Patient Presentation

        The overt illness may begin with acute flu-like symptoms (approximately 85% of cases[11]) that may include fever (sometimes followed by subnormal temperature), recurrent sore throat, headache, marked fatigue, malaise, myalgias, muscle weakness and easy fatigability, exercise intolerance, often painful lymphadenopathy, abdominal pain, and sensitivity to light and cold.  Some experience fever or night sweats.  Younger children and some adult patients may experience a gradual onset, suggesting that there may be a precursor phase.  Indeed, the question has been raised that gradual onset, with perhaps a later acute episode, may be more frequent than previously thought[30].

        In CFIDS, many or all of these problems persist over extended periods with additional symptoms of sleep disturbance (hypersomnia or insomia), photophobia and other eye complaints, hyperacusis, menstrual irregularities, and a variety of very troubling  neuropsychological problems:  cognitive difficulties (short term memory loss, difficulty concentrating and organizing, sporadic confusion), and emotional changes that include anxiety and secondary depression, etc.  Symptoms can vary from person to person and over time in the same person.  Many patients will not seek medical attention until their symptoms have continued for weeks or months (note that the 1988 CDC criteria require an illness of at least 6 months duration; in such cases, particularly with children, or where onset is gradual, this criterion may be too stringent[31]).

        While CFIDS sometimes causes only mild impairment, in severe cases patients may be completely bedridden.  It is vital to recognize that fluctuations in severity and symptoms, within the course of a day and/or weeks, are very common.  The patient's outward appearance is not a good indicator of severity as she or he may appear, though not feel, healthy at the time seen.

        Frequently, patients with CFIDS have seen numerous physicians in an often frustrating search for a useful diagnosis.  The sense of being ill in ways never before experienced is deeply unsettling, so patients can develop a powerful need to explain their complex and troubling constellation of symptoms.  Both doctor and patient can become doubtful and defensive when confronted with seemingly vague and variable manifestations of this disease and the uncertainty regarding its cause and course.  Furthermore, routine blood tests and x-rays may be unremarkable.  Careful consideration is needed to identify the limited number of objective signs among many subjective symptoms, which, though they may at first appear nebulous and idiosyncratic, in actuality often have common patterns.

        Patients may be very sensitive to the physician's attitude, and to the physician's thoroughness, open-mindedness, objectivity, and willingness to work  with them in an attempt to understand and treat the illness. It is crucial to respect the patient's account of the illness.  Bear in mind that CFIDS patients may have difficulty telling their story because of the cognitive problems.  Both the physician and patient need to have the patience and perserverance, first to arrive at a correct diagnosis, and then to proceed with management.  One useful clue in the initial diagnosis is the history of acute onset of this prolonged illness in someone previously functioning well who has no secondary gain from being ill and every desire to get well.

Discussion of symptoms

        1) Fatigue/exhaustion - Physicians must distinguish chronic fatigue syndrome or chronic fatigue and immune dysfunction syndrome from simple chronic fatigue, a symptom common to many disorders.  Failure to make that distinction (easily made, as will be seen) has led to much confusion.

        For severely affected patients the term "fatigue" does not adequately capture the devastating exhaustion that is beyond anything previously experienced.  The unique presentation of the intensity of fatigue of CFIDS is diagnostic.  Daily activities such as getting dressed, walking up stairs, preparing a meal, etc. become difficult or impossible and may be followed, immediately or by many hours or even a day later, by worse fatigue and weakness.  With overexertion, an exacerbation of symptoms for one to four days is common, sometimes leaving the patient bedridden for this time. For such patients, life as they know it grinds to a halt.  School, housework, or work outside the home may become impossible and help in the home from someone else is vital.  Those who are less afflicted may be able to continue work and other aspects of their lives on a modified basis.  The degree of fatigue (and other symptoms) may fluctuate and, during periods of remission, patients may try to do too much leading to a relapse.

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.Figure 2.  Fibromyalgia Tender Points

                2) Myalgias and arthralgias - Muscle aching, tenderness to touch, weakness, and easy fatigability are common.  Reduced aerobic work capacity with increased blood lactate during submaximal exertion has been noted[32].  When the neuromuscular symptoms are characteristic of fibromyalgia (a syndrome of widespread pain in combination with tenderness at 11 of the 18 specific tender point sites), (Figure 2), there is a typical distribution, identifiable with a careful history and tender point exam[33].  The muscle weakness and fatigue often combine with generalized fatigue to make it very difficult to maintain conditioning.  Deconditioning phenomena may be difficult to distinguish from primary manifestations.  Muscle cell changes have been reported, and muscle group atrophy has been noted[34].  The arthralgias are occasionally migratory and may be without redness and swelling.

    3) Neuropsychological disturbances - Symptoms of multilevel brain dysfunction and peripheral neuropathy appear in most patients with CFIDS.
 

        a) Cognitive impairment: Patients often have difficulty concentrating, poor short term memory, spatial disorientation, and periodic mild confusion or a sense of  being "in a fog".  They (or the family) may report subtle impairments of speech, paraphasias, dyscalculia, dysgraphia, problems with abstract thinking, sequencing and organization of ideas.  Routine tasks such as the spelling of familiar words, the ability to recall well-known names or directions may suddenly become unfamiliar and difficult.  In some patients these problems may be transient, often occurring at times of the day when fatigue is greater, but in others they may be more or less persistent.  Recent neuropsychological research has shown reduction in most patients in the ability to acquire new information as well as significant drops in IQ [35,36,37]. New difficulty with serial sevens is commonly observed.  There are some      reports of changes in the brain noted on MRI[19,38] and on SPECT and BEAM scans, the latter showing abnormalities in the frontal and temporal lobes[38,39].  PET scans frequently show hypometabolism in the limbic structures[39,40].

             b) Sleep disturbances including insomnia (ie: DIMS - Disorder of initiating and maintaining sleep) and hypersomnia are very common.  There appears to be disruption of non-REM sleep in CFIDS patients as compared to the REM sleep abnormalities seen in patients with primary major depression.  Nightmares are frequent.  Sleep may be difficult to achieve in spite of exhaustion and may be nonrestorative.  Patients often complain of being as tired upon wakening as when they went to bed.  There is speculation that some of the other symptoms are secondary to the profound sleep disturbance[41].

             c) Headaches: This may be the presenting complaint.  Migraine headaches may appear for the first time or previously controlled migraines can recur in a new pattern.  A dull, painless sensation of pressure is also commonly reported, as is headache in the "sweatband distribution".  With those having symptoms of fibromyalgia, scalp and suboccipital muscle pain often coincide with tenderness to touch, particularly at points of muscle insertion.

             d) Emotional changes:  Common complaints include irritability and emotional lability, generalized anxiety and/or panic attacks and frequent feelings of grief, self-doubt, isolation, despair, and hopelessness.  Suicidal thoughts are not unusual and should be taken seriously and explored.  These symptoms vary, often in concert with the fluctuations of other organic symptoms.

          N.B. The interrelationship between CFIDS and various psychological symptoms, particularly depression, has been the subject of much controversy.  Some clinicians assert that patients with CFIDS have a higher prevalence of past depression and/or a family history of affective disorder which may predispose these patients to CFIDS[42,43].  A well-controlled Australian study, however, reports that the incidence of pre-illness affective or other psychiatric disorders among patients with CFIDS is not greater than the general population[44].

             The presence of the neuropsychological impairments described above suggests that there may well be both primary biological CNS factors and secondary psychological reactions.  The presence of primary CNS factors are suggested by theconcurrent appearance of cognitive and sleep symptoms with the presumably biologically based symptoms of irritability, lability, panic, and dysphoria.  One study has noted the possibility of limbic encephalopathy[39], while another speculates that there may be viral interference with cellular production of neuro-transmitters[22]. A careful history will usually reveal that such symptoms do occur in the earliest stages of the illness and are followed by the emergence of more familiar patterns of psychiatric illness and/or reactive states[34,45].  These secondary reactions may include exacerbation of a pre-existing affective disorder or maladaptive coping style or may precipitate the onset of a major depressive episode or an anxiety disorder in a patient with no previous psychiatric history.  Typical psychological reactions undertandably arise as a result of fear and frustration in reaction to the sudden onset of a severe, disabling, exhausting, mysterious, unpredictable and seemingly endless and untreatable multisystem illness.  CFIDS patients, particularly those who were previously robust people, grieve for lost physical stamina and control over their lives.  The struggle to make major changes in life circumstances and style, forced passivity and dependency, and a periodic sense of helplessness all take their emotional toll.  Experiences of cognitive dysfunction and the recognition of unpredictable or impaired intellectual competence are particularly frustrating and frightening.  Disbelief and dismissal on the part of physicians can only add to the self-doubt, despair, and sense of isolation and helplessness.

             In essence, the depression frequently seen, like that present with other chronic medical illnesses, probably has two causes: biological factors related to the illness and secondary reactions to the many symptoms and impairments.  CFIDS-related depression can range from mild and episodic to more prolonged and suicidally severe (See the Psychiatric Differential Diagnosis section).

        4) Neuro-sensory disturbances - CFIDS patients report fluctuation of sensory input as  disease process waxes and wanes.  While this is commonly reported, no mechanisms plain this phenomenon have been satisfactorily presented. Models looking at multi-level, multi-sensory tasks (e.g. driving) point to involvement of cognitive, sensory, inhibitory, and pathophysiological dysfunction, individually or in combination.
 

             a) Visual and ocular manifestations are common.  Visual disturbances such as blurring, photophobia, floaters and general eye strain while performing routine visual tasks are frequently reported.  Disruption of depth perception and peripheral vision and the inability to judge moving objects (e.g. other cars) can be severe enough to cause patients to reduce or even give up their driving.  Dry eye and related environmental sensitivities are also common[46,47].

             b) Other sensory, balance, autonomic and motor difficulties:  Patients complain of tinnitus and hyperacusis; distortions of taste and smell, dizziness, light-headedness and parathesias in their face and extremities.  Reduction in both heat and cold sensitivities point to possible fluctuations in the hypothalamic-endocrine mechanisms.  Difficulty with fine motor movement, gait and balance are common. Previously well coordinated people may become clumsy.  The neurological examination may reveal a positive Romberg sign and difficulty with tandem walking.  Muscle fasciculations and myoclonic jerks are common.

        5) Other symptomatology - It appears that CFIDS may involve many body systems.  While there are specific symptoms, the net effect in these patients is that they feel sick in a way never experienced before.

a) The acute flu-like pattern that may have been present initially can repeatedly recur.
b) Multiple allergies, environmental, nasal etc. plus food and other sensitivities are common.
c) Weight changes are also common, typically weight loss at the beginning followed by weight gain, possibly related to diminished activity or metabolic alteration.  Carbohydrate craving has been reported.
d) Gastrointestinal complaints include abdominal pain with diarrhea and/or constipation, intestinal gas, and irritable bowel syndrome.
e) Cardiovascular symptoms include heart palpitations, tachycardia, and other rhythm disturbances.  Dyspnea on exertion may transiently occur.
f) Premenstrual syndrome may occur for the first time or be aggravated if present before onset.
g) Urinary frequency and dysuria also may come and go.
h) Skin rashes include two types: flushing of the cheeks with exertion and a non-exertional fine lace-like rash on the neck and chest.
i) Sexual activity - Watch for reduced libido or dysfunction, as well as anxiety around sexual expectations.  Diminished capacity can cause increased stress in the relationship.