Gulf War syndrome

Gulf War syndrome (GWS), also known as Gulf War illness (GWI), is a chronic multisymptom disorder affecting returning military veterans and civilian workers of the 1990–91 Gulf War. A wide range of acute and chronic symptoms have been linked to it, including fatigue, muscle pain, cognitive problems, rashes and diarrhea. Approximately 250,000 of the 697,000 U.S. veterans who served in the 1991 Gulf War are afflicted with enduring chronic multi-symptom illness, a condition with serious consequences. From 1995 to 2005, the health of combat veterans worsened in comparison with nondeployed veterans, with the onset of more new chronic diseases, functional impairment, repeated clinic visits and hospitalizations, chronic fatigue syndrome-like illness, posttraumatic stress disorder, and greater persistence of adverse health incidents. According to a report by the Iraq and Afghanistan Veterans of America, veterans of Iraq and Afghanistan may also suffer from the syndrome.

Suggested causes have included depleted uranium, sarin gas, smoke from burning oil wells, vaccinations, combat stress and psychological factors.

Classification
Medical ailments associated with Gulf War syndrome have been recognized by both the Department of Defense and the Department of Veterans Affairs. Since so little concrete information was known about this condition the Veterans Health Administration (VHA) originally classified individuals with related ailments believed to be connected to their service in the Persian Gulf a special non-ICD-9 code DX111, as well as ICD-9 code V65.5. There is no formal definition of the term "Gulf War syndrome" or "Gulf War illnesses".

Signs and symptoms


According to an April 2010 U.S. Department of Veterans Affairs (VA) sponsored study conducted by the Institute of Medicine (IOM), part of the U.S. National Academy of Sciences, 250,000 of the 696,842 U.S. servicemen and women in the 1991 Gulf War continue to suffer from chronic multi-symptom illness, popularly known as "Gulf War Illness" or "Gulf War Syndrome." The IOM found that the chronic multi-symptom illness continues to affect these veterans nearly 20 years after the war.

According to the IOM, "It is clear that a significant portion of the soldiers deployed to the Gulf War have experienced troubling constellations of symptoms that are difficult to categorize," said committee chair Stephen L. Hauser, professor and chair, department of neurology, University of California, San Francisco (UCSF). "Unfortunately, symptoms that cannot be easily quantified are sometimes incorrectly dismissed as insignificant and receive inadequate attention and funding by the medical and scientific establishment. Veterans who continue to suffer from these symptoms deserve the very best that modern science and medicine can offer to speed the development of effective treatments, cures, and—we hope—prevention. Our report suggests a path forward to accomplish this goal, and we believe that through a concerted national effort and rigorous scientific input, answers can be found."

Questions still exist regarding why certain veterans showed, and still show, medically unexplained symptoms while others did not, why symptoms are diverse in some and specific in others, and why combat exposure is not consistently linked to having or not having symptoms. The lack of data on veterans' pre-deployment and immediate post-deployment health status and lack of measurement and monitoring of the various substances to which veterans may have been exposed make it difficult—and in many cases impossible—to reconstruct what happened to service members during their deployments nearly 20 years after the fact, the committee noted. The report called for a substantial commitment to improve identification and treatment of multisymptom illness in Gulf War veterans focussing on continued monitoring of Gulf War veterans, improved medical care, examination of genetic differences between symptomatic and asymptomatic groups and studies of environment-gene interactions.

A variety of signs and symptoms have been associated with GWS:

Birth defects have been suggested as a consequence of Gulf War deployment. However, a 2006 review of several studies of international coalition veterans' children found no strong or consistent evidence of an increase in birth defects, finding a modest increase in birth rate defects that was within the range of the general population, in addition to being unable to exclude recall bias as an explanation for the results. A 2008 report stated that "it is difficult to draw firm conclusions related to birth defects and pregnancy outcomes in Gulf War veterans", observing that while there have been "significant, but modest, excess rates of birth defects in children of Gulf War veterans", the "overall rates are still within the normal range found in the general population". The same report called for more research on the issue.

Causes
The United States Congress mandated the National Academies of Science Institute of Medicine to provide nine reports on Gulf War Syndrome since 1998. Aside from the many physical and psychological issues involving any war zone deployment, Gulf War veterans were exposed to a unique mix of hazards not previously experienced during wartime. These included pyridostigmine bromide pills (given to protect troops from the effects of nerve agents), depleted uranium munitions, and anthrax and botulinum vaccines. The oil and smoke that spewed for months from hundreds of burning oil wells presented another exposure hazard not previously encountered in a warzone. Military personnel also had to cope with swarms of insects, requiring the widespread use of pesticides. High powered microwaves were used to disrupt Iraqi communications and though it is unknown whether this might have contributed to the syndrome, recent research suggests that safety limits for electromagnetic radiation are too lenient.

United States Veterans Affairs Secretary Anthony Principi's panel found that pre-2005 studies suggested the veterans' illnesses are neurological and apparently are linked to exposure to neurotoxins, such as the nerve gas sarin, the anti-nerve gas drug pyridostigmine bromide, and pesticides that affect the nervous system. The review committee concluded that "Research studies conducted since the war have consistently indicated that psychiatric illness, combat experience or other deployment-related stressors do not explain Gulf War veterans illnesses in the large majority of ill veterans."

Pyridostigmine bromide nerve gas antidote
The US military issued pyridostigmine bromide (PB) pills to protect against exposure to nerve gas agents such as sarin and soman. PB was used as a prophylactic against nerve agents; it is not a vaccine. Taken before exposure to nerve agents, PB was thought to increase the efficacy of nerve agent antidotes. PB had been used since 1955 for patients suffering from myasthenia gravis with doses up to 1,500 mg a day, far in excess of the 90 mg given to soldiers, and was considered safe by the FDA at either level for indefinite use and its use to pre-treat nerve agent exposure had recently been approved.

Given both the large body of epidemiological data on myasthenia gravis patients and follow up studies done on veterans it was concluded that while it was unlikely that health effects reported today by Gulf War veterans are the result of exposure solely to PB, use of PB was causally associated with illness. However a later review by the Institute of Medicine concluded that the evidence was not strong enough to establish a causal relationship.

Organophosphate pesticides
The use of organophosphate pesticides and insect repellents during the first Gulf War is credited with keeping rates of pest-borne diseases low. Pesticide use is one of only two exposures consistently identified by Gulf War epidemiologic studies to be significantly associated with Gulf War illness. Multisymptom illness profiles similar to Gulf War illness have been associated with low-level pesticide exposures in other human populations. In addition, Gulf War studies have identified dose-response effects, indicating that greater pesticide use is more strongly associated with Gulf War illness than more limited use. Pesticide use during the Gulf War has also been associated with neurocognitive deficits and neuroendocrine alterations in Gulf War veterans in clinical studies conducted following the end of the war. The 2008 report concluded that "all available sources of evidence combine to support a consistent and compelling case that pesticide use during the Gulf War is causally associated with Gulf War illness."

Sarin nerve agent
Many of the symptoms of Gulf War syndrome are similar to the symptoms of organophosphate, mustard gas, and nerve gas poisoning. Gulf War veterans were exposed to a number of sources of these compounds, including nerve gas and pesticides.

Chemical detection units from Czechoslovakia, France, and Britain confirmed chemical agents. French detection units detected chemical agents. Both Czech and French forces reported detections immediately to U.S. forces. U.S. forces detected, confirmed, and reported chemical agents; and U.S. soldiers were awarded medals for detecting chemical agents. The Riegle Report said that chemical alarms went off 18,000 times during the Gulf War. After the air war started on January 16, 1991, coalition forces were chronically exposed to low but nonlethal levels of chemical and biological agents released primarily by direct Iraqi attack via missiles, rockets, artillery, or aircraft munitions and by fallout from allied bombings of Iraqi chemical warfare munitions facilities.

In 1997, the US Government released an unclassified report that stated:


 * "The US Intelligence Community (IC) has assessed that Iraq did not use chemical weapons during the Gulf war. However, based on a comprehensive review of intelligence information and relevant information made available by the United Nations Special Commission (UNSCOM), we conclude that chemical warfare (CW) agent was released as a result of US postwar demolition of rockets with chemical warheads in a bunker (called Bunker 73 by Iraq) and a pit in an area known as Khamisiyah."

Over 125,000 U.S. troops and 9,000 UK troops were exposed to nerve gas and mustard gas when the Iraqi depot in Khamisiyah was destroyed.

Recent studies have confirmed earlier suspicions that exposure to sarin, in combination with other contaminants such as pesticides and PB were related to reports of veteran illness. Estimates range from 100,000 to 300,000 individuals exposed to nerve agents.

While there are suggestions low-level exposure to nerve agents may be responsible for GWS, 2008 RAC report states that "evidence is inconsistent or limited in important ways".

Chronic inflammation
The 2008 report on Gulf War Illness and the Health of Gulf War Veterans suggested a possible link between GWS and chronic, nonspecific inflammation of the central nervous system that cause pain, fatigue and memory issues, possibly due to pathologically persistent increases in cytokines and suggested further research be conducted on this issue.

Ruled out
Several potential causes of GWS have been ruled out, including "depleted uranium, anthrax vaccine, fuels, solvents, sand and particulates, infectious diseases, and chemical agent resistant coating".

Oil well fires
During the war, many oil wells were set on fire in Kuwait by the retreating Iraqi army, and the smoke from those fires was inhaled by large numbers of soldiers, many of whom suffered acute pulmonary and other chronic effects, including asthma and bronchitis. However, firefighters who were assigned to the oil well fires and encountered the smoke, but who did not take part in combat, have not had GWI symptoms. The 2008 RAC report states that "evidence [linking oil well fires to GWS] is inconsistent or limited in important ways".

Depleted uranium


Depleted uranium (DU) was widely used in tank kinetic energy penetrator and autocannon rounds for the first time ever during the Gulf War and has been suggested as a possible cause of Gulf War syndrome. A 2008 review by the U.S. Department of Veterans Affairs found no association between DU exposure and multisymptom illness, concluding that "exposure to DU munitions is not likely a primary cause of Gulf War illness". However there are suggestions that long-term exposure to high doses of DU may cause other health problems unrelated to GWS.

In the Balkans war zone depleted uranium was also used, however no GWS-like symptoms or illnesses have been identified. This is seen as evidence of DU munitions' safety. While depleted uranium from shrapnel fragments has been shown to move into neurological tissues, this has not been linked to any adverse effects, and comparisons between veterans with embedded DU fragments and those without have not found any consistent differences. A group of veterans with high levels of uranium in their urine from embedded particles have been monitored for any adverse health effects of these particles dissolving, and no such effects have been identified.

Anthrax vaccine
Iraq had loaded anthrax, botulinum toxin, and aflatoxin into missiles and artillery shells in preparing for the Gulf War and these munitions were deployed to four locations in Iraq. During Operation Desert Storm, 41% of U.S. combat soldiers and 75% of UK combat soldiers were vaccinated against anthrax. Reactions included local skin irritation, some lasting for weeks or months. While the Food and Drug Administration (FDA) approved the vaccine, it never went through large-scale clinical trials, unlike most other vaccines in the United States.

While recent studies have demonstrated the vaccine is highly reactogenic, and causes motor neuron death in mice, there is no clear evidence or epidemiological studies on Gulf War veterans linking the vaccine to Gulf War Syndrome. Combining this with the lack of symptoms from current deployments of individuals who have received the vaccine led the Committee on Gulf War Veterans' Illnesses to conclude that the vaccine is not a likely cause of Gulf War illness for most ill veterans.

Combat stress
Research studies conducted since the war have consistently indicated that psychiatric illness, combat experience or other deployment-related stressors do not explain Gulf War veterans illnesses in the large majority of ill veterans, according to a U.S. Department of Veterans Affairs (VA) review committee.

An April 2010 Institute of Medicine review found, "the excess of unexplained medical symptoms reported by deployed [1991] Gulf war veterans cannot be reliably ascribed to any known psychiatric disorder", although they also concluded that "The constellation of unexplained symptoms associated with the Gulf War illness complex could result from interplay between both biological and psychological factors."

Diagnosis
Multisymptom illness is more prevalent in Gulf War I veterans than veterans of previous conflicts, but the pattern of comorbidities is similar for actively deployed and nondeployed military personnel.

Treatment
The Institute of Medicine reviewed the evidence for treatments for symptoms associated with Gulf War syndrome and related conditions. They concluded that selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors and cognitive behavioural therapy were most likely to be beneficial to patients.

Epidemiologic research
Epidemiologic studies have been performed evaluating many suspected etiologic factors for Gulf War illness as seen in veteran populations. Below is a summary of epidemiologic studies of veterans displaying multisymptom illness and their exposure to suspect conditions from the 2008 U.S. Veterans Administration report.

A fuller understanding of immune function in ill Gulf War veterans is needed, particularly in veteran subgroups with different clinical characteristics and exposure histories. It is also important to determine the extent to which identified immune perturbations may be associated with altered neurological and endocrine processes that are associated with immune regulation. Very limited cancer data have been reported for U.S. Gulf War veterans in general, and no published research on cases occurring after 1999. Because of the extended latency periods associated with most cancers, it is important that cancer information be brought up to date and that cancer rates be assessed in Gulf War veterans on an ongoing basis. In addition, cancer rates should be evaluated in relation to identifiable exposure and location subgroups.

Controversy
Similar syndromes have been seen as an after effect of other conflicts &mdash; for example, 'shell shock' after World War I, and post-traumatic stress disorder (PTSD) after the Vietnam War. A review of the medical records of 15,000 American Civil War soldiers showed that "those who lost at least 5% of their company had a 51% increased risk of later development of cardiac, gastrointestinal, or nervous disease."

A November 1996 article in the New England Journal of Medicine found no difference in death rates, hospitalization rates or self-reported symptoms between Persian Gulf veterans and non-Persian Gulf veterans. This article was a compilation of dozens of individual studies involving tens of thousands of veterans. The study did find a statistically significant elevation in the number of traffic accidents suffered by Gulf War veterans. An April, 1998 article in Emerging Infectious Diseases similarly found no increased rate of hospitalization and better health overall for veterans of the Persian Gulf War in comparison to those who stayed home.

Despite these studies, on November 17, 2008, a congressionally appointed committee called the Research Advisory Committee on Gulf War Veterans' Illnesses, staffed with independent scientists and veterans appointed by the Department of Veterans Affairs, announced that the syndrome is a distinct physical condition. The committee recommended that Congress increase funding for research on Gulf War veterans' health to at least $60 million per year. In January 2006, a study led by Melvin Blanchard and published by the Journal of Epidemiology, part of the "National Health Survey of Gulf War-Era Veterans and Their Families", stated that veterans deployed in the Persian Gulf War had nearly twice the prevalence of chronic multisymptom illness, a cluster of symptoms similar to a set of conditions often called Gulf War Syndrome.

In March 2013, a hearing was held before the Subcommittee on Oversight and Investigations of the Committee on Veterans’ Affairs, U.S. House of Representatives, to determine not whether Gulf War Illness exists, but rather how it is identified, diagnosed and treated, and how the tools put in place to aid these efforts have been used.

Related legislation
On March 14, 2014, Representative Mike Coffman introduced the Gulf War Health Research Reform Act of 2014 (H.R. 4261; 113th Congress) into the United States House of Representatives. The bill would alter the relationship between the Research Advisory Committee on Gulf War Illnesses (RAC) and the United States Department of Veterans Affairs (VA). The bill would make the RAC an independent organization within the VA, require that a majority of the RAC's members be appointed by Congress instead of the VA, and state that the RAC can release its reports without needing prior approval from the Secretary of Veterans Affairs. The RAC is responsible for investigating Gulf War syndrome, a chronic multisymptom disorder affecting returning military veterans and civilian workers of the Gulf War.

In the year prior to the consideration of this bill, the VA and the RAC were at odds with one another. The VA replaced all but one of the members of the RAC, removed some of their supervisory tasks, tried to influence the board to decide that stress, rather than biology was the cause of Gulf War syndrome, and told the RAC that it could not publish reports without permission. The RAC was originally created in 1997, after Congress decided that the VA's research into the issue was flawed, and focused on psychological causes, while mostly ignoring biological ones.

In popular culture

 * The X-Files, 1990s The Black Oil TV series plot device, is a subterranean oil that is believed to be an alien disease causing agent, evoking the hypothesis that the Gulf War syndrome was caused by the Kuwaiti oil. In particular, the 2001 Vienen episode includes the suggestion that "The Black Oil contagion could be dispersed by an oil-rig fire.
 * NCIS Season 6 episode Toxic dealt with a disease purportedly affecting veterans of the Afghanistan and Iraq wars related to the Gulf War syndrome.