|Systemic Lupus Erythematosus||
Causes and Influences
Renal / Kidney
Central Nervous System
The Laboratory investigations
Antibodies in SLE
Criteria for SLE
Assessment of severity
Principles of therapy
Definition - - SLE / LUPUS
SLE is a chronic inflammatory illness characterised by a immunoregulatory disturbance and producing a multisystem disorder including skin, joints, blood, kidney, lung, brain, and other organs.
It was originally described by BIETT in 1822.
Various influences are associated with the disease. These
The prevalence is between 2.9-400 / 100000
Definite FAMILIAL relationships are noted and genetic profiles have been described.
ENVIRONMENTAL factors are also found
HORMONAL Influences are also considered important in pathogenesis. These include especially estrogenic influences.
Perhaps the major mechanism of disease however is the Immunological abnormalities. These are manifested in several ways
The Pathological changes that one sees on histology of the tissues is largely non specific
But some specific changes are seen - including :
HAEMATOXYLIN BODIES AND INCLUSION BODIES OF LE CELLS:
Joint and Musculoskeletal manifestations
ARTHRALGIA - This is common and is pain in the joints with little to find on examination -other than regional tenderness. The pain can be severe and is often worse in the morning, and associated with some stiffness-especially in the hands. However the patient often complains of continuous pain ALL over.
ARTHRITIS - This is characterised by the presence of swelling of the synovial joint lining and is SYMMETRICAL and usually NON EROSIVE
JOINT DEFORMITY may be seen - although uncommon. A variety of ulnar deviation which is reversible is seen in the hands called Jaccouds arthropathy.
TENOSYNOVITIS - this is a tendonitis and is often seen in particular in the flexor hand tendons, but may manifest also as regional enthesitis or bursitis problems.
AVASCULAR NECROSIS is an orthopaedic problem which is associated with the disease but also with use of medications in the disease - especially STEROIDS
Clearly the most visible and common manifestation of SLE
is the skin disease :
PERIVASCULAR INFILTRATES of inflammatory cells
FOLLICULAR PLUGGING - plugging and blocking of the follicles
DERMAL ATROPHY - thinning of the dermal skin layer
IMMUNOFLUORESCENCE GRANULAR IgG DEPOSITS - immune antibody fixation in the skin and dermis layer.
The skin disease has several subtypes - classified according to the severity and type of rash.
ACUTE CUTANEOUS L.E- This is characterised by the classical BUTTERFLY RASH. It tends to EXACERBATE WITH FLARES of the SLE and is characterised by
SUBACUTE CUTANEOUS L.E :
This is a rash seen in patients and is described as SYMMETRICAL SUPERFICIAL NON SCARRING It is distributed especially on the
There are circular ANNULAR LESIONS NON SCARRING ALOPECIA - hair loss, which is patchy in the scalp is seen in 50% of cases. PHOTOSENSITIVITY is VERY common finding.
An ASSOCIATION with certain genetic markers are seen - HLAB8 DR3 ENA(Ro)
Interestingly , in this variety of SLE there is a LOW INCIDENCE of LUPUS NEPHRITIS
This is characterised by ERYTHEMATOUS PLAQUES with SCALING of the
PERICARDITIS- inflammation of the lining around the heart is seen in 30% and presents with chest pain , malaise and sometimes breathlessness.
The clinical findings may be absent with a pericardial effusion identified on an XRAY or cardiac ultrasound..ie it can be ASSYMPTOMATIC.
However a pericardial RUB may be heard on auscultation of the heart on examination.
Occasionally the fluid in the pericardial space can increase in volume, and rarely the fluid in the confined space can compress the heart itself and result in CARDIAC TAMPONADE- with heart failure. In addition, scarring down of the pericardium can result in CARDIAC CONSTRICTION, another cause of right heart failure.
MYOCARDITIS occurs in 25% of patients and is manifested by persistent TACHYCARDIA, ST-T CHANGES on electrocardiogram, congestive heart failure with breathlessness, and ARRHYTHMIA with palpitations or tachycardia complications.
ENDOCARDITIS implies involvement of heart valves with inflammation and sterile VEGETATIONS called LIBMAN SACKS VEGETATIONS.
The MITRAL and AORTIC valves are most commonly involved.
The problem ranges from MILD to SEVERE.
There is an association between the valvular lesions and the ANTI PHOSPHOLIPID ANTIBODY / Lupus anticoagulant.
EMBOLI are a potential complication of clots to the brain and there is a potential for stroke. Involvement of BLOOD VESSELS, may cause significant morbidity. This can be the result of a vasculopathy or vasculitis, or due to accelerated atherosclerosis - a potential complication of steroid therapy.
CORONARY ARTERITIS and STEROID related ATHEROGENESIS may cause myocardial infarction.
PERIPHERAL VASCULOPATHY is also well documented.
There are several manifestations of this:
LIVEDO RETICULARIS- a lace like rash on the body, which is cold sensitive.
ANTIPHOSPHOLIPID ANTIBODY is seen more commonly in patients with lupus and used to be called the lupus anticoagulant. This is associated with, mid-trimester abortions, thrombosis of blood vessels- arterial and venous, central nervous system disease and headaches / migraine, mitral valve lesions and also thrombocytopenia - low platelet counts.
ANGIOEDEMA associated with C2 / C4 DEFICIENCY and C1 ESTERASE INHIBITOR DEFICIENCY
LARGE VESSEL VASCULITIS - a process which is relatively INFREQUENT
VASCULITIS of small and medium vessels may be seen more commonly and LYMPHOCYTES/GRANULOCYTES are seen in the walls of the vessels.
LEUKOCYTOCLASTIC CHANGE is more frequent with RUPTURED CELLULAR DEBRIS.
IMMUNOGLOBULIN / C3 DEPOSITS may be identified in the walls of the blood vessels.
SLE : Pulmonary disease
PLEURITIS / PLEURAL EFFUSION- inflammation of the lining of the lung.
PNEUMONITIS - inflammation within the lung tissue - similar to pneumonia.
PULMONARY HAEMORRHAGE - pulmonary bleeding.
INTERSTITIAL LUNG DISEASE - a progressive scarring of the lung tissue.
SHRINKING LUNG SYNDROME - an interesting feature where the lung volumes decrease. This is felt to relate to elevation of the diaphragms as a consequence of weakness of the muscular diaphragm. INFECTIONS - with pneumonia and sinusitis must be distinguished by disease activity. STEROIDS / IMMUNE THERAPY may reduce the host defences, and infection may follow rapidly.
PULMONARY EMBOLISM - occurs with the development of clot in the leg, which dislodges and travels to the lung vessels - obstructing them. The result is chest pain and breathlessness. PULMONARY HYPERTENSION. - With the occlusion and narrowing of the blood vessels, and with the scarring and fibrosis of the lung tissue, as well as a general increase in tone of the blood vessels within the lung, the pulmonary pressures rise, resulting in breathlessness, and potential progressive right sided heart failure - COR PULMONALE.
The gastrointestinal tract can be involved in several
ways. Most commonly are :
ESOPHAGEAL DYSMOTILITY - results in dysphagia - difficulty swallowing food with a tendency for the food to get stuck. There is an association with this and RAYNAUDS.
ABDOMINAL PAIN : One of the most interesting and difficult management problems in SLE. This can be ACUTE/SUBACUTE and has several mechanisms:
SEROSITIS - inflammation of the peritoneum - the lining of the abdominal wall.
VASCULITIS: which can result in visceral BOWEL GANGRENE
PEPTIC ULCERATION - especially related to DRUGS: - the Nonsteroidal anti-inflammatories and high dose cortisone.
HEPATITIS - and inflammation of the lining around the liver -peri-hepatitis, is an additional potential problem, although generally uncommon.
Kidney / Renal disease :
This is perhapsthe most vital organ involved in lupus and frequently, its involvement determines the outcome of the disease in the majority of patients.
Inflammation in the kidney is called nephritis. This can be renal GLOMERULAR involvement or INTERSTITIAL involvement .
50% OF PATIENTS develop renal disease.
Several subtypes are known.
Several classification systems exist - but the best and most recognised is the World Health Organisation (W.H.O) CLASSIFICATION These are :
2. PURE MESANGIAL NEPHRITIS with MESANGIAL CELL PROLIFERATION AND MATRIX THICKENING
3. FOCAL SEGMENTAL Glomerulonephritis (GN) - with SEGMENTAL PROLIFERATION
4. DIFFUSE PROLIFERATIVE GN with PROLIFERATION /CRESCENTS / and FIBRINOID MATERIAL visible in the glomeruli
5. MEMBRANOUS GN. - with BASEMENT MEMBRANE THICKENING
6. ADVANCED SCLEROSING GN. - with END STAGE FIBROSIS and scarring
Mortality from renal disease has improved dramatically over the
past few years with identification of the more severe subtypes and appropriate therapy.
Therefore an examination of the urine for blood and protein is vital as well as an examination of the urine sediment with a microscope. An increase in the protein or blood in the urine is a possible indication for renal biopsy to determine the subtype of renal disease and determination of aggression and type of therapy.
CNS - Central Nervous System disease
CNS disease Is extremely common and has a wide spectrum of involvement.
TIA - transient ischaemic attack with transient weakness or neurological deficit.
STROKE - established neurological deficit.
CHOREA - an involuntary movement disorder
MYELOPATHY - spinal cord disease.
POLYNEUROPATHY - peripheral nerve disease - with weakness or sensation disturbance in the limbs.
LYMPHADENOPATHY- enlarged lymph nodes are seen in 50% of patients.
HEPATOMEGALY - an enlargement of the liver.
SPLENOMEGALY - an enlarged spleen
The laboratory investigations in SLE.
I generally do aBlood Count, ESR (Sedimentation rate) and a CRP - C-Reactive Protein.
The CRP is usually not elevated in lupus unless there is coincidental infection or inflammation from another cause. The ESR is usually elevated in active disease or inflammation and infection.
ANAEMIA : is seen in 40% of cases and is usually the anaemia of
I also then do a spectrum of antibody
tests - including, antinuclear antibody ANA, anti DNA
antibody, extractable nuclear antibodies - especially ENA sm, ENA rnp, and antihistone
antibody if drug induced lupus is suspected.
A renal function assessmentshould include a test for blood and protein and microscopy. A blood Urea nitrogen and Creatinine, as well as a 24 hour urine collection to investigate the Creatinine clearance and protein production over 24 hours is necessary. Where appropriate, a liver function is done.
Achest Xray, Electrocardiogram and Pulmonary function tests are done as deemed appropriate.
Antibody tests include:
DS DNA (Double stranded DNA)
ANTI HISTONE antibody.
The Antinuclear antibodies:
An antibody is a protein made by the B cell lymphocyte of the body, under the stimulus of the T lymphocyte cell. The initial T cell response follows presentation to the T Cell of antigen, by an antigen presenting cell - usually a macrophage.
The original stimulating antigen in lupus is not known, but felt by many to be an infective agent - possibly a virus or retroviral particle.
The T Cell requires a particular self gene marker to respond to the cell presenting the antigen to it. If it does not see these self gene markers - no reaction will occur.
The self gene marker is related to the HLA gene series - that provides markers for risk factor of disease.
The antibodies in Lupus are associations with the disease and not necessarily causal.
Thus damage to an organ may expose tissue antigens to the macrophage, and antibodies may therefore be produced as a result of damage, rather than causing the damage in the first place.
These antibodies are antibodies to self and hence the terminology - autoimmune - immune to self
The tests done are :
Chronic active hepatitis
Primary Biliary cirrhosis
Drug induced lupus
Anti DNA antibody :Antibodies to double-stranded DNA are more specific to SLE and are measured using the CRITHIDIA ASSAY. The METHOD of this assay uses a Crithidia organism.
This is a FLAGELLATE WITH A KINETOPLAST CONTAINING HELICAL double stranded DNA WITHOUT HISTONES.
Antibody can be made to detect this.
DNA BOUND TO KINETOPLAST IS DETECTED BY FLUORESCENT ANTIGLOBULIN SERUM.
Extractable Nuclear Antibody :
They are LABELLED WITH PHOSPHOROUS AND PRECIPITATED WITH ANTIBODY.
Several are described:
ANTI -U1 RNP Other than SLE may be seen in
Mixed connective tissue disorder :MCTD
MAY IDENTIFY PRECURSORS TO SYSTEMIC SCLEROSIS
They also identify a subset of lupus patients with LESS RENAL DISEASE
ANTI-Ro (SS-A) Seen in:
ANTI-Sm Seen in SLE
The Fluorescent Staining characteristics of the antibodies are as follows
IN FACT : There are multiple clinical manifestations and
therefore Criteria are identified for diagnosis by the American
College of Rheumatology (ACR) These criteria are more for the classification of the
disease and do not mean that therapy must be withheld because not all criteria have been
Once the diagnosis is made , it is important to
evaluate the severity of disease
and establish the degree of organ involvement This is done clinically and with laboratory tests.
Assessment of disease Severity
FEVER / FATIGUE / WEIGHT LOSS
High levels of antibodies ANF / ANTI DNA
SLE : The Principles of Therapy
Once an assessment is made of disease activity - a plan can be made for therapy.Always remember that Lupus patients also get all the common minor illnesses seen with non-lupus individuals. Not every problem is due to the Lupus, and not every problem represents a complication thereof.
There is a tendency for some Doctors and Medical personel to fear the disease, which is a problem that is lessened with the experience of the practitioner.
It is however very important to remain vigilant.
Therefore it is recommended that a Rheumatologist see the patients and hopefully coordinate therapy, but involve the Family physician, and other paramedical staff - including Physical therapists, Occupational therapists, other involved staff and certainly, the patient and family concerned.
EDUCATION is very important
The principles are :
2. MANAGEMENT of the CHRONIC DISEASE
For mild disease a conservative approach is required but for severe disease an aggressive approach becomes necessary.
For the joint manifestations - judicial use of Nonsteroidal anti-inflammatories (NSAIDS) are almost always required - especially if there is swelling and stiffness of the joints. Analgesics are useful for pain control - and should be used depending on severity of the discomfort. Antimalarials ie plaquenil, are particularly useful for joint and skin disease and should be seen as a controller of the underlying process, rather than symptomatic therapy alone. For the skin disease, topical cortisone preparations in different strengths are useful. For the face, topical steroids should be avoided unless in dilute format as they can cause skin thinning. However severe disease sometimes warrants usage under guidance of a dermatologist if necessary. Antimalarials are useful for skin disease control. Monitoring of eye toxicity is required for long term use of the antimalarials.
Use of corticosteroid tablets should be used for severe disease, where function is impaired and NSAIDS are not helping for joint problems, and for major organ involvement. Corticosteroids can be used in oral form or in intravenous pulse therapy for severe organ disease.
Immunosupression is used for severe internal organ
involvement and to reduce requirement for the steroids - steroid
sparing agents. Their usage requires expert knowledge
as monitoring is required for side effects.
TOTAL LYMPHOID IRRADIATION
DIALYSIS has altered the prognosis of millions of patients in end stage renal failure, as has transplantation for thousands of individuals.
For chronic disease the aim of therapy is :
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Original Article - copyright
Dr D Gotlieb : drdoc on-line
Updated Oct 2001