Systemic Lupus Erythematosus (SLE) - "the" autoimmune disease of the whole body!

Systemic lupus erythematosus or SLE is a common multisystem connective tissue disease. It is an autoimmune disease where body’s immune system attacks against its own cells in the body; here organs, tissues, and cells in the body undergo damage mediated by tissue binding auto antibodies and immune complexes.

How Common is SLE?

The prevalence varies according to geography and between populations; here it is more common and severe among Asians and Black Americans. Females are commonly affected than males with a ratio of 9:1. Peak age of onset of the disease is 20 – 40 years.

SLE is caused by interactions between susceptibility genes and environmental factors, resulting in an abnormal immune response. The immune response includes hyperactivity and hypersensitivity of T and B lymphocytes; ineffective regulation of antigen availability and ongoing antibody responses. The end result of these abnormalities is sustained production of pathogenic auto-antibodies and formation of immune complexes that bind to target tissues.

Around 50 antigens (antibodies attack the antigens which are molecules in the cells) targeted by SLE auto-antibodies. Most antibodies are directed against hidden (intracellular & intra-nuclear) antigens.Pathology and clinical features of the disease are dependent on which antibodies and immune complexes are present and what their target tissues are.

The actual trigger of the disease is unknown, but there are several predisposing factors. Like,

• Heredity- gene defects which run in the family
• Genetics- gene defects which occur suddenly
• Complements
• Sex hormone status
• Environmental Factors
• Drugs: hydralazine, methyldopa, isoniazid, minocycline
• Hormones: Oral contraceptive pill (OCP), Hormone replacement therapy (HRT)
• Ultra violet light
• Viral agents

Interpretation of clinical manifestations is important so as to diagnose the disease, to assess the severity of the disease and to estimate possible consequences of therapeutic interventions. Since it is a multisystem disorder patient can present with various symptoms (complains that are made by patient) which varies according to the body system it affects most.

1. Raynaud’s phenomenon
2. Mucocutaneous features (skin conditions)
3. Musculoskeletal features (muscles and joint involvements)
4. Renal features
5. Cardiologic features
6. Pulmonary features
7. CNS features
8. Heamatological features
9. Other manifestations

1. Raynaud’s phenomenon

Raynaud’s phenomenon consists of spasm of the arteries in fingers, usually precipitated by cold and relieved by heat. The disorder is usually bilateral with fingers affected more commonly than toes. There will be a color change in the skin of the fingers from white or pale followed by blue and then red. Here vasoconstriction causes skin pallor followed by blue causing cyanosis dueto sluggish blood flow, then redness secondary to hyperaemia (reflex high blood flow).The duration of the attacks is variable but they cansometimes last for hours. Numbness, a burning sensationand severe pain occur as the fingers warm up. In chronic, severe disease tissue infarction (cell death) and loss of fingers can occur.In SLE, arthritis (joint pains) with Raynaud’s phenomenon is the commonest presentation.

2. Mucocutaneous Features (mucus membranes and skin manifestations)

1) Oral ulcers

They get painful mouth ulcers which last longer and can lead to scar formation.

2) Skin Manifestations are particularly common

· They get a characteristic rash on face called Malar or butterfly rash which is raised erythematous (red), occasionally scaly itchy, rash distributed over cheeks and nose and it is photosensitive(more prominent with sun exposure)

· Another rash called Discoid rash; which is a circular shaped, with a raised surface, scaly; there is hyperpigmented (darkend) erythematous ring, depigmented (lightened) center. May cause hair loss if the lesions occur on scalp.

· Subacute Cuatneous Lupus Erythematosus (SCLE) is migratory, non-scarring rash

· Periungual Erythema

· Vasculitic rash

· Livedo reticularis is a purple ring-like rash which is also seen in Antiphospholipid syndrome

· Recurrent urticaria & pigmentation

3. Musculoskeletal Features

Joint manifestations are different from rheumatoid arthritis since it does not cause serious joint deformities. Features are

· Arthralgia & myalgia (joint and muscle pains) occurs in 95% of patients

· Mild morning stiffness (inability of moving joints with felling of stiffness)

· Tenosynovitis (inflammation of synovial membranes mostly in hands)

· Small joint synovitis

· Nevertheless joint deformities may occur due to tendon inflammation & damage called Jaccoud’s arthropathy in 10%

· Joint pains mainly occur in hands, wrist, and knees; but joint deformities occur in very few patients.

· Muscle weakness (myositis – 5%)

4. Renal Features

Renal involvement is a main determinant of the prognosis, yet majority does not show any symptoms; symptomatic patients will have heavy haematuria (passage of blood with urine), proteinuria (passage of protein with urine), or urinary casts. Ultimately patients will either go into end stage renal disease, nephrotic syndrome or hypertension

5. Cardiologic Features

· Chest pain due to pericarditis (inflammation of the pericardium which is the outer layer of the wall of the heart)

· Myocarditis which is inflammation of the cardiac muscle

· Libman-Sacks sterile endocarditis (inflammation of inner layer of the wall of the heart )

· Accelerated atherosclerosis

· Myocardial infarction

6. Pulmonary Features

· Pleurisy (inflammation of the pleura which is the lining of the pleural cavity and lung) patients may present with chest pain

· Pleural effusion (collection of fluid in the pleural space)

· Lung fibrosis due to interstitial inflammation leading to a condition called shrinking lung syndrome, here patients may present with difficulty in breathing, shortness of breathing

· Intra-alveolar haemorrhage here patients may present with coughing out blood

7. Central nervous system features

In the absence of active disease patient may have features like; fatigue, poor concentration

Active involvement of SLE or Cerebral lupus will present as a diffuse entity like

· Cognitive dysfunction (impaired memory/ reasoning)

· Headache

· Seizures

· Psychosis

· Aseptic meningitis

· Cranial nerve lesions

· Visual hallucinations

· Chorea – also in antiphospholipid syndrome

· Transverse myelitis

Or else it can present as a vascular occlusive disease

· Transient ischaemic attacks

· Strokes

8. Haematological Features

Here antibody-mediated destruction of peripheral blood cells can occur giving rise to

· Neutropaenia (low neutrophils)

· Lymphopaenia (low lymphocytes) it is a guide to disease activity

· Thrombocytopaenia (low platelet counts )

· Heamolytic anaemia (low haemoglobin levels)

· ESR is elevated and it is a marker of disease activity

· C reactive proteins CRP is normal unless there are serositis or infection

9. Other Manifestations

Which are vague symptoms which cannot be attributed to any particular disease here these types of symptoms will last for months without particular specific symtoms. These are as follows

· Fatigue or tendency to get tired easily

· Malaise or unfitness

· Fever occurs without any particular reason and last for weeks

· Anorexia or loss of appetite

· Weight loss

Since there are several clinical features that a patient can present with; the diagnosis is made based on diagnostic criteria revised by American Rheumatism Association

Here 4 out of 11 features should be present serially or simultaneously and it is 95% specific & 75% sensitive in diagnosing a patient with SLE.

Revised American rheumatism association criteria.

1. Malar rash
2. Discoid rash
3. Photosensitivity
4. Oral ulcers
5. Arthritis – nonerosive arthritis
6. Serositis – Pleuritis,pericarditis
7. Neurological involvement
8. Renal involvement – Proteinuria, cellular casts
9. Haematological involvement –  anaemia, leukopaenia, thrombocytopaenia
10. Antinuclear antibody present in serum
11. Immunological disorder – anti dsDNA antibody, anti sm antibody detected in serum

There is no definite cure for SLE. There are general management issues and pharmacological management issues depending on the severity of symptoms.

The goal of management is control acute sever flare ups; suppress the symptoms to an acceptable level; prevent end organ damage.

General Management

I. Education regarding the chronic nature of disease and possibility of relapses

II. Asking the patient to avoid sun exposure and use sun blocks with sun protection factor of 25-50

Pharmacological Management

In mild non-life threatening disease management is directed to suppress symptoms

Non-steroidal anti inflammatory drugs NSAID are given for pain relief; antimalarials like hydroxyl chloroquine, chloroquine are given for cutaneous and joint symptoms, as an alternative to or as supplement to steroids, not used in acute treatment of organ threatening disease.

In mild to moderate disease with rashes, synovitis, pleuropericarditis a short course oral steroids are given to control the disease activity. But in acute life threatening disease where there is renal or cerebral involvement high dose of intravascular corticosteroids or cytotoxic drugs like cyclophosphomide are given.

In relation to prognosis, 5 Year survival is more than 90% with less incidence of early mortality which can occur in unfortunate instances due to target organ failure.