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Rheumatology
SLE - Systemic Lupus Erythematosus
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Systemic lupus erythematosus (SLE) is a multisystem, potentially fatal autoimmune
disease that can involve the skin, joints, muscles, heart, lung, kidneys,
peripheral nerves, central nervous system (CNS), and blood. The severity
is largely determined by which organs are involved, patients with CNS or
renal involvement often having the most serious disease. The diagnosis of
SLE is made if patients fulfill at least 4 of the 11 criteria designated
by the American College of Rheumatology.
Criteria for the classification of SLE
(If any 4 or more of 11 criteria are met)
(REF: Arthritis Rheum 1982 Nov;25(11):1271-7 )
L = Lymphopenia, leukopenia, anemia, thrombocytopenia
U = Urine abnormality as proteinuria or cellular casts
P = _leuropericarditis
U = Ulcers of mouth
S = Skin discoid or malar rash, photosensitivitiy
A = Arthritis
N = Neurologic Sx as seizure, psychosis
A = Autoantibodies as ANA, Anti-DNA, ANti-Sm, Anti-CardioLipin Ab
The 1982 revised criteria for the classification of systemic lupus
erythematosus
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF,
Schaller JG, Talal N, Winchester RJ
The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included in the 1982 revised criteria because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.
Skin Manifestations
including the typical malar rash & the Discoid lupus erythematosus (DLE)
lesions that are scarring and occur either alone or in association with SLE.
Subacute cutaneous LE (SCLE) includes two types of lesions: psoriasiform
and annular polycyclic.
Renal Manifestations
Renal disease is common in most patients with SLE and can be asymptomatic
until there's advanced disease.
The excretion of more than 500 mg of urinary protein /24 hours (or greater
than 3+ proteinuria on dipstick testing), the presence of casts (including
RBCs, hemoglobin, granular, tubular, or mixed), hematuria (more than 5 RBCs
/hpf) or pyuria (more than 5 WBCs/hpf ), or an elevated serum creatinine
level is evidence of renal disease and should prompt the clinician
to a more thorough investigation of renal status and referral to a specialist.
The World Health Organization (WHO) classification of lupus nephritis is
the standard by which most lesions are classified and can prognosticate survival
of the kidney.
Mesangial abnormalities (WHO class II) - in 40% of the patients,
Focal glomerulonephritis (class IIIA and class IIIB) -in 20% of the
patients,
Diffuse proliferative glomerulonephritis (class IV) - in 40% of the
patients, and
Predominant membranous lesion (class V) - in less than 10 % of
the patients.
Class I and class II lesions require no treatment. Class III lesions
can undergo transition to a more proliferative and diffuse process, necessitating
treatment. The consequences of nephrotic syndrome, hypertension, hyperlipidemia,
and hypercoagulability, seen with both class IV and class V lesions, can
increase mortality in these patients. Class V (membranous) lesions usually
have a slowly progressive course, and treatment varies, including steroids
or immunosuppressives, neither of which have been shown to alter the course
of the disease. Class IV (diffuse proliferative) lesions affect more than
50% of the glomeruli, with progression to renal failure in most cases.
Musculoskeletal Manifestations
common, including acute arthritis, typically involving the small joints of
the hands, wrists, and knees, is usually episodic and symmetrical in
distribution. Avascular necrosis (AVN) is seen in 5% of SLE patients,
affecting the hip most commonly but also the shoulder, knee, and ankle.
Cardiac Manifestations
Pericarditis is the most common cardiac Sx (precordial chest pain and a
pericardial rub), 20 to 30% in most large series.
Myocarditis presenting as dysrhythmias and/or cardiomegaly is a less common
manifestation .
Libman-Sacks endocarditis, with sterile verrucous vegetations on the mitral
valve, is less common.
Premature atherosclerosis is a major cause of morbidity and mortality in
SLE.
Pulmonary Manifestations
include pleuritis, pulmonary alveolar hemorrhage, pneumonitis, pulmonary
infiltrates, chronic interstitial lung disease, shrinking lung syndrome,
pulmonary hypertension, and pulmonary embolism. Acute pneumonitis frequently
responds to corticosteroids (1 mg per kg per day). Pulmonary alveolar hemorrhage
is a rare but serious manifestation and carries a high mortality. Very aggressive
treatment is required for improved survival, and cytotoxic agents or
plasmapheresis may be necessary.
Patients with chronic interstitial lung disease can present with typical symptoms of restrictive lung disease, including nonproductive cough, dyspnea on exertion, and basilar rales on physical examination. Pulmonary hypertension may be a finding in many of the collagen-vascular diseases and occurs in 1 to 2% of SLE patients. Pulmonary hypertension can present insidiously with progressive exertional dyspnea, and early disease can be detected by an abnormal carbon monoxide diffusing capacity (DL CO) on pulmonary function testing. Pulmonary embolus is a serious potential complication of antiphospholipid (APL) antibody syndrome (discussed later) in patients with SLE. Pleuritic chest pain in an SLE patient cannot be assumed to be due to SLE serositis. In an SLE patient with a normal chest film, pulmonary embolus must be excluded.
Gastrointestinal Manifestations
Abdominal pain, anorexia, nausea, and vomiting are common gastrointestinal
manifestations of SLE. Serositis is the most common underlying causative
disorder and frequently responds to moderate doses of corticosteroids. The
presenting manifestation of mesenteric vasculitis can be lower abdominal
pain accompanied by frank or occult rectal bleeding, and perforation of the
bowel can result. If the diagnosis of mesenteric vasculitis is suspected,
intensive investigation should be undertaken, with appropriate treatment
with high doses of steroids. Acute pancreatitis can occur in SLE patients,
manifesting as abdominal pain, nausea, vomiting, and elevated serum amylase.
Neuropsychiatric Manifestations
Diffuse manifestations are the most common CNS presentation in NP-SLE patients
(60% of cases).
The most common histologic finding in the brain of SLE patients is a vasculopathy, with associated microinfarcts. True vasculitis is rare. The evaluation of an SLE patient with CNS manifestations includes cerebrospinal fluid (CSF) evaluation for routine studies, antineuronal antibodies (seen in patients with diffuse manifestations), quantitative CSF immunoglobulins, and oligoclonal bands (elevations commonly seen in active CNS SLE disease). Magnetic resonance imaging (MRI) can sometimes demonstrate small, high-signal-intensity vascular lesions but cannot define active disease.
Treatment of the diffuse manifestations may include administration of antiseizure drugs or antipsychotics but usually requires high-dose steroids (1 mg per kg per day) or pulse high-dose steroids (1 gram per day for 3 days). Refractory cases sometimes respond to intravenous cyclophosphamide, plasmapheresis, or a combination of these. Focal manifestations seen in association with APL antibodies are treated with anticoagulation, in addition to the aforementioned medications.
Hematologic Manifestations
Cytopenias, including anemia, leukopenia, lymphopenia, and thrombocytopenia,
are frequent findings in SLE.
Malignancy
Malignancy continues to increase in SLE patients with increasing use of
alkylating agents. Over 100 cases of non-Hodgkin's lymphoma have been reported,
and there is an increased frequency of gynecologic cancers. In one series,
the mean time from onset of treatment to cancer was only 4.1 years. Frequent
surveillance, including Papanicolaou smears and mammograms, is important.
Antiphospholipid Antibodies
A variety of clotting abnormalities, including the presence of the lupus
anticoagulant, manifested as a prolonged activated partial thromboplastin
time (APTT) that does not normalize with mixing studies. Patients with the
lupus anticoagulant, a false-positive result on VDRL testing, or a high titer
of anticardiolipin antibodies fall under the umbrella term of "APL
antibody-positive" and are predisposed to thrombotic events.
The APL antibody syndrome describes the
association of these APL antibodies with arterial and venous thrombosis,
recurrent fetal loss, and immune thrombocytopenia. Management of SLE patients
with APL antibodies who have never had a thrombotic event is usually with
low-dose aspirin therapy. Once patients have had a thromboembolic event,
lifelong anticoagulation with warfarin is established, with an INR (International
Normalized Ratio) of 3.0, to prevent recurrent events.
(REF: Medicine 1985;64:285)
Arthralgias, arthritis, myalgias, fever, and mild serositis may improve on nonsteroidal anti-inflammatory drugs (NSAIDs) including salicylates.
The dermatitides of SLE, fatigue, and lupus arthritis may respond to antimalarials. Doses of 400 mg hydroxychloroquine daily may improve skin lesions in a few weeks. Side effects are uncommon and include retinal toxicity, rash, myopathy, and neuropathy. Regular ophthalmologic examinations should be performed at least annually, since retinal toxicity is related to cumulative dose. Other therapies include sunscreens (an SPF rating 15 is recommended), topical or intralesional glucocorticoids, quinacrine, retinoids, and dapsone. Recent studies suggest that daily oral doses of dihydroepiandrosterone may lower disease activity in patients with mild SLE. Systemic glucocorticoids should be reserved for patients with disabling disease unresponsive to these conservative measures.
Life-threatening, severely disabling manifestations of SLE that are responsive
to immunosuppression should be treated with high
doses of glucocorticoids (1 to 2 mg/kg per day). When disease
is active, glucocorticoids should be given in divided doses every 8 to 12
h.
Acutely ill lupus patients, including those with proliferative GN,
can be treated with 3 to 5 days of 1000 mg intravenous
"pulses" of methylprednisolone, followed by maintenance daily
or alternate-day glucocorticoids. Disease flares are probably controlled
more rapidly by this approach, but it is unclear whether long-term outcome
is changed.
The use of cytotoxic agents (azathioprine, chlorambucil,
cyclophosphamide, methotrexate, mycophenolate mofetil) in SLE
is probably beneficial in controlling active disease, reducing the rate of
disease flares, and reducing steroid requirements. Patients with lupus nephritis
have significantly less renal failure and better survival if treated with
combinations of glucocorticoids plus intravenous cyclophosphamide; azathioprine
as the second drug is less beneficial but is also effective in preventing
renal failure.
Algorithm for the treatment of SLE
REF:
Classification of Vasculitis Correspondence
(NEJM
12-2-1999;341:23)
Arthritis Rheum 1990 Aug;33(8):1101-7
The American College of Rheumatology 1990 criteria for the classification
of Wegener's granulomatosis.
Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, Calabrese
LH, Fries JF, Lie JT, Lightfoot RW Jr, et al NIAID, NIH, Bethesda,
MD.
Criteria for the classification of Wegener's granulomatosis (WG) were developed
by comparing 85 patients who had this disease with 722 control patients with
other forms of vasculitis. For the traditional format classification, 4 criteria
were selected: abnormal urinary sediment (red cell casts or greater
than 5 red blood cells per high power field), abnormal findings on chest
radiograph (nodules, cavities, or fixed infiltrates), oral ulcers or nasal
discharge, and granulomatous inflammation on biopsy. The presence of 2 or
more of these 4 criteria was associated with a sensitivity of 88.2% and a
specificity of 92.0%. A classification tree was also constructed with 5 criteria
being selected. These criteria were the same as for the traditional format,
but included hemoptysis. The classification tree was associated with a
sensitivity of 87.1% and a specificity of 93.6%. We describe criteria which
distinguish patients with WG from patients with other forms of vasculitis
with a high level of sensitivity and specificity. This distinction is important
because WG requires cyclophosphamide therapy, whereas many other forms of
vasculitis can be treated with corticosteroids alone.
Arthritis Rheum 1990 Aug;33(8):1065-7
The American College of Rheumatology 1990 criteria for the classification
of vasculitis. Introduction.
Hunder GG, Arend WP, Bloch DA, Calabrese LH, Fauci AS, Fries JF, Leavitt
RY, Lie JT, Lightfoot RW Jr, Masi AT, et al - Mayo Clinic, Rochester,
MN.
02252003
Harrison Online 2-2003
Rakel: Conn's Current Therapy 1999
Patient Fact Sheet on SLE from ARA
New Approaches for Treatment of SLE - Annals of Internal Medicine,
15 December 1998 by Philip M. Bulman and Gene Hunder
Rational Approach to Dx of SLE 1999 Richard Wernick, MD, Carolyn Coyle, MD
[Hospital
Medicine 35(4):16-22, 1999]
