The connective tissue disorders are a diffuse group of diseases that include the rheumatoid diseases (rheumatoid arthritis, ankylosing spondylitis), the collagen vascular diseases (systemic lupus erythematosus (SLE), scleroderma, the vasculitides), granulomatous diseases and inherited connective tissue disease (e.g. Ehlers-Danlos syndrome).
The factors of importance to the anaesthetist are firstly, the widespread systemic nature of the diseases, and secondly, the drug treatment that is used.
Problems and special considerations
With the exception of the rheumatoid diseases, connective tissue disorders are rare in the antenatal population. Although many are autoimmune disorders, which tend to have an increased incidence in females, the onset of significantly symptomatic disease is frequently towards the end of reproductive life. Both spontaneous abortion and late pregnancy loss are increased in women who do become pregnant. Preterm delivery is also increased.
Drug treatment
Drug treatment frequently includes long-term oral corticosteroids, which may be associated with gestational diabetes and fetal adrenal suppression, and may also include immunosuppressive agents such as azathioprine, chlorambucil, cyclophosphamide or methotrexate. Low-dose aspirin and subcutaneous heparin are often used in SLE. In arthritic conditions, non-steroidal anti-inflammatory drugs (NSAIDs) are invariably used. Monoclonal antibody therapy is used in severe forms of rheumatoid arthritis.
Cardiopulmonary involvement
Pericardial effusions are common, especially in rheumatoid and collagen disorders. A restrictive pericarditis may ensue. Valvular dysfunction can occur. Any unexplained dyspnoea or tachycardia should therefore prompt further investigation. A miscellany of electrocardiographic changes may be seen, and echocardiography is useful in assessing both valvular and ventricular function. Connective tissue disorders may also be associated with hypertension, and seem to be associated with an increased incidence of pre-eclampsia.
Pleural effusions and impaired pulmonary function of both restrictive and obstructive patterns may occur, and pulmonary vasculitis may be a feature of both collagen and vasculitic disorders, rarely leading to spontaneous pulmonary haemorrhage. Pulmonary hypertension may also be present.
Women with scleroderma may be at increased risk of chronic aspiration because of impaired gastrointestinal motility. These women may also have significant airway problems.
Haematological involvement
Thrombocytopenia and anaemia may be present or occur anew, and may be difficult to differentiate from the typical gestational picture or conditions such as HELLP syndrome.
Multiple antibody formation
This is a significant problem in women with SLE, although it may also occur in other autoimmune connective tissue disorders. Maternal antibodies cause difficulty and delay in obtaining adequately cross-matched blood for transfusion. In severe cases, there may be maternal coagulation disorders that may be thrombotic or may increase risk of bleeding.
Anticardiolipin antibodies are associated with increased pregnancy loss and increased maternal morbidity. Treatment with aspirin combined with heparin has been associated with a decrease in miscarriage rate. Anti-Ro antibodies may cross the placenta and cause fetal cardiac conduction defects, rendering the fetus bradycardic and unable to mount a tachycardic response to stress; this may occur in 2% of neonates whose mothers have antiRo antibodies. If present, Doppler echocardiography is recommended every 1-2 weeks between 16 and 28 weeks, as this is considered the vulnerable stage for the fetus. Expedited delivery and neonatal pacing may be required.
Musculoskeletal problems
Musculoskeletal involvement is a feature of several connective tissue disorders. Women with scleroderma classically have very tight perioral skin and may also have involvement of the temporomandibular joints; both may limit mouth opening.
Cervical arthritis and consequent reduction of neck mobility is a feature of several connective tissue disorders. Kyphoscoliosis may also be seen, which may complicate neuraxial analgesia/anaesthesia.
Tissue fragility and skin involvement
Several conditions (e.g. certain forms of Ehlers-Danlos syndrome) may be associated with increased fragility of tissues including blood vessels, leading to an increased susceptibility to trauma and bleeding; even frequent non-invasive blood pressure reading may cause bruising. Uterine rupture and delayed wound healing have both been reported.
Bullous diseases such as pemphigus and epidermolysis bullosa are characterised by formation of large bullae on the skin and mucous membranes in response to minor trauma. Although extremely rare, cases have been reported in pregnancy, and there are significant implications for the anaesthetist. Any airway instrumentation (including pressure from a facemask) can provoke bullous formation, and bullae may also form in the trachea. Regional anaesthesia is recommended in these cases.
Management options
Early antenatal assessment is vital, and pre-conception counselling is ideal. If pregnancy has occurred unexpectedly, expert advice should be sought about the relative risks of teratogenicity of immunosuppressive drugs, and the patient counselled appropriately.
Many women with connective tissue disorders have multisystem involvement, and disease activity may change during pregnancy. Detailed history and examination is necessary, with particular reference to drug treatment and symptoms or signs suggestive of cardiac or pulmonary disease. The possibility of difficulty with airway management and cardiopulmonary involvement should be remembered if anaesthesia is required for termination of pregnancy. Maternal mobility may be limited by the underlying disease. The skin should be examined for fragility and ease of intravenous access, which may be facilitated by the use of ultrasound guidance. Investigations should include electro- and echocardiography, pulmonary function tests, chest radiography and full biochemical and haematological investigation.
Women who continue with pregnancy should be regarded as high-risk and receive consultant obstetric care. Serial monitoring of the mother should include assessment of cardiac, pulmonary and renal reserve. Mothers needing maintenance NSAIDs throughout pregnancy will require fetal cardiac monitoring during the third trimester, because of the risk of premature closure of the ductus arteriosus and potential fetal renal compromise.
An individualised, multidisciplinary plan is required, depending on the particular disorder involved. There should be provision for high-dependency level of care during and after delivery. In the absence of coagulation disorder, regional analgesia is not contraindicated; however, recent coagulation studies and a platelet count must be reviewed. Regional anaesthesia is considered unwise by some authorities because of the risk of major haemorrhage during surgery, but a risk-benefit analysis must be made for each patient. Both increased and decreased efficacy of local anaesthetic techniques have been reported in patients with connective tissue disorders, possibly due to altered uptake of local anaesthetic; a history of previous problems should be discussed. If difficulty with the airway is considered to be a major potential risk, relative contraindications to regional anaesthesia are usually outweighed by the benefits. There are no absolute contraindications to regional anaesthesia in these circumstances. A plan for a difficult airway should be made and equipment available; awake fibreoptic intubation may be necessary. Published case reports indicate successful management of individual cases using both general and regional techniques.
Key points
• Connective tissue disorders encompass a wide variety of clinical conditions. Each woman must be assessed on an individual basis.
• Many connective tissue disorders are associated with cardiac, pulmonary and renal dysfunction.
• Drug treatment frequently includes corticosteroids.
• Early and detailed antenatal assessment with serial monitoring during pregnancy are essential.
• Regional analgesia and anaesthesia are not contraindicated, but careful assessment of the balance of risks and benefits is necessary.
Further reading
Clowse ME, Jamison M, Myers E, James AH. A national study of the complications of lupus in pregnancy. Am J Obstet Gynecol 2008; 199: 127:e1-6.
Marder W, Littlejohn EA, Somers EC. Pregnancy and autoimmune connective tissue diseases. Best Pract Res Clin Rheumatol 2016; 30: 63-80.
Marker-Hermann E, Fischer-Betz R. Rheumatic diseases and pregnancy. Curr Opin Obstet Gynecol 2010; 22: 458-65.
Saar P, Hermann W, Muller-Ladner U. Connective tissue diseases and pregnancy. Rheumatology 2006; 45: 30-2.