Seth A. Eisen, MD; Han K. Kang, DrPH; Frances M. Murphy, MD; Melvin S. Blanchard, MD; Domenic J. Reda, PhD; William G. Henderson, PhD; Rosemary Toomey, PhD; Leila W. Jackson, PhD; Renee Alpern, MS; Becky J. Parks, MD; Nancy Klimas, MD; Coleen Hall, MS; Hon S. Pak, MD; Joyce Hunter, MSN; Joel Karlinsky, MD; Michael J. Battistone, MD; Michael J. Lyons, PhD; and the Gulf War Study Participating Investigators*
Grant Support: By the Cooperative Studies Program of the U.S. Department of Veterans Affairs Office of Research and Development.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Seth A. Eisen, MD, MSc, St. Louis Veterans Affairs Medical Center (151 JC), 915 North Grand Avenue, St. Louis, MO 63106; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Eisen and Blanchard: St. Louis Veterans Affairs Medical Center (151 JC), 915 North Grand Boulevard, St. Louis, MO 63106.
Dr. Kang: U.S. Department of Veterans Affairs, 1722 I Street, Washington, DC 20006.
Dr. Murphy: U.S. Department of Veterans Affairs, 811 Vermont Avenue NW, Washington, DC 20420.
Dr. Reda, Ms. Alpern, and Ms. Hall: Hines Veterans Affairs Hospital, CSPCC (151-K), PO Box 5000, Hines, IL 60141.
Dr. Henderson: University of Colorado Health Care Outcomes Program, Mail Stop F-443, PO Box 6508, Aurora, CO 80045-0508.
Dr. Toomey: Boston University, 648 Beacon Street, 6th Floor, Boston, MA 02215.
Dr. Jackson: Department of Epidemiology, John Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205.
Dr. Parks: Department of Neurology, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110.
Dr. Klimas: Miami Veterans Affairs Medical Center, 1201 NW 16th Street, (111-I), Miami, FL 33125.
Dr. Pak: Wilford Hall Air Force Medical Center, 2200 Bergquist Drive, Lackland AFB, TX 78236.
Ms. Hunter: Deaconess College of Nursing, 6150 Oakland Avenue, St. Louis, MO 63139.
Dr. Karlinsky: Veterans Affairs Boston Healthcare System, West Roxbury Campus, 1400 VFW Parkway, West Roxbury, MA 02132.
Dr. Battistone: Salt Lake City Veterans Affairs Medical Center, 500 Foothill Drive, Salt Lake City, UT 84148.
Dr. Lyons: Boston University, 648 Beacon Street, 2nd Floor, Boston, MA 02215.
Author Contributions: Conception and design: S.A. Eisen, H.K. Kang, F.M. Murphy, M.S. Blanchard, D.J. Reda, W.G. Henderson, B.J. Parks, H.S. Pak, M.J. Lyons.
Analysis and interpretation of the data: S.A. Eisen, H.K. Kang, F.M. Murphy, M.S. Blanchard, D.J. Reda, W.G. Henderson, R. Toomey, L.W. Jackson, R. Alpern, B.J. Parks, N. Klimas, C. Hall, H.S. Pak, J. Karlinsky, M.J. Battistone.
Drafting of the article: S.A. Eisen, F.M. Murphy, M.S. Blanchard, L.W. Jackson, R. Alpern, J. Karlinsky.
Critical revision of the article for important intellectual content: S.A. Eisen, F.M. Murphy, M.S. Blanchard, D.J. Reda, W.G. Henderson, R. Toomey, L.W. Jackson, N. Klimas, H.S. Pak, J. Karlinsky, M.J. Battistone, M.J. Lyons.
Final approval of the article: S.A. Eisen, F.M. Murphy, M.S. Blanchard, D.J. Reda, W.G. Henderson, R. Toomey, L.W. Jackson, R. Alpern, N. Klimas, H.S. Pak, J. Hunter, J. Karlinsky, M.J. Battistone, M.J. Lyons.
Provision of study materials or patients: S.A. Eisen, N. Klimas, J. Hunter, M.J. Battistone.
Statistical expertise: S.A. Eisen, D.J. Reda, W.G. Henderson, R. Alpern.
Obtaining of funding: S.A. Eisen, H.K. Kang, F.M. Murphy, W.G. Henderson.
Administrative, technical, or logistic support: S.A. Eisen, H.K. Kang, M.S. Blanchard, D.J. Reda, W.G. Henderson, L.W. Jackson, J. Hunter, M.J. Battistone.
Collection and assembly of data: S.A. Eisen, H.K. Kang, R. Toomey, B.J. Parks, J. Hunter, J. Karlinsky, M.J. Battistone.
United States military personnel reported various symptoms after deployment to the Persian Gulf during the 1991 Gulf War. However, the symptoms' long-term prevalence and association with deployment remain controversial.
To assess and compare the prevalence of selected medical conditions in a national cohort of deployed and nondeployed Gulf War veterans who were evaluated by direct medical and teledermatologic examinations.
A cross-sectional prevalence study performed 10 years after the 1991 Gulf War.
Veterans were examined at 1 of 16 Veterans Affairs medical centers.
Deployed (n = 1061) and nondeployed (n = 1128) veterans of the 1991 Gulf War.
Primary outcome measures included fibromyalgia, the chronic fatigue syndrome, dermatologic conditions, dyspepsia, physical health–related quality of life (Short Form-36 [SF-36]), hypertension, obstructive lung disease, arthralgias, and peripheral neuropathy.
Of 12 conditions, only 4 conditions were more prevalent among deployed than nondeployed veterans: fibromyalgia (deployed, 2.0%; nondeployed, 1.2%; odds ratio, 2.32 [95% CI, 1.02 to 5.27]); the chronic fatigue syndrome (deployed, 1.6%; nondeployed 0.1%; odds ratio, 40.6 [CI, 10.2 to 161]); dermatologic conditions (deployed, 34.6%; nondeployed, 26.8%; odds ratio, 1.38 [CI, 1.06 to 1.80]), and dyspepsia (deployed, 9.1%; nondeployed, 6.0%; odds ratio, 1.87 [CI, 1.16 to 2.99]). The mean physical component summary score of the SF-36 for deployed and nondeployed veterans was 49.3 and 50.8, respectively.
Relatively low participation rates introduce potential participation bias, and deployment-related illnesses that resolved before the research examination could not, by design, be detected.
Ten years after the Gulf War, the physical health of deployed and nondeployed veterans is similar. However, Gulf War deployment is associated with an increased risk for fibromyalgia, the chronic fatigue syndrome, skin conditions, dyspepsia, and a clinically insignificant decrease in the SF-36 physical component score.
*For a list of the Gulf War Study Participating Investigators, see the Appendix.
The prevalence and association of medical conditions with deployment to the 1991 Gulf War are controversial.
This cross-sectional study, performed 10 years after the 1991 Gulf War, compared the prevalence of 12 conditions between 1061 deployed and 1128 nondeployed U.S. veterans. Only fibromyalgia (2% vs. 1.2%), the chronic fatigue syndrome (1.6% vs. 0.1%), skin conditions (34.6% vs. 26.8%), and dyspepsia (9.1% vs. 6.0%) were more common among deployed veterans.
Short-term conditions that resolved weren't assessed. Fifty-three percent of deployed eligible veterans and 39% of nondeployed eligible veterans participated in the study.
Only a few health conditions seem to be associated with Gulf War deployment.
Sample selection flowchart.
Table 1. Sociodemographic Characteristics in 1991 and Self-Reported Health Characteristics in 1995 of Individuals Who Completed the 1995 Survey according to Their Participation in the Present Study
Table 2. Sociodemographic and Military Service Characteristics of Deployed and Nondeployed Participants at the Research Examination
Table 3. Population Prevalence of Illnesses or Symptoms Reported by the 1061 Deployed and 1128 Nondeployed Gulf War Veterans Who Participated in the Research Examination
Table 4. Population Prevalence of Illnesses Present on Clinical Evaluation among the 1061 Deployed and 1128 Nondeployed Gulf War Veterans Who Participated in the Research Examination
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Zucker Hillside Hospital
June 8, 2005
Mind-Body Dualism in the Aftermath of War
According to Eisen et al., ten years after the Gulf War, 1.6% of deployed veterans fulfilled criteria for chronic fatigue syndrome (1). In a stark display of mind-body dualism, the authors label chronic fatigue syndrome a "medical outcome", "medical illness" and "medical condition" and postpone the presentation of existing psychiatric and neuropsychological data. The authors' bias avoids the confrontation with the complexity of this illness and thus misinforms the reader.
As defined in 1994, chronic fatigue syndrome is a theoretical construct to be used exclusively for the study of etiology and management of patients with persistent tiredness and other unexplainable complaints (2). The construct was not intended for clinical use and its authors were commendably careful to avoid the implication that the chronic fatigue illness is a "medical" disease or "psychiatric" disorder.
The cartesian separation of soul and matter was a courageous manifesto for the independence of science in an era of religious obscurantism. Today, the dualism is counterproductive as it leads to mechanistic oversimplifications inadequate to explain most suffering. It is therefore important to remember that mysteriously ill Gulf veterans have a very high rate of posttraumatic stress (18%) and somatoform (26%) disorders (3). Posttraumatic stress symptoms and unexplainable somatic complaints were strongly correlated with each other (3,4) and with war zone trauma and severity of depression (4). Symptoms consistent with borderline personality were also produced or exagerated by war-related trauma in the Operation Desert Strom (5). These findings demonstrate once again that somatic complaints do not occur or exist in a mind-less vacuum, but that they are generated, modified and maintained by the interplay of pathology, culture and illness behavior.
1. Eisen SA, Kang HK, Murphy FM, et al. Gulf War veterans' health: Medical evaluation of a U.S. Cohort. Ann Intern Med 2005;142:881-90.
2. Fukuda K, Strauss SE, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Study Group. Ann Intern Med 1994;121:953-9.
3. Labbate LA, Cardena E, Dimitreva J, et al. Psychiatric syndromes in Persian Gulf veterans: an association of handling dead bodies with somatoform disorders. Psychother Psychosom 1998;67:275-9.
4. Ford JD, Campbell KA, Storzbach D, et al. Posttraumatic stress symptomatology is associated with unexplained illness attributed to Persian Gulf military service. Psychosom Med 2001;63:842-9.
5. Axelrod SR, Morgan CA 3rd, Southwick SM. Symptoms of posttraumatic stress disorder and borderline personality in veterans of Operation Desert Storm. Am J Psychiatry 2005;162:270-5.
Dartmouth-Hitchcock Medical Center
June 9, 2005
Gulf War Illness: The Gorilla in the Room
Eisen and colleagues described a constellation of illnesses that are more common in veterans who were deployed in the 1991 Gulf War (1). Their discussion, and an accompanying editorial (2), omits discussion of a major potential contributor to the heightened incidence of diseases such as fibromyalgia and chronic fatigue syndrome in returned combatants: psychological trauma. Common sense suggests that the horror of war can be at least a partial explanation for such physical symptoms. That similar symptoms were reported in combatants in other wars lends credence to this theory (2). For the benefit of returned combatants, and for victims of other forms of psychological trauma, it will be important to understand the link between the psychological trauma of war and physical symptoms better.
Timothy Lahey, MD Dartmouth-Hitchcock Medical Center Lebanon, NH
1. Eisen SA, Kang HK, Murphy FM, et al. Gulf War veterans' health: medical evaluation of a U.S. cohort. Ann Intern Med. 2005;142(11):881-90.
2. Komaroff AL. Unexplained suffering in the aftermath of war. Ann Intern Med. 2005;142(11):938-9.
Steven R Brenner
Dept. Neurology, Saint Louis Veterans Admin. Med. Center and Dept. Neurology Saint Louis University
June 14, 2005
Parvovirus B19 as cause of Post Gulf War Symptomatology
Gulf war deployment appeared to be associated with an increased risk of fibromyalgia, chronic fatigue syndrome (CFS), skin conditions and dyspepsia.
Although CFS and fibromyalgia may be related to a variety of causes, Parvovirus B19 has been associated with development of chronic fatigue syndrome and may have been significant in the Gulf War region during the 1st Gulf War since there was an epidemic of Parvovirus B19 related aplastic crisis in the region, 48 patients being hospitalized at the Saudi Aramco-Dhahrain Health Center between July 1991 and March, 1992 (1).
Military personnel living in close proximity would facilitate respiratory spread of a transmissible virus such as Parvovirus B19 and involvement of the local population would also be expected.
CFS and arthralgia may follow parvovirus B19 infection, five patients out of 51 with acute B19 infection going on to develop Centers for Disease Control criteria for diagnosis of CFS, however there was no characteristic pattern of B19 markers/autoantibodies in patients with B19 associated chronic fatigue, one patient being negative for anti-B19 IgG at followup (2).
CFS can persist for years after human parvovirus B19 infection, and acute B19 infection is accompanied by raised circulating levels of IL-1b, IL-6, TNF-a and IFN-g and raised circulating levels of TNF-a and IFN-g persist and are accompanied by MCP-1 in patients who develop CFS (3). CFS may be caused by a variety of microbial and other triggers, however CFS triggered by B19 virus is clinically indistinguishable from idiopathic CFS and exhibits similar cytokine abnormalities (3).
Parvovirus may also be associated with skin conditions, since it causes erythema infectiosum in the acute infection. An increased prevalence of parvovirus B19 DNA has been found in systemic sclerosis skin (4).
Parvovirus B19 may be considered in development of post Gulf War symptomatology such as CFS. References: 1. A Mullouh, A Qudah. An epidemic of aplastic crisis cause by human parovirsu B19.
Pediatr Infect Dis J. 1995; 14: 31-4. 2. J Kerr, J Bracewell, I Laint, et. al. Chronic fatigue syndrome and arthralgia following parvovirus B19 infection. J. Rheumatol 2002; 29: 595- 602. 3. J Kerr, D Tyrrell. Cytokines in parvovirus B19 infection as an aid to understanding chronic fatigue syndrome. Curr Pain Headache Rep. 2003; 5: 333-41. 4. T Ohtsuka, S Yamazaki. Increased prevalence of human parvovirus B19 DNA in systemic sclerosis skin. Br J Dermatol 2004; 150: 1091-5.
HÃ´pital ClÃ©menceau- UnitÃ© Infomyalgies
June 29, 2005
Fibromyalgia syndrome/Chronic Fatigue syndrome dualism through War and Peace
In a recent study, Eisen et al.  demonstrate increased prevalence of chronic fatigue syndrome [CFS] in deployed 1991 Gulf War veterans (1,6 vs 0,1 % in undeployed or in general population).The authors try to explain the increased risk for CFS, and incidently for dermatologic conditions and dyspepsia in Gulf War syndrome [GWS], without any comment on an other increased prevalence, that of fibromyalgia [FM] : 2 % vs 1,2 %, often considered as a poorly defined CFS-related condition. Some specific comments could have been welcome on : - FM definition, criteria and evaluation [2,3] or mechanisms : some information on bacterial or viral infections and treatments, immunity disorders or influence of toxics in GWS and chronic illness could have been considered even if the same increased prevalence of FM (2-fold) and CFS (10-fold) has been similarly observed in an other population and a quite different situation (women with endometriosis) . - nosology : Fibromyalgia is a defined entity whose diagnosis needs some discriminative and sometimes sophisticated investigations whereas fibromyalgia syndrome [FMS] could indicate variable symptoms and numerous subgroups linked to the fact that fibromyalgia is the usual outcome of several chronic illnesses (evolution from CFS to FM is practically one way). FM or FMS can coexist with other central sensitivity syndromes  such as irritable bowel syndrome, migraine, dysmenorrhea, restless legs syndrome, temporo-mandibular pain and dysfunction, myofascial pain syndrome, female urethral syndrome... All these neuroendocrine immune dysfunctions share biological abnormalities and pathophysiological mechanisms. However the dualism FMS/CFS is one more time demonstrated with their percentage increases after Gulf war or other events [1,4]. This is supported by several biological findings (ribonucleases abnormalities observed mainly in CFS, coherent increase of cerebrospinal fluid Nerve Growth Factor /Substance P or blood pyruvate/acyl carnitine  in FMS only). The FMS/CFS concept is a comfortable but unclear label that every physician may afford. To use it in absence of occasional co-morbidity would give up fibromyalgia on the Dark Side of the functionnal diseases. Bibliography 1.Eisen SA, Kang HK, Murphy FM, Blanchard MS, Reda DJ, Henderson WG, Toomey R, Jackson LW, Alpern R, Parks BJ, Klimas N, Hall C, Pak HS, Hunter J, Karlinsky J, Battistone MJ, Lyons MJ. Gulf War Veterans' Health: Medical Evaluation of a U.S. Cohort. Annals of Internal Medicine;142(11);881-890, 2005. 2.Yunus MB : fibromyalgia syndrome clinical features and spectrum. Journal of Musculoske Pain;2(3);5-19, 1994. 3.Eisinger J. Evaluation clinique de la fibromyalgie. Rev Med Int;24:237-42, 2003. 4.Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod.;17(10):2715-24, 2002. 5.Eisinger J. Metabolic abnormalities in fibromyalgia. Clinical Bulletin of Myofascial Therapy. 3(1) ; 3-22, 1998.
Eisen SA, Kang HK, Murphy FM, Blanchard MS, Reda DJ, Henderson WG, et al. Gulf War Veterans' Health: Medical Evaluation of a U.S. Cohort. Ann Intern Med. 2005;142:881–890. doi: 10.7326/0003-4819-142-11-200506070-00005
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Published: Ann Intern Med. 2005;142(11):881-890.
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