Systemic Sclerosis in pregnancy

Systemic Sclerosis in Pregnancy (scleroderma)

1. What every clinician should know

Clinical features and incidence

Systemic sclerosis is a connective tissue disease that affects women five times more frequently than men. It usually affects women in their 40s and 50s and is characterized by diffuse vasculopathy, immunologic abnormalities and widespread fibrosis of the skin and internal organs. The incidence of systemic sclerosis ranges from 0.6 million-122 million per year, depending on region and period reported. There are also racial variations, with blacks having a higher age-specific incidence rate and more severe disease than whites.

Systemic sclerosis is divided into two subsets. The first is limited systemic sclerosis group, which is usually more stable. Typical patients are older and describe the onset of symptoms with Raynaud’s phenomenon 10-15 years before the diagnosis. It is usually years to decades before the patient develops organ compromise (esophageal hypomobility, interstitial lung disease, pulmonary hypertension or biliary cirrhosis). Over 50% have anticentromere antibodies.

The second subset, diffuse systemic sclerosis, affects young or middle age women. They usually have an abrupt onset of symptoms, such as edema on the hand, feet, and face or Raynaud’s phenomenon. They may develop GI, pulmonary, renal or cardiac dysfunction, as well as hypertension.

2. Diagnosis and differential diagnosis

A. Establishing the diagnosis

A rheumatologist should make the diagnosis of systemic sclerosis. The American College of Rheumatology diagnosis for systemic sclerosis requires one major criterion (proximal scleroderma), or two minor criteria (sclerodactyly, digital pitting or scars or loss of substance from finger pads, or bibasilar pulmonary fibrosis).

Initial labs should include ESR (greater than 25mm/hr) and hemoglobin, which can be a predictor of the disease activity. Anti-topoisomerase-I, anti-centromere, anti-Scl 70, anti-RNA polymerase III, anti-fibillarin/U3 RN and anti-U1RNP antibodies may help differentiate between the subtypes.

B. Differential diagnosis

The differential diagnosis includes rheumatoid arthritis, systemic lupus erythematous, dermatomyositis, Sjögren’s syndrome, and early, mixed, or undifferentiated connective tissue disease. Skin thickening confirms the diagnosis in over 90% of patients. Discussion with the patient’s rheumatologist is helpful in diagnosing and managing the disease.

3. Management

Patient is at her highest risk of developing cardiopulmonary and renal problems earlier in the disease process (fewer than 4 years) and should consider delaying the pregnancy until it has stabilized. She should have a careful evaluation to determine the type, and duration of the disease, as well as extent of visceral involvement and autoantibody analysis. She should also stop other potentially teratogenic medications prior to pregnancy (Methotrexate, D-Penicillamine, and cyclophosphamide). If the patient is on an ACE inhibitor she should have a trial off of it to see if her blood pressure can be controlled with another medication.

Antepartum

During the pregnancy she should closely monitor her blood pressure with home blood pressure monitor and report even slight elevations as this can be an early sign of renal involvement. Closely monitor serum creatinine levels, proteinuria, and for hemolytic anemia.

Serial growth ultrasounds should be obtained due to the risk of IUGR.

If renal crisis develops during the pregnancy an ACE inhibitor should be started and the patient should be counseled on the potential adverse effects of the medication on the fetus. If the patient is in the first trimester she should consider termination of the pregnancy to allow treatment of the disease. If she develops these complications during the third trimester, there should be consideration of preterm delivery to allow treatment of the mother.

When evaluating for preterm labor, avoid beta-adrenergic agonists.

Intravenous immunoglobulin may be given to control skin and joint involvement.

Intrapartum

During delivery, warming of the room, IV fluids, and the patient to avoid triggering Raynaud’s phenomenon.

Care should be taken if cesarean delivery or episiotomy is necessary, but there should be no delay for either as most will usually heal.

Postpartum

Following delivery, close follow up and early reinstitution of medication.

4. Complications

Complications due to the condition

The biggest concern during pregnancy is the development of renal crisis, which is characterized by malignant hypertension and reduction in renal function. Close monitoring of the patient’s blood pressure with prompt evaluation of serum creatinine, proteinuria, and evidence of hemolytic anemia if there is even a slight elevation. If there is evidence of renal crisis the patient should be started on an ACE inhibitor immediately.

Management complications

ACE inhibitors are a contraindicated during pregnancy due to their association with major fetal abnormalities. They have been associated with anhydramnios, fetal renal atresia, fetal pulmonary hypoplasia and fetal death. There have been reports of use in pregnancy without fetal complications, but the provider should counsel the patient on the potential risks.

5. Prognosis and outcome

Maternal and fetal/neonatal outcomes

Overall pregnancy outcomes are favorable for both the fetus and the mother. In one study with 91 pregnancies, 29% delivered preterm with one fetal demise. A second study with 20 patients had a preterm delivery rate of 40%, with two fetal demises at 25 and 28 weeks. Approximately 50% of the infants were small for gestational age.

Patients with fewer than 4 years of disease who have diffuse cutaneous scleroderma, or have antitopoisomerase or RNA polymerase III antibodies are at higher risk for worsening disease. In one prospective series, 61% the disease remained stable, 20% experienced improvement while 20% experienced some worsening.

Many patients report improvement of their Raynaud’s phenomenon during pregnancy, most likely due to increased cardiac output and decrease in vascular resistance, but it may worsen following pregnancy.

Cardiopulmonary problems do not cause any worse outcome compared to patients with cardiopulmonary problems from other causes.

Gastrointestinal reflux worsened, but can be treated with histamine blockers or proton pump inhibitors.

Some women experience worsening of their skin symptoms following delivery.

Long term impact

The long term impact on her health depends on the type of disease and any progression during pregnancy.

6. What is the evidence for specific management and treatment recommendations

LeRoy, EC, Black, C, Fleischmajer. “Scleroderma (Systemic Sclerosis): classification, subsets, and pathogenesis”. J Rheumatology. vol. 15. 1988. pp. 202-5. (This article lays the foundation for how most people classify and characterize scleroderma.)

Steen, VD. “Pregnancy in Scleroderma”. Rheum Dis Clin N Am. vol. 33. 2007. pp. 345-58. (Dr. Steen is a leading expert in the area of systemic sclerosis.)

Steen, VD. “Pregnancy in women with systemic sclerosis”. Obstet Gynecol. vol. 94. 1999. pp. 15-20.

Miniati, I, Guiducci, S, Mecacci, F. “Pregnancy in systemic sclerosis”. Rheumatology. vol. 47. 2008. pp. iii16-iii18.

Chung, L, Flyckt, RLR, Colón, I. “Outcomes of pregnancies complicated by systemic sclerosis and mixed connective tissue disease”. Lupus. vol. 15. 2006. pp. 595-9.

“Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee: Preliminary criteria for the classification of systemic sclerosis (scleroderma)”. Arthritis Rheum. vol. 23. 1980. pp. 581-90.

Abignano, G, Buch, M, Emery, P, Del Galdo, F. “Biomarkers in the Management of Scleroderma: An Update”. Curr Rheumatol Rep. vol. 13. 2011. pp. 4-12.

Chifflot, H, Fautrel, B, Sordet, C. “Incidence and Prevalence f Systemic Sclerosis: A systemic Literature Review”. Semin Arthritis Rheum. vol. 37. 2007. pp. 223-35.

Mayes, MD, Lacey, JV, Beebe-Dimmer, J. “Prevalence, Incidence, Survival, and Disease Characteristics of Systemic Sclerosis in a Large US Population”. Arthritis and Rheumatism. vol. 48. 2003. pp. 2246-55.

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Systemic Sclerosis in pregnancy