viernes, 22 de febrero de 2019

Rheumatoid Arthritis and Pregnancy

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By Ananya Mandal, MDReviewed by April Cashin-Garbutt, MA (Cantab)

Rheumatoid arthritis (RA) is an immunological disease affecting numerous systems. A rheumatoid arthritis patient getting pregnant may have a serious impact on the pregnancy as well as on the disease process.

Females commonly are more frequent sufferers from immunological disorders affecting joints including:

systemic lupus erythematous
juvenile idiopathic arthritis
Sjogren's syndrome
Scleroderma
Reiter's syndrome
psoriatic arthritis
dermatomyositis/polymyositis etc.

In fact RA is three times more common in females than in males. Thus pregnancy is a condition that might be encountered among RA patients. Practitioners need to aware of several aspects of pregnancy in RA patients.

Pregnancy and immune status

Pregnancy may alter the immune state that can have an impact on the course of any autoimmune illness, including RA.

It was in 1931 that Dr. Hench observed that there is a two to five fold decrease in risk to develop RA during pregnancy in healthy women.

Further in 1992 Silman and colleagues performed a study where they noted that women with RA reported that pregnancy had a protective effect on their disease severity.

Pregnancy and RA severity

Especially in the last three months of the pregnancy (third trimester) the symptoms of RA significantly reduce.

In addition more than three quarters of pregnant patients with RA show improvement in their condition in the first or second trimester.

However, the improvement in the condition may be temporary and flares may occur right after birth of the baby.

90% of women with RA develop a flare up of the condition along with rise in rheumatoid factor titre within 3 months after delivery.

The risk of flare ups remain for the subsequent 9 months after delivery. A flare up may be more common if the woman is breastfeeding. Furthermore patients with no RA before pregnancy also may be at a 5 times higher risk of the disease after delivery.

While three quarters of all patients show some improvement in their symptoms during pregnancy, around a quarter of patients continues to have active disease or may even show a worsening of the condition that necessitates treatment during pregnancy.

Pathology of RA in pregnancy

During pregnancy the female hormones including serum estradiol, 17-a-hydroxyprogesterone and 11-deoxycortisol are increased in the blood. Corticosteroids are known to exert anti-inflammatory and immunosuppressant actions. This could be the reason why most patients with RA show improvement during pregnancy.

Furthermore Estrogen can decrease the stromal cell production of interleukein-1 (IL-1), IL-6 and TNF-alpha that play important roles in RA. Progesterone also decreases T cell response.

Pregnancy in itself leads to decreased production of T-helper cell (Th1)-associated cytokines like IL-1 and interferon-gamma and increased production of Th2-associated cytokines like IL-4 and IL-10. This may have a beneficial role in RA pathogenesis.

Pathology of flare ups after delivery

After delivery there is a risk of flare up of RA. This could be due to decrease in the anti-inflammatory steroid levels and other elevated hormones. Further there is a change from a Th2 to a helper Th1 cytokine profile after delivery.

Some studies have shown that the hormone that induces breast milk coming in – Prolactin, exhibits Th1-type cytokine-like effects. Hence, elevated levels of prolactin after delivery may be responsible for a flare-up.

Effects of RA during pregnancy

Most women with RA have an uneventful and safe pregnancy with no significant complications. There is no effect of the condition on the unborn baby. Further having RA does not affect fertility in a woman.

There may, however, be a decrease in sexual drive, dysfunction in release of the ovum or egg for fertilization and defective hypothalamic-pituitary-adrenal axis that may cause difficulty in conception.

Symptoms of RA are diminished during pregnancy. In later stages of pregnancy there may be low back pain and edema of the feet. However, these symptoms are unrelated to RA. There is a higher risk of anemia and blood counts need to be monitored.

Management of RA with pregnancy

For most pregnant RA patients anti-rheumatic drugs may not be required since the symptoms are reduced and much improved. There is however a risk of side effects on the fetus with certain drugs used in RA. Notable among these is Methotrexate.

Drugs that can be used safely in pregnant patients with RA include:-

Aspirin in high dose should be avoided during all stages of pregnancy especially later in pregnancy. In low dose it is safer (less than 80mg per day).
Other NSAIDs may be used in the first and second trimester of pregnancy if needed.
Corticosteroids are usually considered safe during pregnancy. Low dose prednisone is the preferred drug and is considered safe both for mother and the baby.
Hydroxychloroquine is one of the Disease modifying anti rheumatoid arthritis drugs that has no adverse on the baby in doses of 200-400 mg/day. It is thus preferred as the disease-modifying agent during pregnancy, along with sulfasalazine.
Sulfasalazine is considered safe in pregnancy and can be used in all stages of pregnancy.
D-Penicillamine, Cyclophosphamide and Methotrexate are contraindicated during pregnancy as they may cause fetal damage. Gold salts, Azathioprine, Cyclosporine may be used only if the benefits outweigh the risks. There is little evidence of safety with use of other agents like Leflunamide, Infliximab, Etarnercept etc. in pregnant patients with RA.