SYSTEMIC LUPUS

ERYTHEMATOSUS

Yidana Daniel B.

OUTLINE

• Introduction and Definition

• Epidemiology

• Pathogenesis

• Aetiology

• Pathology

• Clinical features and Diagnosis

• Investigations

• Treatment

• Course and Prognosis

• Conclusion

Introduction

• ‘Lupus’ in Latin means wolf. This term was used in

the middle ages to describe erosive skin lesions

evocative of a wolf’s bite.

• In 1846, Viennese Physician, Ferdinand Von

Hebra introduced the term ‘butterfly rash’ and was

the first to use the name Lupus erythematosus.

• Many other physicians have since discovered and

named various conditions associated with the

disease.

Definition

• SLE is an inflammatory, multisystem disorder with

arthralgia and rashes as the commonest clinical

features and cerebral/renal disease as the most

serious problem.

Epidemiology

• Prevalence rates in the USA is about 10-400 per

100000.

• Common in African-American women

• Disease is 9 times more common in women than

in men

• Peak age is between 20 and 40 years (women in

their fertile years).

Pathogenesis

• 1. Ineffective Phagocytosis of apoptotic cells.

• 2. Breakdown in tolerance ( B cells and T cells destroy self cells).

• There is therefore sustained production of auto antibodies and immune complexes that bind tissues.

• There is complement activation and release of cytokines, vasoactive peptides, destructive enzymes and development of chronic inflammation, causing tissue damage.

Aetiology

• Cause is largely unknown. A number of

predisposing factors have however been

implicated;

1. Heredity: Higher concordance rates among

monozygotics (25%), than dizygotics (3%). First

degree relatives have a 3% chance of developing

disease.

2. Genetics: Associations with HLA genes-

HLADRB1, HLA A1, B8 and DR3.

3. Homozygous deficiencies of complement genes-

c1q, c2 or c4.

4. Sex hormone status- commoner in pre-

menopausal women, women who use oestrogen

containing oral contraceptives or women on

hormone replacement therapies.

5. Klinefelter syndrome(XXY), TREX-1, STAT4

CTLA4.

• 6.UV light

• 7. EBV infection

• 8. Tobacco smoking

• 9. Drugs- Hydralazine, procainamide, isoniazid,

penicillamine; here, the CNS and Kidneys are

usually not affected.

Autoantibodies present in SLE:

1. ANA 6. Anti-phospholipid

2. Anti dsDNA 7. Anti-RNP

3. Anti sm 8. Anti-histone

4. Anti-Ro 9.Anti c1q

5. Anti-La 10. Anti-ribosomal P

Pathology

• Biopsies of skin and kidneys reveal igG antibodies

and complement deposition with influx of T

lymphocytes and neutrophils.

Clinical features

1. General features: Fever, severe fatigue, weight

loss.

2. Joints and Muscle symptoms: In more than

90% of patients.

-Symmetrical small joint arthralgia ( hands,

wrists) and Knees and sometimes arthritis.

-Myalgia

3. Mucocutaneous Manifestations:

-Butterfly rash

-Photosensitivity

-Discoid rash

-Vasculitic lesions in finger tips,around the nailfolds,

purpura and urticaria.

Livedo reticularis

- Palmar and plantar rashes

- Scarring alopecia

- Oral and nasal ulcerations

4. Lungs: - Recurrent pleurisy

-Pleural effusions

-Pneumonitis

-Atelectasis

-Restrictive lung disease in few cases

5. CVS: - Pericarditis

- Pericardial effusions

- Libman-sachs endocarditis

- Myocardial infarction

6. Renal: - Lupus nephritis

-Nephrotic syndrome

- ESRD

7. CNS:- Cognitive dysfunction

- Headaches

- Seizures

- Psychosis

- Stroke

- Aseptic meningitis

8. GIT: -Nausea

- Diarrhoea - Hepatomegaly

- Vomiting - Uncommonly Pancreatitis

- Abdominal pain

9. Haematologic: - Anaemia

- Lymphocytopaenia

- Thrombocytopaenia

11. Ocular: - Sicca

- Episcleritis

- Conjuctivitis

- Retinal vasculitis

- Optic neuritis

* Keep in mind the effects of glucocorticoid treatment

12. Lupus and Pregnancy: Recurrent abortions in

those with the antiphospholipid antibody.

-Congenital heart block esp. with anti Ro.

-Teratogenic potential of warfarin and

cyclophosphamide.

- Preterm birth risk associated with high dose

steroids.

Malar Rash

Discoid rash

Recovery after discoid Lupus

Livedo reticularis

Diagnosis

• ACR diagnostic criteria (SOAP BRAIN MD)

Serositis Antinuclear antibodies

Oral and nasal ulcers Immunological disorder

Arthritis Neurologic disorder

Photosensitivity Malar rash

Blood disorder Discoid rash

Renal disorders

• 4 or more of the above, well documented, and

present at any time in a patient’s history is

required to make a diagnosis.

• The diagnosis is based on characteristic clinical

findings and the presence of autoantibodies.

• When a diagnosis is made, it is important to

establish the severity and potential reversibility of

symptoms and to establish the possible

consequences of various therapeutic

interventions.

Investigations

1. FBC, ESR and CRP

2. Urinalysis

3. BUE+Cr

4. Autoantibodies

5. C3, C4

6. Renal biopsy

7. ***CT scan head if need be to rule out other CNS causes.

LUPUS NEPHRITIS

ISN classification of Lupus nephritis

I- Minimal mesangial lupus nephritis

II- Mesangial proliferative lupus nephritis

III- Focal lupus nephritis (3A, 3A/C, 3C)

IV- Diffuse lupus nephritis ( S(A), G(A), S(A/C), G(A/C), S(C) and G(C) )

V- Membranous lupus nephritis

VI- Advanced sclerotic lupus nephritis ( ESRD)

Severity Assessment

1. SLEDAI score: Asseses the presence of a mild or

moderate and Severe flares.

2. SLICC/ACR Damage Index for SLE.

Management

• There is no cure.

1. General measures: -Discuss with patient the

disfiguring effects of cutaneous and the debility

associated with fatigue.

- Avoid UV/sunlight exposure

- Reduce cardiovascular risk factors

Symptomatic treatment

1. Athralgia, arthritis fever – NSAIDs bearing in mind renal function.

If severe, low dose steroids by mouth and hydroxychloroquine.

2. Cutaneous lesions- mild potency steroids for face,

mid to high potency for other areas, consider sunscreens;

Low dose oral steroids, hydroxychloroquine can be used.

3. Serositis- Moderate dose steroids, Azathioprine or mycophenolate.

4. Renal problems-

Class I, II- Low dose steroids

Class III,IV- these are the active stages and require aggressive management to allow remission.

-Induction with high dose steroids and cyclophosphamide

-Maintenance with Azathioprine or Mycophenolate

Class V- ACEI, Steroids, consider other DMARDs

Class VI- Dialysis or Transplantation

5. CNS problems- Require induction and

maintenance medications as in Renal problems.

6. Haematological problems-

Severe haemolytic anaemia is treated initially with

high dose IV Methylprednisolone 1g/day for 3 days.

Severe thrombocytopaenia may also require IV

methylprednisolone.

Course and Prognosis

• Prognosis is good in the absence of major organ

dysfunction.

• There is a long term risk of Lymphoma.

Conclusion

• SLE diagnosis at an early stage is crucial to ensuring favourable prognosis.

• There is no exact cure, symptoms can however be managed.

• Refer early for rheumatological consult.

• Educate patients on the various possible complications of the disease and its treatment, and especially pregnant women on the possible effects on pregnancy.

THANKYOU