By Clinical Associate Professor Peter
Ryan.
Systemic Lupus Erythematosus (SLE) is
a chronic inflammatory disease affecting many parts of the body. Although
there are descriptions outlining the way it can present going back to the
turn of the century, it is only shortly after the second World War when
appropriate blood tests were developed (L.E. cell) that more precise
recognition of the symptoms and signs of SLE was established. Over the last
30 years intensive epidemiological, clinical and laboratory research has
provided many insights into an illness that can have diverse manifestations.
What follows is a brief description of some of the established facts about
SLE with particular reference to the way it is treated.
INCIDENCE
SLE is a worldwide disease. However,
there are some areas in the world in which some populations seem to have a
much higher incidence. In particular, in the black population of the United
States and also Jamaica the incidence may be as frequent as 1 in 250
females. In general terms though SLE is a fairly rare disease and the
approximate number of new cases expected to be seen in Melbourne every year
would be about 50 to 100 (a prevalence of about 1 in 3500). The reason for
this marked variation among different populations is unknown although
genetic factors play a very important role.
AETIOLOGY
The cause(s) of Lupus is or are not
known. It is true to say that there is probably no more studied disease than
Lupus which has provided doctors with intriguing problems which haven't been
clearly solved. Although there are a number of tantalising pieces of
information, we still have much to learn. What is then known about the
causes of SLE?
As you are probably all aware, Lupus
is categorised under the term "auto-immune diseases". Briefly and in
simplistic terms, this means that, for reasons which are not apparent, the
body's immune system mounts an inflammatory attack upon itself and as a
result various organs of the body may become transiently inflamed and, for a
variable period of time, work improperly. This inflammation is continuous
but the intensity tends to occur in episodes. This explains why most
patients' symptoms fluctuate markedly and can improve without any specific
treatment.
There have been various laboratory
animal models of SLE studied for a number of years. The most famous is the
New Zealand black-white mouse. This strain of mice develops an illness which
has many clinical and laboratory similarities to human SLE and has provided
a very accessible means for studying the immunological disturbances and also
means of treatment of SLE. From studies in these mice and from intensive
studies in both individual and families of patients with SLE, it would seem
that both environmental and genetic factors are important. There seems to be
a genetic susceptibility although the exact nature of this is not yet
entirely clear. Probably when someone with a "susceptible" genetic makeup
comes in contact with an environmental agent, possibly a virus, this
autoimmune process is established.
The blood of SLE patients and also
blood from the New Zealand black-white mouse contain various factors known
as autoantibodies. The most intensively studied one is anti-nuclear factor
which was discovered in the late 50's. These factors or antibodies react
with the nuclei of various cells in the body and possibly play a part in the
inflammatory response. There are many other serological factors all of which
have been studied intensively and attempts have been made to relate the
presence or absence of these of various ways SLE may manifest itself. These
are the antibodies your doctor requests to be looked for when he carries out
initial blood tests.
CLINICAL MANIFESTATIONS
SLE is different in every patient. No
two lupus patients are the same and symptoms and signs vary greatly from one
patient to another and also within one patient from time to time. However,
there are definite patterns of the disease and in general terms these tend
to be relatively consistent. For example, some patients have predominantly
problems with their skin and joints and have never had trouble with other
more life threatening organ involvement, such as kidneys or brain. In
general terms clinical features may be divided into two main areas, general
symptoms and specific areas in the body.
GENERAL SYMPTOMS
Certain features are common in all
the various types of Lupus. Without doubt the most consistent feature that
many patients complain of is of a generalised feeling of being unwell often
associated with fevers, lassitude and easy fatigue. As is obvious, there are
many illnesses which can give rise to such similar vague symptoms and it is
for this reason that Lupus is often not diagnosed early on.
SPECIFIC AREAS
The most frequent specific features
of Lupus are really those pertaining to the musculo-skeletal system. Painful
swelling of joints particularly of the hands and wrists, are extremely
common and are often association with aching in and around muscles. Probably
the next most common manifestations are various skin problems. Most patients
know of a facial rash which is usually confined to the cheeks and nose but
may have a wider distribution. Discoid Lupus is really a separate entity and
not usually associated with systemic features although occasionally can be a
skin manifestation of SLE. Other more frequently encountered problems are
pain in the chest due to inflammation of the lining of the lungs and more
infrequently the lining of the heart. Although quite troublesome they
usually do not lead to any major long-term problems.
The kidneys are usually involved in
about half of all patients with Lupus but in the majority it is only mild.
However, kidney involvement needs careful supervision and may entail more
intense treatment usually with high doses of steroids plus or minus immuno-suppressive
drugs such as azathioprine.
A consistent feature of Lupus seen in
nearly all patients is the marked propensity for prolonged sunlight exposure
to cause flare-ups of disease. The precise reason for this is not known but
is probably due to the damaging effect of ultraviolet light on the
superficial cells of the skin causing destruction of their small nuclei,
with the release of chemicals (D.N.A.) into the circulation. It is for this
reason that doctors advise Lupus patients to avoid situations where a high
degree of exposure to sunlight is likely, and to apply liberal quantities of
high grade UV block out creams and lotions.
Alopecia, or falling out of the hair,
although not a common feature of Lupus, is most worrying to the patient as
it can have quite disturbing psychological effects. This usually indicates
that active inflammation is present, but in the vast majority of patients
who suffer from this it is only transient and normal hair growth is to be
expected.
Pregnancy is not contraindicated in
Lupus sufferers and the likelihood of conception is not altered. There is an
increased risk of spontaneous abortions in the second trimester. The
likelihood of the baby of an affected sufferer having SLE is negligible.
TREATMENT
Even for doctors who are very
experienced in treating SLE controversies still arise as to what are the
correct medications and how they should be used. Because of the inherent
fluctuations medical scientists find it very difficult to give precise
scientific data on the appropriateness of each form of therapy to each
particular sub type of lupus. However, a number of general comments can be
made.
In the vast majority of patients,
particularly those in whom musculo-skeletal symptoms are predominant (that
is arthritis) the use of simple anti-inflammatory agents (such as Indocid
and Naprosyn) are of great benefit. At the time of diagnosis most patients
are commenced on these medications and a large number of them are helped
greatly. For reasons which are not entirely clear a number of these
anti-inflammatory agents, particularly Aspirin, seem to be poorly tolerated
by Lupus patients. This also applies to a number of antibiotics,
particularly the Penicillins and the Sulphur drugs. It should be emphasised
though that these antibiotics are not usually contraindicated in the
treatment of other common medical problems that can occur in Lupus patients,
eg. urinary tract infections.
ANTI-MALARIALS
Anti-malarials have been used in the
treatment of Lupus for more than 50 years. There are various different forms
of anti-malarial agents, all of which have minor differences. The most
commonly used one now is Plaquenil and doctors treating Lupus patients often
prescribe this medication early on in the illness. These agents fell into
disrepute in the late 60's and early 70's with the realisation that they
could cause serious eye damage. However, this was probably the result of the
fact that they were used in too high a dose. With the more modern approach
they are used in very low dosage and careful ocular review is carried out.
With this in mind it would seem that once dreaded eye complications are a
thing of the past. Patients on this medications are usually asked to see a
eye doctor at least once a year. Plaquenil, like azathioprine (Imuran) must
not be used if pregnancy is contemplated.
The main stay mode for the majority
of the problems seen in Lupus patients are Cortisone drugs. The most
frequently used of these is prednisolone. Prednisolone in low doses can have
a marked beneficial effects on many features of Lupus particularly the
constitutional symptoms, the arthritis and the inflammation of the lungs and
the skin. In those patients who have ongoing renal inflammation steroids are
usually used in higher doses and for long periods of time. In high doses
over long periods of time, certain unfavourable side effects are nearly
always encountered. The most obvious is the ballooning of the face (Cushingism)
and other features which are not as readily apparent are thinning of the
bones and break down of the lining of the hip joints. Doctors, therefore,
usually make every effort to keep the amount of cortisone to the lowest
possible doses needed to suppress or to withdraw the medication completely.
It is for the latter reason that immuno-suppressives are often introduced.
Unfortunately, in those patients who have severe renal disease, cortisone is
usually needed in fairly high doses for long periods of time and quite
marked side effects become apparent usually after a relatively short period
of time (3 to 6 months). Despite these high doses, progressive loss of
kidney function can occur and this is often a further indication for the
introduction of immuno-suppressives. Azathioprlne (Imuran) is the most
frequently prescribed immuno-suppressive and really is the least noxious of
all these very powerful group of drugs. Because of their effect on
depressing bone marrow production of blood elements regular blood checks are
necessary. Also because of this suppressive effect, patients on this group
of medications are often predisposed to more frequent, and at times quite
severe infections. For this reason patients should be aware that if they are
on these medications and are febrile they should seek medical consultation
as quickly as possible.
Over the last fifteen years, various
newer technologies have been tried in order to obviate some of the problems
discussed above. One technique that has been applied with variable success
is plasma exchange. This requires the patient being placed on a machine
somewhat similar to a kidney dialysis machine which washes the blood of the
patient. Despite initial enthusiasm this technique has been recognised to
have variable beneficial effects and is usually reserved for the use in
patients who have severe life threatening problems, usually severe kidney/or
brain inflammation.
It is obvious from any of the side
effects from the various treatment modalities that there is a great need for
more specific modes of treatment to be developed which have a very low
incidence of side effects.
SUMMARY
SLE is a chronic inflammatory
disorder affecting many organs in the body. It is characterised by
spontaneous remissions and relapses. Because of the fact that any organ in
the body can be involved, symptoms are often diverse and this, in part,
explains the often seen delay in diagnosis. The cause(s) is not known but
this is an area of current intensive active research. Various cortisone
derivatives have remained the mainstay of treatment but there is a strong
realisation amongst doctors who see a lot of patients with lupus, that the
majority of patients' minor annoying symptoms can be relatively easily
controlled without resorting to cortisone.
With increasing sophisticated
laboratory tools lupus is being diagnosed at a much earlier stage and this
has given doctors in general an easier access to establishing the diagnosis
of SLE With regards to diagnosis THE MOST IMPORTANT IS FOR THE DOCTOR TO
THINK OF IT.
This article is current as at
16 July 2003.
