Systemic Lupus Erythematosus

Definition/Description

Lupus erythematosus is an autoimmune disease that can manifest itself in several different ways including: discoid lupus erythematosus (DLE), systemic lupus erythematosus (SLE), drug-induced lupus, late-state lupus, and antiphopholipid antibody syndrome.  With this condition, "the body creates antibodies against its own cells."  These antibodies can be formed against many different tissues and components of the body including RBCs, neutrophils, platelets, lymphocytes, etc.  For this reason, SLE can affect almost any area of a person's body.[1] 

Systemic lupus erythematosus (SLE) is a chronic, rheumatic, inflammatory disease that can affect a person’s skin, joints, kidneys, lungs, heart, nervous system, blood, and mucous membranes. It does not affect all patients in the same way, so patients experience variable organ involvement after being diagnosed with SLE.[1] [2] 

Prevalence

Prevalence & Descriptors SLE
20/100,000 World Prevalence
9:1 Female: Male
Ages of Diagnosis 15-40 Years
  • Occurs in 15-24/100,000 people throughout the world[3]
  • Large variation depending on country and location--high prevalence in Sweden.  14.6/100,000 in NY vs 78.5/100,000 in WI
  • Most likely to occur in women of child-bearing age
  • More common in those of African American, Hispanic, Asian, and Native American decent than in Caucasians[1]
  • 9 times more likely in women compared to men[4]   
  • Most people are diagnosed with the disease between the ages of 15 and 40[2]
  • Rarely diagnosed in the elderly [3]
  • Occurs in 10-20/100,000 children (depends on the population)
  • About 15% of people diagnosed with SLE are younger than 18 years old, and when a person is diagnosed at an early age, the disease progresses more quickly and severely than if diagnosed after the age of 18.[5]
  • More prevalent in those who have a family history of SLE than it is in the general population[1]

Characteristics/Clinical Presentation 

Pathology

     Histological changes within the body occur as a result of immunological changes or immunolgical attack associated with deposits of   immune complexes within various tissues of the body.

SLE can affect many organs of the body, but it rarely affects them all. The following list includes common signs and symptoms of SLE in order of the most to least prevalent. All of the below symptoms might not be present at the initial diagnosis of SLE, but as the disease progresses more of a person’s organ systems become involved.

  • “Constitutional symptoms (fever, malaise, fatigue, weight loss): most commonly fatigue and a low-grade fever
  • Achy joints (arthralgia)
  • Arthritis (inflamed joints)
    This image illustrates the typical distribution pattern of the butterfly (malar) rash that can be a characteristic of SLE.  This picture was included courtesy of: http://images.google.com.
  • Skin rashes
  • Pulmonary involvement (symptoms include: chest pain, difficulty breathing, and cough)
  • Anemia
  • Kidney involvement (lupus nephritis)
  • Sensitivity to the sun or light (photosensitivity)
  • Hair loss
  • Raynaud’s phenomenon
  • CNS involvement (seizures, headaches, peripheral neuropathy, cranial neuropathy, cerebrovascular accidents, organic brain syndrome, psychosis)
  • Mouth, nose, or vaginal ulcers”[1]


  • The most common signs and symptoms of SLE in children and adolescents are: "fever, fatigue, weight loss, arthritis, rash, and renal disease."[5]  

Associated Co-morbidities

  • About 30% of people diagnosed with SLE are also diagnosed with fibromyalgia.[2] 
  • Atherosclerosis[6] [7]
  • Lupus Nephritis- leads to End Stage Renal Disease (ESRD)
  • Anemia[8]
  • Some types of cancers (especially non-Hodgkin's lymphoma and lung cancer) [7][9] [10]
  • Infections
  • Hypertension
  • Dyslipidemia
  • Diabetes Mellitus
  • Osteoporosis
  • Avascular Necrosis [7]

Medications

  • Analgesics[1]: These medications are used to control the pain associated with arthralgia, arthritis, and ulcers that are caused by SLE.[3]
  • Non-Steroidal Anti-inflammatory Drugs (NSAIDS): These medications help to decrease tissue inflammation, and therefore decrease the patient’s joint and muscle pain.
  • Anti-malarials: These medications are used to treat a patient's arthritic, musculocutaneous, and renal symptoms associated with SLE. 
              - Chloroquine (Aralen)[1][3]
              - Hydroxychloroquine (Plaquenil)[3]
  • Corticosteroids[2]: These drugs are only prescribed to patients with severe SLE who experience signs and symptoms that are not improving with any other drug therapy. Corticosteroids can give the patient relief from constitutional symptoms, arthritis, and cutaneous problems caused from SLE.
  • Immunosuppressant Agents: These drugs are used to decrease inflammation, treat lupus nephritis, and suppress the patient's immune system.   
              - Azathioprine (Imuran)
              - Cyclophosphamide (Cytoxan)[1][3]

Diagnostic Tests/Lab Tests/Lab Values

According to the American Rheumatism Association, a patient must exhibit at least 4 of the following criteria concurrently or successively to be diagnosed with systemic lupus erythematosus.
This could be how an oral ulceration looks in a person with SLE.  This image was included courtesy of http://www.thedailystar.net/photo.
  • "Abnormal titer of antinuclear antibodies (ANAs)
  • Butterfly (malar) rash
  • Discoid rash
  • Hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia
  • Neurologic disorder: seizures or psychosis
  • Non-erosive arthritis of two or more peripheral joints characterized by tenderness, swelling, or effusion
  • Oral or nasopharyngeal ulcerations
    This is an illustration of a discoid rash that is characteristic of a patient with SLE.  It is included in this project courtesy of www.googleimages.com
  • Photosensitivity
  • Pleuritis or pericarditis 
  • Positive lupus erythematosus cell preparations, anti DNA, or anti-splice sosomal test or chronic false-positive serologic test for syphilis<span id="fck_dom_range_temp_1269546309419_582" />
  • Renal disorder: profuse proteinuria (>0.5 grams/day) or excessive cellular casts in urine."[1]


The lab tests completed may include:

  • Complete Blood Count: This blood test reveals a patient's total number of red blood cells, white blood cells, platelets, and hemoglobin. Low white blood cell or platelet counts can be indicative of SLE, whereas low red blood cell counts can be indicate of anemia which commonly occurs in conjunction with SLE.
  • Erythrocyte Sedimentation Rate:  An elevated erythrocyte sedimentation rate can reveal a systemic problem. This test is not specific to SLE, but a postitive test could reveal that the patient could potentially have SLE.  
  • Kidney and Liver Tests:  These tests are completed to determine if a patient's kidneys and liver are functioning properly since SLE can affect these systemic organs.
  • Urinalysis:  This test is performed to determine if there are proteins or red blood cells present in a patient's urine.  If so, this could indicate that the kidneys are damaged, potentially from SLE.
  • ANA test:  A positive test reveals that a patient could potentially have SLE, but other infections and diseases can cause this test to be positive as well.  If positive, further testing is necessary to determine if the positive results occurred due to SLE.
  • Chest X-ray: This test is performed to determine if there is inflammation present in the patient's lungs or excessive fluid surrounding his/her heart. 
  • Syphilis Test:  A false-positive syphilis test can reveal that a patient has anti-phospholipids present, and this false-positive test result is indicative that the patient could have SLE.[9] 

Causes

There is no known cause of SLE, but research states that the interaction between a person's genetic make-up, immune system, hormonal balance, and environment could potentially cause SLE.  At this time, autoimmunity is thought to be the primary causative factor of SLE. 

There are certain factors that can predispose a patient to SLE including:

  • Heredity- There is a high prevalence of SLE in first-degree relatives.  The immune abnormalities associated with SLE can be triggered by both internal and external factors. 
  • Stress- It has been determined that stress can provoke changes in the neuroendocrine system causing changes in the function of immune system cells.
  • Bacterial or viral infection- The Epstein-Barr virus has been found to be a risk factor for the development of SLE.   
  • Sunlight or UV exposure
  • Immunizations 
  • Pregnancy- The evidence about whether or not pregnancy can cause exacerbations of SLE is very inconclusive because some studies state that pregnancy does affect the course of SLE, while others state that it has no affect on the course of the disease.   
  • Abnormal levels of estrogen  
  • Certain drugs- Drugs such as hydralazin, anticonvulsants, penicillin, sulfa drugs, and oral contraceptives can change the cellular responsiveness and immunogenicity of self-antigens and therefore make a person more susceptible to SLE.[1]

Systemic Involvement

There are many visceral systems can be affected from SLE, but the extent of the body's involvement differs from person to person.  Some people diagnosed with SLE have only few visceral systems involved, while others have numerous systems that have been affected by the disease.

Musculoskeletal System:
This image was included courtesy of www.google.images.com
  • Arthritis- typically affects hand, wrists, and knees 
  • Arthralgia
  • Tenosynovitis
  • Tendon ruptures
  • Swan-neck deformity
  • Ulnar drift

Cardiopulmonary/Cardiovascular System:

  • Pleuritis
  • Pericarditis
  • Dyspnea
  • Hypertension
  • Myocarditis
  • Endocarditis
  • Tachycarditis
  • Pneumonitis 
  • Vasculitis
  1. Small Vessels Purpura
  2. Large Vessels Papular Lesions
  3. Arterial Thrombosis

Central Nervous System:

  • Emotional instability
  • Psychosis
  • Seizures
  • Cerebrovascular accidents 
    This illustration was included courtesy of http://www.medicinenet.com.
  • Cranial neuropathy 
  • Peripheral neuropathy
  • Organic brain syndrome

Renal System:

  • Glomerulonephritis
    -inflammatory disease of the kidneys    
  • Hematuria
  • Proteinuria
  • Kidney failure[1]

Cutaneous System:

  • Calcinosis 
  • Cutaneous vasculitis
  • Hair loss 
  • Raynaud's phenomenon
  • Mucosal ulcers
  • Petechiae

Blood Disorders:

  • Anemia
  • Thrombocytopenia
  • Leukopenia
  • Neutropenia
  • Thrombosis
Gastrointestinal System:
This picture was included courtesy of http://www.health.com
  • Ulcers--Throat & Mouth
  • Ulcerative colitis/Crohn's disease
  • Peritonitis
  • Ascites
  • Pancreatitis
  • Peptic ulcers
  • Autoimmune Hepatitis [11]

Medical Management (current best evidence)

The medical management for SLE is primarily drug therapy and is based upon the patients symptoms and systemic involvement.  In addition to drug therapy, prevention is also very important when dealing with SLE.  For patients with photosensitivities, flare-ups can be reduced if patients are cautious about the amount of sunlight or UV light that they are exposed to.  Patients with SLE are also encouraged to lead a healthy lifestyle that includes: smoking cessation, controlling alcohol consumption, weight management, and regular exercise.[1][7]  Exercise is beneficial for patients with SLE because it decreases their muscle weakness while simultaneously increases their muscle endurance.  Patients with SLE are also encouraged to participate in support groups, ensure they are taking the correct dosages and amounts of medications, and ensure they visit medical professionals regularly.[1]

New Therapies

Topical Therapy/Medication

NSAIDS

Hormonal Intervention

Immunosupressant Therapy

IV Gamma Globulin

Apheresis

Stem-Cell Transplantation

Biological Therapy[12]

Physical Therapy Management (current best evidence)

Physical therapists can play an important role for patients with SLE during and between exacerbations.  The patient's need for physical therapy will vary greatly depending on the systems involved.   

  • Education: It is essential for patients with skin lesions to have appropriate education on the best way to care for their skin and to ensure they do not experience additional skin breakdown.  
  • Aerobic Exercise:  One of the most common impairments that patients with SLE experience is generalized fatigue that can limit their activities throughout the day.[1]  In a study by Tench et al., it was determined that graded aerobic exercise programs are more successful than relaxation techniques in decreasing the fatigue levels of patients with SLE.  Aerobic activity caused many of the participants with SLE to feel "much better" or "very much better" at the conclusion of the study.  The aerobic exercise program consisted of 30-50 minutes of aerobic activity (walking/swimming/cycling) with a heart rate corresponding to 60% of the patient's peak oxygen consumption.[13]  Another study, completed by Ramsey- Goldman et al., concluded that both aerobic exercise and range of motion/muscle strengthening exercises can increase the energy level, cardiovascular fitness, functional status, and muscle strength in patients with SLE.  In this study, the patients completed aerobic exercise for 20-30 minutes at 70-80% of their maximum heart rate.  The patients who completed range of motion and muscle strengthening activities met 3 times a week for 50 minutes sessions.[14]
  • Energy Conservation: Physical therapists can educate patients on appropriate energy conservation techniques and the best ways to protect joints that are susceptible to damage.  
  • Additionally, physical therapists and patients with SLE should be aware of signs and symptoms that suggest a progression of SLE including those associated with avascular necrosis, kidney involvement, and neurological involvement.[1] 

Differential Diagnosis

+ ACR Diagnostic Criteria SLE
> 4 Present 96% Sensitive; 96% Specific[15]
  1. Malar rash
  2. Discoid rash
  3. Photosensitivity 
  4. Oral ulcers
  5. Arthritis
  6. Serositis
  7. Renal disorders
  8. Neurologic disorder
  9. Hematologic disorder
  10. Immunologic disorder
  11. Antinuclear antibody

       Diagnostic Procedures

         ANA Profile

             if the ANA test is negative, unlikely to have the diagnosis of SLE

             the Lupus Band Test can assist in confirming the diagnosis of SLE with inconsistent clnical findings and can assist in excluding diseases similiar to SLE[16] [17]

                         sensitivity:  93%    specificity:87% 

                         PPV: 64%              NPV:  98%

        Other Differential Diagnoses

  Fibromyalgia

  Undifferentiated Connective Tissue Disease 

  Auto-immune Rheumatic Disease

  Viral Infections-Epstein-Barr, Cytomegalovirus 

  Bacterial Infections

   HIV

   TB

  Malignancies

  Rheumatoid Arthritis

  Vasculitis [5]

  Multiple Sclerosis [18]

Case Reports

Systemic Lupus Erythematosus Case Study

Acase report of a very late-onset systemic lupus erythematous http://www.clinicalgeriatrics.com

Development and management of systemic lupus erythematosus in an HIV-infected man with hepatitis C and B co-infection followed by interferon therapy: a case report   http://www.jmedicalcasereports.com

Case report: multiple sclerosis and SLE revisited http://www.medicaljournal-ias.org/12_3/Bhigjee.pdf

Recent Related Research (from Pubmed)

Resources

Lupus Foundation of America www.lupus.org

Medline Plus: Lupus http://www.nlm.nih.gov/medlineplus/lupus.html

WebMD: Lupus http://lupus.webmd.com/

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 Goodman CC, Fuller KS. Pathology: Implications for the Physical Therapist. 3rd edition. St. Louis, Missouri: Saunders Elsevier, 2009. (Level of evidence 5)
  2. 2.0 2.1 2.2 Goodman CC and Synder TK. Differential Diagnosis for Physical Therapists: Screening for Referral. 4th edition. St. Louis, Missouri: Saunders Elsevier, 2007.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Laranzo D. Elderly-onset systemic lupus erythematosus. Drugs and Aging; 24 (9):701-715. 2007.
  4. O'Neill S, Cervera R. systemic Lupus Erythematosus. Best Practice & Res Clin Rheu 24 (2010) 841-855
  5. 5.0 5.1 5.2 Tucker LB. Making the diagnosis of systemic lupus erythematosus in children and adolescents. Lupus; 16: 546-549. 2007.
  6. Becker-Merok A, Nossent JC. Prevalence, predictors, and outcomes of vascular damamge in systemic lupus erythematosus. Lupus; 18: 508-515. 2009.
  7. 7.0 7.1 7.2 7.3 Bertsias G, Gordon C, Boumpas DT. Clinical trials in systemic lupus erythematosus (SLE): lessons from the past as we proceed to the future- the EULAR recommendations for the management of SLE and the use of end-points in clinical trials. Lupus; 17: 437-442. 2008.
  8. Wingard R. Increased risk of anemia in dialysis patients with comorbid diseases. Nephrology Nursing Journal; 31 (2): 211-214. 2004.
  9. 9.0 9.1 Medical Foundation for Medical Education and Research. Mayo Clinic: Lupus Page. www.mayoclinic.com. Updated October 20, 2009. Accessed February 17, 2010.
  10. Bernatsky S, Boivin JF, Joseph L, et al. An international cohort study of cancer in systemic lupus erythematosus.Arthritis & Rheumatism 2005;52(5):1481–90.
  11. Lupus Foundation of America. How lupus affects the body page. Website updated: 2010. Website accessed: February 17, 2010.
  12. Solsky M, Wallace D. New therapies in systemic lupus erythematosus. Best Practice & Res Clin Rheum: 2002; 16; 293-312
  13. Tench CM, McCarthy J, McCurdie I, White PD, D'Cruz DP. Fatigue in systemic lupus erythematosus: a randomized control trial of exercise. Rheumatology; 42: 1050-1054. 2003. (Level of evidence 1B)
  14. Ramsey-Goldman GR, Schilling EM, Dunlop D, Langman C, Greenland P, Thomas RJ, Chang RW. A pilot study on the effects of exercise in patients with systemic lupus erythematosus. Arthritis Care and Research; 13(5): 262-269. 2000. (Level of evidence 2B)
  15. Hochberg MC. Updating the American College of Rehumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis and Rheumatism 1997; 40: 1725-1734
  16. George R, Kurian S, jacob M, Thomas K. Diagnostic evaluation of the lupus band test in discoid and systemic lupus erythematosus. Int J Dermatol. 1995 34: 170-173
  17. Mehta V, Sarda A, Balachandran C. Lupus band test. Indian J Dermatol Venereol Leprol [serial online] 2010 [cited 2012 Mar 6];76:298-300. Available from: http://www.ijdvl.com/text.asp?2010/76/3/298/62983
  18. Bhiglee AI, Bill PL. Case Report: Multiple sclerosis and SLE revisited. Medical Journal of Islamic Academy of Sciences; 12 (3): 79-84. 1999.