Lucinda Bateman, MD

Presented October 12, 2003 at the Chicago Patient Symposium sponsored by the CFS

Society of Illinois Radisson Hotel, O'Hare-Rosemont, Illinois I am writing this article as a

clinician and primary care provider (PCP), a doctor who sits face to face, month after

month, with the individuals whose lives are impacted by CFS/FM. It is from that

 perspective that I coined the term "syndrome subsets" for the purpose of describing how,

 in the absence of a "magic bullet," I address the symptoms of patients who meet criteria

for CFS/FM. It routinely   becomes a juggling act of interpreting and balancing many factors: age, gender, genetics, geographic location, underlying or associated diseases (from straightforward to atypical, subtle or overlapping), personality, mood state, medication side effects, insurance and disability status-not to mention the varied ways the symptoms of the CFS and FM case

definitions are manifest between individuals.

Develop a Management Approach
Although CFS and FM have published case definitions, there is in reality a heterogeneous

 spectrum of patients with chronic fatigue that presents to primary care providers.

Although we lack a "cure," there are many things one can do to improve the symptoms of

some patients. This article attempts to rank the subsets of symptoms that I find most

rewarding to identify and treat. First we identify familiar medical problems and implement

standard treatments. In our clinic, we complete a lengthy interview in which we review

life experiences that might have affected mental and physical health. The patient must

 also have completed all "health maintenance" testing (pap, mammogram, colonoscopy,

PSA, etc). We perform a physical examination, review recommended screening lab tests,

build a problem list and implement good management of all identified medical problems

such as hypothyroidism, hypertension, depression or lumbar disc herniation. But when

that is done, our patient usually still has the symptoms of CFS/FM. For the purpose of

this article, I use the term "syndrome subsets" for clusters of symptoms that occur in

some patients but not others, respond to treatment, but don't stand alone as a diagnosis

in terms of total symptom resolution. These may be underlying or overlapping conditions,

symptoms of CFS/FMS, or true subsets of CFS/FMS yet to be objectively delineated. I

address them below in order of how gratifying it is in terms of symptom improvement, and

specify which sub-group of patients we find most likely to fit the symptom subset.

1. Orthostatic Intolerance
WHO? Adolescents and young adults with distinct flu-like onset CFS, plus some others.

The Orthostatic Intolerance (OI) spectrum includes syncope, orthostatic dizziness,

palpitations, tachy- and brady-arrhythmias, headaches and generalized weakness. It may

be typical Neurally Mediated Hypotension (NMH), Postural Orthostatic Tachycardia

Syndrome (POTS), or it may present more subtly. Bedside testing for orthostatic

hypotension does not reliably predict who will have positive findings on Tilt Table testing,

but it does have some utility. We still do, as part of our routine physical examination,

 pulse and blood pressure, supine and standing at 1 minute and 3 minutes. It is a useful

way to teach the patient about OI and prepare them for Tilt Table testing. We refer our

patients in which we suspect OI to experienced Tilt Table technicians who are familiar

with the CFS NMH research and use good methodology. Patients with positive tests may

require vigorous IV fluids and close monitoring until stable. One of our patients was

hospitalized by the cardiologist for observation. Interventions for OI. (Adapted to the

patient and available resources) · Sodium and fluids to approximate 1-3 gms of NaCl +

1-3 Liters H20 per day. It is a challenge to keep this up, but it is inexpensive and readily

available. This is a conservative recommendation based on the idea that a high sodium

"American Diet" is about 6 gms a day, a "No Added Salt" diet is about 3 gms, and a "low

sodium diet" contains about 1 gm. · ProAmatine (midodrine) 2.5-15 mg every 3-4 hours,

 usually three times per day. Slowly titrate to desired effect · Florinef 0.1 mg once or

twice a day · Avoid getting overheated or dehydrated. Consider support hose.

2. Sleep Disorders
WHO? Almost everyone with CFS and/or FMS. There are many subcategories of sleep

disorders, but compensating sleep is important and may depend on your ability to identify

 contributors to disrupted sleep. Common sleep disrupters include restless legs syndrome

 (RLS), myoclonus and periodic limb movement (PLM); obstructive sleep apnea (OSA);

mood disorders that impact sleep (depression, anxiety, PTSD, bipolar disorder); nocturnal

 pain, snoring of a partner, children, noise and many others. Natural sleep is best, but

chronically abnormal sleep is insidiously harmful as well. There is no perfect medication for

sleep. Almost all have some adverse effect on sleep stages. Keep working until a

satisfactory result is obtained. Non pharmacologic Interventions for sleep can be helpful.

Prepare for sleep. Quiet the room. Develop good sleep hygiene. Set regular cycles of sleep

and awakening. Interventions for abnormal movements
· Reduce or stop all caffeine. Definitely no caffeine after about 2 PM. · Avoid alcohol near

 bedtime, or any excessive alcohol intake. · Reduce or stop drugs that cause abnormal

 movements. · Sinemet or Mirapex 0.125-1.5 mg (start low and work up slowly) ·

Klonopin 0.25-1 mg, or other medium to long acting benzodiazepines in low doses. ·

Neurontin 100-1800 mg · Light stretching or exercise · Electrolytes-calcium, magnesium,

potassium
Interventions for obstructive sleep apnea · Weight loss · Treat and prevent reflux

Treat asthma, upper airway allergies and vasomotor rhinitis · Maximize sleep positions. ·

Consider palate or nasal surgery if indicated · CPAP, BiPap, oxygen, as indicated
Medications for Sleep" Short acting sleep "initiators" · Ambien 5-10 mg, Sonata 5-10 mg,

Restoril (temazepam) or other short acting benzodiazepines · Melatonin (pulse for a few

days to "reset" the circadian rhythm)
Longer acting sleep "sustainers": · Amitriptyline or other TCA's in low doses, trazodone

25-300 mg · Neurontin 100-1800 mg, Gabitril 2-12 mg, Topamax 12.5-150 mg, Zonegran

100-200 mg · Seroquel 25-100 mg, Zyprexa 2.5-10 mg · Benzodiazepines: Klonopin or

Xanax 0.5-1 mg · Muscle Relaxants: Zanaflex 2-12 mg, Flexeril 5-10 mg, others

3. Insulin Resistance Syndrome (IRS or Metabolic Syndrome X)
WHO? Overweight, sedentary, middle-aged adults with CFS or FM and a family history of

diabetes. Risk factors for IRS are present in 48% of patients in our clinic who meet criteria

 for FM. Signs of IRS include: obesity or tendency to gain weight easily and in "apple"

body shape, family history of Type II diabetes, borderline or frank hypertension, Type IV

hyperlipidemia (low HDL, high TG), prior high glucose or reactive hypoglycemia, elevated

fasting insulin levels, markers for Type II Diabetes (elevated HgA1C or fasting glucose)

and fatigue, fluid retention, aches, and peripheral neuropathy. Factors driving IRS that

cannot be adjusted include genetic predisposition and advancing age. On the other hand,

 some factors driving IRS can and should be manipulated to advantage, including: physical

 activity: muscle action and bulk, body fat (fat cells are very insulin resistant), and

carbohydrate consumption-both the amount and type of carbohydrate, and medications.
Basic IRS Dietary Recommendations · Eat just enough lean protein each meal to feel

satisfied until the next meal. · Keep fat consumption relatively low. · Choose leafy, fibrous,

 colorful (dark green, red, yellow) vegetables while minimizing vegetables high in starch or

sugar (potatoes, peas, corn) · Consume fiber because it helps slow the absorption of

carbohydrates. · Eat fruit fresh and whole, not juiced or combined with sugar.
Any moderate well balanced diet that achieves the goal is fine. Pick a diet most

compatible with a permanent eating style. If IRS is borderline for Type II DM, consider

Glucophage (metformin), which may help with weight loss and isn't as likely to cause

edema as other oral agents.
IRS Exercise Goals · Weight train to gradually increase muscle tone, bulk and strength. ·

 "Cardio" or aerobic exercise utilizes the muscles so they will burn more glucose and burn

 it more efficiently. Exercise below anaerobic threshold. · Both types of exercise can be

done supine, supported, or in water to minimize fatigue and orthostatic intolerance.

4. Subtle Presentations of Mood Disorders, Primary or Secondary
WHO? Those with family history of mood disorder, childhood emotional trauma, serious

lifetime personal stressors.
Nearly everyone with CFS or FM develops some degree and form of anxiety or depression

 secondary to the devastating losses of their chronic illness. Counseling, structured

support groups or study can help them recognize the loss, work through stages of grief

and recovery, and try to improve any abusive, unsupportive or stressful circumstances.

We encourage them to treat the mood disorder regardless of the cause. Treatment can

include: insight, change, reduced stress, stress management, counseling, medications,

etc. Obvious, subtle or "mixed" primary mood disorders may exist as well, and may actually

 be a risk factor for developing FM or CFS. Mood stabilizing agents of often helpful for

more than just "mood;" they may also moderate pain, fatigue, migraine and sleep.

Generalized anxiety and obsessive compulsive disorder traits respond to SSRIs,

benzodiazepines, anti-convulsants, beta blockers, and many others. Bipolar disorder

manifest as irritability, insomnia and cycling energy levels may be present and amenable

to specific pharmacologic management. Severe depression unresponsive to front-line

agents deserves special and continued attention. ECT for severe depression may help

unrelenting pain as well as the mood.

5. Subclinical Allergies and Asthma
WHO? CFS and FMS. Young, middle aged and older, women and men.
If any signs or symptoms are present, we treat empirically and use symptom improvement

to guide therapy. These symptoms might include nasal congestion or rhinorrhea, sore

throats, cough or exercise induced cough, frequent secondary infections of the upper or

 lower airways, shortness of breath, exercise intolerance, respiratory sleep disturbances,

etc. Some useful allergy treatments
· Nasal steroids or anticholinergics improve nasal congestion and obstruction ·

Non-sedating antihistamines prevent and resolve symptoms: · Claritin, Clarinex, Allegra,

 Zyrtec (reserve the "D" [signifying decongestant] for exacerbations when you can

sacrifice sleep and feeling "wired") · Advair inhaler (steroid + bronchodilator). Mild

subclinical airway reactivity is very common in both CFS and FM. · Avoid the offending

agents. · Allergy desensitization shots. · Move to a new location. It may take a year or

two to develop allergies in a new place. · Consider reflux as a potential cause or

aggravating factor.

6. Physical deconditioning and decline
WHO? Middle aged women, and anyone who has been chronically ill for more than 6

months.
Once the symptoms above are in good control, we begin to address physical conditioning.

Care is taken to adapt to the individual patient and resources available to them. Physical

Improvement Areas
· Flexibility. Stretching is well tolerated and helps improve stiffness and some pain. Do

gently daily or several times a day and adapt to pain areas. Physical therapists, trainers,

massage therapist can teach proper technique. · Muscle tone, bulk and strength:

Strengthening is moderately to well tolerated depending on myofascial pain component.

In general it is better to do less weight and more reps. Strengthen symmetrically and

 globally. · "Cardio" or aerobic capability: Variable tolerance exists among patients. High or

intense levels are usually poorly tolerated by all, but mild to moderate intensity may be OK

 for many with FMS. Those with classic CFS are sometimes quite intolerant. If you treat

OI or adapt exercise to OI, it may be better tolerated.

7. Hormone Replacement
WHO? Middle aged women and men with FMS. Hormones exert a multisystem effect on

the body, and thus can help moderate an array of symptoms. At the same time, hormone

replacement may only temporarily alleviate a symptom until compensatory feedback

 mechanisms begin to operate. For example, extra thyroid hormone may improve overall

well being initially, but eventually the hormone excess will suppress production of TSH and

 thyroid gland atrophy may occur, thus reducing intrinsic thyroid hormone production.

Since there is much we have to learn about these complex systems, we tend to follow

conservative, time-tested approaches to hormone replacement.
Potentially Helpful Hormones (if appropriate!)
· Thyroid replacement-T4, T3 and combos, synthetic versus animal-goal: low normal TSH.

 · Estrogen, testosterone, progesterone-weigh the risks and benefits in each patient.

HRT can potentially be helpful in moderating almost every symptom of FM, but it varies

with the affected individual. · DHEA-maybe helpful in some patients. There are pros and

 cons and it has not been systematically studied. · Human Growth Hormone-may be

helpful if levels are low. Our experience, however, has been disappointing. ·

Corticosteroids (hydrocortisone, prednisone)-supplementation will contribute to adrenal

suppression and may lack sustained efficacy. We reserve use for standard interventions

such as allergies, asthma, or focal musculoskeletal inflammation. · Florinef for OI-Adrenal

suppression and hypokalemia may occur, so this should be weighed against efficacy and

symptom severity.

8. Fatigue
WHO? CFS or FMS with severe fatigue. FMS subgroups tolerate stimulants much better

than patients with immune and infection symptoms only (CFS)
We treat fatigue directly only after addressing sleep, mood, pain, OI, polypharmacy,

deconditioning and other issues. Then we proceed with care and follow-up, because in

some patients, agents that mitigate fatigue may create more problems than they solve.

Sometimes they make a big difference. Here are the most common agents used to directly

 treat fatigue: · Wellbutrin SR 100-150 mg or Wellbutrin XL up to 300 mg each AM. ·

Provigil (modafinil) 50-400 mg. Long acting. May disrupt sleep patterns if sleep is

untreated. · Adderal (mixed salts of Dexedrine) 5-30 mg twice a day. Schedule II. ·

Ritalin (methylphenidate) 5-20 mg 2-3 times a day. Schedule II. · Effexor XR 150-300 mg

 each AM

9. Focal pain
WHO? Middle age and older, men and women. Younger people with prior injury.
Sometimes when faced by widespread chronic pain, we forget to identify and treat

common focal pain areas: osteoarthritis or degenerative joints, tendonitis and bursitis,

lumbar or cervical disc herniation, Trigger Points, Tender Points.
Selected focal pain modalities · Cox II and NSAIDS (Vioxx, Celebrex, Bextra, ibuprofen,

naproxen, etc) for pain related to swelling or inflammation. · Physical therapy, massage,

chiropractic techniques. · Local Injections of steroid, anesthetic, or Botox · Lidoderm

Patches---superficial nerve pain or tender points. · Capsaicin cream or other topicals ·

Surgical interventions.

10. Migraine headaches
WHO? Mostly those with FMS and mood symptoms, but all groups to a lesser degree.
One thing to remember is that the general treatment of sleep, mood, allergies, and pain

(FMS) often reduces migraines. For the remainder, design a good acute regimen to have

on hand at home for a severe migraine. When migraines are frequent, work to establish a

 preventive regimen.
Acute migraine medications
· Phenergan or compazine suppositories · Midrin, Fioricet, or Fiorinal, or others. ·

Tryptans: Imitrex, Zomig, Axert, Relpax, etc… · Strong, short acting oral opiates if

necessary.
Migraine prevention regimens
· Neurontin (weight neutral), Zonegran or Topamax (weight stable or loss) · Depakote

(weight gain) · propranolol XL or metoprolol XL (may cause fatigue, asthma, depression)

· amitriptyline, nortriptyline, doxepin (some may worsen orthostatic hypotension,

cause tachycardia, contribute to weight gain)

11. Possible underlying or intermittent infections
WHO? Most with CFS and some patients with FM, especially those with allergies, asthma

or diabetes.
While subject to debate, the idea of secondary infections or viral reactivation in the

setting of CFS/FM remains important to many providers, perhaps because empiric

treatments sometimes seem to help. As long as antibiotics are used chronically for acne

and long term prophylaxis for herpes is acceptable, it is probably within the bounds of

 reasonable medicine for an individual physician to empirically prescribe an antimicrobial for

their patient with CFS or FM. If such a decision is made, it should be done with caution,

monitoring both for positive effects and for potential adverse effects. Potential situations

include the use of antivirals or atypical antibiotics when a specific organism is suspected

such as mycoplasma, Chlamydia, Lyme, herpes viruses, etc.

12. Irritable Bowel Syndrome
WHO? All ages who have anxiety or depression, and almost all FMS patients.
Abdominal or pelvic pain is a common symptom of these disorders, and may be difficult to

sort out in terms of contribution from ovarian or endometriosis pain, bladder spasm and

discomfort, gall bladder dysfunction, etc. One approach to IBS
· Complete a reasonable, cost effective workup and then provide support and reassurance.

 · Develop a high fiber diet with plenty of oral fluids. Encourage regular exercise as

tolerated. · Provide anti-spasmotics or benzodiazepines (hyoscyamine, Librax, etc) for

PRN use. · Utilize antidepressants that alter bowel motility and improve "nerve" pain

(TCA, SSRI). Assess and treat anxiety if present. · Consider overlap with endometriosis,

interstitial cystitis and gall bladder disease. · At some point, consider colonoscopy to rule

out inflammatory bowel disease, infections, sprue, and malignancy. · Zelnorm 6 mg bid for

 constipation predominant IBS.

Dr. Bateman attended the Johns Hopkins School of Medicine, returned to the University of

 Utah for internal medicine residency, and became certified in Internal Medicine in 1991.

She is the co-founder and current Executive Director of a Utah based non-profit,

 Organization for Fatigue and Fibromyalgia Education and Research. Throughout her career

, her interest has gradually become more focused on the diagnosis and management of

 "chronic fatigue," inspired in part by the silent suffering of her sister with chronic fatigue,

Shauna Bateman Horne. In 2000 Dr. Bateman opened her fatigue consultation clinic and

has since evaluated more than 800 patients with unexplained chronic fatigue, CFS and

FMS.