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Systemic
Lupus Erythematosus(SLE): A Chronic Autoimmune DiseaseThe Case
What
is SLE ?
What
are the presenting symptoms?
What
may be the cause?
What
has gone wrong?
How
may it progress?
What
are the drug regimens for SLE?
What
can we offer to Miss Chan?
Patient
Support Groups
References
and suggested readings
Patient with SLE can be classified
using criteria set out by American Rheumatism Association 2(Tab.
1), these are not necessarily relate to disease severity. These criteria
were established as a classification tool to guide in selecting patient
for clinical and laboratory studies. Nevertheless, they have been useful
in the assessment of both pediatric and adult patients who may or may not
have SLE 3.
| Table 1 Criteria for classification of SLE |
| Malar (butterfly) rash
Discoid-lupus rash Photosensitivity Oral or nasal mucocutaneous ulcerations Nonerosive arthritis Nephritis : Proteinuria > 0.5g/day, Cellular casts Encephalopathy*: Seizures, Psychosis Pleuritis or pericarditis Cytopenia Positive immunoserology*: Antibody to nDNA, Antibodies to Sm nuclear antigen, Positive LE-cell preparation, Biologic false-positive test for syphillis Positive antinuclear antibody test |
| Four of 11 criteria provide a sensitivity of 96% and a specificity
of 96%
*Any one item satisfies that criterion |
Heredity: genetically- influenced of immunoregulatory disturbance; such as failure of negative feedback suppression of antibody production against ' self '. The contribution of HLA molecule to relative risk for developing SLE depends upon the ethnic groups studied 1. However, some evidence is firm, for example, the identical twin with SLE has a 30% chance of developing the disease; first degree relatives have a 5% chance. Certain races , such as blacks and Orientals ,are more prone to SLE. The exact incidence or prevalennce of SLE in Hong Kong is not recorded. Based on a group of approximated 350 SLE patients that fllowed up in a local hospital which is serving about 1,000,000 people, the prevalance of SLE in Hoing Kong is about 35 per 100,000. The true figure may be even higher, since significant number of patients are followed up by private doctors.
Complement
Deficiencies : complement consumption is prominent feature of active SLE,
but there is also a link with inherited deficiencies of complement components.
Thus the majority of individual who are homozygous for C2 or C4 deficiency
develop lupus or lupus like syndrome.
Sex
hormone status : oestrogenic influence on self-recognition, and perhaps
on antibody regulation. Women are much more often affected than men. Hormonal
changes and menses can adversely influence symptoms, and that pregnancy
and the puerperium are times when the disease flare is likely to occur.
Known environmental triggers include:
Drug-induced
lupus : a patient who is a DR4 positive, a slow acetylator and hypertensive
who is administered hydralazine has a high chance of developing drug-induced
lupus. Kidney and brain are often not involved and will settle completely
when the drug is withdrawn, but the auto-nuclear antibody (ANA) may remain
positive for years. The inhibition of C4 binding by hydralazine may be
relevant. For procainamide-induced SLE the anti-H2a/b antibody system may
be involved. Moreover, a large number of drug have been incriminated as
rare causes, including antibiotics, anticonvulsants, antihypertensive and
penicillamine (Tab. 2).
Role of Infection : The significance of the role of infection in activation
of SLE is controversial. There is an impression that viral or bacterial
infection may precede disease activation, but symptoms of viral infections(fever,
malaise, chills, arthralgia) are thought to be produced by IFN gamma, so
that this mediator may actually be the herald of destabilization rather
than a fresh or reactivated viral infection. Electron-dense particles identified
as C-type viruses have been seen in SLE kidney sections, but this is not
a regular finding. Retroviruses may have involvement in reactions, but
there is no pathogenic evidence for their presence in SLE patients. However
the negative findings consistent with the possibility that anti-idiotype
may perpetuate an autoimmune state once is initiated (i.e. act as an autoantigen)
and generate circulating idiotype- anti-idiotype complex.
In SLE both lesions and autoantibodies are not confined to any one organ. A bizarre collection of autoantibodies are found, some of which react with the DNA and other nuclear constituents of all cells in the body. Pathological changes are widespread and are primarily lesions of connective tissue with fibrinoid (an eosinophilic amorphous material ) necrosis. They can affect the skin (the ' lupus' butterfly rash on the face), kidney glomeruli, joints, membranes and blood vessels. The synovium of joints may be oedematous and may contain fibrinoid deposits. Haematoxylin bodies ( round blue homogenous haematoxylin stained deposits) are seen in inflammatory infiltrates and are though to result from the interaction of antinuclear antibodies and cell nuclei.
The exact mechanism is unknown. The
immunological mechanisms of the disease may include:
Polyclonal
B-cell activation. Increased numbers of B cells lead to hyperglobulinaemia.
The
production of ANA and the autoantibodies.
Impaired
T cell regulation of the immune response.
Failure
to remove immune complements from the circulation. Circulating immune complex
cause arthralgia, deposition of immune complex in the tissue causes vasculitis
and many other features of the diseases, including glomerulonephritis which
may lead to chronic ill health and early death of the patient.
Many immunological abnormalities are
also seen, including antibodies to human IgG, nuclear protein, smooth muscle,
cytoplasm, organ specific antibodies e.g. thyroid, leucocyte, platelets,
red cells, clotting factors and cryoglobulins with varying clinical effect.
However, their role in the pathogenesis, if any, is unknown.
The arthritis is usually intermittent. Chronic progressive destruction of joints as seen in the rheumatoid arthritis and osteoarthritis does not occur, but deformities such as ulnal deviation may develop in a few patients.
Kidney is the most important organ
involvement of SLE. The degree of involvement predicts the prognosis of
the patient. Although end stage renal disease is still a significant cause
of morbidity, infection is now the leading cause of morbidity and mortality.
This may be related primarily to the use of high-dose steroids and cytotoxic
drugs.
Active
SLE, with fever and pleurisy should be treated with
prednisolone 30mg daily initially, the dose
then reduced over the course of a few weeks to a maintenance level of around
5-10mg daily. It may be possible to stop treatment within a few month.
For profound haemolytic anemia or thrombocytopenia require large doses
of prednisolone perhaps 60-80mg daily, usually in combination with immunosuppressive
drug such as azathioprine (2mg/kg/day). Chlorambucil is an alternative
and cyclophosphamide is reserved for patient with life threatening disease.
Moreover, immunosuppressive drugs also have a useful steroid-sparing effects.
The antimalarial drug hydroxychloroquine( 400mg daily) is useful for suppressing
the disease activity in patients with minor manifestations such as skin,
joint and general constitutional symptoms. Although the risk of retinal
damage is small at the prescribed dose, this is potentially serious side
effect. Therefore, an ophthalmological examination should be performed
every 6 months.
Other adjunctive therapy such as splenectomy, plasma exchange( plasmapheresis)
and bone marrow transplantation may be considered in some situations, but
their benefit have not been proven and they are mainly reserved for experimental
use. The use of anti-oestrogen or synthetic androgen for human SLE is either
disappointing or inconclusive.
Treatment of specific complications associated with SLE also has improved patient outcome. This includes the use of antihypertensives, anticonvulsants, and antipsychotics as well as vasodilators for severe Raynaud's phenomenon and anticoagulants for the treatment of thrombosis.
If she is actually diagnosed of having SLE, she should be told about the disease. Close follow up is essential to monitor response to therapy an to adjust the treatment accordingly. Education is extremely important to help the patient understand the natural history of their treatment as well as the potential complications.
The following is the advice provided by Hong Kong Lupus Association:
1. Maintain regular balanced diet and adequate rest : a healthy body can help to fight the disease , slow down its progression and sustain vigorous treatment.
2. Avoid prolonged exposure to sunlight or UV light : around 50% of patients will have exacebations following exposure to UV light. One possible mechanism suggested was: UV light induces keratinocytes to secrete IL-1, that stimulates B cell and induce T cells to produce growth factors. However the exact mechanism is unknown.
3. Take only the prescribed medications : to avoid potential drug interactions .SLE patient are more prone to drug sensitivity and some drugs may induce SLE-like illness.
4. Avoiding the
use of any hormonal product , including oral contraceptive :
estrogen accelerate and predispose to SLE, other
contraceptive measures
have to be used if necessary.
Moreover, Miss Chan should be informed there is no major contraindication to pregnancy. However, there is an increased rate of fetus loss and complications may arise during pregnancy which may due to vasculitis affecting the placental blood supply ; specialist care should be available. On the other hand, the danger of sudden stopping high-dose steroids must be emphasized because resulting adrenal insufficiency may be life-threatening.
Dealing with problems of self-image and self-esteem
is particularly important in managing such a chronic disease of young age.
This chronic illness frequency makes it impossible for the patient to develop
their desired independence and social community. So team approach with
the help of medical specialists, social workers, and psychologist trained
to deal with chronically ill patient often are very helpful. The opportunity
for SLE patients to meet and discuss their
concerns and experience about the disease
are very valuable.
1. Hong Kong Lupus Association. Hong Kong
PO Box 13390
(Organized by SLE patients to provide
counseling and sharing among the patients)
2. The Hong Kong Society for Rehabilitation.
Tel: 25497744
1/F, 2 Ko Shing Street, Sheung Wan,
Hong Kong.
(Organized by social workers to provide
nursing care, counseling and financial support)
2. Cassidy JT, Petty RE,(eds). Text book of Pediatric Rheumatology (2nd Ed.). New York: Churchill Livingstone Inc, 1990.
3. Lang BA, Silverman
ED. A Clinical Overview of Systemic Lupus Erythematosus in the Childhood.
Pediatrics in Review. May 1993; 14(5): 194-201.
2. Klinman DM, Steinberg AD. Systemic Lupus Erythematosus and Overlap Syndromes. In: M Samter, (eds). Immunological Diseases Volume II (4th ed). Boston: Little , Brown and Company, 1988. Publishing Ltd, 1991.
3. Cassidy JT, Petty RE,(eds). Text book of Pediatric Rheumatology (2nd Ed.). New York: Churchill Livingstone Inc .
by David 1/6/98
