SYSTEMIC LUPUS ERYTHEMATOSUS

This is a multisystem connective tissue disease

It is characterized by the presence of numerous autoantibodies, circulating immune complexes, and widespread immunologically mediated tissue damage.

PREVALENCE

• Peak age: between 20-40 years (reproductive life)

• Predominant sex: female to male ratio 9: 1

ETIOLOGY

The exact cause of SLE is unknown. Following are the predisposing factors.

• Genetic predisposition

• Environmental factors e.g.

• Ultraviolet rays (sunlight).

• Drugs e.g. hydralazine, procainamide cause SLE more commonly, isoniazid, methyldopa, and chlorpromazine less commonly while phenytoin, carbamazepine, penicillamine, sulphasalazine, and lithium

• Pregnancy and puerperium (due to estrogen changes).

PATHOGENESIS

This is a multifactorial disorder in which there is a profound disturbance of immune regulation.

A defect of suppressor T lymphocytes is associated with polyclonal B lymphocytes activation and the uncontrolled production of autoantibodies and immune complexes.

The inflammatory process in SLE may occur by the two mechanisms.

• Autoantibodies react with cell nuclei therefore antigen-antibody reaction results in inflammation

• Deposition of immune complexes in the tissue causing vasculitis.

CLINICAL FEATURES

Most patients experience exacerbations interspersed with periods of relative remissions.

True remission with no symptoms and requiring no therapy occurs in up to 20% of cases.

Severity varies from mild and intermittent to persistent and fulminant.

Systemic manifestations

Fatigue, fever, anorexia, and weight loss is prominent.

Musculoskeletal manifestations (in >90%).

• Joint involvement is the most common clinical feature.

Almost all patients feel arthralgia and myalgia: most of them develop intermittent arthritis.

• Pain is often out of proportion to physical findings. Joints are painful but characteristically appear normal on clinical
examination.

• Small joints are involved in a symmetrical fashion just like in RA.

• Joint deformities are unusual and erosions are rare.

• Myopathy can be inflammatory (during periods of active disease) or secondary to glucocorticoid therapy.

Skin lesions (in 80%)

• Erythema on the cheeks of the face and across the bridge of the nose (butterfly rash) is characteristic of SLE.

It is present in about 50 % of cases and is photosensitive.

• Photosensitivity – Prolonged exposure to sunlight can cause exacerbations of the disease.

• Loss of scalp hair occurs and is usually patchy.

• Discoid Lupus Erythematosus (DLE) occurs in about 20% of cases of SLE and presents as circular erythematous lesions with scaliness and telangiectasia; scarring causes disfiguring.

DLE occurs over the scalp, cars, face, and sun-exposed areas of aims, bac,k, and chest.

• Purpura, subcutaneous nodules, nail fold infarcts, ulcer, urticaria, and gangrene of digits.

Slightly painful ulcers in the mouth (occurring on hard & soft palate) and in the nose are frequent.

• Raynaud’s phenomenon may be severe enough to result in digital gangrene.

Kidneys (in 50%)

• Clinically significant renal involvement occurs in about 50% of cases but end-stage renal failure occurs in a minority of patients.

• Renal involvement ranges from insignificant proteinuria to nephrotic syndrome and renal failure.

Urine analysis shows hematuria and proteinuria > 0.5 g day.

• Patients with rapidly deteriorating renal function require prompt and aggressive therapy with a high-dose corticosteroid and cytotoxic drugs. A biopsy is not necessary unless the disease fails to respond.

• Hypertension – may occur due to either nephrotic syndrome or renal failure.

CNS (in 60%)

• Mild cognitive dysfunction is the most common CNS manifestation.

Headache, depression, and psychosis are also common.

• Focal infarcts, seizures, cerebellar dysfunction, aseptic meningitis, transverse myelitis, optic sensorimotor neuropathy may occur.

• Abnormal EEG occurs in 70% of cases.

• CSF shows elevated protein levels in 50% of patients. Oligoclonal bands may be found.

• CT scans and angiograms are most likely to be positive when focal neurological deficits are
present.

Vascular changes

Thrombosis to vessels of any size can be a major problem in SLE.

Hematological changes

• Anemia of chronic disease is present in most of the patients and some have Coomb’s positive hemolytic anemia.

• Lymphopenia and mild thrombocytopenia are common.

• Lupus anticoagulant is an antibody against phospholipid causing antiphospholipid antibody syndrome (APLA) that results in thrombocytopenia, recurrent atrial or venous thrombosis, recurrent abortions, and valvular heart disease. ‘

It is present in about 10% of cases of SLE and requires anticoagulation.

Cardiovascular manifestations

• Pericarditis (most common) rarely progresses to pericardial effusion and tamponade.

• Myocarditis is often associated with pericarditis manifests as tachycardia, cardiomegaly, or heart failure.

A severe valvular lesion, primarily of the mitral and aortic valves, may occur.

• A non-infective endocarditis involving mitral valve (called Libman-Sacks syndrome ) occurs but rarely.

• Myocardial infarction may result from coronary arteritis, thrombosis, or premature atherosclerosis secondary to chronic corticosteroid use.

Respiratory manifestations

• Pleurisy and pleural effusion are common.

• Lupus pneumonitis causes fever, dyspnea, cough. X-ray shows fleeting infiltrates.

Gastrointestinal manifestations

• Nausea, diarrhea, and vague abdominal discomfort are common

• Vasculitis of the intestine is the most dangerous manifestation presenting with acute crampy abdominal pain, vomiting, and diarrhea.

Intestinal perforation can occur.

Eye changes

• Retinal vasculitis is a serious manifestation; blindness can develop over a few days.

• Examination reveals areas of narrow retina arterioles and white exudates adjacent to vessels.

REVIEW OF CLINICAL FEATURES OF SLE

Musculoskeletal

• Arthralgia, non-deforming arthritis.

• Involvement of small joints but less morning stiffness than in RA.

• Myopathy.

Skin

• Butterfly rash

• Alopecia

• Photosensitivity

• Discoid lupus

• Vasculitic lesions

• Raynaud’s phenomenon

Kidney

• Proteinuria, nehrotic syndrome

• Renal failure

• Hypertension

Vessels

Thrombosis

CNS

• Depression, psychosis

• Seizures, cerebral infarction (stroke)

Blood

• Anemia, thrombocytopenia, lymphopenia

• Lupus anticoagulant.

Respiration

Pleurisy, pleural effusion, lupus neumonitis.

Eye

Retinal vasculitis – blindness

Blood

• Anemia thrombocytopenia, lymphopenia

• ALA Syndrome

TYPES

Chronic Discoid Lupus Erythematosus (DLE)

It is a benign variant of SLE in which skin involvement is often the only feature although systemic abnormalities may occur with time.

The rash appears on the face as well-defined erythematous plaque that progresses to scarring and pigmentation.

Drug-induced SLE

• It is usually characterized by arthralgia and mild systemic features, rashes, and pericarditis, but often without the involvement of kidneys and CNS.

• It usually disappears when the drug causing is stopped. Hydralazine is the most common cause.

Other drugs involved are

Isoniazid

Methyldopa

Chlorpromazine

Penicillamine.

• All patients have ANA but Anti- dsDNA and hypocomplementemia is rare- a helpful feature to distinguish from idiopathic SLE.

INVESTIGATIONS

Blood  FBE/ESR

Normocytic normochromic anemia –

Leucopenia

Thrombocytopenia^

Lymphopenia

ESR/CRP

• ESR is raised and correlates with disease activity.

• C-reactive protein is normal.

DIAGNOSTIC CRITERIA FOR SLE

Immunological findings

Antinuclear antibodies (ANA)

Serum ANA is positive in more than 95% of cases.

It is the best screening test, however, a positive ANA test is not specific for SLE; it may be positive in many other conditions.’ Therefore a positive ANA test supports the diagnosis of SLE’ but is not specific. A negative ANA test makes the diagnosis unlikely but not impossible.

SLE AND PREGNANCY

• SLE patients in remission are not likely to have exacerbations during pregnancy, however, women with active SLE, especially those with renal disease, have an increased frequency of exacerbations of their disease.

Pre-eclampsia is a frequent complication of pregnancy.

• Fertility rates are normal in SLE but spontaneous abortion occurs in 10-30% of women especially in those who have lupus anticoagulant and/or anticardiolipin antibodies.

• Disease flares in a small proportion, especially during the first 6 weeks postpartum.

ASSOCIATIONS

Following conditions are associated with positive ANA.

• Systemic lupus erythematosus (95%)

• Systemic sclerosis (80%)

• Sjogren’s syndrome (605)

• Polymyositis and dermatomyositis (30%)

• Rheumatoid arthritis (30%)

• Still’s disease (30%).

Anti-double stranded DNA (anti-dsDNA)

It is relatively specific for SLE but present in only 60% of cases; the level fluctuates with disease activity.
Antibodies to double-stranded DNA may also be present in non-SLE patients such as other connective tissue diseases, chronic infections, chronic hepatitis, and interstitial lung disease.

VDRL

Serological tests for syphilis (VDRL) are falsely positive in about 30% of patients.

Serum complement

Serum complements level is low in active disease

Urinalysis

With active nephritis, urinalysis shows proteinuria, hematuria, and red cell casts or granular casts.

24-hour urinary protein is also performed.

Serum creatinine

It should be performed periodically to assess the
renal status.

.Antiphospholipid antibodies

There are three types of antiphospholipid antibodies that may be present in SLE:

1. Antiphospholipid antibodies causing false-positive tests for syphilis.

2. Lupus anticoagulant: (in 7%) it is the risk factor for venous and arterial thrombosis and miscarriage. It is identified by the prolongation of APTT.

3. Anticardiolivin antibody : (in 25%) causing recurrent venous or arterial thrombosis, recurrent fetal loss, or thrombocytopenia. skin ulcers, mental status changes, and mitral regurgitation may also
present.

High serum levels of ANA and anti- dsDNA, raised ESR and low levels of complements usually reflect disease activity, especially in patients who develop nephritis.

PROGNOSIS

In most of the patients, disease pursues a relapsing and remitting course. 10-year survival rates are
> 85%. In some patients, there is severe impairment of vital structures such as lungs, heart, brain, or
kidneys. Infections especially with opportunistic organisms have become the number one cause of
death followed by active SLE, chiefly due to renal or CNS disease.

TREATMENT

There is no cure for SLE therefore management plan is

• To control acute severe flares.

• To develop maintenance strategies in which symptoms are suppressed to an acceptable level, usually at the cost of some drug side- effects.

NSAIDs (Non-steroidal anti-inflammatory drugs)

Mild disease with arthralgia, arthritis, fever, and mild serositis may improve on NSAIDs.

Glucocorticoids

Systemic glucocorticoids are reserved for patients with life-threatening, severely disabling manifestations of SLE such as CNS or renal involvement, myocarditis, pericarditis, or significant thrombocytopenia.

Chloroquine

This is useful in the management of troublesome skin lesions or arthralgia that cannot be controlled
with NSAIDs.

Immunosuppressive drugs

Immunosuppressive drugs such as azathioprine, cyclophosphamide can also be used