Gulf War Illness: Challenges Persist.

It has been more than 20 years since the United States and coalition forces entered Kuwait and Iraq. Actual combat was of remarkably short duration: less than 1 week of sustained ground activity and 6 weeks of air missions. Thus, it was surprising when approximately 200,000 returning US veterans were affected by a chronic multi-symptom illness that came to be known as Gulf War Illness (GWI). There were many challenges in investigating GWI, not least of which was that it took several years before the condition was officially taken seriously. There were multiple exposures to potentially causal agents on and off the battlefield, but these exposures were documented incompletely if at all, leaving epidemiologists to rely on self-report for information. In the past 2 years, significant controversy has arisen over the future directions of the field. Despite these challenges, several studies have implicated exposure to acetylcholinesterase inhibitors such as pyridostigmine bromide in the genesis of the condition. The story of GWI can inform research into other conditions and guide future work on veterans' health.

Historical approaches to post-combat disorders.

Almost every major war in the last century involving western nations has seen combatants diagnosed with a form of post-combat disorder. Some took a psychological form (exhaustion, combat fatigue, combat stress reaction and post-traumatic stress disorder), while others were characterized by medically unexplained symptoms (soldier's heart, effort syndrome, shell shock, non-ulcer dyspepsia, effects of Agent Orange and Gulf War Syndrome). Although many of these disorders have common symptoms, the explanations attached to them showed considerable diversity often reflected in the labels themselves. These causal hypotheses ranged from the effects of climate, compressive forces released by shell explosions, side effects of vaccinations, changes in diet, toxic effects of organophosphates, oil-well fires or depleted-uranium munitions. Military history suggests that these disorders, which coexisted in the civilian population, reflected popular health fears and emerged in the gaps left by the advance of medical science. While the current Iraq conflict has yet to produce a syndrome typified by medically unexplained symptoms, it is unlikely that we have seen the last of post-combat disorders as past experience suggests that they have the capacity to catch both military planners and doctors by surprise.

Somatic hypotheses of war syndromes.

Since the end of the American Civil War, unexplained symptoms in military personnel arising after a war or peace mission have frequently been described. The pattern of symptoms is highly similar for all of the various war syndromes although the conditions of each war or peace mission are widely different. Many somatic hypotheses have been formulated to explain these syndromes; a considerable proportion of them are already outdated. In the last few years much attention has been given to Gulf War Syndrome and to unexplained symptoms of military personnel who were sent to Cambodia, Rwanda, Burundi, Zaire, or the former Yugoslavia. In this review the symptoms of war syndromes will be considered in more detail and the suggested somatic explanations will be discussed. During the last decade the following somatic causes have been suggested as possible explanations for these symptoms: (persistent) infection, abnormal immune response, administration of multiple vaccinations within a short period of time, use of malaria chemoprophylaxis, neurological abnormalities, exposure to toxicological substances and environmental factors. The various investigations performed to study these hypotheses are discussed. The fact that bias regularly occurs in the course of these investigations is pointed out. For the future, a reliable investigation of a war syndrome should be a prospective multidisciplinary study and should distinguish between causative and sustaining factors.