Journal of Occupational & Environmental Medicine, 38: 14-16, 1995

Chronic Fatigue Illness and OPERATION Desert Storm

Garth L. Nicolson, Ph.D. 
Nancy L. Nicolson, Ph.D.
Department of Molecular Pathology, The Institute for Molecular Medicine, 16371 Gothard Street H, Huntington Beach, California 92647

	Approximately 50,000 veterans of Operation Desert Storm returned in 1991 from the Persian Gulf with a collection of symptoms characterized by disabling fatigue, intermittent fever, arthralgia, myalgia, impairments in short-term memory, headaches, skin rashes and a collection of additional symptoms that has defied a careful case definition.1  This disorder has been called Persian Gulf War Syndrome (GWS) or Desert Storm Illness.  It has been agreed that many Gulf War veterans do have medical problems, but it has also been argued that the symptoms of GWS are not well established as criteria for particular illnesses and they do not readily fit into common diagnosis categories.1  This has resulted in unknown diagnoses, or worse, they have been diagnosed with psychological problems, such as Post Traumatic Stress Disorder (PTSD).  All of the military personnel that we have interviewed were particularly disdainful of this explanation for GWS.
	Recently Major General Ronald Blanck, commanding officer of Walter Reed Army Medical Center in Washington DC, stated that the symptomology of GWS is analogous to Chronic Fatigue-Immune Dysfunction Syndrome (CFIDS).2  In fact, the symptoms of 650 Desert Storm veterans with GWS fit quite closely with the symptoms of CFIDS3,4 (Figure 1).  The classical working case definition of CFIDS is that of Holmes et al.5, who proposed that CFIDS is primarily characterized by persistent or relapsing, debilitating fatigue or easy fatigability in a person who has no previous history of similar symptoms, that does not resolve with rest and is severe enough to reduce or impair average daily activity below 50% of the patient's premorbid activity level.  In addition to the absence of clinical conditions that could easily explain the symptoms, such as malignancies or autoimmune diseases, patients present with mild fever, sore throat, arthralgia, myalgia, generalized muscle weakness, headaches, painful lymph nodes, sleep difficulties, and neuropsychologic complaints, such as memory loss, photophobia, confusion, transient visual scotomata, irritability and depression.5  These symptoms closely parallel those found in GWS (Figure 1).
	Desert Shield/Storm veterans that have some of the multiple chronic symptoms shown in Figure 1 may eventually have their diagnoses linked to chemical exposures in the Persian Gulf, such as oil spills and fires, smoke from military operations, chemicals on clothing, pesticides, chemoprophylactic agents, chemical weapons and others.  In some cases, such exposure may have resulted in Multiple Chemical Sensitivities (MCS).  MCS shares some but not all of the symptoms listed in Figure 1.  Moreover, in many of the soldiers with GWS, the spread of the illness to immediate family members is not consistent with a diagnosis of MCS.  
	Many of the symptoms of GWS may be caused by chronic host responses to infectious agents resulting in cytokine production.4  Hyman6 has been examining Desert Storm veterans for the presence of bacteria in their urine and has found that many Gulf War veterans have evidence of bacterial infections that can be successfully treated with sevral courses of broad spectrum antibiotics.  There were also a number of endogenous infective agents in the Persian Gulf.  Parasites such as Leishmaniasis and bacteria such as Cholera  are endemic to the Middle East.  However, diagnostic tests are available for many of these agents, and there have been no reports that they are causing GWS or CFIDS.  
	We suggested that most of the GWS-CFIDS symptoms can be explained by chronic pathogenic mycoplasma infections.7  Mycoplasma infections usually produce relatively benign diseases limited to particular tissue sites or organs, such as urinary tract or respiratory infections.  However, the types of mycoplasmas that we have detected in Desert Storm veterans and may be causing the chronic fatigue and other symptoms are very pathogenic, colonize a variety of organs and tissues, and are difficult to treat.  These mycoplasmas are not easily detected but can be identified by a technique that we developed called Gene Tracking.8  In our preliminary study on veterans with GWS-CFIDS and their families, we have found evidence of mycoplasmic infections in about one-half of the GWS patients' blood leukocytes.  Not every Desert Storm veteran had the same type of mycoplasma DNA sequences inside their leukocytes.  Even pathogenic mycoplasmas, such as Mycoplasma fermentans (incognitus) or Mycoplasma penetrans,  should be treatable with multiple courses of antibiotics,9 such as doxycycline (100-200 milligrams/day) or other antibiotics (Cipro).  Of the 73 Desert Storm veterans who had most of the GWS-CFIDS symptoms listed in Figure 1, 55 had good responses with doxycycline, and after multiple courses of antibiotic eventually recovered.7  
	We consider it quite likely that many of the Desert Storm veterans suffering from the GWS-CFIDS symptoms may have been infected with microorganisms, quite possibly pathogenic mycoplasmas and other pathogens (bacteria), and such infections can produce the symptoms in Figure 1, sometimes long after exposure.  This would also explain the mildly contagious nature of GWS in some veterans, and the appearance of similar GWS-CFIDS symptoms in their immediate family members.
	For example, Subject A is an Army officer who served in the Gulf War with the 101st Airborne Division (Air Assault).  He was deployed on the deep insertions into Iraq.  His unit did not come under enemy fire, and he considered his service relatively uneventful, until months after he returned to the U.S.  What started out as a relative benign series of flu-like illnesses became progressively worse with intermetant fever, coughing, nausea, gastrointestinal problems, skin rashes, joint pain, memory loss, vision problems and severe headaches.  Then his wife began to have chronic fatigue and gynecological problems, aching joints, headaches, and her stomach began to swell, causing severe pain.  His 7 year-old daughter also became ill with similar flu-like symptoms that did not go away and progressively became worse, resulting in chronic fatigue, skin lesions, vomiting, headaches, aching joints, and inability to gain weight.  Several other families of Gulf War veterans at his base had similar health problems.  These families were being told that their symptoms were the result of psychological problems (PTSD), but their symptoms were more consistent with CFIDS.  Subject A and his family were placed on several 6 week cycles of doxycycline.  They and others on their base have completely recovered and no longer have GWS-CFIDS. 
	Subject B was an Air Force intelligence officer attached to the 5th Special Forces Group based at King Fahd Airport west of Dhahran and the 160th Special Operations Unit at King Khalid Military City.  He was involved in the Special Forces operations in Iraq.  After his return to the U.S., he noticed that he had a constant sore throat, night sweats, fever, shortness of breath, dizziness, joint pain, short term memory loss, vision problems, diarrhea and other bowel problems, skin rashes and severe to moderate fatigue.  He eventually left the military and could not obtain treatment from VA hospitals for his GWS-CFIDS.  He tested positive for M. incognitus, received several courses of doxycycline, and he has completely recovered.
	Subject C is a Special Forces officer now in the Delta Force at Fort Bragg, NC.  He was in charge of  SEAL units that were involved in some of the most sensitive covert missions during Operation Desert Storm.  He presented after the Gulf War with chronic fatigue, fever, stomach cramps, joint pain, skin rashes, memory loss, dehydration, headaches, heart pain and other symptoms.  His vision became so diminished that physicians at Womack Army Hospital were considering surgery.  After several courses of doxycycline, he completely recovered and has recently been promoted.
	Unfortunately, not all Desert Storm veterans with GWS-CFIDS responded to doxycycline or Cipro.  In addition, some veterans have MCS and cannot take macrolide antibiotics.  Our results and those of other investigators who are examining other possible agents and their role in GWS-CFIDS strongly suggest that there are multiple causes for these illnesses, but a sizable fraction of veterans with GWS-CFIDS may have  identifiable chronic infections that can be successfully treated.

References

1.	NIH Technology Assessment Workshop Panel. The Persian Gulf Experience and Health. JAMA. 1994;272:391-396.

2.	Schmidt P, Blanck RM. Gulf War Syndrome and CFS.  CFIDS Chron. 1995;8:25-27.

3.	Shafran S.  The chronic fatigue syndrome.  Amer J. Med. 1991;90:730-739.

4.	Bell DS.  Chronic fatigue syndrome update.  Postgrad Med. 1994;96:73-81.

5.	Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, et al.  Chronic Fatigue Syndrome: A working case definition.  Ann Int Med. 1988;108:387-389.

6.	Hyman ES.  A urinary marker for systemic coccal disease.  Nephron.  1994;68:314-326.

7.	Nicolson GL, Nicolson NL.  Doxycycline treatment and Desert Storm  JAMA. 1995; 273:618-619.

8.	Nicolson NL, Nicolson GL.  The isolation, purification and analysis of specific gene-containing nucleoproteins and nucleoprotein complexes.  Meth Mol Genet. 1994;5:281-298.

9.	Lo S-C, Buchholz CL, Wear DJ, Hohm RC, Marty AM.  Histopathology and doxycycline treatment in a previously healthy non-AIDS patient systemically infected by Mycoplasma fermentans (incognitus strain).  Mod Pathol.  1991;6:750-754.

Figure Legend

Figure 1. Comparison of symptoms in approximately 650 Desert Storm veterans suffering from Desert Storm Illness with symptoms of CFIDS (data of Shafran3 and Bell4).