Purpose: To better understand the health problems
of veterans of the Persian Gulf War by analyzing previous war-related
illnesses and identifying possible unifying factors.
Data Source: English-language articles and books
on war-related illnesses published since 1863 that were located primarily
through a manual search of bibliographies.
Data Extraction: Publications were assessed for information
on the clinical characteristics of war-related illnesses and the research
methods used to evaluate such illnesses.
Data Synthesis: Poorly understood war syndromes have
been associated with armed conflicts at least since the U.S. Civil War.
Although these syndromes have been characterized by similar symptoms (fatigue,
shortness of breath, headache, sleep disturbance, forgetfulness, and impaired
concentration), no single recurring illness that is unrelated to psychological
stress is apparent. However, many types of illness were found among evaluated
veterans, including well-defined medical and psychiatric conditions, acute
combat stress reaction, post-traumatic stress disorder, and possibly the
chronic fatigue syndrome. No single disease is apparent, but one unifying
factor stands out: A unique population was intensely scrutinized after
experiencing an exceptional, life-threatening set of exposures. As a result,
research efforts to date have been unable to conclusively show causality,
have been subject to reporting bias, and have lacked similar control populations.
In addition to research limitations, war syndromes have involved fundamental,
unanswered questions about the importance of chronic somatic symptoms
and the factors that create a personal sense of ill health.
Conclusion: Until we can better understand what constitutes
health and illness in all adult populations, we risk repeated occurrences
of unexplained symptoms among veterans after each war.
After returning home in 1991, some veterans of the Persian
Gulf War began reporting diverse symptoms that have been collectively
called a mystery illness or the Gulf War syndrome (1).
Extensive programs have been initiated by the governments of the United
States, Great Britain, and Canada to provide medical care for veterans
of the Persian Gulf War, to define any new syndrome, and to determine
the causes of the veterans' illnesses (2-4). In the search
for the cause of a previously uncharacterized complex of signs and symptoms
(or syndrome), the question arises whether a similar illness occurred
during or after previous wars. If an analogous illness affected veterans
of other wars, its cause may be related to common wartime experiences
rather than to a unique event during the Persian Gulf War. In this historical
review, war-related syndromes from the U.S. Civil War to the Persian Gulf
War were analyzed to identify possible unifying factors.
U.S. Civil War
During the U.S. Civil War, Da Costa (5) did
one of the first studies of a war syndrome. Da Costa evaluated 300 soldiers
referred to him for a syndrome that he called irritable heart; this syndrome
was principally characterized by shortness of breath, palpitations, and
sharp or burning chest pain, particularly on exertion. Other symptoms
included fatigability, headache, diarrhea, dizziness, and disturbed sleep
(Table 1). There was no consistent sign of physiologic
disease, and most patients appeared to be in fair overall health.
Symptoms of the irritable heart syndrome were not restricted
to soldiers who had been in combat, and Da Costa believed that the condition
occurred in civilian populations. Because many of the patients had had
a recent episode of diarrhea, upper respiratory infection, or febrile
disease, Da Costa concluded that an infectious disease was the cause in
48% of patients. Thirty-five percent of cases were attributed to strenuous
military duties and 18% to miscellaneous causes. Da Costa reported that
38% of patients recovered from the disorder and that administration of
several drugs, including digitalis, may have had a beneficial effect.
On the basis of Da Costa's clinical descriptions, it is
difficult to confidently determine specific diagnoses; however, various
illnesses could have caused the symptoms in these patients (6,
7). Few patients had conclusive evidence
of heart disease. Many patients were debilitated from malnutrition, lack
of exercise, infectious diseases (including malaria and typhoid), and
other adverse medical conditions. Some patients had symptoms of a psychological
illness or stress reaction (8).
In addition to the irritable heart syndrome, a war-related
illness attributed primarily to psychological factors was reported during
the U.S. Civil War. Young soldiers with obsessive thoughts of home received
a diagnosis of a severe form of homesickness called "nostalgia,"
which was characteristically accompanied by extreme apathy, loss of appetite,
diarrhea, and sometimes fever (9, 10).
World War I
A syndrome similar to the one described by Da Costa became a major problem
during World War I: Soldiers had to be evacuated to England because of
shortness of breath, palpitations, and chest pain (11).
Affected soldiers also commonly reported fatigue, headache, dizziness,
confusion, concentration problems, forgetfulness, and nightmares (Table
1) (12-14). This complex of symptoms
became known as soldier's heart or the effort syndrome because symptoms
were exacerbated by effort. It was also called the Da Costa syndrome,
disordered action of the heart, and, in the United States, neurocirculatory
At the beginning of World War I, the effort syndrome was
frequently attributed to cardiac hypertrophy caused by heavy marching
packs compressing the chest (16, 17).
However, as the war progressed, the effort syndrome was believed to encompass
a mixed group of illnesses and causes, including constitutional nervous
weakness and physical weakness; an infectious disease or debility from
previous infections; exhaustion from lack of sleep and exertion in the
trenches; the effects of poison gas; malingering; and, rarely, heart disease
In some cases, onset of symptoms was also associated with acute stress
resulting from combat or burial duties (12, 22).
Digitalis and other drugs did not benefit patients with
the effort syndrome, but a structured rehabilitation program with a graduated
exercise regimen and encouragement from a supervising medical staff were
effective (12, 22).
It was also found that if symptoms of the effort syndrome were attributed
to heart disease, recovery and return to duty were hindered (12,
13). As a result, physicians were advised
not to tell soldiers that they had a heart condition so that the soldiers
would not think of themselves as patients who required evacuation from
the front (12, 21, 22,
A concerted clinical and research program was developed
during World War I to determine the causes and most effective treatment
of the effort syndrome (11). This program
involved clinical care and empirical observations in two specialized hospitals
in England (12) and a specialized referral
center in the United States (7, 17).
After the war, the Medical Research Council continued to oversee clinical
evaluation and additional studies for the British government (11).
Further investigations were given high priority because the effort syndrome
was the third most common reason for disability and compensation assessment
in England; 44 000 veterans eventually received pensions for this condition
(11, 14, 25).
Although clinical studies published at the end of the war
(26-28) indicated that the effort syndrome
was caused by psychological factors, there was little agreement on what
specific symptoms constituted the effort syndrome, whether it was primarily
a physiologic or psychological illness, and even what the official name
of the condition should be (29). However,
there was a consensus that the effort syndrome was not caused exclusively
by unique wartime exposures, because many soldiers reported having had
similar symptoms before the war (12, 19,
Each year for 5 years after World War I, a survey was mailed
to 601 British veterans who had received a diagnosis of the effort syndrome
and who had received pensions (30). Data from this survey
and available medical records identified 52 veterans who had developed
various defined illnesses, including 22 cases of pulmonary tuberculosis
and 6 confirmed cases of cardiac disease. The health of most other veterans
had remained stable, and mortality did not increase.
In addition to the effort syndrome, an acute illness attributed
to combat stress (which was called shell shock or trench neurosis) was
investigated during World War I. This acute combat stress reaction was
first attributed to a strange new disease, possibly caused by concussion
from modern weapons; however, a psychological cause was soon determined
Typical manifestations of acute combat stress reaction included breakdown
in battle, dazed or detached manner, exaggerated startle response, and
severe anxiety (32, 33).
During World War I, it was determined that soldiers with
shell shock could be rapidly rehabilitated if they were cared for near
the front, expecting a quick recovery (32).
After soldiers with shell shock were taken away from their comrades and
treated as patients in a hospital, they were much less likely to return
to combat. Also, the British used the nonspecific term "not yet diagnosed,
nervous (NYD)" for the initial designation of possible victims of
shell shock; this designation prevented soldiers from concluding that
they had a medical condition that required hospitalization (32,
World War II
At the beginning of World War II, the effort syndrome again became an
important medical consideration for the British military (14).
Whether the effort syndrome was predominantly a physiologic or psychological
illness had not been resolved (14, 34).
However, after Wood's influential clinical studies of 200 patients (35-37),
the effort syndrome was generally considered to be a psychoneurosis and
not a medical disease (7).
Acute combat stress reaction (which was known as battle
fatigue, combat exhaustion, or operational fatigue among aviation personnel
during World War II) also became better understood at this time (33,
38). Studies of combat personnel determined
that acute combat stress reaction frequently manifested as somatic symptoms,
including fatigue, palpitations, diarrhea, headache, impaired concentration,
forgetfulness, and disturbed sleep (Table
As in World War I, soldiers with acute combat stress reaction
were more likely to return to duty if they were treated quickly and near
their combat units and received a diagnosis of a normal response to extreme
stress rather than an abnormal condition. Consequently, use of such diagnostic
labels as "war neurosis" was discouraged because they connoted
that soldiers were sick and should be treated as patients (33,
Possibly because the effort syndrome had been attributed to psychological
causes during World War II, it was not reported as a major medical problem
during the Korean Conflict (7). Since the
1940s, the effort syndrome has been identified less frequently as a unique
disease entity (41-43), but the lineages
of many illnesses not related to war have been traced back through the
effort syndrome to the Da Costa syndrome. Such illnesses include anxiety
neurosis and manic-depressive conditions (44),
panic disorders (45), the mitral valve prolapse
syndrome (17, 46),
the hyperventilation syndrome (47), and
the chronic fatigue syndrome(48).
As in World War I and World War II, acute combat stress reaction was
an important clinical problem during the Korean Conflict (33,
The most prominent illness related to the Vietnam War was post-traumatic
stress disorder (49), which was initially
called post-Vietnam syndrome (50, 51).
Whereas acute combat stress reaction is the immediate consequence of psychological
trauma, post-traumatic stress disorder more often refers to the long-term
consequences of extreme psychological stress (52).
Post-traumatic stress disorder has also been recognized as a problem in
veterans of both the Korean Conflict and World War II (53),
especially former prisoners of war (54,
55), and has been found in civilians exposed
to extreme trauma not related to war (51).
No other prominent, poorly understood war syndrome was associated with
the Vietnam War (56-58), although controversy
about the role of Agent Orange (dioxin) exposure in the development of
various medical problems and birth defects continues (59).
Chronic somatic symptoms have generally not been linked to the effects
of herbicide exposure in Vietnam. However, it is noteworthy that the somatic
symptoms frequently described by Vietnam veterans who may have been exposed
to Agent Orange (56, 58,
60) are similar to the symptoms commonly
associated with other war-related illnesses (61), including
acute combat stress reaction (39) and post-traumatic
stress disorder (62-68) (Table
Persian Gulf War
After Iraq invaded Kuwait in August 1990, 697 000 soldiers from the United
States, 45 000 soldiers from Great Britain, and 4500 soldiers from Canada
were deployed to the Persian Gulf during a 5-month buildup period; this
period was followed by a 39-day air war and a 4-day ground war in February
1991. Far fewer casualties than anticipated occurred among coalition forces,
and morbidity rates were low compared with those in previous wars (69,
After the war ended, troops returned home, and veterans from diverse
military units of the United States, Great Britain, and Canada began reporting
various chronic symptoms, often referred to as the Gulf War syndrome (71-77).
Fatigue, headache, muscle and joint pain, diarrhea, skin rashes, shortness
of breath, and chest pain have been common symptoms (Table
1) (2, 78-80).
Various neuropsychological symptoms also have been common -- particularly
sleep disturbances, impaired concentration, forgetfulness, irritability,
and depression. Currently, no characteristic physical sign or laboratory
abnormality has been identified (2, 80,
No medical reports of similar unexplained illnesses among other coalition
troops or among persons indigenous to the Persian Gulf have been published.
During World War II, no similar unexplained illnesses were seen among
the British and U.S. forces stationed in the Persian Gulf (82).
Personal accounts of family members developing symptoms similar to those
of relatives who served in the Persian Gulf War and increased birth defects
among children born after the war have been reported (2,
83). Other recent war-related conditions
have been associated with medical and psychological problems among family
members (59, 84), but
accounts of health problems among family members of veterans who received
a diagnosis of a war-related illness did not increase during World War
I or World War II.
The health problems experienced by veterans after service in the Persian
Gulf War have been considered a serious matter by the involved governments,
a response similar to that seen for the effort syndrome in World War I.
A tri-agency coordinating board has been established in the United States
to supervise a comprehensive clinical and research program (85-87),
and compensation is being provided to disabled war veterans who have unexplained
illnesses (U.S. Public Law 103-446, 2 November 1994). In addition, the
U.S. Department of Veterans Affairs, the U.S. Department of Defense, and
the governments of Great Britain and Canada have established self-referred
health registries and specialized centers that provide comprehensive clinical
examinations and medical care (2-4).
Clinical evaluation of more than 80 000 veterans and initial epidemiologic
surveys have identified a broad range of health problems (2,
80, 88, 89),
including symptoms of post-traumatic stress disorder in 5% to 15% of some
veteran populations (90-94); however, a
new or unique syndrome has not yet been identified (80).
Preliminary results of epidemiologic studies of veterans of the Persian
Gulf War show no overall increase in hospitalization rates (95),
birth defects (96), or mortality due to
medical causes (97).
Available information on the nature and cause of illnesses among veterans
of the Persian Gulf War has been evaluated by five independent panels
in the United States (70, 98-101).
These panels did not identify a new illness (70,
or establish a case definition of a unique syndrome (70,
98, 99, 101);
they concluded that veterans of the Persian Gulf War had numerous illnesses
that resulted from various causes (70, 98).
However, one advisory committee concluded that a rare or mild illness
could be missed by large case series, such as the Persian Gulf health
registries, which have examined approximately 10% of all U.S. veterans
of the Persian Gulf War (100).
Comparison of War Syndromes
Since the U.S. Civil War, two general categories of war-related
illnesses have been recognized: one poorly understood group thought to
be associated with physiologic disease and another group of psychological
illnesses attributed to wartime stress (Table
2). Although there have been two general types of war-related illnesses,
war syndromes have not been consistently defined or identified by a pathognomonic
physical sign or laboratory abnormality. As a result, the diagnosis of
a physiologic or psychological illness in individual patients has been
imprecise and has depended on self-reported symptoms and the impression
of the examining physician (8, 13,
34, 61, 98).
The war syndromes thought to be associated with organic
pathology have been characterized by two similarities that could indicate
a related disease. From the Da Costa syndrome to the more recent Gulf
War syndrome, the first common feature has been the similarity of reported
symptoms. Shared symptoms include fatigue, shortness of breath, headache,
sleep disturbances, impaired concentration, and forgetfulness (Table
1). Common symptoms alone, however, do not show that veterans of various
wars had a related disease process, because such symptoms are nonspecific
and are frequently found in all adult populations (102-106),
particularly among persons with psychological stress (39,
and post-traumatic stress disorder (62,
A second possible unifying factor has been the high frequency
of reported diarrhea and other infectious diseases preceding the onset
of these syndromes (5, 13,
The significance of this factor is unclear because crowded populations
of military personnel, particularly troops sent to tropical and developing
regions, have an inevitably high rate of infectious disease (58,
82). However, no unique, deployment-related
syndrome has been reported after large peacetime military exercises. In
addition, infectious diseases have not been proven to cause chronic somatic
symptoms in the absence of measurable signs of disease (110),
except possibly among persons prone to depression (111,
112). Nevertheless, convalescence can be
prolonged after many infections (113),
and the chronic fatigue syndrome, although not associated with characteristic
signs of disease, is suspected of having an infectious origin (114).
Other than these two similarities, there is little additional
evidence of a single, unique war syndrome that is unrelated to psychological
stress. However, 19th-century and early 20th-century clinical characterizations
are difficult to compare with modern data, and the psychological aspects
of illness were not as well appreciated and reported in the past. Furthermore,
because of the general improvement in health and nutrition during this
century, it is difficult to compare the illnesses of military populations
of different eras.
Although historical data are difficult to compare, ample
evidence shows that numerous complex factors were responsible for the
health problems of war veterans, as in any population, and that many illnesses
were described after successive wars. A substantial proportion of veterans
with chronic somatic symptoms were found to have various physiologic and
psychological illnesses (13, 30,
80, 89). In
addition, veterans of each war had high rates of acute combat stress reaction
and post-traumatic stress disorder (33).
Still other veterans had illnesses that meet the recently suggested criteria
for a diagnosis of the chronic fatigue syndrome (48,
70, 89, 115).
Although no single, recurring war-related disease has been
identified, many aspects of the process used during the past 130 years
to evaluate the health problems of veterans have been repeated with each
war. The most important and consistent factor is that this process has
involved medical evaluation after the critical event, thereby precluding
a definitive demonstration of causality. Consequently, numerous illnesses
that occur after a war may be attributable to wartime exposure, and epidemiologic
studies, regardless of their size or design, cannot conclusively resolve
medical, legal, and political questions about the causes of post-war health
problems (116). In addition to the problems of interpreting
the results of retrospective studies, it has been difficult to identify
similar control populations because of the exceptional nature of wartime
experiences and the unique characteristics of military populations.
Because studies of war-related illnesses have been done
after exposure and without similar control groups, research efforts have
frequently been limited to the evaluation of a series of clinical cases.
Research efforts have been further hampered because war syndromes have
not been associated with characteristic and measurable signs of disease
that would allow for the development of specific case definitions (8,
98). In addition to these research limitations,
the problem of diagnostic labeling has played a critical role in the evaluation
of war syndromes. The naming of a syndrome has repeatedly exerted a powerful
effect on the medical approach toward, official recognition of, and patient
perception of these poorly understood conditions (11,
33). A medically recognized diagnosis fundamentally
alters the lives of active-duty military personnel and veterans, influencing
everything from type and location of duty assignment to medical treatment,
expectations of recovery, and eligibility for compensation (13,
37). The influence of a medical classification
has also been found to be substantial among nonmilitary populations (117-119).
Despite enormous progress in medical science, poorly understood
war syndromes have recurred at least since the U.S. Civil War. No single,
previously uncharacterized illness or underlying cause that is unrelated
to psychological stress is apparent from the available reports. However,
many illnesses have been found among war veterans evaluated for these
syndromes. As expected in any large adult population exposed to complex
environmental and psychological conditions, various health problems have
Although no unique war-related disease is evident, one unifying
factor has been prominent in the evaluation of these syndromes: A unique
population was intensely scrutinized after experiencing an exceptional,
life-threatening set of exposures. The process by which these syndromes
were evaluated and defined is the most evident similarity.
Designing studies to evaluate the health of war veterans
inevitably presents several serious methodologic problems (116).
For example, it is difficult to obtain accurate health and risk factor
data after a potentially harmful experience, particularly if there has
been extensive or sensational media coverage, because of reporting bias
(120-122). During wartime conditions, it is not feasible
for the military to collect comprehensive exposure data among combat troops
because the primary focus must be to fight and win the war.
An apparent solution to these methodologic problems is to
gather more extensive baseline medical and exposure data and to design
large prospective studies before any future conflict. As a result of numerous
recent overseas deployments, the U.S. Department of Defense is developing
a greatly enhanced surveillance system. For military operations in Bosnia,
which began in 1995, environmental and infectious disease surveillance
teams have been deployed; U.S. troops are being provided extensive health
guidance before, during, and after the operation; medical and psychological
screening will occur before and after deployment; and a repository for
serum collected before and after deployment is being established (123).
Intensive surveillance will substantially aid in the evaluation
of veterans' health. However, it will be difficult to design prospective
studies to answer all post-war health questions because the location and
nature of each war varies too greatly to predict every health risk. In
addition, studies of military populations alone will not sufficiently
explain war-related syndromes because these syndromes involve fundamental,
unanswered questions about health and illness. To more fully understand
the health of any population, military or civilian, research efforts will
have to be done to answer two basic questions: 1) What is the relation
between chronic, non-specific symptoms and physiologic and psychological
illness (124-127)? 2) What factors -- medical,
environmental, psychological, or social -- create a personal sense of
ill health (128-131)?
Evaluating fundamental questions of health in large populations
is always extraordinarily difficult, but is particularly so after traumatic
and complex wartime events. Nevertheless, unless these difficult questions
are answered, we risk repeated occurrences of unexplained symptoms among
veterans after each war.
This work was supported by the U.S. Naval Medical Research
and Development Command, NMC, NCR, Bethesda, MD.
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Table 1. Somatic Symptoms Commonly Associated
with War-Related Medical and Psychological Illnesses*
War and Illness
||U.S. Civil War Da Costa Syndrome
||World War I, Effort Syndrome
||World War II, Combat Stress Reaction
||Vietnam, Agent Orange Exposure
||Vietnam and Other Conflicts, Post-Traumatic
||Persian Gulf, Unexplained Illnesses
|Fatigue or exhaustion
|Shortness of breath
|Palpitations and tachycardia
|Muscle or joint pain
Table 2. Comparison between Categories of War-Related
Category of Illness
|U.S. Civil War
||Da Costa syndrome
|World War I
(soldier's heart, neurocirculatory asthenia)
|World War II
||Agent Orange exposure
||Post-traumatic Stress disorder
|Persian Gulf War
||Gulf War syndrome