Reprinted with permission of the Annals of Internal Medicine. The American College of Physicians is not responsible for the accuracy of this translation. Reference: Ann Intern Med 1996;125:398-405.
REVIEW
War Syndromes and Their Evaluation: From the U.S. Civil War to the Persian Gulf War
Kenneth C. Hyams, MD, MPH1
F. Stephen Wignall, MD2
Robert Roswell, MD3
The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the U.S. Navy, Department of Defense, or Department of Veterans Affairs.
Abstract
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.
Introduction
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.
War Syndromes
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 asthenia (15).
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 (12-14, 18-23). 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, 24).
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, 22).
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 (31, 32). 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, 33).
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
1) (39).
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, 39,
40).
Korean Conflict
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,
38).
Vietnam War
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 1).
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, 70).
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, 81).
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, 98, 100) 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, 56,
107) and post-traumatic stress disorder (62, 63, 108).
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, 19, 109). 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).
Conclusions
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 developed.
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
Symptom | 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 Stress Disorder |
Persian Gulf, Unexplained Illnesses |
Fatigue or exhaustion | + | + | + | + | + | + |
Shortness of breath |
+ | + | + | + | + | + |
Palpitations and tachycardia |
+ | + | + | + | ||
Precordial pain | + | + | ||||
Headache | + | + | + | + | + | + |
Muscle or joint pain |
+ | + | ||||
Diarrhea | + | + | + | + | ||
Excessive sweating | + | + | + | |||
Dizziness | + | + | + | + | + | |
Fainting | + | + | ||||
Disturbed sleep | + | + | + | + | + | + |
Forgetfulness | + | + | + | + | + | |
Difficulty concentrating |
+ | + | + | + | + |
Category of Illness
War |
Physiologically Attributed |
Psychologically Attributed |
U.S. Civil War | Da Costa syndrome (irritable heart) |
Nostalgia |
World War I | Effort syndrome (soldier's heart, neurocirculatory asthenia) |
Shell shock trench neurosis) |
World War II | Effort syndrome | Battle fatigue, Combat exhaustion, operational fatigue |
Korean Conflict | Battle fatigue, combat exhaustion |
|
Vietnam War | Agent Orange exposure | Post-traumatic Stress disorder (Post-Vietnam syndrome) |
Persian Gulf War | Gulf War syndrome | Post-traumaticstress disorder |
-end-