Systemic Lupus Erythematosus

Systemic Lupus Erythematosus is an autoimmune disease that affects multiple systems of the body.

The presentation of the disease varies from patient to patient and may range from

mild cutaneous involvement to severe damage to the CNS and multiple organs.

Also called as:

LE syndrome
Libman-Sacks disease
Disseminated lupus erythematosus
Lupus

SYSTEMIC LUPUS ERYTHMATOSUS

It is an autoimmune disease that affects multiple systems of the body. The

presentation of the disease varies from patient to patient and may range from

mild cutaneous involvement to severe damage to the CNS and multiple organs.

The exact etiology of SLE is not known. Several genetic, immunological,

endocrine and environmental factors are believed to play a very important role in

the pathogenesis of SLE.

Etiology

SLE has multifactorial origin with an unknown exact cause. It's presumed

that SLE is caused by genetic susceptibility with an environmental

trigger. That cause defects of the immune system. vitamin D deficiency is associated with SLE.

Genetics

1. Genetics:

Genetics is believed to contribute strongly to SLE development. . More

than 50 genes are identified with association to SLE and most of

them code for proteins implicated in immune system. Mutations in these

genes causes deficiency of components of the immune system like the

complement proteins C1q, C1r, C1s, C4 and C2 together with TREX1 (3’-5’

Exonuclease). Some genes involved in SLE are the genes coding for HLA

class I, class II and class III genes (HLA-DRB1, HLA-DR2, HLA-DR3), IRF5-TNPO3,

ITGAM and BANK1.

Drug Induced

2. Drug Induced:

Drug Induced Lupus Erythmatosus presents similar

symptoms like SLE but is caused by chronic drug use for treatment of long-term

illness. It doesn’t persist for long after the drugs are discontinued. Some of the

most common causes of drug induced SLE is the administration of the following

drugs: hydralazine, procainamide, quinidine, with hydralazine being the most

common cause by far. Hydralazine is useful treating hypertension and

heart failure.

Pathophysiology

SLE is a chronic condition because of type III hypersensitivity response. Reticulate

and stellate acral pigmentation with high titer of anti-cardiolipin

antibodies are an indicator of possible SLE. People with SLE have increased

polyclonal B cell activation, which results in increased B cell count. T cells

regulate the response of B-cells and infiltrate target tissues, have signaling defects ,

adhesion, co-stimulation, gene transcription, and alternative splicing. Low

complement protein C3 levels are seen in SLE.

The pathogenesis of SLE occurs by stimulation of both innate and acquired

immune systems.

In the Innate immune system, activation can either be dependent on Toll-like

receptors (TLR) or be TLR-independent. TLRs are stimulated by exposure to

extracellular DNA and RNA, along with demethylated DNA. This leads to

downstream activation of Interferon Regulatory Family (IRF-3) and further

leads to release of pro-inflammatory mediators. Neutrophils also play a role in

activation of the innate immune system by releasing their granular contents

into the extracellular space.

T cells and B cells are also involved in the pathogenesis of SLE. Expression of

Fas ligand on both cells increases and T cells are programmed to release more

cytokines for activation of B cells.

Signs and Symptoms

Skin lesions

1. Skin lesions are commonly seen. Red scaly patches of skin, rashes, hair

loss and mouth and nasal ulcers are common. Lesions on the skin can be

categorized into chronic cutaneous (discoid) lupus, subacute cutaneous

lupus and acute cutaneous lupus.

Joint

2. Most common symptom is Joint pain and is the main chief complaint

in patients with SLE.

3. Anemia is seen along with low platelet count and low WBC count in

some cases. Autoantibodies to phospholipids and cardiolipins are

detected in blood, along with prolonged partial thromboplastin time

(PTT).

Carditis

4. Any one of Pericarditis, Myocarditis or Endocarditis may be seen in SLE.

The Endocarditis in SLE is non-infectious and is called Libman-Sacks

endocarditis.

Pleuritis

5. Pleuritic pain and Pleurisy are seen in SLE, which results in reduced lung

volume.

Lupus nephritis

6. Lupus nephritis is a well-known and common complication of SLE. The

involvement may be mild subnephrotic proteinuria to severe cases with diffuse

progressive glomerulonephritis causing chronic kidney damage. Lupus

nephritis usually seen early in SLE disease course. New-onset

hypertension, hematuria, proteinuria, lower extremity edema, and

increased creatinine levels suggests lupus nephritis. Renal Biopsy

helps in staging the lupus nephritis and rules out other renal causes.

Neuropsychiatric syndromes

7. Neuropsychiatric syndromes can result when SLE affects the central or

peripheral nervous system. The most common neurological symptom of

SLE is intractable headaches. Other manifestations can be Mood

disorders, Cognitive Dysfunction, Cerebrovascular disease, Seizures,

Polyneuropathy, Anxiety disorder, Psychosis, Depression and so on. Rare

conditions like Guillain-Barre Syndrome and demyelinating syndrome

are also seen in SLE. Neurological disorders contribute to a significant

percentage of morbidity in patients with SLE.

Eye involvement

8. Eye involvement is seen in one-third of SLE patients. Dry eye syndrome

and Secondary Sjogren syndrome are the most common manifestations,

along with Ischemic optic neuropathy, retinopathy and glaucoma.

Abortion

9. SLE is a cause of increased rate of fetal death and spontaneous abortion

in pregnant women.

Muscle pain

10. Fatigue and muscle pain are some other complaints seen in SLE.

Treatment

There is no cure for SLE. The treatment involves preventing flares and reducing

the severity and duration of any flare-up of symptoms that is seen.

Medication for SLE

1. Medication for SLE is given to prevent and treat flares that is commonly observed.

Mainstay of treatment in SLE:

NSAIDs
Corticosteroids
Immunosuppressants
Hydroxychloroquine
Methotrexate

DMARDs

Disease-modifying antirheumatic drugs (DMARDs) are given to

preventively reduce the incidence of flares.

Corticosteroids and Hydroxychloroquine

are used to treat flares. Hydroxychloroquine in particular

is approved for treatment of SLE with other drugs.

Cytotoxic drugs

2. Cytotoxic drugs like cyclophosphamide and mycophenolic acid are used

to treat Lupus Nephritis.

Lifestyle changes

3. Lifestyle changes like avoiding sunlight and avoiding activities that cause

fatigue are important.

Kidney transplantation

4. Kidney transplantation may be required for Lupus patients who have

end stage renal disease.

Pregnancy

5. Proper management of pregnancy in mothers who have SLE is

important, as infants born to such mothers are usually healthy. Women

are also advised against conception while having SLE because it can be harmful

for the baby.

QUESTIONS & ANSWERS

What are the common symptoms of SLE?

Common symptoms of SLE are

Early in the disease course we may notice -

Extreme tiredness (fatigue)
Malaise
Fever
Loss of Appetite
Weight Loss

As the disease progress we may notice -

Joints involvement - pain and swelling of joints

Chest pain
Hair loss
Mouth ulcers
Swollen lymph nodes
Red rash

Most common site for rash in SLE?

Face - is commonest site
Red and butterfly-shaped rash
Cheeks and Nose are common to be affected
Following exposure to sunlight

Why the rash in SLE is called as 'Butter Fly Rash'?

Characteristic feature of the rash in SLE - Classic malar rash:

Flat red coloured rash in the cheeks and bridge of the nose.
Because of its shape it is called as - "butterfly rash"
Rash is painless. No itching found in the rash area.
The rash looks more prominent when exposed to sunlight.

In case of identical twins, if one is affected then what is the chance that another child also will be affected?

In identical twins if one is affected then there is 24% chance that the other child will also be affected in SLE.

What are the other names for SLE?

LE syndrome
Libman-Sacks disease
Disseminated lupus erythematosus
Lupus

Most common cause of death in SLE?

SLE has high risk of cardiovascular disease

Cardiovascular disease is the most common cause of death in SLE patients.

Why SLE is is included in the list of 'The Great Imitator' as

medical conditions?

SLE is mistaken for other illnesses and behaves like other diseases masking the

original diagnosis.

Why is SLE more common in females?

Association with genes on the X-chromosome

Women are at ten times more risk of developing SLE than men,

Risk of SLE is 14 times more in Klinefelter syndrome (47, XXY).

This suggests an association with genes on the X-chromosome.

Lupus

Hormonal influence

Hormonal influence – Significant risk factors for SLE.

Estrogen stimulates –

CD8+ and CD4+ T cells,
B cells, macrophages, thymocytes,
Release of some specific cytokines (e.g., IL-1),
Expression of HLA and endothelial cell adhesion molecules (VCAM, ICAM).

Estrogens and prolactin promote autoimmunity

Increase the B-cell activation factor production
Modulate lymphocyte and plasmacytoid dendritic cells (pDC) activation.

Estrogen-containing Contraceptives and HRT :

The use of estrogen-containing contraceptives and postmenopausal hormone replacement therapy can cause flares in patients with SLE and have been associated with a higher incidence of SLE.



Estrogen	Flares SLE
Prolactin	Elevated levels of prolactin are seen in patients with SLE
Androgen	Immunosuppressive

Elevated levels of prolactin are seen in patients with SLE.

Androgens is immunosuppressive.

Which symptoms are more common in females in SLE?

SLE more common in Female than Male. Some symptoms are more common in

males and some symptoms are more common in females.


	Symptoms more commonly seen
	Females	Males
	Relapses	Seizures
	Low WBC count	Serositis
	arthritis	Kidney disease
	Raynaud's phenomenon	Dermatological Involvement
	Psychiatric symptoms	Peripheral neuropathy

Most common joints involved in SLE?

Small joints of the hand and wrist are commonest joint involved

Which is the commonest cutaneous manifestation of SLE?


	Cutaneous manifestation
1	Malar rash	65.0%
2	Alopecia	63.0%
3	Photosensitivity	59.5%
4	Oral ulcers	44.7%

What are the types of dermatological manifestations of SLE?


	Types of skin manifestations of SLE
1	Acute cutaneous lupus	Rash	“Butterfly rash”- Classically
2	Subacute cutaneous lupus	Red, scaly patches of skin with distinct edges	Ring-shaped or raised lesions
3	Chronic cutaneous lupus	Discoid lupus - Thick red scaly patches	Carpet tack sign

Which drug has highest incidence of causing drug-induced Lupus?


	Drug induced Lupus Most commonly seen in [ highest Incidence]
1	Procainamide
2	Hydralazine

Which clinical manifestations are more common in SLE in Children?

SLE in children tends to be more severe than in adults,

More common manifestations -

Malar rashes
Nephritis
Pericarditis
Hematologic abnormalities
Hepatosplenomegaly


	SLE in Children	SLE in Older People
More Common	Malar rashes Nephritis Pericarditis Hematologic abnormalities Hepatosplenomegaly More severe than in adults	Pulmonary involvement Serositis
Less Common	Pulmonary involvement	Raynaud's malar rash nephritis neuropsychiatric complications

Which clinical manifestations are more common in SLE in Older People?

More insidious onset

More pulmonary involvement and serositis

Less commonly seen - Raynaud's, malar rash, nephritis, and neuropsychiatric complications

What are the Lupus-specific mucocutaneous lesions?

Lupus-specific lesions include

(1). Acute cutaneous lupus erythematosus (ACLE) includes localized, malar, and generalized,

(2) Subacute cutaneous lupus erythematosus (SCLE) includes annular and papulosquamous,

(3) Chronic cutaneous lupus erythematosus (CCLE) includes classic discoid lupus erythematosus (DLE), hypertrophic/verrucous, lupus panniculitis/profundus, lupus tumidus, chilblains lupus, mucosal discoid lupus, and lichenoid discoid lupus.

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