Lupus:

Despite improvements in diagnosis and therapy,
there is still much to unravel.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with
multifactorial aetiology and involvement of most organs or systems at some stage:
the muscloskelatal system, skin, lungs, kidneys, heart, and central nervous system.

Until 25 years ago, lupus was considered a serious and frequently fatal disease,
but advances in diagnosis and treatment have greatly improved prognosis, with current
expected ten year survival rates being greater than 80%.(1,2) Reasons for this include
a greater awareness of SLE among physicians and the wider availability of antinuclear
antibody testing, resulting in earlier diagnosis and identification of many patients with
milder disease with better prognosis. Additionally, advances in specific treatment and
general care have improved survival and quality of life. These include the more judious
use of corticosteroids, antimalarials and immunosuppressive drugs, better hypertensive
agents (angiotensin-converting-enzyme inhibitors), antibiotics, renal dialysis and
transplantation.

Although most fatalities among patients with SLE are due to renal and central nervous
system involvement or infections, 3 co-morbid conditions and complications of therapy
account for the remainder of deaths. Patients with SLE are particularly prone to infections.
Although presumed immunodeficiency associated with the disease appears to be primarily
responsible,4 overzealous use of corticosteroids and other immunosuppressive drugs
increases the risk of infection. Various bacterial, viral and opportunistic infections have been documented, but certain types of infections occur more frequently.
Herpes zoster infections have been reported at a rate of 16 episodes per 1000 patient-years
and its dissemination is significantly associated with immunosuppressive therapy.5 Cases of
Salmonella bacteraemia, gram-negative polyarticular septic arthritis and pneumococcal
sepsis suggest concurrent defective reticuloendothelial function.
Recent reports have documented the occurrence of Pneumocystis carnii pneumonia in
patients with SLE.6 The presence of any of these infections should be considered in the
febrile lupus patient. Prophylactic antibiotic cover for invasive and dental procedures and
vaccination against influenza and pneumoccal infections should be standard care.

During the past decade, increasing attention has been focused on steroid-associated
coronary artery disease, a preventable cause of mortality.
One study found a ninefold increase in death from coronary artery disease in SLE patients.
7 Thus, management should be directed not only to maintaining corticosteroid doses as low
as possible (with the use of antimalarials and other steroid sparing agents), but also
preventing and aggressively treating known risk factors for coronary artery disease.

As survival rates have improved, recent studies have also looked at outcome measures
other than survival. Gladman and Urowitz reviewed morbidity outcomes, including renal
failure, artherosclerosis and coronary artery disease, avascular necrosis of bone, and
cognitive neuropsychological dysfunction, and advocated the widespread use of a "damage
index" for clinical epidemiological studies 9 and individual patient care.
This is now a worldwide trend.

Over the past decade, there has been a clearer delineation of lupus "subsets"
:neonatal lupus erythematosus syndrome (NLE) and the antiphospholipid syndromes (APS).
NLE is a rare condition of congenital complete heart block with or without the transient
manifestations of lupus dermatitis in the infant, and is associated with the transplacental
passage of maternal autoantibodies to Ro (SS-A) or La (SS-B) ribonucleoproteins.10
About a third of patients with SLE have Ro and/or La antibodies, but maternal SLE need
not be present for NLE to occur. At present, it is not possible to predict whether an infant
whose mother has anti-Ro/SS-a or anti-La/SS-B antibodies will develop lupus dermatitis,
but the specificity of maternal autoantibodies helps to predict congenital heart block.11
The occurrence and severity of neonatal lupus are unrelated to maternal disease activity
or severity.

No specific treatment of NLE skin lesions is necessary. Cardiac disease is more
problematic and is best treated by a team of obstetricians, paediatricians and/or
cardiologists. Approximately a third of the infants with complete heart block die before
the age of three years, and most survivors require a pacemaker.12 The mother of the
affected infant should be informed that she is at high risk of developing a rheumatic
disease later in life and that NLE may occur in subsequent pregnancies.
These women must have early antenatal care in subsequent pregnancies, be classified
as "high risk" and be cared for by an obstetrician.

Although many autoantibodies identified in patients with SLE are useful only in diagnosis, antiphospholipid antibodies, especially the lupus anticoagulant and anticardiolipin antibodies,
have achieved clinical prominence as markers of hypercoagulable state that occurs in
patients with connective tissue disease or in the primary antiphospholipid syndrome.
Primary APS is defined by the presence of antiphospholipid antibody (lupus anticoagulant
or high titre anticardiolipin antibody at least two occasions) and the presence of either
venous thrombosis, arterial thrombosis, recurrent abortions (especially second trimester)
or thrombocytopenia.13 A multitude of other abnormalities of the skin, cardiac valves and
central nervous system can occur but their specificity is less clear. Positive tests
(often fluctuate) for APS can also occur in rheumatoid arthritis, drug-induced lupus,
AIDS (acquired immune deficiency syndrome) and other infectious disorders, without the
clinical features of APS.

Treatment trials in pregnant women who have antiphospholipid antibody and receive
treatment to protect the fetus (rather than for maternal active SLE) suggest that a regimen
of moderate dose heparin and low dose aspirin improves fetal outcome. 14 Controlled trials
in pregnant SLE patients show that both high dose14 and low dose15 prednisolone
increase the rate of prematurity and maternal complications.

The last two decades have seen dramatic improvement in SLE-associated morbidity and
mortality as a result of improved diagnostic techniques and therapy.
However, despite efforts to elucidate the pathogenesis of SLE, no clear unifying concepts
have yet emerged.
When they become known, not only will treatment become more targeted and reduce
morbidity, but also the disordered immunobiology of many other diseases may become
apparent.

Indi Rasaratnam Assistant Lecturer,
Department of Medicine, Monash University, Fellow in Rheumatology,
Alfred Healthcare Group, Eastern Healthcare Network,
Victoria, Australia

Peter Ryan Clinical Associate Professor of Medicine,
Monash University.
Head, Rheumatology Unit, Alfred Healthcare Group,
Eastern Healthcare Network, Victoria, Australia.

Reprinted from
THE MEDICAL JOURNAL OF AUSTRALIA
Vol. 163, 16 October 1995 pages 398-399.

1. Barlow JE, Austin HA, Tsokos GC, et al Lupus nephritis.
Ann Intern Med 1987: 106; 79-94

2. Boumpas DT, Fessler BJ,
Austin HA, et al Systemic lupus erythematosus: emerging concepts.
Part 2: Dermatologic and joint disease, the antiphospholipid antibody syndrome,
pregnancy and hormonal therapy, morbidity and mortality, and pathogenesis (review)
Ann Intern Med 1995;
123(1): 42-53

3. Ginzler E, Berg A.
Mortality in systemic lupus erythematosus.
J Rheumatol 1987: 14 Suppl 13:: 218-222

4. Duffy KN, Duffy CM, Gladmann DD.
Infection and disease activity in systemic lupus erythematosus:
a review of hospitalised patients.
J Rhematol 1991; 18: 1180-1184

5. Kahl LE.
Herpes zoster infections in systemic lupus erythematosus: risk factors and outcome.
J Rheumatol 1994; 21: 84-86

6. Porges AJ, Beatie SL, Ritchlin C.et al.
Patients with systemic lupus erythematosus at risk for Pneumocystis carnii pneumonia.
J Rheumatol 1992; 19:1191-1194

7. Jonsson H, Nived O, Sturfelt G.
Outcome in systemic lupus erythematosus: a prospective study of patients from a defined
population.
Medicine 1989; 68: 141-150

8. Gladmann DD, Urowitz MB.
Morbidity in systemic lupus erythematosus.
J Rheumatol 1987; suppl 13: 223

9. Bombardier C, Gladmann D, Urowitz M. et al.
Derivation of the SLEDAI: a disease activity index for lupus patients.
Arthritis Rheum 1992; 35: 630-640

10. Petri M, Watson R, Hochberg MC.
Anti-Ro antibodies and neonatal lupus.
Rheum dis clin North Am 1989; 15: 335-360

11. Bunyon JP, WinchesterRJ, Slade SG, et al.
Identification of mothers at risk for congenital heart block and other neonatal lupus
syndromes in their children.
Comparison of enzyme-linked immunosorbent assay and immunoblot for measurement
of anti-SS-A/Ro and anti-SS-b/La antibodies.
Arthritis Rheum 1993; 36: 1263-1273

12. Waltuck J, Bunyon JP.
Autoantibody-associated congenital heart block: outcome in mothers and children.
Ann Intern Med 1994; 129: 544-551

13. Petri M.
Antiphospholipid antibodies: lupus anticoagulant and anticariolipin antibody.
Curr Probl Dermatol 1992; 4(5): 177-201

14. Cowchock FS, Reece EA, Balaban D, et al.
Repeated fetal losses associated with antiphospholipid antibodies:
a collaborative randomised trial comparing prednisolone with low-dose heparin treatment.
Am J Obstet Gynecol 1992; 166: 1318-1323

15. Silver RK, MacGregor SN, Sholl JS, et al.
Comparative trial of prednisolone plus aspirin versus aspirin alone in the treatment of
anticardiolipin antibody-positive obstetric patients.
Am J Obstet Gynecol 1993; 169: 1411-1417

The Victorian Lupus Association Inc. in no way endorses
any products, medical procedures, or medical practitioners mentioned.
This article is provided as a guide, and or, for information purposes only.