Gulf War Syndrome: The Final Chapter?

Dr. Sartin is on the speaker’s bureau for Ortho-McNeil, Inc and Pfizer Inc. In 2000, I authored an article in Mayo Clinic Proceedings that summarized the scientific evidence that had accumulated on “Gulf War Syndrome” up to that point. After reviewing a myriad of studies, including basic science and epidemiological inquiries, I validated the results of preliminary studies and concluded that, although many veterans had subjective feelings of illness, there was little objective evidence for a single condition afflicting Gulf War veterans. As might be expected, more research was recommended to delineate the uncertainties surrounding this highly charged issue. Since that publication, more studies have been performed, and now the Institute of Medicine (IOM) has issued the final of a series of comprehensive reports encompassing more than 14 years of scientific data. Drawing on previous efforts, the authors reiterated their view that, “although deployed veterans report more symptoms and more severe symptoms than their nondeployed counterparts, there is not a unique symptom complex (or syndrome) in deployed Gulf War veterans.” Mortality and rates of hospitalization were not higher among Gulf War veterans, and no increase in birth defects was seen. Objective measures of disease, such as pulmonary function testing and peripheral nerve electromyography, showed no differences between deployed veterans and their nondeployed peers. However, the IOM’s authors again noted that Gulf War veterans experienced various symptoms and were diagnosed as having multisymptom conditions, such as fibromyalgia and chronic fatigue syndrome, at a higher rate than their peers. Psychiatric disorders were more common. Retrospective studies suggest a small increase in the risk of developing amyotrophic lateral sclerosis, although the absolute risk remains very low (0.43 cases per 100,000). Along the way, a number of hypotheses fell by the wayside or remained ensnared in a web of ambiguity. The Mycoplasma theory promoted primarily by Nicolson has not been confirmed; in fact, a multicenter study found no evidence of mycoplasmas as the etiology of veterans’ complaints and found doxycycline to be no better than placebo at improving symptoms and functional measures. Reports from Haley’s group of well-defined illness clusters related to exposure to chemical weapons, insect repellents, and pyridostigmine bromide (used prophylactically to neutralize the toxicity of chemical agents) have not been replicated by other researchers, and the Seabee cohorts that were studied look increasingly like outliers not representative of Gulf War veterans as a whole. A host of potential exposures during the first Gulf War were examined by the IOM group, including potentially toxic medications (eg, pyridostigmine), anthrax and other vaccines, depleted uranium, and chemical munitions. These were found to be either of negligible significance or unverifiable and heavily tainted by recall bias: “The rarity of direct assessment of exposure critically hinders evaluation of the potential health effects of specific exposures.” Furthermore, a recent controlled study by Roy et al found that combined use of pyridostigmine and insect repellents diethyltoluamide (DEET) and permethrin was not harmful when used as directed. By far the most contentious issue has been the potential exposure to chemical agents, particularly resulting from the demolition of Iraqi chemical weapon stocks at Khamiseyah in March 1991. More than a decade of review of military records, epidemiological investigation, and computer modeling has failed to answer the simple questions: were servicemen significantly exposed to sarin and cyclosarin, and did anyone become ill from this exposure? The fact remains that studies to date of possibly exposed troops have not indicated any major health effects. The latest IOM report is the product of an exhaustive assessment by well-respected experts in toxicology, occupational health, and numerous medical subspecialties and should, by rights, be the authoritative word on Gulf War illnesses. Although the negative findings should be reassuring to veterans and policymakers, it is unlikely that the controversy will abate. Lack of accurate data and adequate models for exposure mean that the etiology of symptoms reported by many Gulf War veterans will almost certainly remain obscure. Indeed, some veterans groups have indicated they have no intention of accepting this report at face value. On the day the IOM report was released, businessman Ross Perot, whose foundation provided funding for many studies of Gulf War illnesses (including those of Haley) was quoted in response, “There are multiple symptoms. Well, big deal. That doesn’t prove it’s not caused by chemical and biological weapons. These men were wounded.” As we confront another large group of veterans returning from the current war in the Persian Gulf, it behooves us