The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (21 page)

For people with mild psoriasis, creams, ointments, and solutions such as
calcipotriene (Dovonex)
and
calcitriol (Vectical)
, both derivatives of vitamin D
₃
, and
tazarotene (Tazorac)
, a vitamin A derivative, can be used alone or, in more severe cases, combined with topical corticosteroids. These include
halobetasol propionate (Ultravate)
, which comes in cream and ointment form,
diflorasone diacetate (Psorcon)
,
fluticasone propionate (Cutivate)
, and
mometasone (Elocon)
. They can also be used with systemic therapies like methotrexate.

The prescription scalp solution and ointment
Taclonex
contains both
calcipotriene
and the potent steroid
betamethasone dipropionate
, which slow down skin cell growth and reduce inflammation and itch.

Topical steroids cause atrophy and thinning of the skin and are typically used only for limited periods. But if medium- or high-potency steroids are combined or alternated with Dovonex, for example, their use can be extended. Both Tazorac and Dovonex can be irritating, especially on the face and places where skin rubs against skin, like the groin or the armpit. Combining Dovonex and Ultravate can extend a period of remission or improvement up to six months. A common regimen is to use Dovonex and Ultravate twice a day for two weeks, then apply Ultravate only on weekends (but not on the face or areas like the groin).

Dovonex can also be alternated with other “superpotent” topical steroids, such as
clobetasol (Temovate)
or
Psorcon
, which otherwise must be used for limited periods because of their thinning effects on skin. For scalp psoriasis, a two-week cycle of Temovate scalp application solution twice a day is followed by a cycle of Dovonex solution twice a day on weekdays and Temovate twice a day on weekends. Dovonex also increases the effectiveness of systemic therapies, allowing lower doses to be used and reducing the number of treatments with PUVA (ultraviolet light combined with the light-sensitizing drug psoralen—see “Light Therapy” later in this chapter).

Tazorac
works best for women with thick, stable plaques rather than inflamed patches or thin skin. It must be used sparingly, however, because it can cause irritation and redness on unaffected skin surrounding treated plaques. Using Tazorac at night and a topical steroid in the morning can minimize this problem. As with other vitamin A derivatives, it cannot be used during pregnancy.

An older topical prescription,
dithranol (anthralin, Dritho-Scalp
)
, is used to treat plaque psoriasis. It slows down the growth of skin cells associated with psoriatic plaques.

Tacrolimus (Protopic)
and
pimecrolimus (Elidel)
are topical nonsteroidal, anti-inflammatory treatments approved for eczema that can also help improve psoriasis in sensitive areas such as the face, genitals, and skin folds.

Women with psoriasis may undergo therapy that exposes affected areas to ultraviolet light B (UVB), with or without medications that sensitize the skin to UV.

Ultraviolet light has several wavelengths. Most of the solar radiation that penetrates the earth’s atmosphere is ultraviolet A (UVA), which penetrates more deeply into the skin and causes wrinkling and other signs of sun damage. UVB is a shorter wavelength and is the chief culprit in sunburn. Both UVA and UVB have been implicated in skin cancer.

For some people, moderate exposure to natural sunlight can help psoriasis. More intense but controlled exposure to UVB produces more of the reaction in the skin that helps clear plaques. In PUVA, the light-sensitizing drug psoralen produces a greater reaction by the skin when a person is exposed to ultraviolet A. PUVA does carry an increased risk of skin cancer.

“Phototherapy UVB is not the same spectrum of light as sunlight. It’s given in graded fashion, starting with low doses and increasing gradually to try to avoid burns, and we often cover the face,” explains Dr. Lebwohl. “Study after study shows there’s no increase in skin cancers in people treated with UVB for psoriasis. But PUVA is clearly carcinogenic. About one out of six PUVA-treated patients will develop a skin cancer during his or her lifetime—typically squamous cell carcinoma, which usually is easily cured. The more PUVA you get, the more likely you are to get skin cancers.”

The
Excimer laser
is a small (less than an inch in diameter) intense beam of ultraviolet B light (UVB) that can be aimed at single lesions. The Excimer laser is recommended for women with lesions in specific areas of the body. It may take several sessions with the laser to completely clear an area.
²⁴

Women with psoriasis may be put on oral medications, such as the immunosuppressant
cyclosporine (Neoral, Sandimmune)
,
methotrexate
, and derivatives of vitamin A called
retinoids.

Acitretin (Soriatane)
is the only oral retinoid specifically approved for psoriasis. It promotes the normal growth of skin cells and speeds up shedding. It keeps working in the body after it is discontinued, so pregnancy must be avoided for two to three years after stopping the drug (see
page 159
).
²⁵

You can’t donate blood for transfusion during treatment and for up to three years afterward, and women of childbearing potential shouldn’t drink alcohol while on the drug and for two months after discontinuing it. Alcohol can convert the short-acting acitretin to a longer-acting form that can stay in the body 60 times longer, increasing the chances of side effects.

It should also not be taken with vitamin A, either in multivitamins or separate supplements, because the accumulation of vitamin A in the body can cause problems with vision, skin, and bone loss. Like other vitamin A therapies, it can cause birth defects. Soriatane can’t be combined with other retinoids, such as oral
isotretinoin (Accutane)
or topical
tretinoin (Retin-A, Renova).

“Pustular psoriasis responds well to isotretinoin, formerly known as Accutane, which stays in the body for a much shorter period than acitretin; 31 days after you stop using it, it’s out of your system. Isotretinoin also works well with ultraviolet light. So as long as we know a woman is not planning on becoming pregnant (and for at least 31 days after finishing the drug), she can go on isotretinoin,” says Dr. Lebwohl. “Methotrexate and cyclosporine are very effective for psoriasis. But they do have serious drawbacks. Cyclosporine can damage the kidney; methotrexate can damage the liver and causes fetal death.”

Another oral medication,
apremilast (Otezla)
, is approved for people with moderate to severe plaque psoriasis for whom phototherapy or systemic therapy is not appropriate.
²¹
It works differently than other psoriasis medications by targeting an enzyme called
phosphodiesterase 4 (PDE4)
to regulate the inflammatory network within cells. It is taken twice a day.

Alefacept (Amevive)
was the first “biological” therapy approved for psoriasis. It causes a decline in the “memory” T cells, which trigger psoriasis plaques by setting off inflammation and abnormally rapid growth of skin cells.
²⁶
Treatment involves weekly intravenous or intramuscular injections for 12 or 24 weeks and can produce remissions that last as long as 18 months.

In RA and in psoriasis, the inflammatory molecule
tumor necrosis factor alpha (TNFα)
is produced in elevated levels, leading to bone and tissue damage in the joints. The anti-TNF drugs
infliximab (Remicade)
,
etanercept (Enbrel)
, and
golimumab (Simponi)
block TNFα by binding to it, preventing it from triggering inflammation, and can produce very dramatic improvements in psoriasis and psoriatic arthritis.

Infliximab is given by intravenous (IV) infusion in a doctor’s office. Etanercept is given by self-injection just under the skin once or twice per week, and golimumab is also injected subcutaneously, but only once a month.

Ustekinumab (Stelara)
, a new drug that inhibits two other inflammatory cytokines,
interleukin 12
and
23
(
IL-12, IL-23)
, is approved for plaque psoriasis and psoriatic arthritis.
²⁷
The first injection (given by a healthcare provider under the skin, or
subcutaneously
) is followed by a second at four weeks and then every 12 weeks.

The biggest problem for women involves medications used to treat psoriasis, some of which cause birth defects. Soriatane and Accutane stay in the body for varying periods of time. With Soriatane (which is stored in fatty tissues), women must use two forms of birth control beginning a month before treatment is started and for two to three years after it ends. Accutane stays in the body for 31 days, so women must avoid pregnancy during treatment and for 31 days after stopping the drug.

Breast-feeding is not recommended while taking the drug and for two to three years after treatment is stopped. Methotrexate is also teratogenic (harmful to the fetus) and not recommended during pregnancy or breast-feeding. Information is limited on the safety of Ultravate during pregnancy.

“There’s a tremendous amount of data among women who underwent organ transplants and were on cyclosporine during pregnancy. So it does appear to be very safe. The adverse effect appears to be a reduction in birth weight,” comments Dr. Lebwohl.

PUVA is not approved for use during pregnancy. While there do not appear to be any PUVA-related birth defects, there is a slight risk of miscarriage. “It certainly merits discussion with the patient. PUVA does involve a drug that you take by mouth; it gets into your skin and requires activation by ultraviolet light. However, the fetus isn’t exposed to ultraviolet light, so it should be safe,” he adds. Some women develop a facial rash or discoloration called melasma during pregnancy when exposed to ultraviolet light. Called “the mask of pregnancy,” melasma can also occur in pregnant women undergoing PUVA therapy, on the arms as well as the face.

Acitretin also may interfere with low-dose, progestin-only oral contraceptives (such as
Micronor
), so women are advised to use birth control pills containing both estrogen and progestin. Oral contraceptives may affect levels of cyclosporine.

The TNF inhibitors Remicade and Enbrel should only be used during pregnancy if necessary; no harmful effects have been seen on a developing fetus, but risk can’t be completely ruled out. (See
pages 50
to
51
.)

You and your doctor need to go over all of your psoriasis medications if you plan on becoming pregnant.

Psoriasis doesn’t seem to be affected by hormonal fluctuations, so it may or may not improve with menopause. There are no known interactions between psoriasis medications and the estrogens or progestins used in hormone replacement (although there has been no research in the area).

Psoriasis medications have not been well studied in older adults. But it is known that older people are more likely to experience side effects, and medications can stay in the body longer than in younger people. “For example, methotrexate is excreted more slowly when you’re older because your kidneys
don’t work as well. Methotrexate also increases the risk of high blood pressure in people over 65. Cyclosporine directly raises blood pressure, as well,” says Dr. Lebwohl. Older women should discuss all medications with their physician, including any unusual side effects they may be experiencing.

We actually lose hair all the time; each day you may shed as many as 100 hairs as part of the normal growth cycle. Each hair on your head grows about a half inch per month for an average of four to seven years, then enters a “resting” phase (or telogen) lasting two to three months. About 85 percent of the hair on your scalp is growing at any given moment; 15 percent of your hair is in the resting stage. At the end of the resting stage, the hair falls out and a new hair grows in its place.

In alopecia areata, hair follicles are attacked by cell-killing (cytotoxic, NK) T cells, resulting in the arrest of the hair growth stage, explains Madeleine Duvic, MD, professor of Medicine, Interim Chair, Department of Dermatology, and director of the Alopecia Areata National Registry at the M. D. Anderson Cancer Center at the University of Texas in Houston. “The hair breaks off because of the
inflammatory infiltrate, so you get a little stubble. But the hair follicles are still there—they are just damaged and that is why hair breaks off,” explains Dr. Duvic.

Recent research has uncovered multiple immune signaling pathways that promote attacks on hair follicles.
²⁸
It’s unclear how those immune signals may influence the severity of the attacks, how long they last, or why they can suddenly stop. But hair regrowth often resumes spontaneously, says Dr. Duvic.

According to the NAAF, the autoimmune attack causes hair follicles to go into a dormant state where they become very small and produce barely visible hairs (or no hair) for months or even years. The scalp is the most commonly affected area, but any hair-bearing site can be affected alone or together with the scalp. Illness and stress may play a role, though most people with alopecia areata are otherwise healthy. “When there’s a stressor like an illness, or a fever, or a loss of blood that can synchronize your hair. And after you’ve been sick, your hair starts falling out, you lose the resting hairs that are synchronized; that’s telogen effluvium, which is reversible and different from alopecia areata,” says Dr. Duvic.

Alopecia areata occurs in men and women of all ages and races, but it often begins in childhood. Genes play a role; at least one out of five persons with alopecia areata has someone else in the family with the disorder. When the disease occurs before age 30, it’s more likely there’s a family history. Alopecia areata often occurs in families whose members have asthma, allergies, eczema, or other autoimmune diseases such as thyroiditis, diabetes, rheumatoid arthritis, lupus, vitiligo, pernicious anemia, or Addison’s disease.

Recent research indicates that some people may have genetic markers that both increase their susceptibility and influence the severity of the autoimmune attacks on hair follicles.
²⁹

Alopecia areata may cluster with vitiligo (see
page 161
), rheumatoid arthritis, lupus, ulcerative colitis, celiac disease, and Hashimoto’s thyroiditis, as well as the nonautoimmune skin disorders atopic dermatitis and eczema.