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.
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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.