The medically unexplained illnesses in Gulf War participants have been called a "Mystery Illness," and as such it is instructive to compare and contrast it with other puzzling and controversial illnesses that have been and currently are reported. A unique feature of the Gulf War cases is the relatively short time period and restricted geographic localization of potential causative exposures. This feature of the condition raises suspicion that there was a single (or limited number of) environmental agents responsible for causing the illness.

A. Multiple Chemical Sensitivities (MCS)

The term "multiple chemical sensitivities" was first used by Cullen in 1987. He defined it as: "an acquired disorder characterized by recurrent symptoms, referable to multiple organ systems, occurring in response to demonstrable exposure to many chemically unrelated compounds at doses far below those established in the general population to cause harmful effects. No single widely accepted test of physiologic function can be shown to correlate with symptoms."

MCS is the new name given to a condition previously called Environmental Illness (EI), originally proposed by Randolph in the 1950s. Patients with a variety of symptoms but without physiological abnormalities were considered to suffer from a previously undescribed form of sensitivity or allergy to environmental chemicals, foods, and/or drugs, for which restrictive diets and environmental avoidance measures are prescribed.

The list of environmental chemicals purported to cause the condition and trigger symptoms is large and heterogeneous, but items most frequently mentioned by these patients are pesticides, perfumes, organic solvents, vehicle exhaust fumes, fuels, glues, and carpeting.

Theories of pathogenesis have included immunotoxic, neurotoxic, and psychosomatic mechanisms, but clinical or experimental evidence conclusively validating these theories has yet to appear. A number of independent studies now establish that many patients with the diagnosis of MCS or EI are immunologically normal by objective laboratory test.

Based on a number of published studies of persons diagnosed as MCS, the most frequently reported symptoms, in descending order of frequency, are as follows:

Memory loss
Difficulty concentrating
Ocular and respiratory irritation
Musculoskeletal pain
Visceral pain

The concept of MCS and the theories and diagnostic methods of its proponents have continued to be highly controversial for the past 40 years.

Relation to Gulf War Participants with Unexplained Illness

Discussions of the unexplained medical complaints in Gulf War participants occasionally include reference to MCS. In some cases veterans carry both diagnoses concurrently. In other cases, these complaints are viewed as identical with or as a subset of MCS. The summaries of illness reported among Gulf War participants with unexplained medical complaints examined by the VA show similarities and differences with those reported in MCS. However, the absence of substantial abnormalities on physical examination and laboratory testing is a striking feature of both conditions.

B. Chronic Fatigue Syndrome (CFS)

A committee of the Centers for Disease Control's Division of Viral Diseases in 1988 proposed the name "Chronic Fatigue Syndrome" and established a working case definition[63] to "improve the comparability and reproducibility of clinical research and epidemiological studies, and to provide a rational basis for evaluating patients who have chronic fatigue of unknown cause." In brief, the diagnosis must fulfill the following 2 major criteria:

1. New onset of debilitating fatigue that does not resolve on bedrest, severe enough to reduce daily activity > 50% for more than 6 months.

2. Other clinical conditions are excluded by appropriate evaluation.

and 6 or more of the following 11 symptom criteria:

1. Mild fever.
2. Sore throat.
3. Painful cervical or axillary lymph nodes.
4. Unexplained generalized muscle weakness.
5. Muscles discomfort or myalgia.
6. Fatigue for 24 hrs after exercise that would have previously been tolerated.
7. Generalized headache of a type not previously experienced.
8. Migratory non-inflammatory arthralgia.
9. Neuropsychologic complaints.
10. Sleep disturbance.
11. Description of the main symptom complex as initially developing over a few hours to a few days.

and 2 or more of the following 3 physical criteria documented by a physician on two or more occasions at least 1 month apart:

1. Temperature 37.6-38.6C (oral) or 37.8-38.3C (rectal)
2. Nonexudative pharyungitis.
3. Palpable or tender cervical or axillary lymph nodes or Eight or more of the symptom criteria.

The name and working case definition of CFS arose from reports beginning in 1985 of clusters and individual case reports of a possible new disease with numerous general and specific symptoms without physical or laboratory abnormalities. The illness was first believed to be a chronic Epstein-Barr virus (EBV) infection because of the presence of EBV antibodies, but further epidemiological investigations revealed that the types and titers of the antibodies in these patients were not clearly distinguishable from those in age-matched healthy controls.

The case definition of CFS was intended as an operational concept designed for research purposes, and the criteria reflect the original concept of the disease as an infectious process. Subsequently, investigators have searched for evidence of infection by other viruses, notably HHV-6 and HTLV-l, to explain the etiology of CFS, but to date a specific causative virus (or group of viruses) has not yet been identified. One theory postulates that CFS can be explained as a chronically "activated" immune system, possibly initiated by a viral infection.

In the past a number of illness "epidemics" have been reported with similar features of subjective symptoms without significant physical abnormalities or identifying diagnostic laboratory tests. Some of these events are:

Los Angeles Co. Hospital Illness (1934)
Iceland disease (1948)
London Middlesex Hospital disease (1952)
Royal Free Hospital Disease (1955)
Incline Village (NV) outbreak (1984)

Relation to Gulf War Participants with Unexplained Illness

As with MCS, there are similarities and differences between CFS and the unexplained medical complaints in Gulf War participants, but all 3 illnesses are subjective without diagnostic objective criteria by physical examination or laboratory testing.

C. Symptoms in the General Population

When considering the rate of occurrence of the reported symptoms in Gulf War veterans, it is instructive to examine what is known about the general occurrence of medical complaints in the population. A number of studies have looked at the prevalence of common symptoms in various outpatient populations. The incidence for some of the symptoms associated with Gulf War veterans is very similar, or even higher, in various groups of subjects studied. For instance, fatigue was reported by between 22 and 51 percent, and headache by 14 to 49 percent.[64]

Additionally of interest, a high percentage of these common complaints cannot be diagnosed with a clear organic etiology, and many of the symptoms do not improve through specific treatment.[65]

One of the clear but challenging goals of researchers in the Gulf War health phenomenon will be to determine what differences exist between the veterans conditions and those that exist at some background in the general population.

D. Other Coalition Forces

One striking feature of the post-war health phenomenon is the fact that it has been reported only in US personnel. The Saudi Arabian Ministry of Health, in meetings both with Senator Shelby and with Under Secretary of Defense Dorn, has stated that they have not observed any reports of the typical mix of symptoms being reported by some veterans, nor have they observed in their public health surveillance program any unexpected increase in unusual health problems of any sort. They also have specifically stated that there were no reports during the war of any civilians being treated for any injury typical of exposure to chemical warfare agent.

Other European and Middle East region governments who supplied forces to the coalition, during meetings with Senator Shelby, have stated that they have not observed unexplained incidence of disease in their troop populations who served during the war.

The Task Force received presentations by, and enjoyed the participation of, the Director General of the United Kingdom's Chemical & Biological Defense Establishment, Dr. Graham Pearson.

The United Kingdom deployed approximately 45,000 troops to the Persian Gulf War, referred to in their military parlance as Operation Granby. These troops comprised 31,000 ground troops, 5 destroyer/frigates, 5 mine sweepers, 10 support ships, and 75 combat aircraft. The British ground contingent consisted of their 1st Armoured Division, with the 7th and 4th Armoured Brigades, division troops, and several infantry battalions tasked with enemy prisoner of war (EPW) handling. These units were almost exclusively made up of active duty military personnel; only 3.6% were reservists.

For the conduct of the ground war, the British division fell under the operational control of the US VII Corps, and was placed on the inner hinge of the wide sweeping attack around Iraq's western flank.

Although no pattern of illness has been apparent in either the British military medical channels, or in the state-sponsored medical system, with regard to those military veterans who had been deployed into the theater of war, the public there followed with interest the increasingly frequent accounts in the American media regarding the so-called "Gulf War Illness". This interest was heightened following a feature on US reports of a Gulf related illness broadcast during a BBC current affairs program on 7 June 1993. Subsequently, the Minister for the Armed Forces appeared on a later edition of this program, dated 7 July 1993, to urge any Gulf War veterans who were experiencing health problems that they believed may be connected with their Gulf service to contact the Ministry of Defense. As of 17 March 1994, 28 veterans had contacted the Ministry, 14 of who took up the offer of medical assessment by a military consultant. By 17 March 1994, 11 of these had been examined and all have been diagnosed as having standard ailments. Thus, we are not aware of any British soldiers who have undiagnosed medical problems that are similar to those being described for US veterans.

Several similarities exist in potential exposures to the British contingent and the US forces that may ultimately be of use to researchers; in addition to being in the same environmental conditions, the widespread administration of antibiological warfare vaccines and pyridostigmine bromide (nerve agent pretreatment) within both forces are two of interest.

The British report no incidents of detecting chemical or biological warfare agents, and concur in the assessment that chemical or biological agents were not used during the conflict.