LUPUS: A GP Guide to Diagnosis
The striking female preponderance of lupus in humans and the deleterious effects of female sex hormones on laboratory mice with lupus suggests that oestrogens may significantly worsen the disease. This has practical clinical importance for the management of women with lupus. The younger patient may want to discuss pregnancy and the oral contraceptive pill while the older sufferer may wish to consider hormone replacement therapy.
There are a number of issues which have to be considered in the woman with lupus who desires pregnancy or is already pregnant.
Older medical texts suggested that flares of lupus were common and could be dangerous in pregnancy.
A number of larger, better clinical studies have now addressed the issue.
The results of these studies are equivocal with some suggesting no greater disease activity and others recording an increased frequency of flares. Those finding more frequent flares have in common that the increased frequency was not dramatic, nor did the flare-ups tend to be particularly severe.
Studies at St. Thomas' Hospital, London, reported that 62% of women had flares during pregnancy compared with 42% in non-pregnant controls over a similar period. Most flare-ups involved the skin or joints and were mild. The renal disease of lupus, lupus nephritis, did occur more frequently in pregnancy but, again, not dramatically so.
Well-controlled or quiescent lupus pregnancy was associated with fewer flares and this was also so with renal disease. Where possible, the planning of pregnancy during a period of disease inactivity is recommended.
It can be difficult to distinguish the normal bodily changes of pregnancy from mildly active lupus.
Joints are often tight, slightly swollen and achy in pregnancy, hair fall is increased and the healthy flush and increased pigmentation of the face or palms may seem like a mild lupus rash.
Pre-eclampsia, which is more common in lupus pregnancies, causes oedema, increased blood pressure and protein in the urine. This may be hard to distinguish from nephritis but pre-eclampsia does not cause cells or casts to be seen on microscopy of the urine by a laboratory and these features would indicate nephritis.
It should also be remembered that the ESR and complement proteins go up in pregnancy and are less reliable laboratory indicators of flare-ups.
Except with the uncommon and severe lupus nephritis flares, in general, greater disease activity does not seem to predispose to fetal loss. Pre-maturity and low weight for gestational age are more common in the pregnancies of those women with active disease and they are also more likely to require an assisted or caesarean delivery.
Although medication use is wisely minimised in pregnancy, most preparations used in lupus are safe.
Prednisolone does not pass through the placenta and is safe to use for flare-ups.
Azathioprine and hydroxychloroquine do not appear to harm the baby although conclusive proof is lacking. Their continued use must be weighed against the risk of stopping the agent and it seems especially sensible to continue azathioprine in a mother who has had renal disease.
Low dose aspirin is safe, while stronger anti-inflammatories are best minimised and paracetamol used for most aches and pains.
Cyclophosphamide and methotrexate should not normally be used in pregnancy.
The greater occurrence of pre-maturity, low birth weight and instrumental or caesarean deliveries have been mentioned as has the greater risk of pre-eclampsia.
Miscarriage, which can be recurrent and late (second trimester and stillbirth), is a sad and fairly frequent occurrence for a particular group of lupus mothers.
As well as miscarriage, they are at greater risk of arterial and venous thrombosis (DVT and pulmonary embolus) and are found to have certain antiphospholipid antibodies in their blood.
Around one third of lupus women have such antibodies and they should be tested for these before pregnancy and in early gestation.
The tests are for:
1 Anticardiolipin antibodies |
(immunology laboratory) |
2 VDRL |
(immunology laboratory) |
3 Dilute Russell Viper Venom Time |
(haematology laboratory) |
If there are such antiphospholipid antibodies or early miscarriages in the history, aspirin 75 mg per day is recommended.
If thrombosis or late miscarriage is documented, low dose subcutaneous heparin is often required and appears to be safe. Warfarin is teratogenic and is not recommended.
In these patients, as with all the issues in lupus pregnancy, careful liaison between the patient, GP and a specialist team which includes the lupus specialist and obstetrician have greatly improved the success of pregnancy outcome and the determination of the complex management decisions required.
One third of lupus mothers have an antibody called anti-Ro which needs to be tested for by an immunology laboratory.
Up to one in ten of such women will have a baby with so called "neonatal lupus". This usually produces only a transient red rash in the baby and this rash does not scar or need steroid creams. Avoiding exposing the baby to sunlight and using sun block may help.
A few babies with neonatal lupus have blood count abnormalities and, rarely, some develop heart block. Such congenital heart block should be tested for in Ro-positive mothers using ultrasound scans. It is not evident before 18-20 weeks of gestation. Management is difficult and specialised. The baby may not survive but many do and may later need a pacemaker. It should be emphasised that congenital heart block is uncommon even in Ro-positive mothers.
Mothers who have had one baby with neonatal lupus have greater chance of another in subsequent pregnancies.
In general, pregnancy is a rewarding time for women with lupus and it can be pursued safely in most cases. Access to a specialised hospital team is of fundamental importance. All lupus pregnancies should be regarded as "high risk" and home or community births discouraged.
Like the question of "lupus flare" in pregnancy, whether HRT causes greater disease activity in lupus is not conclusively decided.
New onset of lupus in long-term HRT users appears more common than in nonusers and some studies do suggest that lupus sufferers who take HRT have frequent flares. This increased frequency of flares does not, on present evidence, seem dramatic. The results of a large prospective study "SELENA" are awaited in the USA.
Women with lupus are more likely, especially if they have received cyclophosphamide, to have an early menopause. Steroid use, too, is high in this group, therefore osteoporosis is likely to be more frequent and severe than in non-lupus sufferers.
Atheroma, especially heart disease, is more frequent and early in the lupus population. There are, therefore, strong grounds for promoting the benefits of HRT to this group of patients if these can be balanced against the risks.
With the possibility of flare being increased, it is best to avoid HRT in women with unstable or highly active disease, for example, active nephritis, and because of the pro-thrombotic effects. HRT (and raloxifene) are best avoided in women with antiphospholipid syndrome.
In those with inactive mild to moderate and stable lupus, the benefits of HRT may be considerable and the risks and benefits discussed with the patient who should be empowered to choose as an informed partner in the decision.
Dr. Neil M.M. Buchanan
Consultant Rheumatologist
Royal Hampshire County Hospital
Romsey Road
Winchester
Hampshire, SO22 5DG