Shortly after their return from Gulf War (GW) deployment in 1991, some GW veterans began reporting a constellation of health symptoms that generally did not meet criteria for well-defined medical conditions or syndromes. Symptoms included joint pain, headaches, memory and attention difficulties, skin rash, gastrointestinal difficulties, breathing problems, and sleep difficulties. Clinicians were faced with the problem of identifying what was causing these symptoms and with how to treat them. Researchers took on the challenge of identifying the most important features of this illness in their first attempts at a case definition. The initial attempts at identifying the most important symptoms of Gulf War illness (GWI) were done by using a one-time health symptom report (cross-sectional studies). This one-time assessment of function has not proven effective for determining a case definition of GWI given that many GW veterans have symptoms that may come and go or change over time. Given that current estimates suggest at least 25 percent of Gulf War veterans (170,000 veterans) have reported some type of persisting multi-symptom illness and in order to stimulate more appropriate treatment avenues for this large number of ill veterans, it is essential that a better case definition of GWI be devised right away. This refined case definition should take change over time into account and examine the reasons why some veterans have reported improved or worse symptom profiles over time. This examination should include evaluations of prior treatment effectiveness as well as individual environmental exposures and genetic susceptibility to those exposures.

A new approach to solving the case definition problem in GWI is to employ a case study design that takes symptom change over time into account (longitudinal study). This is possible only by employing a large longitudinally followed cohort of GW veterans in order to document persistent, increasing, declining, and late-emerging symptoms. The Ft. Devens cohort from the Department of Veterans Affairs (VA) Boston Healthcare System is uniquely suited to provide this function because these veterans were initially assessed just days after their return from deployment and at two additional time points during the past 19 years. To our knowledge, this is the only cohort with the ability to compare multiple time points over virtually the entire time span since the end of the war. The reason why it is important to devise an improved case definition of GWI for researchers and clinicians is to provide a gold-standard definition to be used in future treatment trials. A major limitation to current treatment trials is the lack of consistently used case criteria for GWI and as such evaluating the effectiveness of individual therapies is dependent as much upon the case criteria used as on the specific treatment employed. This makes evaluating the effectiveness of different treatment trials extremely difficult. This proposed study will include follow-up testing of this well-established cohort of GW veterans by using an online web survey to update current health symptoms. In addition, a smaller sample of veterans will be asked to give a blood sample to identify possible predisposing or current markers of illness. Health symptoms from the online survey (Time 4) will be compared with prior health symptoms from previous studies (Time 1-3) of this cohort in order to compare health symptom changes over time. Study goals will be to devise a new case definition for GWI (that will be compared with current case definitions) and to identify potential reasons for improvement of function or worsening of function over time. Results of this study could not only allow for a true comparison of future treatment trials but may also lead to important clues regarding which treatments may be most effective for different groups of ill veterans (based on prior illness trajectories and predisposing genetic susceptibilities).