War syndromes and their evaluation: from the U.S. Civil War to the Persian Gulf 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. 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. Table 1. Somatic Symptoms Commonly Associated with War-Related Medical and Psychological Illnesses* 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 value 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 prominen