Chronic Fatigue Illness and Operation Desert Storm

To the Editor: 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 or Desert Storm Illness (DSI). It has been agreed that many Gulf War veterans do have medical problems, but it has also been argued that the symptoms of DSI 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 posttraumatic stress disorder (PTSD). All of the military personnel that we have interviewed were particularly disdainful of this explanation for DSI. Recently, Major General Ronald Blanck, commanding officer of Walter Reed Army Medical Center in Washington, DC, stated that the symptomatology of DSI is analogous to that of Chronic FatigueImmune Dysfunction Syndrome (CFIDS) 3,4 (Figure 1). The classic workingcase definition of CFIDS is that of Holmes et al5, 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, which 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 autoimmmune 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 DSI (Figure 1).Fig. 1: Comparison of symptoms in approximately 650 Desert Storm veterans suffering from Desert Storm Illness with symptoms of CFIDS (data of Shafran3 and Bell4).Desert Shield/Storm veterans that have some of the multiple chronic symptoms shown in Figure 1 may eventually have their disagnoses 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 DSI, the spread of the illness to immediate family members is not consistent wiht a diagnosis of MCS. Many of the symptoms of DSI may be causes 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 succssfully treated with several courses of broadspectrum antibiotics. There were also a number of endogenous infective agents in the Persian Gulf. Parasites such as Leishmania and bacteria such as Vibrio cholerae are endemic to the Middle East. However, diagnotic tests are available for many of these agents, and there have been no reports that they are causing DSI or CFIDS. We suggested that most of the DSI-CFIDS symptoms can be explained by chronic pathogenic mycoplasma infections.7 Mycoplasma infections usually produce relatively benign disesases 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 that 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 DSI-CFIDS and their families, we have found evidence of mycoplasmic infections in about onehalf of the DSI patients' blood leukocytes. Not every Desert Storm veterans 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 to 200 milligrams/day) or other antibiotics (ciprofloxacin). Of the 73 Desert Storm veterans who had most of the DSI-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 DSI-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 DSI in some veterans, and the appearance of similar DSI-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 maneuvers into Iraq. His unit did not come under enemy fire, and he considered his service relatively uneventful, until months after he returned to the United States. What started out as a relatively benign series of flulike illnesses became progressively worse with intermittent 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 flulike 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 their symptoms were the result of psychological problems (PTSD), but their symptoms were most 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 DSI-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 United States, 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 Veterans Affairs hospitals for his DSI-CFIDS. He tested positive from M. incognitus, received several courses of doxycycline, and 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 DSI-CFIDS responded to doxycycline or ciprofloxacin. 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 DSI-CFIDS strongly suggested that there are multiple causes for these illnesses, but a sizable fraction of veterans with DSI-CFIDS may have identifiable chronic infections that can be successfully treated. Garth L. Nicolson, PhD David M. Bruton Jr., M.D. Chair in Cancer Research; Department of Tumor Biology; The University of Texas; Anderson Cancer Center Houston, TX Nancy L. Nicolson, PhD Rhodon Foundation for Biomedical Research; Kingwood, TX