Definition, epidemiology, etiology, clinical presentation and management of SLE

1. SLE

2. INTRO
• SLE is a fluctuating multisystem disease with a
diversity of clinical presentations
• Abnormal immunologic function and
formation of antibodies against “self” antigens
underlie the pathogenesis of SLE

3. INTRO
• The hallmark of SLE is the development of
autoantibodies to cellular nuclear components
that leads to a chronic inflammatory
autoimmune disease

4. EPIDEMIOLOGY
• The incidence of SLE varies among ethnic
groups with the annual incidence in adults
ranging from 1.9 to 5.6 per 1,00,000 persons
per year, with a prevalence of 124 cases per
1,00,000 persons
• The disease occurs predominantly in women,
with a reported female-to-male ratio
approaching 10:1

5. EPIDEMIOLOGY
• Those afflicted with SLE are usually diagnosed
between the ages of 15 and 45
• SLE is reported to be less prevalent in whites
than in other ethnic groups, including blacks,
Hispanics, Native Americans, and Asians

6. ETIOLOGY
• Still unknown
• Genetic, environmental, and hormonal factors
all may play a role in loss of “self” tolerance
and expression of disease

7. ETIOLOGY
• Familial and twin studies indicate a genetic
predisposition for the development of SLE
• First-degree relatives of SLE patients are about
20 times more likely to develop SLE than the
general population; more than 5% of cases are
familial

8. ETIOLOGY
• Multiple genes contribute to SLE susceptibility,
and at least 100 genes have been linked to SLE in
humans
• Environmental agents that may induce or activate
SLE include sunlight, drugs, chemicals such as
hydrazine (found in tobacco) and aromatic
amines (found in hair dyes), diet, environmental
estrogens, and infection with viruses or bacteria

9. ETIOLOGY
• Additionally, androgen may inhibit and
estrogen may enhance the expression of
autoimmunity
• Elevated circulating prolactin levels have been
associated with lupus in males and females

10. PATHOPHYSIOLOGY

11. CLINICAL PRESENTATION

13. Clinical features
• Nonspecific signs and symptoms such as
fatigue, fever, anorexia, and weight loss are
seen frequently in patients with active disease
• Musculoskeletal involvement is very common
in with arthritis and arthralgia frequently the
chief complaint on initial presentation of the
disease

14. Clinical features
• All major and minor joints may be affected,
and the pattern of arthritis is often recurrent
and of short duration, presenting mainly as
joint stiffness, pain, and sometimes
inflammation
• Objective evidence of musculoskeletal disease
often is missing

15. Clinical features
• The most well known Manifestations in the
skin is the butterfly rash, which occurs over
the bridge of the nose and the malar
eminences
• Skin lesions characteristic of discoid lupus
occur in 10% to 20% of patients with SLE and
may occur without other clinical or serologic
evidence of lupus

16. Clinical features
• Other cutaneous manifestations include vasculitis
(which may be ulcerative), livedo reticularis, periungual
erythema, Raynaud’s phenomenon, and alopecia
• Another common source of symptomatology in SLE is
the pulmonary system, with manifestations such as
pleurisy, coughing, and dyspnea
• Lupus pneumonitis may present
• Pulmonary hypertension

17. Clinical features
• Cardiac manifestations of SLE often present as
pericarditis, myocarditis, electrocardiographic
changes, or valvular heart disease
• Neuropsychiatric manifestations of SLE may
present in many ways, including headaches,
psychosis, depression, anxiety, seizure, stroke,
peripheral neuropathy, cognitive impairment,
and others

18. Clinical features
• Symptoms associated with gastrointestinal
manifestations often are nonspecific for lupus and
include dyspepsia, abdominal pain, nausea and
difficulty swallowing
• Vasculitis and venous occlusion owing to thrombosis
may be problematic if not diagnosed and treated
promptly
• Hepatitis and pancreatitis also may be present and may
be secondary to drugs used to treat SLE or the disease
itself

19. Clinical features
• Anemia is found in many patients with SLE
• Leukopenia, usually mild, is present in about half of SLE
patients
• Thrombocytopenia may occur in SLE, often during
disease exacerbation, but is usually mild and does not
increase bleeding tendency
• Thrombotic events occur in more than 10% of patients
with SLE

20. Clinical features
• Clinical evidence of renal involvement, such as
a rising serum creatinine or proteinuria level,
generally is associated with a poorer outcome
compared with patients without renal
involvement
• Progression to end-stage renal disease is a
major cause of morbidity and mortality in SLE

23. DIAGNOSIS
• Once the disease is suspected, serologic tests may be
helpful in making the diagnosis
• A serologic test used extensively to aid in the diagnosis
of SLE is the fluorescent antinuclear antibody (ANA)
test
• Nearly all SLE patients are ANA-positive, but other
diseases also can be associated with a positive test
• On the basis of clinical presentation

24. PROGNOSIS
• In earlier years, SLE was associated with a
poor prognosis, but improved significantly
nowadays
• However, CAD and infection are still among
the leading causes of death among SLE
patients

25. Treatment
• Desired treatment outcomes for the patient
with SLE are twofold:
(a) Management of symptoms and induction of
remission during times of disease flare and
(a) Maintenance of remission for as long as
possible between disease flares

26. Nonpharmacological management
• A balanced routine of rest and exercise, while
avoiding overexertion
• Avoidance of smoking
• Alfalfa sprouts should be avoided
• Limit exposure to sunlight

27. Pharmacological management

28. Nonsteroidal Antiinflammatory Drugs
• Many patients with mild disease, initial
treatment with a nonsteroidal
antiinflammatory drug (NSAID) is a logical
choice
• The dose used should be adequate to provide
antiinflammatory effects

29. Major cautions while using NASIDs in
SLE
• Nephrotoxicity
• Hepatotoxicity
• Aseptic meningitis

30. Antimalarial Drugs
• Antimalarial agents such as chloroquine and
hydroxychloroquine have been used successfully
in the management of discoid lupus and SLE
• Manifestations of SLE that can be managed with
antimalarials are cutaneous manifestations,
arthralgia, pleuritis, mild pericardial
inflammation, fatigue, and leukopenia

31. Antimalarial Drugs
• Takes long time for response
• Hydroxychloroquine 200 to 400 mg/day
• Chloroquine 250 to 500 mg/day

32. Antimalarial Drugs
Side effects of these drugs include
• CNS effects (e.g., headache, nervousness,
insomnia, and others)
• pigmentary changes of the skin and hair,
• Gastrointestinal disturbance (e.g. nausea),
• Reversible ocular toxicities such as cycloplegia
and corneal deposits

33. Corticosteroids
• Most controlled trials of corticosteroid
therapy have been conducted in patients with
severe lupus nephritis, but evidence suggests
that corticosteroids are also effective in the
management of severe cases of CNS disease,
pneumonitis, polyserositis, vasculitis,
thrombocytopenia, and other clinical
manifestations

34. Corticosteroids: When to start?
• NSAIDs and anti-malarials are unresponsive
• Severity of disease

35. Corticosteroids: How to start?
• Mild disease: Prednisone 10 to 20 mg/day
• Severe disease: Prednisone 1 to 2 mg/kg daily

36. Steroid pulse therapy
• Steroid pulse therapy is the administration of
short-term, high-dose intravenous corticosteroids
with the goal of inducing remission in SLE
patients with serious, life-threatening disease
• Intravenous methylprednisolone 500 to 1000 mg
for 3 to 6 consecutive days. Pulse therapy usually
is followed by highdose prednisone (1 to 1.5
mg/kg per day) therapy that is tapered rapidly to
low-dose maintenance therapy

37. Steroid pulse therapy – Cautions!!
• Although generally well tolerated,
methylprednisolone pulse therapy may result
in significant adverse effects, including
• Infection
• Gastrointestinal disturbances
• Rapid increases in blood pressure
• Arrhythmias
• Seizures, and sudden death

38. Cytotoxic Drugs
• Usually used in combination with
corticosteroids
• Based on controlled trials, combination
prednisone and cyclophosphamide has
become standard treatment for focal and
diffuse proliferative lupus nephritis

39. Cytotoxic Drugs
• Cyclophosphamid plus corticosteroids, the
current standard of care, decreases the risk of
developing end-stage renal failure requiring
dialysis and renal transplantation
• When used in combination with corticosteroids,
cyclophosphamide is dosed at 1 to 3 mg/kg for
oral therapy and 0.5 to 1 g/m2 of body surface
area for intravenous therapy

40. Of course ! Its not without risks...
• Suppression of hematopoiesis
• Opportunistic infections
• Bladder complications (e.g., hemorrhagic
cystitis and cancer)
• Sterility
• Teratogenesis
• N & V

41. Alternative
• Mycophenolate mofetil has been investigated
as an alternative to cyclophosphamide for
induction of remission
• In some trials, mycophenolate mofetil was
more effective than standard
cyclophosphamide therapy, achieving a higher
rate of complete and partial remissions

42. Azathioprine
• Azathioprine can be used as a “steroid-
sparing” agent, allowing for the reduction of
corticosteroid doses
• Azathioprine may be useful in treating early
onset and less-severe nephritis

43. Azathioprine
• Long-term maintenance azathioprine therapy
also may prevent renal flares after successful
induction with cyclophosphamide
• Azathioprine is given orally in doses of 1 to 3
mg/kg per day, often in combination with
corticosteroids for severe disease

44. Azathioprine ADRs
• Myelosuppression
• Opportunistic infections including herpes
zoster
• Cancer
• Hepatotoxicity
• Ovarian failure

45. ALTERNATIVE AND
EXPERIMENTAL TREATMENTS
• Plasmapheresis
• Immunoglobulin for lupus nephritis

47. Drug-Induced Lupus
• Up to 10% of SLE cases may be drug-induced
• 80 drugs have been implicated as causing
drug-induced lupus (DIL)
• Procainamide and hydralazine are associated
most commonly

48. Drug-Induced Lupus
• Musculoskeletal symptoms are the most
common clinical manifestations, while renal
manifestations and CNS involvement are rare.
• Other common features of DIL include fever,
fatigue, pericarditis, pleurisy, and weight loss.