One-fourth of the veterans of the 1990-91 Gulf War complain of persistent memory and concentration problems, chronic headaches, widespread pain, gastrointestinal problems, and other chronic abnormalities not explained by well-established diagnoses. Treatments are ineffective and symptoms do not improve over time. Gulf War Syndrome or Gulf War Illness (GWI) is a controversial diagnosis, and some have questioned whether it really exists.
Now a new report from the Research Advisory Committee on Gulf War Veterans’ Illnesses has concluded that Gulf War Illness is real and that it is probably attributable to pyridostigmine bromide (PB), a prophylactic for nerve gas poisoning and pesticide exposures. Its major conclusions:
- Gulf War illness is a serious condition that affects at least one fourth of the 697,000 U.S. veterans who served in the 1990-1991 Gulf War.
- Gulf War illness fundamentally differs from trauma and stress-related syndromes described after other wars.
Evidence strongly and consistently indicates that two Gulf War neurotoxic exposures are causally associated with Gulf War illness: 1) use of pyridostigmine bromide (PB) pills, given to protect troops from effects of nerve agents, and 2) pesticide use during deployment.
The Research Advisory Committee on Gulf War Veterans’ Illnesses was mandated by Congress and appointed in 2002. The report, published November 17, 2008, is an exhaustive review of all available data, including some that is unpublished. It runs to 454 pages, has multiple authors and consultants, lists 1840 references and has multiple appendices. I can’t pretend to have mastered all the information, but I have read enough to understand the basis of their conclusions. They are based on good evidence and logic, but they leave me with some doubts.
Evidence Suggesting GWI Isn’t Real
Skeptics have pointed out that ill-defined syndromes are often reported after wars, attributed to everything from shell shock (World War I) to Agent Orange (Vietnam). Two 1996 articles in the New England Journal of Medicine found no difference in hospitalizations or in death rates from illness in Gulf War veterans. A 1998 study found that Gulf War veterans were less likely to be hospitalized for unexplained illnesses and were healthier overall than veterans who were not deployed. In a 2000 study, factor analysis did not identify a unique Gulf War syndrome. A 2006 report by the U.S. Institute of Medicine found that although veterans of the first Gulf War report significantly more symptoms of illness than soldiers of the same period who were not deployed, studies have found no cluster of symptoms that constitute a syndrome unique to Gulf War veterans. The Committee’s report addresses these and other arguments and rejects them.
If GWI Is Real, What Is It?
The Committee says “there is no question that Gulf War illness is a real condition with real causes and serious consequences for affected veterans.” I don’t think anyone questions that these people are really impaired and are suffering, but that doesn’t say anything about diagnosis or cause.
GWI is a “complex of multiple symptoms not explained by familiar medical or psychiatric diagnoses.” It “does not fit neatly into our current concepts of disease.” We don’t really even have an acceptable case definition. Diagnosis depends on subjective self-reports of symptoms. There are no objective findings on routine clinical tests.
Objective findings on non-routine and experimental tests have generally been of small magnitude, uncertain significance, and have not resulted in anything useful for diagnosis. The report continues:
…neuropsychological studies in Gulf War veterans consistently indicate that symptomatic veterans are affected by persistent, but subtle, “subclinical” central nervous system damage. Symptomatic veterans exhibit decrements in attention and executive system functioning, memory, visuospatial skills, psychomotor functioning, and mood. In some instances, study results reflected slowed response latencies across several cognitive domains. Measured deficits are generally modest and are not identified in all Gulf War veterans with cognitive symptoms. Characterizing Gulf war illness-related cognitive effects requires careful testing and analytic methods…
And I would add that it requires considering that many of these tests are effort-dependent: individuals who report symptoms may not try as hard to succeed.
There is some overlap with other multisystem illnesses like chronic fatigue syndrome (CFS), fibromyalgia, and multiple chemical sensitivity (MCS); but the Committee believes they are distinct entities. “The illness appears not to be the result of a single cause producing a well-known effect” and a synergistic effect of multiple causes may be implicated. “Studies consistently indicate that Gulf War illness is not the result of combat or other stressors and that Gulf War veterans have lower rates of posttraumatic stress disorder than veterans of other wars.” The Committee concludes: “No similar widespread, unexplained symptomatic illness has been identified in veterans who have served in war zones since the Gulf War, including current Middle East deployments.”
In various studies of different populations with different diagnostic criteria, the prevalence of unexplained multisystem illness ranged from 8-36% in those who were not deployed and 29-65% in those who served in the Gulf.
Other Factors Not Ruled Out
The Committee looked at a large number of suspects including psychological stress, Kuwaiti oil fires, depleted uranium (DU), vaccines, nerve agents, infectious disease, fine sand and airborne particulates, exhaust from tent heaters, other fuel exposures, solvents, and freshly applied CARC (chemical agent resistant coating) paint. The evidence was not sufficient to either implicate or rule out most of these.
They found a consistent association of Gulf War illness with exposure to the nerve gas antidote pyridostigmine bromide (PB) and pesticides across studies of Gulf War veterans, with a convincing dose/response relationship. Those exposed to one suspected cause were usually exposed to several. Rates of GWI and exposures were higher among Army and Marines than Navy and Air Force, higher among enlisted men than officers, and higher among forward troops than rear troops. The other suspects that couldn’t be entirely ruled out could be involved due to multiple exposures and synergism (the combined effects of two agents).
Other Gulf War Illnesses
Additional illnesses have been linked to the Gulf War:
- Brain cancer: Veterans who were downwind from the Khamisiyah munitions demolitions in March 1991 have died from brain cancer at twice the rate of other Gulf War veterans. It is suspected, but not proven, that low levels of the chemical warfare nerve agents sarin and cyclosarin were released into the air during that operation.
- Birth defects: There was a significant, but modest, excess of birth defects in children of Gulf War veterans compared to non-deployed veterans. But information on specific types of birth defects was inconsistent, and overall rates were within the normal range found in the general population.
- Effects on spouses: There didn’t seem to be any consistent effects on spouses. A mysterious “burning semen” phenomenon was reported by wives but was never explained. On the other hand, Gulf veterans’ spouses had significantly fewer skin anomalies, such as moles, skin tags, and scars. (This is a good example of the random “noise” that plagues studies like this.)
- ALS: A cluster of cases of amyotrophic lateral sclerosis (Lou Gehrig’s disease) was found, mainly in the Air Force. In September, 2008, VA Secretary James Peake announced that all U.S. veterans, of all eras, would be given presumptive service connection for ALS.
There was a similar controversy about illness due to Agent Orange after the Vietnam war. Eventually, the VA agreed to presumptively recognize a series of health conditions related to Agent Orange. Vietnam veterans with one or more of these conditions do not have to show that their illness(es) is (are) related to their military service to get disability compensation:
- Chloracne occurring within 1 year of exposure to Agent Orange.
- Non-Hodgkin’s lymphoma.
- Soft tissue sarcoma (other than osteosarcoma, chondrosarcoma, Kaposi’s sarcoma, or mesothelioma).
- Hodgkin’s disease.
- Porphyria cutanea tarda (must occur within 1 year of exposure).
- Multiple myeloma.
- Respiratory cancers, including cancers of the lung, larynx, trachea, and bronchus.
- Prostate cancer.
- Acute and subacute transient peripheral neuropathy (must appear within 1 year of exposure and resolve within 2 years of date of onset).
- Type 2 diabetes.
- Chronic lymphocytic leukemia.
In addition, veterans’ children with spina bifida are covered.
Think about this for a minute. How many of those veterans would have developed diseases like diabetes and prostate cancer if they had never gone to Vietnam? Compensating victims of Agent Orange means we have to compensate a lot of other people who are not victims.
The same thing is true for GWI. If 8-36% of the nondeployed have the same symptoms, diagnosing the 29-65% of the deployed who have those symptoms means we will be labeling far too many.
Incidentally, I find the 65% figure questionable, and so did the Committee—they estimated 1/4 to 1/3.
There are special provisions that allow Gulf War veterans disabled by chronic symptoms that are not explained by a specific diagnosis to receive disability compensation for “undiagnosed illnesses.” You’d think everyone who served in the Gulf would be reporting difficult-to-diagnose symptoms for purposes of financial gain, but as of February, 2008, just 2% of Gulf War veterans had applied. Despite all the reports of bothersome symptoms, most patients with GWI are employed and functioning reasonably well.
Effects of PB and Pesticides
Only about 62% of ground troops reported using pesticides and only about half of them took PB for varying periods (sometimes very brief). Some of them used higher-than-recommended amounts of pesticides: these exposures were reduced by stricter guidelines in Iraq, but that resulted in more cases of leishmaniasis.
According to the FDA website:
- Pyridostigmine bromide was first approved in 1955, and has been prescribed by doctors to treat patients with myasthenia gravis for over 40 years. To date, no long-term health problems thought to be associated with pyridostigmine bromide have been reported by these patients.
- The reported side effects and the signs of overdose of PB overlap but do not match the GWI syndrome. Symptoms reported for acute pesticide toxicity and for long-term low-dose exposure to pesticides in peacetime are not a good match for GWI either.
- Both PB and pesticides are acetylcholine-sterase inhibitors. It’s been suggested that the combination and the concomitant exposure to other risk factors may have caused unexpected synergisms. There is also some evidence that people with certain genetic polymorphisms might be uniquely susceptible.
Paradoxically, PB has been tried as a treatment for multisystem illnesses like CFS and fibromyalgia.
Anthrax shots attracted attention because they caused a high incidence of mild reactions and because they were given in a hush-hush setting and often weren’t even identified. They had not been extensively tested but military authorities decided the military risk outweighed the risk of the vaccine and justified omitting informed consent. They imposed secrecy for security reasons—we didn’t want the enemy to know we thought they had biological weapons and were protecting our troops.
The military does a lot of things for military reasons that would not be acceptable in a civilian setting. They couldn’t afford to have a flu epidemic depleting their troops, so everyone was required to get annual flu shots back when the package inserts said “Not intended for children or healthy adults.”
The troops didn’t like the idea of taking PB tablets. Those who got side effects from them were more likely to report symptoms of GWI later on. I remember when I was a flight surgeon we required our flyers to take a test dose to make sure they wouldn’t have any bad reactions that would interfere with flying skills. Some of them objected strenuously to taking medicine when they weren’t sick, but they would have faced a court-martial for disobeying orders if they didn’t comply. Anecdotally, I don’t remember any of them complaining of side effects from the test dose.
There were frequent false alarms of chemical warfare. Initial alarms could be triggered by factors such as fuel vapors and engine exhaust, oily smoke, blowing sand, and low batteries on the units. Initial alarms had to be verified by further, more accurate tests. Verification was often not possible in battlefield situations. Logs went missing. The most likely exposure to chemical agents, at Khamisiyah, was never actually verified. It was rated “likely” but not certain.
Such activities led to a lot of suspicion and resentment. It contributed to a mindset that the government was lying and was knowingly endangering personnel. Some people were on the lookout for any symptom that might corroborate their suspicions.
Hundreds of studies have been done; millions of dollars have been spent. The report recommends spending much more to study GWI further, to do long-term follow up, and to find effective treatment. I have mixed feelings about this. Research money is short. It’s hard to quantify exposures this long after the fact; it’s hard to decide what treatments to test when you don’t know the cause. There have already been some poorly conceived attempts to treat GWI with long courses of antibiotics and with various alternative therapies.
On the other hand, we might learn something that we could apply to other illnesses and to future wars.
When a subject is as highly charged as this one, I despair of ever knowing the truth. We all want to support our troops. We want to give their symptoms a name. We want to find a cause.
With all the emotions and the political concerns, it is practically impossible to maintain true scientific objectivity. The very choice of what to study and how to study it embodies some degree of bias. The Committee’s report was a noble effort, but I’m not entirely convinced. It bothers me that the symptoms are subjective and poorly defined. It bothers me that the known effects of PB/pesticides are not a good match for the symptoms of GWI. If you look at enough factors, you are guaranteed to find significant correlations that are not causal. Before I read this study I didn’t know what to think about GWI. Now, after reading it, I still don’t know.
This article appeared in both the Science-Based Medicine Blog and in Skeptic magazine