal bodily sensations as abnormal, and to react to bodily sensations with affect and cognitions that intensify them and make them alarming, ominous and disturbing – i.e. symptom amplification (22,23). Thus, it may not be necessary to postulate that stress causes the symptoms, but rather that stress causes the benign symptom pool of daily life to be noticed and causes the individual to attach a special significance to them. The cascade of media coverage, together with uncertainty, fear and also perhaps the initial governmental handling of the problem further fuelled suspicion and paranoia. Unwin et al. (9) comment on the reportedly large numbers of US personnel who, before the active conflict, reported the anticipation of attack by chemical weapons, biological weapons or both as their greatest fear. Even years later, Unwin et al. found nearly all Gulf War veterans remember wearing nuclear-biological-chemical suits and hearing chemical alerts, 26% reporting a SCUD missile explosion nearby and 9% believed that they had been exposed to a chemical attack (9), even though the evidence that there was any definite chemical attack is absent. Post-traumatic stress disorder (PTSD) has been a diagnosis given in many such individuals. This diagnosis has numerous pitfalls, even in war veterans. Haley et al. have questioned the diagnosis of PTSD in many cases. They estimated that the prevalence of PTSD is virtually nil in Gulf War veterans. They argue that questionnaire studies overestimate PTSD prevalence, but even if this is true it does not necessarily follow that this rules out psychological factors altogether. An important stressor may have occurred upon returning home and having one’s fears of toxicity reinforced by the publicity attached to this ‘mysterious illness’ developing in Gulf War veterans. These psychological factors are simply part of a culture that is looking for a syndrome and accountability. This approach to assign a ‘cause’ to a collection of common symptoms and to then label it as a disease has been reviewed elsewhere (24). The phenomenon does not produce the symptoms, but rather the behaviour of Gulf War veterans. It is intriguing, for example, that despite the extensive discussion and research taking place with Canadian, British and American war veterans, there have been very few reports of a Gulf War syndrome in many of the other participating countries who sent soldiers to the Persian Gulf. Many of these participating countries have sophisticated medical systems and ample opportunity for soldiers who feel ill to seek attention. RISK FACTORS FOR BEING A GULF WAR SYNDROME PATIENT Since the vast majority of veterans do not believe they have this as yet undefined syndrome, one can study © 2001 Harcourt Publishers Ltd
The problem of Gulf War syndrome
those who believe they do and try to compare the two groups to find risk factors for not only the symptoms, but also the belief system that is associated with those symptoms. Gray et al. (15) compared 70 000 Gulf War veterans who sought medical attention in the Department of Veteran Affairs Persian Gulf Veterans’ Health Registry with nearly 700 000 who did not in order to determine the personnel most likely to seek medical evaluation. Risk factors that clearly do not have overt or likely significant biological implications (in terms of toxic exposure, for example) include the fact that married personnel, female personnel and health care workers were the most likely to seek treatment for these symptoms. Also a predictor of bringing post-war symptoms to medical attention was hospitalization in the 12 months prior to the war. Thus, those Gulf War veterans suspected of having Gulf War syndrome may simply be those who are most apt to fear health consequences and seek attention for symptoms that may very well be entirely benign and shared by many veterans not seeking medical attention. One sees the same with fibromyalgia. The symptoms of widespread discomfort and fatigue are common in the population. What distinguishes patients from normals is that they seek medical attention for their problems. STUDIES OF PATHOLOGY IN GULF WAR VETERANS Attempts to find specific forms of pathology (or any pathology at all) associated with ‘Gulf War symptoms’ have been unrewarding. Using batteries of urine and blood tests as well as more specialized tests, abnormalities are few and inconsistent (3,4,6,7). Most of the toxins of concern in the Gulf War are encountered first by the respiratory system, especially from oil well fires, pesticides and possible biochemical warfare. However, there has been little investigation into this aspect, particularly as the only pulmonary symptoms have been shortness of breath and cough, with no specific lung pathology that can be identified to indicate lung damage. In two non-population based studies of very small groups of veterans complaining of cough, the researchers found those complaining of cough were more likely to have inflammation of the upper airways than healthy people without cough, and minor abnormalities in overall lung function (22). Of course, this merely tells us that those complaining of cough were likely telling the truth. It tells us little about the cause of the cough, as one would find the same results in non-soldiers who have chronic, unexplained cough. The question that is not addressed is: Does being a Gulf War veteran bring any greater risk of having a cough than not being a Gulf War veteran? There is no evidence. We also know that the air © 2001 Harcourt Publishers Ltd
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quality in the Gulf, despite all the oil fires, was no worse than that in a number of North American cities (26,27). There has been limited research evaluating both the immune system and urinary tract in small groups of patients reporting a multitude of non-specific symptoms (4,29,30). No abnormalities could be found in patients studied thus far. Finally, the nervous system has been evaluated for evidence of pathology. There has been extensive theorizing by Haley et al. about neurotoxicity (30), but no clear proof. Jamal et al. (32) thought there was evidence of neurotoxicity, but the study was later found to be highly deficient, both in selection of subjects (14 of 40 available) and misinterpreting the results of nerve conduction studies (33). As Amato et al. noted, given that 700 000 soldiers (from Canada, the UK and the USA) were in the Gulf War, it is inevitable that one is going to find some of them developing neurologic conditions or symptoms in their lifetime. The question is: Are they any more at risk for doing so after having been in the Gulf War? Given the difficulty in finding clear evidence of neurotoxicity despite the large number of potential exposures, this seems unlikely. Finally, researchers who tested neuropsychological functioning found no evidence to suggest brain injury or other nervous system dysfunction or a correlation between neuropsychological function and any exposures related to the war. Instead, there was a strong correlation between neuropsychological function and emotional function (34). Thus, despite a multitude of symptoms, and in some cases disability, there is little, if any, pathology to be found in these Gulf War veterans. THE HEALTH OF SOLDIERS NOW AND THEN This is not the first time there have been controversies regarding health outcomes in war veterans – which is a final reason to question the existence of a new, unique syndrome. There is nothing new about the complaints of Gulf War veterans compared to veterans of previous wars. Hyams et al. review the history of post-war syndromes from the American Civil War to the Vietnam War (35). The Civil War led to controversies of ‘irritable heart’ syndrome, World War I to DaCosta’s syndrome, World War II to combat stress reaction, Vietnam to Agent Orange exposure and Post-Traumatic Stress Disorder. Hyam, et al. show that although there is a wide array of symptoms, they have remained similar over a 150-year period. CONCLUSION The trouble with looking for an entirely undefined, unknown syndrome is that one is inevitably going to find Medical Hypotheses (2001) 56(6), 697–701
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some patients who really do have symptoms and disease. That is in part because wars have always had some measure of health effects, often with multiple factors involved. Symptoms are a part of normal, healthy (veteran or civilian) existence. It is therefore normal for Gulf War veterans to have many of these ‘normal’ symptoms, and they may even have had them before the war. What is abnormal is the sociocultural environment in which these symptoms exist, and it is that environment that needs more investigation. The post-war environment is one of emotional distress of a variety of forms, of fears of toxic exposure, and, to some extent perhaps, the understandable feeling of injury over the fact that when one has put one’s life on the line for one’s country, the country ought to extend the utmost efforts in protecting the health of the heroes that return. In the expectation of a syndrome from toxic exposures, the many non-specific symptoms of these soldiers may have multiple (otherwise benign) causes, yet will be attributed to a unique exposure-related syndrome. Further, hypervigilance alone will cause healthy subjects to register normal and otherwise benign bodily and mental symptoms that they might otherwise have ignored, attach a special, ominous significance to them, and suggest the need to embark on medical attention for them (22,23). In the expectation of a Gulf War syndrome, future symptoms amplified and registered in this way will quite naturally be attributed to that mysterious syndrome, particularly if the medical community reinforces this belief. There is thus a failure of the medical community in the Gulf War syndrome controversy, not so much in failing to identify a specific syndrome, but in failing to recognize that many factors affect perceptions of health and illness. These factors often have little to do with the origin of symptoms themselves, but do contribute to illness perception (33). Further, there has been a failure to recognize that the existence of multiple, sometimes chronic and unexplained, symptoms is common in the general population and not necessarily relevant to disease, but rather relevant to one’s perceptions of illness. There is also much that the Governments could have done (especially in terms of collecting pre-conflict health data and maintaining data about exposures) that was not done. Efforts to remedy this for future conflicts have since been underway (20). Veterans can be told that being a Gulf War veteran does not make one immune from being a normal citizen again, experiencing the many illnesses and health issues that arise in the future, irrespective of past war exposures. Finally, they have anxieties and perhaps even depression. That is normal and natural for what they experienced, and for what they are being put through now by those who would investigate them for Gulf War Syndrome on the one hand, and those that would label them with Medical Hypotheses (2001) 56(6), 697–701
‘psychological disorder’ on the other. In many cases, they may have neither. They may just be healthy warriors, who deserve the opportunity to put the Gulf War behind them. REFERENCES 1. Haley R. W., Kurt T. L., Hom J. Is there a Gulf War Syndrome? Searching for syndromes by factor analysis of symptoms. JAMA 1997; 277: 215–222. 2. Iowa Persian Gulf Study Group. Self-reported illness and health status among Gulf War veterans. A population-based study. JAMA 1997; 277: 238–245. 3. Kroenke K., Koslowe P., Roy M. Symptoms in 18, 495 Persian Gulf War veterans. JOEM 1998; 40: 520–528. 4. Fukuda K., Nisenbaum R., Stewart G., Thompson W. W., Robin L., Washko R. M. et al. Chronic multisystem illness affecting air force veterans of the Gulf War. JAMA 1998; 280: 981–988. 5. Proctor S. P., Heeren T., White R. F., Wolfe J., Borgos M. S., Davis J. D. et al. Health status of Persian Gulf veterans: Self-reported symptoms, environmental exposures and the effect of stress. Int J Epidem 1998; 27: 1000–1010. 6. Escalante A., Fischbach M. Musculoskeletal manifestations, pain, and quality of life in Persian Gulf war veterans referred for rheumatologic evaluation. J Rheumatol 1998; 25: 2228–2235. 7. Coker W. J., Bhatt B. M., Blatchley N. F., Graham J. T. Clinical findings for the first 1000 Gulf War veterans in the Ministry of Defense’s medical assessment programme. BMJ 1999; 318: 290–294. 8. Ismail K., Everitt B., Blatchley N. F., Hull L., Unwin C., David A. et al. Is There a Gulf War syndrome? Lancet 1999; 353: 179–182. 9. Unwin C., Blatchley N. F., Coker C., Ferry W., Ferry S., Hotopf M. et al. Health of UK servicemen who served in Persian Gulf War. Lancet 1999; 353: 169–178. 10. Kipen H. M., Hallman W., Kang H., Fiedler N. Prevalence of chronic fatigue and chemical sensitivities in Gulf registry veterans. Arch Environ Health 1999; 54: 313–318. 11. Ishøy T., Suadicani P., Guldager B., Appleyard M., Ole Hein H. et al. State of health after deployment in the Persian Gulf. Dan Med Bull 1999; 46: 416–419. 12. Ishøy T., Suadicani P., Guldager B., Appleyard M., Gyntelberg F. Risk factors for gastrointestinal symptoms. Dan Med Bull 1999; 46: 420–423. 13. Suadicani P., Ishøy T., Guldager B., Appleyard M., Gyntelberg F. Determinants of long-term neuropsychological symptoms. Dan Med Bull 1999; 46: 423–427. 14. Gray G. C., Smith T. C., Kang H. K., Knoke J. D. Are Gulf War veterans suffering war-related illnesses? Federal and civilian hospitalizations examined, June 1991 to December 1994. Am J Epidemiol 2000; 151: 63–71. 15. Gray G. C., Hawksworth A. W., Smith T. O. et al. Gulf War veterans’ health registries. Who is most likely to seek evaluation? Am J Epidemiol 1998; 148: 343–349. 16. Kroenke K., Price R. K. Symptoms in the community. Arch Intern Med 1993; 153: 2474–2480. 17. Hyams K. C. Developing case definitions for symptom-based conditions: The problem of specificity. Epidemiol Review 1998; 20: 148–156. 18. Simon G., Gater R., Kisely S., Piccinelli M. Somatic symptoms of distress: An international primary care study. Psychosom Med 1996; 58: 481–488. 19. Verbrugge L. M., Ascione F. J. Exploring the iceberg. Common symptoms and how people care for them. Med Care 1987; 25: 539–569.
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20. Landrigan P. J. Illness in Gulf War veterans. Causes and consequences. JAMA 1997; 277: 259–261. 21. Gray G. O., Smith T. O., Knoke J. D., Heller J. M. The postwar hospitalization experience of Gulf War veterans possibly exposed to chemical munitions destruction at Khamisiyah, Iraq. Am J Epidemiol 1999; 150: 532–540. 22. Barksy A., Goodson J. D., Lane R. S., Cleary P. D. The amplification of somatic symptoms. Psychosom Med 1988; 50: 510–519. 23. Barsky A. J. Amplification, somatization, and the somatoform disorders. Psychosom 1992; 33: 28–34. 24. Barsky A. J., Borus J. F. Functional somatic syndromes. Ann Intern Med 1999; 130: 910–921. 25. Das A. K., Davanzo L. D., Poiani G. L., Zazzali P. G., Scardella A. T., Warnock M. L. et al. Variable extrathoracic airflow obstruction and chronic laryngotracheitis in Gulf War veterans. Chest 1997; 115: 97–101. 26. Environmental Protection Agency. Kuwait oil fires: Interagency interim report. Washington (DC): Environmental Protection Agency, 1991. 27. Simons M. British study disputes lengthy climatic role for Kuwait oil fires. New York Times C4, 1991. 28. Klaustermeyer W. B., Kraske G. K., Lee K. G., Kurohara M. L. Allergic and immunologic profile of symptomatic Persian
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30. 31.
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Gulf War veterans. Ann Allergy Asthma Immunol 1998; 80: 269–273. Southern P. M., Patel S., Hander R. M. Does examination of urinary sediment identify individuals with Gulf War syndrome? A pilot study. Am J Med Sci 1998; 315: 225–229. Knoke J. D., Gray G. C., Garland F. C. Testicular cancer and Persian Gulf war syndrome. Epidemiol 1998; 9: 648–653. Haley R. W., Kurt T. L. Self-reported exposure to neurotoxic chemical combinations in the Gulf War. A cross-sectional epidemiologic study. JAMA 1997; 277: 231–237. Jamal G. A., Hansen S., Apartopoulous F., Peden A. The ‘Gulf War Syndrome’. Is there evidence of dysfunction in the nervous system? J Neurol Neurosurg Psychiatry 1996; 60: 449–451. Amato A. A., McVey A., Cha C., Matthews E. C., Jackson C. E., Kleingunther R. et al. Evaluation of neuromuscular symptoms in veterans of the Persian Gulf war. Neurology 1997; 48: 4–12. Sillanpaa M. C., Agar L. M., Milner I. B., Podany E. C., Axelrod B. N., Brown G. 1997. Gulf War veterans: A neuropsychological examination. J Clin Exper Neuropsych 1997; 19: 211–219. Hyams K. C., Wignall F. S., Roswell R. War syndromes and their evaluation: From the U.S. civil war to the Persian Gulf war. Ann Intern Med 1996; 125: 398–405.
Medical Hypotheses (2001) 56(6), 697–701
The problem of Gulf War syndrome R. Ferrari,1 A. S. Russell2 1
Edmonton, Alberta, Canada Department of Rheumatic Diseases, University of Alberta, Edmonton, Alberta, Canada
2
Summary Following a war with widespread attention to and concern over the potential for numerous biological and chemical warfare exposures, some Gulf War veterans returned home and developed various illnesses. Although some of these illnesses are readily diagnosable, the so-called Gulf War syndrome has remained a controversial and nebulous diagnosis. It is characterized by multiple, subjective symptoms, and by a lack of objective pathology. To date, the search for a single disease entity and a biological model to explain this illness has been unsuccessful. Wars have long affected the health of veterans in multiple ways, and a single disease entity is not likely as a viable explanation for these outcomes. Given the nature of the illness, and its overlap with many other controversial chronic illnesses, we suggest that the biopsychosocial model may provide a better solution to this diagnostic conundrum. © 2001 Harcourt Publishers Ltd
INTRODUCTION The difficulty with Gulf War syndrome is that the medical community is searching for a unique syndrome without knowing what it looks like. There are no formal case definitions or diagnostic criteria for Gulf War syndrome as the syndrome did not evolve from identifying specific diseases or pathology in patients, but rather from the appearance of patients with common, non-specific and widely varying subjective symptoms, and the expectation that there should be an underlying ‘Gulf War disease’ to explain it all. Throughout preparations for the Gulf War and during the war itself, the soldiers and their families were made aware of the very real potential for toxic exposures and the soldiers even took drugs and other agents to prevent such toxicity. Inevitably, as we shall discuss later, wars always affect the health of soldiers in some way (often via multiple factors). Over several months or years some soldiers returning from the Persian Gulf developed symptoms noted by their families and their physicians. Of
course, many out of the 750 000 returning troops were bound to develop symptoms/illnesses anyway; this being normal part of civilian/veteran life. Obviously, given the discussions that had already taken place before the Gulf War about toxic exposures, the tremendous media attention and the current trends in Western society regarding environmental illnesses, their exposure in the Gulf was blamed. As there is also an understandable paranoia that the government and the military are capable of conspiracy, covering up and denying any serious threat to the soldiers’ health, their conclusion (and that of some physicians) that Gulf War was to blame was a natural one. It is suggested that upon review of the efforts thus far, no unique Gulf War syndrome exists. What has happened is a failure to recognize: a) the pattern of normal symptoms in the community and how common they are; b) that war causes ill health in a variety of ways, and there is nothing unique about that; and c) that the media, the government and the medical community by their behaviour can engender an environment that makes it difficult for soldiers to see that their symptoms better fit a benign explanation than some ominous new syndrome.
Received 7 July 2000 Accepted 7 July 2000
SYMPTOMS BEING REPORTED
Correspondence to: Dr R. Ferrari, 12779-50 Street, Edmonton, Alberta, Canada T5A 4L8. Phone: 780-990-8310; Fax: 780-473-3529; E-mail: [email protected]
There are neither specific symptoms that identify Gulf War syndrome nor any overall specific pattern of symptoms that Gulf War veterans report. Of those veterans 697
698
Ferrari and Russell
who are believed to possibly be ill with the toxic exposures in the Gulf War, various surveys of samples ranging from small groups (tens) to over 70 000 give a prevalence of symptoms ranging from 5–50% (1–15). The most common symptoms seem to be fatigue, followed by depressed mood or anxiety, and then pain. The symptoms are not only non-specific, but the relative prevalence pattern (in terms of distribution of symptoms) is very similar to that reported in general population surveys (16–19). It is true that the Gulf War veterans and the general population samples have some demographic differences, but it is equally true that the Gulf War veterans are likely to carry the background population risk of having such symptoms (at least 5–10%) even if they were not victims of toxic exposure. Gulf War veterans do not report a more selective or specific pattern of symptoms when compared, for example, to Bosnia veterans, but do report them more frequently (8). Haley et al. attempted to find a symptom pattern, and thought they did (1), but their study is severely hampered by selection bias: it was not population-based, but rather focused on a very small group of soldiers (249) from one unit, and had only 41% of the available members of the battalion unit participate. In addition, there were no controls from any source and all information regarding symptoms and toxic exposures was self-reported with no attempt to verify the exposures described (20). Indeed, larger and better designed studies failed to uphold Haley’s suggestion of specific symptom groupings that could separate these symptoms from the ‘normal’ ones found in the general population or in subjects with other well-recognized illnesses (4,7,8,17,21). Further complicating the difficulty of specificity is the lack of a specific onset of symptoms. Kroenke et al. found, in a study of 18 000 veterans, that about 40% of the symptoms being reported did not being until more than one year after the return from the war, and they found no correlation between symptoms and self-reported exposures in this large population (3). This study was much larger (over 18 000 subjects) and more thorough than those of Haley and others (5). PSYCHOLOGICAL DISORDERS AND FACTORS Among the more common symptoms being reported are anxiety or depressed mood. Depression and anxiety may have somatic symptoms that accompany the psychological distress, but it could also be that the effect of stress is to amplify various common, even normal, symptoms that have benign origins and are frequent in the general population. When one is expecting symptoms, especially with the possibility of an ominous new disease, one is in a state of hypervigilance, the result of which is to register Medical Hypotheses (2001) 56(6), 697–701
normal bodily sensations as abnormal, and to react to bodily sensations with affect and cognitions that intensify them and make them alarming, ominous and disturbing – i.e. symptom amplification (22,23). Thus, it may not be necessary to postulate that stress causes the symptoms, but rather that stress causes the benign symptom pool of daily life to be noticed and causes the individual to attach a special significance to them. The cascade of media coverage, together with uncertainty, fear and also perhaps the initial governmental handling of the problem further fuelled suspicion and paranoia. Unwin et al. (9) comment on the reportedly large numbers of US personnel who, before the active conflict, reported the anticipation of attack by chemical weapons, biological weapons or both as their greatest fear. Even years later, Unwin et al. found nearly all Gulf War veterans remember wearing nuclear-biological-chemical suits and hearing chemical alerts, 26% reporting a SCUD missile explosion nearby and 9% believed that they had been exposed to a chemical attack (9), even though the evidence that there was any definite chemical attack is absent. Post-traumatic stress disorder (PTSD) has been a diagnosis given in many such individuals. This diagnosis has numerous pitfalls, even in war veterans. Haley et al. have questioned the diagnosis of PTSD in many cases. They estimated that the prevalence of PTSD is virtually nil in Gulf War veterans. They argue that questionnaire studies overestimate PTSD prevalence, but even if this is true it does not necessarily follow that this rules out psychological factors altogether. An important stressor may have occurred upon returning home and having one’s fears of toxicity reinforced by the publicity attached to this ‘mysterious illness’ developing in Gulf War veterans. These psychological factors are simply part of a culture that is looking for a syndrome and accountability. This approach to assign a ‘cause’ to a collection of common symptoms and to then label it as a disease has been reviewed elsewhere (24). The phenomenon does not produce the symptoms, but rather the behaviour of Gulf War veterans. It is intriguing, for example, that despite the extensive discussion and research taking place with Canadian, British and American war veterans, there have been very few reports of a Gulf War syndrome in many of the other participating countries who sent soldiers to the Persian Gulf. Many of these participating countries have sophisticated medical systems and ample opportunity for soldiers who feel ill to seek attention. RISK FACTORS FOR BEING A GULF WAR SYNDROME PATIENT Since the vast majority of veterans do not believe they have this as yet undefined syndrome, one can study © 2001 Harcourt Publishers Ltd
The problem of Gulf War syndrome
those who believe they do and try to compare the two groups to find risk factors for not only the symptoms, but also the belief system that is associated with those symptoms. Gray et al. (15) compared 70 000 Gulf War veterans who sought medical attention in the Department of Veteran Affairs Persian Gulf Veterans’ Health Registry with nearly 700 000 who did not in order to determine the personnel most likely to seek medical evaluation. Risk factors that clearly do not have overt or likely significant biological implications (in terms of toxic exposure, for example) include the fact that married personnel, female personnel and health care workers were the most likely to seek treatment for these symptoms. Also a predictor of bringing post-war symptoms to medical attention was hospitalization in the 12 months prior to the war. Thus, those Gulf War veterans suspected of having Gulf War syndrome may simply be those who are most apt to fear health consequences and seek attention for symptoms that may very well be entirely benign and shared by many veterans not seeking medical attention. One sees the same with fibromyalgia. The symptoms of widespread discomfort and fatigue are common in the population. What distinguishes patients from normals is that they seek medical attention for their problems. STUDIES OF PATHOLOGY IN GULF WAR VETERANS Attempts to find specific forms of pathology (or any pathology at all) associated with ‘Gulf War symptoms’ have been unrewarding. Using batteries of urine and blood tests as well as more specialized tests, abnormalities are few and inconsistent (3,4,6,7). Most of the toxins of concern in the Gulf War are encountered first by the respiratory system, especially from oil well fires, pesticides and possible biochemical warfare. However, there has been little investigation into this aspect, particularly as the only pulmonary symptoms have been shortness of breath and cough, with no specific lung pathology that can be identified to indicate lung damage. In two non-population based studies of very small groups of veterans complaining of cough, the researchers found those complaining of cough were more likely to have inflammation of the upper airways than healthy people without cough, and minor abnormalities in overall lung function (22). Of course, this merely tells us that those complaining of cough were likely telling the truth. It tells us little about the cause of the cough, as one would find the same results in non-soldiers who have chronic, unexplained cough. The question that is not addressed is: Does being a Gulf War veteran bring any greater risk of having a cough than not being a Gulf War veteran? There is no evidence. We also know that the air © 2001 Harcourt Publishers Ltd
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quality in the Gulf, despite all the oil fires, was no worse than that in a number of North American cities (26,27). There has been limited research evaluating both the immune system and urinary tract in small groups of patients reporting a multitude of non-specific symptoms (4,29,30). No abnormalities could be found in patients studied thus far. Finally, the nervous system has been evaluated for evidence of pathology. There has been extensive theorizing by Haley et al. about neurotoxicity (30), but no clear proof. Jamal et al. (32) thought there was evidence of neurotoxicity, but the study was later found to be highly deficient, both in selection of subjects (14 of 40 available) and misinterpreting the results of nerve conduction studies (33). As Amato et al. noted, given that 700 000 soldiers (from Canada, the UK and the USA) were in the Gulf War, it is inevitable that one is going to find some of them developing neurologic conditions or symptoms in their lifetime. The question is: Are they any more at risk for doing so after having been in the Gulf War? Given the difficulty in finding clear evidence of neurotoxicity despite the large number of potential exposures, this seems unlikely. Finally, researchers who tested neuropsychological functioning found no evidence to suggest brain injury or other nervous system dysfunction or a correlation between neuropsychological function and any exposures related to the war. Instead, there was a strong correlation between neuropsychological function and emotional function (34). Thus, despite a multitude of symptoms, and in some cases disability, there is little, if any, pathology to be found in these Gulf War veterans. THE HEALTH OF SOLDIERS NOW AND THEN This is not the first time there have been controversies regarding health outcomes in war veterans – which is a final reason to question the existence of a new, unique syndrome. There is nothing new about the complaints of Gulf War veterans compared to veterans of previous wars. Hyams et al. review the history of post-war syndromes from the American Civil War to the Vietnam War (35). The Civil War led to controversies of ‘irritable heart’ syndrome, World War I to DaCosta’s syndrome, World War II to combat stress reaction, Vietnam to Agent Orange exposure and Post-Traumatic Stress Disorder. Hyam, et al. show that although there is a wide array of symptoms, they have remained similar over a 150-year period. CONCLUSION The trouble with looking for an entirely undefined, unknown syndrome is that one is inevitably going to find Medical Hypotheses (2001) 56(6), 697–701
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some patients who really do have symptoms and disease. That is in part because wars have always had some measure of health effects, often with multiple factors involved. Symptoms are a part of normal, healthy (veteran or civilian) existence. It is therefore normal for Gulf War veterans to have many of these ‘normal’ symptoms, and they may even have had them before the war. What is abnormal is the sociocultural environment in which these symptoms exist, and it is that environment that needs more investigation. The post-war environment is one of emotional distress of a variety of forms, of fears of toxic exposure, and, to some extent perhaps, the understandable feeling of injury over the fact that when one has put one’s life on the line for one’s country, the country ought to extend the utmost efforts in protecting the health of the heroes that return. In the expectation of a syndrome from toxic exposures, the many non-specific symptoms of these soldiers may have multiple (otherwise benign) causes, yet will be attributed to a unique exposure-related syndrome. Further, hypervigilance alone will cause healthy subjects to register normal and otherwise benign bodily and mental symptoms that they might otherwise have ignored, attach a special, ominous significance to them, and suggest the need to embark on medical attention for them (22,23). In the expectation of a Gulf War syndrome, future symptoms amplified and registered in this way will quite naturally be attributed to that mysterious syndrome, particularly if the medical community reinforces this belief. There is thus a failure of the medical community in the Gulf War syndrome controversy, not so much in failing to identify a specific syndrome, but in failing to recognize that many factors affect perceptions of health and illness. These factors often have little to do with the origin of symptoms themselves, but do contribute to illness perception (33). Further, there has been a failure to recognize that the existence of multiple, sometimes chronic and unexplained, symptoms is common in the general population and not necessarily relevant to disease, but rather relevant to one’s perceptions of illness. There is also much that the Governments could have done (especially in terms of collecting pre-conflict health data and maintaining data about exposures) that was not done. Efforts to remedy this for future conflicts have since been underway (20). Veterans can be told that being a Gulf War veteran does not make one immune from being a normal citizen again, experiencing the many illnesses and health issues that arise in the future, irrespective of past war exposures. Finally, they have anxieties and perhaps even depression. That is normal and natural for what they experienced, and for what they are being put through now by those who would investigate them for Gulf War Syndrome on the one hand, and those that would label them with Medical Hypotheses (2001) 56(6), 697–701
‘psychological disorder’ on the other. In many cases, they may have neither. They may just be healthy warriors, who deserve the opportunity to put the Gulf War behind them. REFERENCES 1. Haley R. W., Kurt T. L., Hom J. Is there a Gulf War Syndrome? Searching for syndromes by factor analysis of symptoms. JAMA 1997; 277: 215–222. 2. Iowa Persian Gulf Study Group. Self-reported illness and health status among Gulf War veterans. A population-based study. JAMA 1997; 277: 238–245. 3. Kroenke K., Koslowe P., Roy M. Symptoms in 18, 495 Persian Gulf War veterans. JOEM 1998; 40: 520–528. 4. Fukuda K., Nisenbaum R., Stewart G., Thompson W. W., Robin L., Washko R. M. et al. Chronic multisystem illness affecting air force veterans of the Gulf War. JAMA 1998; 280: 981–988. 5. Proctor S. P., Heeren T., White R. F., Wolfe J., Borgos M. S., Davis J. D. et al. Health status of Persian Gulf veterans: Self-reported symptoms, environmental exposures and the effect of stress. Int J Epidem 1998; 27: 1000–1010. 6. Escalante A., Fischbach M. Musculoskeletal manifestations, pain, and quality of life in Persian Gulf war veterans referred for rheumatologic evaluation. J Rheumatol 1998; 25: 2228–2235. 7. Coker W. J., Bhatt B. M., Blatchley N. F., Graham J. T. Clinical findings for the first 1000 Gulf War veterans in the Ministry of Defense’s medical assessment programme. BMJ 1999; 318: 290–294. 8. Ismail K., Everitt B., Blatchley N. F., Hull L., Unwin C., David A. et al. Is There a Gulf War syndrome? Lancet 1999; 353: 179–182. 9. Unwin C., Blatchley N. F., Coker C., Ferry W., Ferry S., Hotopf M. et al. Health of UK servicemen who served in Persian Gulf War. Lancet 1999; 353: 169–178. 10. Kipen H. M., Hallman W., Kang H., Fiedler N. Prevalence of chronic fatigue and chemical sensitivities in Gulf registry veterans. Arch Environ Health 1999; 54: 313–318. 11. Ishøy T., Suadicani P., Guldager B., Appleyard M., Ole Hein H. et al. State of health after deployment in the Persian Gulf. Dan Med Bull 1999; 46: 416–419. 12. Ishøy T., Suadicani P., Guldager B., Appleyard M., Gyntelberg F. Risk factors for gastrointestinal symptoms. Dan Med Bull 1999; 46: 420–423. 13. Suadicani P., Ishøy T., Guldager B., Appleyard M., Gyntelberg F. Determinants of long-term neuropsychological symptoms. Dan Med Bull 1999; 46: 423–427. 14. Gray G. C., Smith T. C., Kang H. K., Knoke J. D. Are Gulf War veterans suffering war-related illnesses? Federal and civilian hospitalizations examined, June 1991 to December 1994. Am J Epidemiol 2000; 151: 63–71. 15. Gray G. C., Hawksworth A. W., Smith T. O. et al. Gulf War veterans’ health registries. Who is most likely to seek evaluation? Am J Epidemiol 1998; 148: 343–349. 16. Kroenke K., Price R. K. Symptoms in the community. Arch Intern Med 1993; 153: 2474–2480. 17. Hyams K. C. Developing case definitions for symptom-based conditions: The problem of specificity. Epidemiol Review 1998; 20: 148–156. 18. Simon G., Gater R., Kisely S., Piccinelli M. Somatic symptoms of distress: An international primary care study. Psychosom Med 1996; 58: 481–488. 19. Verbrugge L. M., Ascione F. J. Exploring the iceberg. Common symptoms and how people care for them. Med Care 1987; 25: 539–569.
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