Authors: Rita Baron-Faust,Jill Buyon
The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (53 page)
Treatment for fibromyalgia usually involves a combination of medication and exercise, along with behavior modification techniques, cognitive behavioral therapy, and stress reduction.
“Regular analgesics don’t work very well in pain amplification syndromes. Things like acetaminophen and nonsteroidal anti-inflammatory drugs have virtually no effect in pain amplification syndromes. Opioids (such as
tramado
l
) also do not seem to work well,” comments Dr. Clauw. “The best drugs for these syndromes are those that act on the central nervous system and the neurotransmitters serotonin and norepinephrine.”
Three medications have been approved specifically for fibromyalgia:
duloxetine (Cymbalta)
,
10
milnacipran (Savella)
,
11
and
pregabalin (Lyrica)
.
12
Cymbalta and Savella act like antidepressants that prevent excess reabsorption (
reuptake
) of the neurochemicals
serotonin
and
norepinephrine
in the brain, helping to dampen overactive pain signals from nerves (
neuropathic pain
). They can also aid sleep and improve fatigue.
It’s unknown whether Cymbalta can harm an unborn baby, but it may cause problems in a newborn if taken during the third trimester of pregnancy. So you need to let your doctor know if you plan to (or want to) become pregnant.
9
,
10
The most common side effect with Savella is nausea. Other side effects include headache, constipation, dizziness, insomnia, hot flushes, excessive sweating, dry mouth, and palpitations.
11
A 2013 study of milnacipran led by Dr. Clauw showed it produced clinically meaningful improvements in FMS pain for up to three years.
13
Lyrica also affects the brain chemicals
serotonin
and
norepinephrine
, helping to block overactive nerve signaling. It also targets
substance P
and another excitatory neurotransmitter,
glutamate
.
8
Lyrica’s side effects can include dizziness, drowsiness, and weight gain.
12
Other medications used in fibromyalgia include the tricyclic antidepressant
amitriptyline (Elavil)
, the muscle relaxant
cyclobenzaprine (Flexeril)
, the selective serotonin reuptake inhibitor (SSRI) antidepressants
paroxetine (Paxil)
and
fluoxetine (Prozac)
, and
tramadol
, a weak opioid and serotonin and norepinephrine reuptake inhibitor (available with and without acetaminophen).
14
A review of drugs used in fibromyalgia concluded that there are few differences between the three newer medications; they provide an improvement in pain of 30 percent in half of patients who take them, and improvements in pain of 50 percent in a third of patients. Paroxetine, fluoxetine, and tramadol are considered second-line treatments, the review noted.
14
Atypical antidepressants, such as
bupropion (Wellbutrin)
and
nefazodone (Serzone),
which affect the neurotransmitters norepinephrine and dopamine, have been shown to help FMS patients whose major complaints are fatigue or cognitive problems.
Women who have orthostatic hypotension or palpitations may benefit from increasing fluid intake, along with sodium and potassium; low doses of
beta-blockers
are also helpful in women with these signs of
autonomic nerve dysfunction
.
Moderate aerobic exercise and gentle stretching with Tai Chi or yoga may be the best prescription for fibromyalgia pain.
Exercise has been shown to relieve pain by boosting
endorphins
(the body’s natural painkiller) as well as depression in patients with rheumatoid arthritis. Physical therapy and other techniques to ease pain include cortisone injections, injections of local anesthetic (such as
procaine
), massage, moist heat,
myofascial release therapy
(in which pressure is applied to trigger points to “release” tightened muscles),
chiropractic
(a technique of spinal manipulation), and
acupuncture
(the application of hair-thin needles to specific points along the body called
meridians
, triggering the release of endorphins and stimulating nerve endings). However, there have been only a few studies of these therapies in fibromyalgia.
Cognitive behavioral therapy (CBT)
is well studied in pain syndromes and other chronic problems. CBT teaches coping skills and behavioral changes to help you manage negative thoughts that can make pain worse. “Every randomized, controlled trial of cognitive behavioral therapy in any chronic illness has been shown to be effective,” remarks Dr. Clauw.
One recent study looked at CBT combined with a tailored exercise program in fibromyalgia. Researchers assigned newly diagnosed patients to 16 twice-weekly sessions of CBT followed by exercise tailored to their pain-related behaviors (including relaxation training, aerobic exercises, and strength and flexibility exercises) with a booster session after three months.
15
The program proved to be highly effective in improving both short- and long-term physical outcomes such as pain, fatigue, and functional disability, as well as psychological outcomes including negative mood and anxiety.
With CBT, you’ll learn relaxation techniques (such as deep breathing and positive visual imagery), how to reframe negative thoughts and behaviors that intensify pain responses, how to effectively solve problems, and how to pace activities to accommodate whatever limitations you may have. The ultimate goal is to provide you with tools to take control over your fibromyalgia . . . and your life.
I’ve probably had endometriosis since I was 16, when I started having severe pain with my periods. It has taken a tremendous toll on me. I developed severe osteoporosis from treatments among other endometriosis-related factors, and over the years I’ve had five surgeries for endometriosis, including hysterectomy. After that, I took hormones for a few years because I had severe menopausal symptoms, but my endometriosis kicked in again, so I had to stop them temporarily. I was diagnosed with Hashimoto’s thyroiditis
in 1991, and I have also developed horrific joint pain. I also have terrible allergies.Although we really can’t say yet (in 2015) whether endometriosis is autoimmune, it is obviously an immune-mediated disease, and women with endometriosis have a greater risk for hypothyroidism, fibromyalgia, chronic fatigue syndrome, rheumatoid arthritis, lupus, Sjögren’s syndrome, and multiple sclerosis, as shown in a study from our research registry published with the National Institutes of Health.
M
ARY
L
OU
B
ALLWEG, FOUNDER AND PRESIDENT
,
E
NDOMETRIOSIS
A
SSOCIATION
Endometriosis
is a painful, chronic condition that affects an estimated 89 million women and girls worldwide, according to the Endometriosis Association, upwards of seven and a half million women just in the United States and Canada.
The problem arises when endometrial tissue, which normally lines the uterus, is found outside the uterus, where it grows in response to estrogen. These implants cause pain and inflammation, irritating the pelvic cavity, the reproductive organs, and/or the bowel. As the inflammation heals, scar tissue can form weblike growths called
adhesions
, which can also cause pain.
Like fibromyalgia, endometriosis often involves a heightened sensitivity to pain.
19
In fact, according to the American Society of Reproductive Medicine (ASRM), 70 to 90 percent of women who suffer with pelvic pain may have endometriosis.
20
And, like FMS and CFS, it is
not
considered an autoimmune disease. However, over the years, some evidence has accumulated to suggest there may be an immune component. Experts note that endometrial implants are tolerated as self-antigens but act as irritants to promote inflammation, and levels of inflammatory cytokines found in many autoimmune diseases are also elevated in women with endometriosis.
21
One study, presented back in 2002 at the World Congress on Endometriosis, found that 12 percent of women with endometriosis also had an autoimmune disorder, such as lupus or multiple sclerosis.
22
In contrast, only 2 percent of women in the general population have either disease.
In another study, researchers from the Endometriosis Association and the National Institutes of Health (NIH) polled 3,680 women aged 14 to 89 with surgically diagnosed endometriosis and asked whether they had ever been diagnosed with an autoimmune disorder, an endocrine disorder, fibromyalgia, chronic fatigue syndrome, and allergies or asthma. More than 20 percent reported having a coexisting condition; 35 percent had either FMS or chronic fatigue, more than 12 percent had asthma (20 percent of the women with autoimmune diseases reported having asthma), and 63 percent of the women suffered allergies.
23
“This suggests an
association
of endometriosis with autoimmune diseases,” the researchers concluded.
Despite decades of research, the exact cause of endometriosis remains unclear. The earliest theory linked endometriosis to “retrograde menstruation,” the purported backward flow of menstrual discharge through the fallopian tubes into the pelvic cavity.
What has become evident is that women with the disease have some type of immune dysregulation that fails to destroy the rogue tissue.
Normally, the scavenger cells of the immune system (
macrophages
) get rid of foreign cells and bacteria, but in endometriosis these “big eaters” don’t clean up all the stray endometrial cells and cell fragments. The macrophages gobble the errant endometrial cells and present the remains of their dinner to T cells, which recognize the tissue as self and don’t attack. There’s also reduced
activity of
natural killer (NK)
T cells, which don’t need to be sensitized to react against viruses or tumors. So inflammation and irritation caused by the implants continue, possibly leading to production of cytokines that foster the growth of endometrial implants.
Studies also show the inflammatory cytokine
tumor necrosis factor-alpha (TNFα)
, elevated in autoimmune diseases, is also elevated in endometriosis, preventing normal programmed cell death and allowing endometrial implants to proliferate.
24
However, drugs that inhibit TNFα have no effect on endometriosis.
25
Other research has found elevations of other inflammatory cytokines, including
interleukin-6 (IL-6)
and
interleuken-8 (IL-8)
.
26
“The theory has been that abnormal amounts of these cytokines and other chemicals produced by immune cells, along with retrograde flow, may overwhelm the immune system’s ability to eliminate migratory endometrial cells,” says David L. Olive, MD, director of the Wisconsin Fertility Institute in Madison. “There are subtle immunologic disorders that occur with endometriosis. Are they the primary disorder or are they the result of endometriosis? We simply don’t know.”
Endometriosis is considered a chronic pain syndrome. Cytokines produced in reaction to endometrial implants may cause malaise, fatigue, fever, and other inflammatory symptoms. Pain from implants may be caused by chemicals such as
prostaglandins
(which are also produced by the uterine lining and cause menstrual cramps). “It’s unclear why endometriosis causes pain in some women, and not in others. It may be specific to the site of the implants, the amount of prostaglandins secreted by the implants, or the implants may secrete chemicals such as nerve growth factor, which can increase the local nerve density as well as increase inflammation,” adds Dr. Olive.
Autoimmune diseases are characterized by the presence of autoantibodies, and researchers have looked for such antibodies in blood and secretions from women with endometriosis. Scientists have found
anti-endometrial antibodies
, which may be triggered by the presence of the endometrial implants and contribute to symptoms.
Antinuclear antibodies (ANAs)
found in lupus have been detected in women with endometriosis, but those antibodies are also found in women without autoimmune disease and in healthy women.
“Endometriosis may coexist with autoimmune disease, but this does not seem to be a common phenomenon. The presence of autoreactive antibodies
in the serum of some patients with endometriosis may be a natural by-product of inflammation and local tissue destruction. The finding of antibodies to ovarian and endometrial nuclear antigens in patients with endometriosis supports the concept of endometriosis being a multiple antibody autoimmune condition. These autoreactive antibodies may play a role in pregnancy loss and infertility in patients with endometriosis, wrote the authors of a 2012 review.
23
However, they conclude that endometriosis remains “enigmatic”—and its autoimmune connection still inconclusive.
