- CFS - Chronic Fatigue Syndrome: What is it?
In December 1994 the International Chronic Fatigue Syndrome Study group - established by the Centers for Disease Control (CDC), Atlanta, USA, with Prof. Umberto Tirelli as the only Italian representative - published an updated CFS case definition on the Annals of Internal Medicine (December 15, 1994, Fukuda et al.). This was to replace the old definition issued six years earlier. According to the updated definition a CFS case is characterized by chronic fatigue persisting for at least 6 months that does not subside with rest, exacerbates as a result of even the slightest efforts and is associated with substantial reduction of previous levels of occupational, social or personal activities. Moreover, four or more of the following symptoms must be present and have persisted for at least six months: impairment in memory and concentration of such a degree as to reduce the previous levels of occupational and personal activities; pharyngitis; painful cervical and axillary lymph nodes; muscle weakness and joint pain without inflammation or swelling; never-experienced-before headache; sleep disturbances; post-exercise weakness lasting at least 24 hours. Of course all clinical conditions that may explain these symptoms must be excluded, for instance hypothyroidism, chronic hepatitis B or C, tumors, certain types of depression, schizophrenia, dementia, nervous anorexia, alcohol abuse and obesity.
Gaining insight into CFS is not easy since it is a serious and complex disease; hence its study requires a joint approach like in similar conditions. Fatigue as a concept is by itself still unclear and the development of a fatigue definition has been a major challenge for the authors. However, it is the authors' opinion that fatigue as a symptom is severe mental and physical exhaustion which is caused even by a minimum effort, but of course, by definition, it is not associated to a known disease; and it differs also from sleepiness and apathy.
Cases of CFS have been reported worldwide, including Europe, Australia, New Zealand, Canada, Island, Japan, Russia and South Africa.
A series of study have been performed at the Centro di Riferimento Oncologico, Aviano, Italy. The first trial outlined the clinical characteristics (U. Tirelli et al., Arch Inter Med, 153, Jan 11, 1993, 116-120) of the first Italian group of patients; then immune abnormalities in patients with CFS were evaluated (U. Tirelli et al., Scand. J. Immunol. 40, 601-608, 1994); the impairment of cognitive functions was assessed by means of PET, a sophisticated method of imaging (U. Tirelli et al., The American Journal of Medicine, 105 (3A) 54S-58S, 1998); the correlation, if any, between CFS and malignancies was studied and also the use of new drugs, in particular high dose immune globulins, magnesium, acetilcarnetine, anti-viral drugs like amantadine and acyclovir and immune modulators like timopentine, was investigated.
Overall, it can be maintained that this severely debilitating disease persists in many patients for several years, whereas in others it improves with time, either by itself or as a result of a drug treatment. Some patients have been cured and others have reported much benefit from the treatments they underwent. Patients are usually young and female between 35-40 years of age. There is practically no evidence of CFS among the elderly (over 65-70), but some cases have been reported among children. The CFS Unit within the Division of Medical Oncology and AIDS at the Centro di Riferimento Oncologico, Aviano, Italy, has so far recorded over 500 CFS cases complying with the CDC case definition.
The NIH National Institute for Allergies and Infective Diseases, USA, has recently issued a booklet called CFS. Information for the Physicians. The authority of the source should dispel any doubts on the existence of the syndrome.
At present different therapies are available for CFS, many of which can alleviate pain and control symptoms, in general, but there is no standard treatment, yet. Much hope is raised by a new drug, Ampligen, a biological response modifier, namely mismatched double-stranded ribonucleic acid. It exerts immunomodulatory activity, antiviral activity against RNA and DNA viruses and antitumor activity that are closely interrelated with each other.
Ampligen regulates both production and activity of various cytokines, including interferon, interleukins and tumor necrosis factor (TNF), and of other components of the immune system, like macrophages, natural killer lymphocytes, T and B lymphocytes. Further Ampligen influences antiviral and immune activity by modulating specific enzymes that play a role in this process.
Given its biological activity, Ampligen has been tested in several studies on patients with CFS and it has shown its effectiveness through a series of objective assays and statistical evaluations. Actually it alleviates symptoms and improves the patients' performance status. Furthermore, a double-blind randomized study has demonstrated that it can increase the capacity of performing everyday occupational activities, hence reducing the level of drug treatment required.
In all trials Ampligen has been well tolerated and no significant side effects have been reported. Ampligen has already been evaluated by FDA in the United States and EMEA in Europe. Before the drug is granted their approval both agencies have required additional investigations which are currently under way.