Systemic Lupus Erythematosus (SLE) Clinical Presentation

  • Author: Christie M Bartels, MD, MS; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Jan 18, 2012
 

History

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect almost any organ system. Its presentation and course are highly variable, ranging from indolent to fulminant.

The triad of fever, joint pain, and rash in a woman of childbearing age should suggest the diagnosis as a classic presentation of SLE.[36, 37] However, patients may present with any of the following types of manifestations[38] :

  • Constitutional
  • Musculoskeletal
  • Dermatologic
  • Renal
  • Neuropsychiatric
  • Pulmonary
  • Gastrointestinal
  • Cardiac
  • Hematologic

In patients with suggestive clinical findings, a family history of autoimmune disease should raise further suspicion of SLE.

Constitutional symptoms

Fatigue, fever, arthralgia, and weight changes are the most common symptoms in new cases or recurrent active SLE flares. Fatigue, the most common constitutional symptom associated with SLE, can be due to active SLE, medications, lifestyle habits, or concomitant fibromyalgia or affective disorders.

SLE-specific fatigue or fever generally occur in concert with other clinical markers. Fever may reflect active SLE, infection, and medications (ie, drug fever). Careful history taking may help to differentiate these, and infections should be carefully excluded. Weight loss may occur in patients with active SLE. Weight gain may also be due to corticosteroid treatment or active disease, such as nephrotic syndrome anasarca or myocarditis.

Musculoskeletal symptoms

Joint pain is one of the most common reasons for the initial clinical presentation in patients with SLE. Arthralgia, myalgia, and frank arthritis may involve the small joints of the hands, wrists, and knees. In contrast to rheumatoid arthritis, SLE arthritis or arthralgia may be asymmetrical, with pain that is disproportionate to swelling.

Dermatologic symptoms

Cutaneous manifestations of SLE comprise 3 American College of Rheumatology (ACR) lupus diagnostic criteria and other clues to a potential diagnosis of lupus.

The first criterion is malar rash, which is characterized by an erythematous rash over the cheeks and nasal bridge. It lasts from days to weeks and is occasionally painful or pruritic.

The second feature is photosensitivity, which may be elicited from patients who are asked if they have any unusual rash or symptom exacerbation after sun exposure, with anticipated duration of approximately 2 days in classic cases.

The third feature may be discoid rash. Discoid lesions often also develop in sun-exposed areas but are plaquelike in character, with follicular plugging and scarring. They may be part of systemic lupus or may represent discoid lupus without organ involvement, which is a separate diagnostic entity.

Alopecia is an often less specific cutaneous feature of SLE. It often affects the temporal regions or creates a patchy pattern of hair loss.

Other cutaneous manifestations related to but not specific to SLE include the following:

  • Raynaud phenomenon
  • Livedo reticularis
  • Panniculitis (lupus profundus)
  • Bullous lesions
  • Vasculitic purpura
  • Telangiectasias
  • Urticaria

Renal features

The kidney is the most commonly involved visceral organ in SLE. Although only approximately 50% of patients with SLE develop clinically evident renal disease, biopsy studies demonstrate some degree of renal involvement in most patients.[39] Glomerular disease usually develops within the first few years of SLE onset and is often asymptomatic.

Acute or chronic renal failure may cause symptoms related to uremia and fluid overload. Acute nephritic disease may manifest as hypertension and hematuria. Nephrotic syndrome may cause edema, weight gain, or hyperlipidemia.

Neuropsychiatric features

The CNS lupus nomenclature has been revised to catalog many manifestations.[40, 41, 42] Due to difficulty distinguishing causal SLE associations with some neurologic symptoms, only seizure and psychosis are included among the diagnostic criteria. Seizures related to SLE may be generalized or partial and may precipitate status epilepticus. Psychosis may manifest as paranoia or hallucinations.

Delirium represents a spectrum of fluctuating altered consciousness characteristic of SLE. Delirium may be caused by CNS vasculitis, encephalopathy, cerebritis, or the manifestations previously called organic brain syndrome. Aseptic meningitis, myelopathy, optic neuropathy, or other demyelinating disorders may also require urgent evaluation.

Transverse myelitis with spastic paraparesis and sensory loss at a given level is a rare but severe complication of SLE or antiphospholipid antibody syndrome. Stroke and transient ischemic attack (TIA) may be related to antiphospholipid antibody syndrome or SLE vasculitis. Posterior reversible encephalopathy syndrome (PRES) is, as the name implies, a reversible encephalopathy linked to hypertension that even may be a presenting feature for young SLE patients.[43]

Cognitive disorders may be variably apparent in many patients with SLE. Formal neuropsychiatric testing reveals deficits in 21-67% of patients with SLE. Whether this represents true encephalopathy, neurological damage, medication effects, depression, or some other process is unclear. A 2010 multicenter study found that depression was associated with significantly poorer cognitive function in 111 patients newly diagnosed with SLE.[44]

Migraine headaches may be linked to antiphospholipid syndrome, although this is less clear. Headache and mood disorders may be the most commonly reported neurologic manifestation of SLE, but cause and effect may be difficult to distinguish.

For additional information on this topic, see the Medscape Reference article Neurologic Manifestations of Systemic Lupus Erythematosus.

Pulmonary features

Pulmonary features of SLE may manifest acutely or indolently, representing a spectrum of SLE complications. Pleurisy with pleuritic chest pain with or without pleural effusions is the most common feature of acute pulmonary involvement in SLE. Shortness of breath or dyspnea may be due to many causes. Pulmonary embolism, lupus pneumonitis, chronic lupus interstitial lung disease, pulmonary hypertension, complement-mediated pulmonary leukoaggregation, alveolar hemorrhage, or infection may be related to lupus disease.

Most seriously, hemoptysis may herald diffuse alveolar hemorrhage, a rare, acute, life-threatening pulmonary complication of SLE.

Gastrointestinal features

In general, gastrointestinal symptoms secondary toSLE itself are less common than adverse effects of medication or nonspecific complaints among persons with SLE. Nausea and dyspepsia are common symptoms in patients with active SLE and are sometimes difficult to correlate with objective evidence of gastrointestinal involvement.

Occassional abdominal pain in active SLE may be directly related to active lupus, including peritonitis, pancreatitis, mesenteric vasculitis, and bowel infarction. Jaundice due to autoimmune hepatobilliary disease may also occur.

Cardiac features

Heart failure or chest pain must be carefully assessed in patients with SLE. Pericarditis is the most common cardiac feature of SLE, manifesting as positional chest pain that is often relieved when the patient leans forward. Myocarditis may occur in SLE with heart failure symptoms. Pulmonary hypertension may present with indolent chest pain or dyspnea.

Coronary vasculitis manifesting as angina or infarction is rarely reported. Libman-Sacks endocarditis is noninfectious but may manifest as symptoms similar to those of infective endocarditis in patients with SLE or antiphospholipid syndrome. More commonly, accelerated ischemic coronary artery disease (CAD) is associated with SLE and may present indolently as atypical anginal equivalents.

Hematologic features

A history of multiple cytopenias such as leukopenia, lymphopenia, anemia, or thrombocytopenia may suggest SLE, among other etiologies. Leukopenia and, more specifically, lymphopenia are common in SLE; this and hypocomplementemia may predispose persons with SLE to frequent infections.

Anemia is occasionally overlooked in young menstruating women, and historic lymphopenia may be overlooked. Thrombocytopenia may be mild or part of a full thrombotic thrombocytopenic purpura (TTP)–like syndrome or antiphospholipid antibody syndrome. A history of recurrent early miscarriages or a single late pregnancy loss may be clues to lupus or isolated antiphospholipid antibody syndrome.[45]

Next

Physical Examination

Almost any organ system can be involved in active SLE. The constellation of several physical findings may suggest a diagnosis of SLE. The American College of Rheumatology (ACR) diagnostic criteria are discussed in Workup. Examination findings are discussed by system.[38]

Fever is a challenging problem in SLE. It can be a manifestation of active lupus, infection, malignancy, or a drug reaction. Low-grade fever is observed in patients on immunosuppressive agents. Lymphadenopathy or splenomegaly may be found.

Patients with fever need to have infectious causes ruled out—both viral and bacterial. Lupus patients may be functionally asplenic and at risk for encapsulated bacterial infections like meningococcemia. Patients with SLE who are on immunosuppressive therapy are at a higher risk of death due to infection from viruses (eg, herpes simplex virus [HSV], cytomegalovirus [CMV], varicella-zoster virus [VZV]) and should be treated accordingly if an infection is suspected.[46] An infection can mimic a lupus flare and delays in diagnosis and institution of treatment result in increased mortality.[47]

Skin and mucous membrane findings

Malar rash is a fixed erythema that typically spares the nasolabial folds (see image below). It is a butterfly-shaped rash that can be flat or raised over the cheeks and bridge of the nose, as shown below.

The classic malar rash, also known as a butterfly The classic malar rash, also known as a butterfly rash, with distribution over the cheeks and nasal bridge. Note that the fixed erythema, sometimes with mild induration as seen here, characteristically spares the nasolabial folds.

Photosensitive rash is often macular or diffusely erythematous in sun-exposed areas of the face, arms, or hands and persists for more than 1 day generally. See the image below.

Photosensitive systemic lupus erythematosus (SLE) Photosensitive systemic lupus erythematosus (SLE) rashes typically occur on the face or extremities, which are sun-exposed regions. Photo courtesy of Dr. Erik Stratman, Marshfield Clinic.

Discoid rash occurs in 20% of patients with SLE and can result in disfiguring scars. The discoid rash can present as erythematous patches with keratotic scaling over sun-exposed areas of the skin. Follicular plugging may create scarring that may be well demonstrated in the ears. Systemic manifestations of SLE may be absent (ie, limited discoid lupus).

Lupus should be considered in all patients who experience painless or painful oral or less frequently vaginal ulcers, although ulcers classically occur more than 3 times per year and are painless. Palatal ulcers are most specific for SLE.

Many other cutaneous findings are not explicitly diagnostic features but support impressions of SLE. Alopecia in SLE often causes hair loss at the temporal regions or creates a patchy pattern. Livedo reticularis is characterized by a lacy, mottled, erythematous skin pattern that develops in some patients with SLE or antiphospholipid antibody syndrome. Raynaud phenomenon may be observed with blue, white, and red color change at the distal digital tips. Capillaroscopy can be performed with an ophthalmoscope to search for dilated capillary nailfold loops. Panniculitis, bullous lesions, vasculitic purpura, and urticaria are other skin lesions that are sometimes seen in SLE.

Musculoskeletal findings

Arthritis of the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints of the hands as well as the wrists is the most common musculoskeletal finding in SLE. Tenderness, edema, and effusions accompany a polyarthritis that is symmetric, nonerosive, and usually nondeforming. Jaccoud arthropathy is the term used to describe the nonerosive hand deformities due to chronic arthritis and tendonitis that develop in 10% of patients with SLE.

Myositis may manifest as weakness in SLE but is more commonly related to overlap syndromes or corticosteroid-induced myopathy. Fibromyalgia, distinguished as myofascial tenderness without weakness, is commonly concomitant with SLE, causing generalized widespread pain, arthralgia, and myalgia.

With focal pain at the hips, knees, and shoulders, for instance, consider avascular necrosis in patients who are taking glucocorticoids. Consider septic arthritis when one joint is inflamed out of proportion to all other joints and or fever is present.

Renal findings

Hypertension or hematuria may signal nephritic SLE. Edema of periorbital or peripheral regions and anasarca are common physical findings related to nephrotic syndrome or volume overload with renal failure. Specific signs and symptoms of renal disease may not be apparent until advanced nephrotic syndrome or renal failure is present; therefore, obtaining a urine analysis and protein estimate and serum BUN and creatinine levels on a regular basis is important.

Neuropsychiatric findings

About 28-40% of neuropsychiatric SLE findings arise before or around the time of diagnosis.[48] Headache is the most commonly seen CNS finding in SLE, occurring in 39-61% of adults and 72% of children,[48] although this is nonspecific. Altered mental status in SLE may be secondary to aseptic meningitis, seizures, psychosis, or organic brain syndrome. All types of seizures have been reported; the most frequent is the grand mal seizure. Sensory or sensorimotor neuropathies occur. Mononeuritis may manifest as the functional loss of one or a few isolated peripheral nerves and is observed in some patients with SLE vasculitis or antiphospholipid disease. Deficits below a dermatomal level or spastic paraperesis should raise consideration of transverse myelitis.

Focal neurologic deficits may represent stroke, transient ischemic attack (TIA), or mononeuritis.

Incidence of stroke is high in SLE, and those with antiphospholipid antibodies are at higher risk for such events.

Cardiopulmonary findings

Pleuropericardial friction rubs and signs of effusions may be found. Tachypnea, cough, and fever are common manifestations of lupus pneumonitis. Hemoptysis may signify pulmonary hemorrhage secondary to the disease. However, infection is the most common cause of infiltrates seen on radiographs. Hemodynamic instability and hypoxia may suggest pulmonary embolism. Heart failure signs or arrhythmias may point to ischemia or inflammatory myocarditis.

Systolic murmurs are reported in up to 70% of cases. Murmurs may represent Libman-Sacks endocarditis, superimposed infective endocarditis, thromboembolic disease, or demand-related phenomena in fever, hypoxia, or anemia. Digital infarcts and splinter hemorrhages may be observed with Libman-Sacks endocarditis. Pulmonary hypertension may be evidenced by a loud P2 heart sound.

Pulmonary hypertension, vasculitis with digital infarcts, and splinter hemorrhages may be observed.

Pericarditis has an incidence of 20-30% and is the most common presentation of heart involvement clinically, although examination rubs are less common. It is usually associated with small effusions, but it may involve larger effusions when uremia is concomitant. Myocarditis can cause heart failure symptoms and arrhythmias.

Gastrointestinal findings

Occassionally, abdominal tenderness and pain may be linked to peritonitis, pancreatitis, mesenteric vasculitis, or non–lupus-related processes. Lupus peritonitis is a less-common serositis that may be present, even in the absence of ascites.

Eye findings

Funduscopic examination is important in patients with visual complaints. Retinal vasculitis can lead to blindness and is demonstrated by sheathed narrow retinal arterioles with white exudates adjacent to the vessels. SLE-associated optic neuritis is uncommon, but should be considered as well in patients with vision loss.[49]

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Contributor Information and Disclosures
Author

Christie M Bartels, MD, MS  Assistant Professor of Rheumatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health

Christie M Bartels, MD, MS is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and American College of Rheumatology

Disclosure: Nothing to disclose.

Coauthor(s)

Richard S Krause, MD  Senior Clinical Faculty/Clinical Assistant Professor, Department of Emergency Medicine, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Viraj S Lakdawala, MD  Clinical Instructor of Emergency Medicine, University of California, San Francisco, School of Medicine; Attending Physician, San Francisco General Hospital

Viraj S Lakdawala, MD is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians

Disclosure: Nothing to disclose.

Mark J Leber, MD, MPH  Assistant Professor of Emergency Medicine in Clinical Medicine, Weill Cornell Medical College; Attending Physician, Lincoln Medical and Mental Health Center

Mark J Leber, MD, MPH is a member of the following medical societies: American College of Emergency Physicians and American College of Physicians

Disclosure: Nothing to disclose.

Daniel Muller, MD, PhD  Associate Professor of Rheumatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health

Daniel Muller, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American College of Rheumatology, and American Holistic Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Carlos J Lozada, MD  Director of Rheumatology Fellowship Program, Professor, Department of Medicine, Division of Rheumatology and Immunology, University of Miami, Leonard M Miller School of Medicine

Carlos J Lozada, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Pfizer Honoraria Speaking and teaching; Amgen Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Elliot Goldberg, MD  Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose.

Gino A Farina, MD, FACEP, FAAEM  Associate Professor of Clinical Emergency Medicine, Albert Einstein College of Medicine; Program Director, Department of Emergency Medicine, Long Island Jewish Medical Center

Gino A Farina, MD, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Julie Hildebrand, MD, and Anuritha Tirumani, MD, to the development and writing of the source articles.

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In systemic lupus erythematosus (SLE), many genetic-susceptibility factors, environmental triggers, antigen-antibody responses, B-cell and T-cell interactions, and immune clearance processes interact to generate and perpetuate autoimmunity.
The classic malar rash, also known as a butterfly rash, with distribution over the cheeks and nasal bridge. Note that the fixed erythema, sometimes with mild induration as seen here, characteristically spares the nasolabial folds.
Photosensitive systemic lupus erythematosus (SLE) rashes typically occur on the face or extremities, which are sun-exposed regions. Photo courtesy of Dr. Erik Stratman, Marshfield Clinic.
This axial, T2-weighted brain MRI demonstrates an area of ischemia in the right periventricular white matter of a 41-year-old woman with long-standing systemic lupus erythematosus (SLE). She presented with headache and subtle cognitive impairments but no motor deficits. Faintly increased signal intensity was also seen on T1-weighted images, with a trace of enhancement following gadolinium that is too subtle to show on reproduced images. Distribution of the abnormality is consistent with occlusion of deep penetrating branches, such as may result from local vasculopathy, with no clinical or laboratory evidence of lupus anticoagulant or anticardiolipin antibody. Cardiac embolus from covert Libman-Sacks endocarditis remains less likely due to distribution.
Table 1. Drugs Associated With Lupus Erythematosus
Definite Association
ChlorpromazineMethyldopa
HydralazineProcainamide
IsoniazidQuinidine
Possible Association
Beta-blockersMethimazole
CaptoprilNitrofurantoin
CarbamazepinePenicillamine
CimetidinePhenytoin
EthosuximidePropylthiouracil
HydrazinesSulfasalazine
LevodopaSulfonamides
LithiumTrimethadione
Unlikely Association
AllopurinolPenicillin
ChlorthalidonePhenylbutazone
Gold



salts



Reserpine
GriseofulvinStreptomycin
MethysergideTetracyclines
Oral contraceptives
*Data from Tierney et al.[51]
Table 1. American College of Rheumatology Diagnostic Criteria
CriterionDefinition
1. Malar rashFixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds
2. Discoid rashErythematous raised patches with adherent keratotic scaling and follicular plugging (Atrophic scarring may occur in older lesions)
3. PhotosensitivitySkin rash as a result of unusual reaction to sunlight, by patient history or physician observation
4. Oral ulcersOral or nasopharyngeal ulceration, usually painless, observed by a physician
5. ArthritisNonerosive arthritis involving ≥2 peripheral joints, characterized by tenderness, swelling, or effusion
6. Serositis(A) Pleuritis: Convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion



or



(B) Pericarditis: Documented by ECG or rub or evidence of pericardial effusion
7. Renal disorder(A) Persistent proteinuria >0.5 g/d or >3+ if quantitation not performed



or



(B) Cellular casts: May be red blood cell, hemoglobin, granular, tubular, or mixed
8. Neurologic disorder(A) Seizures: In the absence of offending drugs or known metabolic derangements (eg, uremia, ketoacidosis, electrolyte imbalance)



or



(B) Psychosis: In the absence of offending drugs or known metabolic derangements (eg, uremia, ketoacidosis, electrolyte imbalance)
9. Hematologic disorder(A) Hemolytic anemia: With reticulocytosis



or



(B) Leukopenia: < 4000/mm3 total on ≥2 occasions



or



(C) Lymphopenia: < 1500/mm3 on ≥2 occasions



or



(D) Thrombocytopenia: < 100,000/mm3 in the absence of offending drugs
10. Immunologic disorder(A) Anti-DNA: Antibody to native DNA in abnormal titer



or



(B) Anti-Sm: Presence of antibody to Sm nuclear antigen



or



(C) Positive finding of antiphospholipid antibodies based on (1) an abnormal serum level of IgG or IgM anticardiolipin antibodies, (2) a positive test result for lupus anticoagulant using a standard method, or (3) a false-positive serologic test for syphilis known to be positive for at least 6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption tests
11. Antinuclear antibodyAn abnormal titer of antinuclear antibody 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
SLE can be diagnosed if any 4 or more of the 11 criteria are present, serially or simultaneously, during any interval of observation.
Table 2. International Society of Nephrology 2003 Revised Classification of SLE Nephritis[57]
ClassClassificationFeatures
Class IMinimal mesangialNormal light microscopy findings; abnormal electron microscopy findings
Class IIMesangial proliferativeHypercellular on light microscopy
Class IIIFocal proliferative< 50% of glomeruli involved
Class IVDiffuse proliferative>50% of glomeruli involved; classified segmental or global; treated aggressively
Class VMembranousPredominantly nephrotic disease
Class VIAdvanced sclerosingChronic lesions and sclerosis
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