A brief discussion on Systemic lupus erythematosus ,SLE a multisystem chronic inflammatory autoimmune disease.

1. Systemic Lupus
Erythematosus
Pratap Sagar Tiwari, MD
Pic reference: autoimmunityblog.com

2. Introduction
• SLE is an chronic inflammatory multisystem autoimmune disease
that can affect the skin, joints, kidneys, lungs, nervous system,
serous membranes, and/or other organs of the body.
• Immunologic abnormalities, especially the production of a
number of antinuclear antibodies, are prominent feature of the
disease.
• The clinical course of SLE is variable and may be characterized by
periods of remissions and of chronic or acute relapses.
• Around 90% of are F, the peak age at onset is betwn 20-30 yrs.

3. Historical Aspects
• The term ‘lupus’ (Latin for ‘wolf’) was first used during the Middle Ages to describe erosive skin
lesions evocative of a ‘wolf’s bite’.
• In 1846 the Viennese physician Ferdinand von Hebra (1816–1880) introduced the butterfly
metaphor to describe the malar rash. He also used the term ‘lupus erythematosus’ and published
the first illustrations in his Atlas of Skin Diseases in 1856.
• Lupus was first recognised as a systemic disease with visceral manifestations by Moriz Kaposi
(1837–1902).
• The systemic form was further established by Osler in Baltimore and Jadassohn in Vienna.
• 1909: The description of the false positive test for syphilis in SLE by Reinhart and Hauck from
Germany (1909).
• 1923: The description of the endocarditis lesions in SLE by Libman and Sacks in New York.
• 1935: The description of the glomerular changes by Baehr .
• 1941: The use of the term diff use connective tissue disease’ by Klemperer, Pollack and Baehr .
• 1948: The beginning of the modern era in SLE was the discovery of the ‘LE’ cell by Hargraves,
Richmond and Morton at the Mayo Clinic ..
Note: An LE cell is a neutrophil or macrophage that has phagocytized the denatured nuclear material of another cell.
The denatured material is an absorbed hematoxylin body (also called an LE body)

4. Natural history and course
Ref: Natural history of systemic lupus erythematosus. SLICC, Systemic Lupus International Collaborating Clinics/American College of
Rheumatology damage index. Reprinted with permission from Bertsias GK, Salmon JE, Boumpas DT. Therapeutic opportunities in
systemic lupus erythematosus: state of the art and prospects for the new decade. Ann Rheum Dis 2010;69:1603–11.

5. Pathogenesis
Environmental Factors
Downloaded from http://jcp.bmj.com/ on November 2, 2015 - Published by group.bmj.com

6. Diagnosis
• The diagnosis of SLE is straightforward in a patient who presents with
several compatible c/f and who has supportive laboratory studies.
• A good example is a young woman who presents with complaints of
fatigue, arthralgia, and pleuritic chest pain and who is found to have
hypertension, a malar rash, a pleural friction rub, mild peripheral
edema. Laboratory :leukopenia, anemia, an ↑ S creatinine,
hypoalbuminemia, proteinuria, an active urinary sediment,
hypocomplementemia, a + Coombs test, and + tests for ANA, including
those to ds DNA & Sm.

7. Laboratory testing
Laboratory tests that may provide diagnostically useful information when SLE is suspected include:
• Complete blood count and differential
• Erythrocyte sedimentation rate and/or C reactive protein
• Urinalysis
• 24-hour urine collection for calculation of creatinine clearance and for quantitation of proteinuria
Autoantibody testing
• Antinuclear antibodies (ANA)
• Antiphospholipid antibodies
• Antibodies to double stranded DNA (dsDNA)
• Anti-Smith (Sm) antibodies
• Measurement of serum complement levels C3 and C4 may also be helpful, since hypocomplementemia is a frequent finding in active SLE.

8. Imaging
Diagnostic imaging may be valuable but is not routinely obtained unless indicated by the
presence of symptoms, clinical findings, or laboratory abnormalities. Examples include:
• Plain radiographs of involved joints
• Renal ultrasonography to assess kidney size and to rule out urinary tract obstruction
when there is evidence of renal impairment
• Chest radiography
• Echocardiography
• Computed tomography (CT) (eg, for abdominal pain, suspected pancreatitis, interstitial
lung disease)
• Magnetic resonance imaging (eg, for focal neurologic deficits or cognitive dysfunction)
• Contrast angiography, which may be valuable if vasculitis affecting medium-sized arteries
is suspected (eg, mesenteric or limb-threatening ischemia)

9. Others
• Biopsy — Biopsy of an involved organ (eg, skin or kidney) is necessary
in some cases.
• In the absence of renal abnormalities, renal biopsy has nothing to
offer and should not be performed.
• Renal involvement occurs in 40–70% of all SLE patients and is a major cause of
morbidity and hospital admissions. Immune complex formation/deposition in
the kidney results in intra-glomerular inflammation with recruitment of
leucocytes and activation and proliferation of resident renal cells .
• Proteinuria of various levels is the dominant feature of lupus nephritis (LN) and
is usually accompanied by glomerular haematuria.
• Urinalysis is the most important and effective method to detect and monitor
disease renal activity.

10. Autoantibodies
• The ANA test is the best diagnostic test for SLE and be performed when SLE
is suspected .
• The ANA is positive in significant titer (usually 1:160 or higher) in virtually
all patients with SLE. The probability of having SLE is less than 0.14 % if the ANA test is negative .
Antinuclear antibodies are also present, usually in lower titer, in a variety of
other disorders
• Sjögren’s syndrome — 68 percent
• Scleroderma — 40 to 75 percent
• Juvenile idiopathic arthritis — 16 percent
• Rheumatoid arthritis — 25 to 50 percent

11. dsDNA and Sm antibodies
• There are two commonly obtained autoantibodies that are highly
specific for SLE: anti-double-stranded DNA (dsDNA) antibodies and
anti-Sm antibodies .
• Sensitivity — 66-95 percent
• Specificity — 75-100 percent
• Predictive value — 89-100 percent

12. ACR criteria
Criterion Definition
Malar rash Fixed erythema, flat /raised, over malar eminences, sparing the nasolabial folds.
Discoid rash Erythematosus raised patches c adherent keratotic scaling and follicular
plugging
Photosensitivity Skin rash as a result of unusual reaction to sunlight, by patient or physician
Oral ulcers Oral/nasopharyngeal ulceration, usually painless, observd by physician (12-45%)
Arthritis Nonerosive arthritis involving 2 or more peripheral joints, characterized by
tenderness, swelling, or effusion (53-95%)
Serositis Pleuritis –H/O pleuritic pain/rub heard by a physician or evidence of effusion OR
Pericarditis - documented by EKG, rub or evidence of pericardial effusion
Renal disorder Persistent proteinuria >0.5 gms/d or >3+ if quantitation not performed OR
Cellular casts - may be red cell, hemoglobin, granular, tubular, or mixed (40-70%)
Note: Mucocutaneous involvement is almost universal in SLE

13. Skin Rashes in SLE
Malar Rash Discoid Rash
Ref: medscape

14. Rhupus: Jacoud arhtropathy
Deformities in the hands such as
ulnar drift at the MCP joints, swan
neck and boutonniere deformities,
and hyperextension at the
interphalangeal joint of the thumb
closely resemble those seen in
rheumatoid arthritis.
The absence of erosions on
radiographs and their reducibility
distinguish this condition from the
deforming arthritis of rheumatoid
arthritis. Courtesy of Dr D Vassilopoulos.

15. ACR criteria
Criterion Definition
Neurologic disorder Seizures OR psychosis - in the absence of offending drugs or known metabolic derangements
(uremia, ketoacidosis, or electrolyte imbalance)
Hematologic
disorder
Hemolytic anemia - with reticulocytosis OR
Leukopenia - <4000/mm 3 total on two or more occasions OR
Lymphopenia - <1500/mm 3 on two or more occasions OR
Thrombocytopenia - <100,000/mm 3
Immunologic
disorders
Anti-DNA - antibody to native DNA in abnormal titer OR
Anti-Sm - presence of antibody to Sm nuclear antigen OR
Positive antiphospholipid antibody on:
1. an abnormal serum level of IgG or IgM anticardiolipin antibodies, or
2. a positive test result for lupus anticoagulant using a standard method, or
3. a false-positive test result for at least 6 months confirmed by Treponema pallidum
immobilization or fluorescent treponemal antibody absorption teston
Antinuclear antibody An abnormal titer of ANA by immunofluorescence or an equivalent assay at any point in time
and in the absence of drugs known to be associated with "drug-induced lupus" syndrome
Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25:1271.

16. Note:
• Although the ACR classification criteria may also be used as a diagnostic
aid, there are several caveats in their use for diagnostic purposes.
• These criteria were developed and validated for the classification of
patients with a longstanding established disease and may exclude patients
with early disease or disease limited to a few organs. Thus, in spite of their
excellent sensitivity (>85%) and specificity (>95%) for patients with
established disease, their sensitivity for patients early in the disease may
be significantly lower.
• Among patients referred for lupus to tertiary care centres, two thirds of
patients fulfil ACR criteria, approximately 10% have clinical lupus but do
not fulfil criteria, and 25% have fibromyalgia-like symptoms and positive
antinuclear antibody (ANA) but never develop lupus.

17. CONSTITUTIONAL SYMPTOMS
• Fatigue, fever, and weight loss are typically present at some time during the course of
the disease, occurring in 50 to 100 %.
• Fatigue is the MC complaint & is occasionally the most debilitating. It occurs in 80-100 %
• Myalgia — Myalgia is common in SLE.
• Weight changes — Weight changes are frequent in patients with SLE and may be related
to the disease or to its treatment.
• Weight loss — Weight loss often occurs prior to the diagnosis of SLE. Unintentional
weight loss may be due to decreased appetite, to the side effects of medications
(particularly diuretics or antimalarials), and to gastrointestinal disease (eg,
gastroesophageal reflux, abdominal pain, peptic ulcer disease, or pancreatitis).
• Weight gain — Weight gain in SLE is usually due to one of two factors: salt and water
retention associated with hypoalbuminemia (eg, due to nephrotic syndrome or protein
losing enteropathy) or increased appetite associated with the use of glucocorticoids.

18. Management
• GENERAL TREATMENT CONSIDERATIONS
• TREATMENT OF SPECIFIC ORGAN INVOLVEMENT

19. GENERAL TREATMENT CONSIDERATIONS
• Sun protection — Avoid exposure to direct or reflected sunlight and
other sources of ultraviolet (UV) light (eg, fluorescent and halogen
lights). A sunscreen with a SPF of 55 or greater is suggested.
• Smoking cessation — Cigarette smoking may increase the risk of
developing SLE, and smokers in general have more active
disease. Hydroxychloroquine is less effective in smokers .
• Immunizations — patients should receive appropriate immunizations
prior to the institution of immunosuppressive therapies.

20. Others
• Avoidance of specific medications : Drugs induce SLE
• Pregnancy and contraception — Pregnancy should be avoided during
active disease due to the high risk of miscarriage and exacerbation. Women
with SLE should be counseled not to become pregnant until the disease has
been quiescent for at least six months.
• Oral contraceptives can cause exacerbations of SLE.
• Pregnant patients with active lupus are generally managed with
glucocorticoids. Other drugs used during pregnancy include nonsteroidal
antiinflammatory drugs (avoided during early pregnancy and in the third
trimester) and hydroxychloroquine (probably safe).
• Cyclophosphamide , cyclosporine , mycophenolate mofetil,
and methotrexate are contraindicated, while azathioprine can be
cautiously used.

21. TREATMENT OF SPECIFIC ORGAN
INVOLVEMENT

22. Medications
• Nonsteroidal antiinflammatory drugs (NSAIDs)
• Antimalarials: hydroxychloroquine
• Glucocorticoids
• Immunosuppressive agents: cyclophosphamide , cyclosporine ,
tacrolimus , leflunomide ,methotrexate , azathioprine , mycophenolate
and belimumab.

23. Medications
• NSAIDs are generally effective for musculoskeletal complaints, fever,
headaches, and mild serositis. Naproxen may have greater relative
cardiovascular safety than other NSAIDs.
• Antimalarials are most useful for skin manifestations and for
musculoskeletal complaints. In addition, in long-term studies, the use
of antimalarials, such as hydroxychloroquine , prevented major
damage to the kidneys and central nervous system . Their use may
also reduce the risk of disease flares, though this is less clear for renal
and central nervous system (CNS) manifestations

24. Glucocorticoids
• Systemic glucocorticoids (eg, high doses of 1-
2mg/kg/d of prednisone or equivalent used alone or in combination
with immunosuppressive agents are generally reserved for patients
with significant organ involvement, particularly renal and CNS
disease.
• Patients with whereas non-organ-threatening disease (eg, cutaneous,
musculoskeletal, constitutional) patients usually respond to 5 to 15
mg of prednisone (or equivalent) daily until a glucocorticoid-sparing
agent or antimalarial can take effect.

25. Medications
• Immunosuppressive medications other than glucocorticoids
(eg, methotrexate , cyclophosphamide , azathioprine , mycophenolate
or rituximab ) are generally reserved for patients with significant
organ involvement and/or for patients who have had an inadequate
response to glucocorticoids.

26. Prognosis
• The overall 5-year survival of SLE is over 90%.
• Mortality within 5 years of diagnosis is usually due to organ failure or
overwhelming sepsis, both of which are modifiable by early effective
intervention.
• However, compared to the normal population, patients with lupus
have a fivefold increased mortality.
• This mainly results from premature cardiovascular disease to which
chronic steroid therapy makes a major contribution.

27. Drugs induce lupus
• Definite -Procainamide , hydralazine , minocycline , diltiazem , penicillamine , isoniazid ,
quinidine , anti-TNF(with infliximab and etanercept ), interferon-a, methyldopa ,
chlorpromazine , and practolol .
• Probable — Anticonvulsants ( phenytoin , ethosuximide , carbamazepine ), antithyroid
drugs, antimicrobial agents (sulfonamides, rifampin , nitrofurantoin ), beta blockers,
lithium , captopril , interferon gamma, hydrochlorothiazide , glyburide , sulfasalazine ,
terbinafine , amiodarone , ticlopidine.
• The presence of drug-induced lupus should be suspected when a patient taking one or
more of the above drugs for at least 1 mnth, and usually much longer, presents with
some combination of arthralgia, myalgia, malaise, fever, rash, and/or serositis.
• The "gold standard" is spontaneous resolution of the disease within 1-7mnths after the
offending drug has been discontinued.
• Treatment is focused on stopping the medication. NSAID and antimalarials can be
temporarily used if constitutional and musculoskeletal symptoms do not clear rapidly.

28. Spontanous LUPUS Drug induced LUPUS
Usual age 20-40 50
F:M 9:1 1:1
Onset Gradual Abrupt
Constitutional symptoms ++ +
Arthalgia/ serositis/ hepatomegaly ++ ++
Rash ++ +
Renal ++ +
CNS ++ -
Hematologic Common Unusual
Immunologic abnormalities
ANA
LE CELLS
ANTI RNP
ANTI HISTONE
ANTI SM
ANTI DSDNA
COMPLEMENTS
IMMUNE COMPLEX
++
++
++
+
++
++
Reduced
Elevated
++
++
+
++
-
-
Normal
Normal

29. End of slides
References:
• Davidson
• Harrison’ s Internal Medicine 18th ed
• Uptodate
• Medscape