Authors

  1. Pullen, Richard L. Jr. EdD, MSN, RN, CNE, CNE-cl, ANEF, FAAN
  2. Hammond, Lori DNP, MSN, RN, CNE-cl, GERO-BC

Abstract

This article presents the pathogenesis, signs, symptoms, and management of systemic lupus erythematosus.

 

Article Content

Systemic lupus erythematosus (SLE), an inflammatory autoimmune disease, results from immune system dysregulation that can cause multiorgan damage, variable signs and symptoms, and periods of flares and remission.1,2 In autoimmune diseases, a person's immune system mistakenly determines their body organs and tissues to be foreign and attacks them. SLE symptoms can range from mild to life-threatening and its diversity and complexity of presentation can create challenges in diagnosis and treatment.1,2 It's often called "the great imitator" because it mimics many diseases.3 This article presents the pathogenesis, signs, symptoms, and management of SLE.

  
Figure. No caption a... - Click to enlarge in new windowFigure. No caption available.

Epidemiology and risk factors

Thirteenth-century physicians used the word "lupus," meaning "wolf" in Latin, to describe a facial rash pattern that was often noted in young women, thinking it resembled the facial features of a wolf.3 "Erythematosus" means "redness" of the skin, a misnomer, because SLE can affect any body organ or tissue.3 The degree of erythema varies among individuals. SLE affects 5 million people globally, including 1.5 million people in the US.4-6 Global health disparities impacting SLE outcomes include poverty, access to insurance, medications, food, housing, transportation, and mental health resources.6,7 People with SLE may find it challenging to cope with chronic pain, fatigue, and disability.1,5 Today, the major causes of death in patients with SLE are renal disease, infections, central nervous system complications, thrombosis, and cardiovascular disease.8,9 More than 80% of people with SLE are expected to live an average lifespan with treatment, close surveillance, and lifestyle modification, compared with 50% of patients living less than 5 years after SLE diagnosis in the 1950s.3,9,10

 

People of Black, Asian, Pacific Islander, Latino, and Native American descent are affected by SLE two to three times more often than White people.4,6,7,11 Multiple genes are implicated in the pathogenic origins of SLE, particularly the major histocompatibility complex, where the human leukocyte antigen region and the toll-like receptor 7 gene are located.1,12 Some medications cause an increase in oxidative stress, including isoniazid, procainamide, hydralazine, and minocycline, and may trigger immune system dysregulation which can lead to an SLE-like syndrome. Smoking; physical injury; emotional stress; and infections such as Epstein-Barr virus, cytomegalovirus, and varicella-zoster virus may predispose a person to the disease.

 

People of all skin tones are at risk for skin damage from UV light from the sun, tanning salons, and indoor halogen lighting.4-6 UV light penetrates deep into the skin and can damage a person's DNA, which can cause an immune system response.9,13

 

The female-to-male ratio of SLE is 9:1 during childbearing years; however, the ratio is 3:1 during childhood and after menopause.4,6,14 Estrogen levels during childbearing years are implicated in disease development and flares. Estrogen stimulates T-lymphocyte and B-lymphocyte activity, giving females a more robust immune system than males and with that, a propensity for autoimmune diseases.1,4,12 On the other hand, testosterone has an immunosuppressive effect on T-lymphocyte and B-lymphocyte activity, possibly protecting males from autoimmune disease.15,16 Research shows that males with SLE don't have abnormal estrogen levels and are just as sexually active and fertile as males without the disease.9 Males with SLE are typically diagnosed after age 40 and may present with more severe renal and cardiovascular manifestations.9

 

Pathogenesis

The pathogenesis of SLE involves an interplay of genetic, hormonal, environmental, and immunologic factors that can lead to tissue injury and DNA damage.1,12,17 DNA damage causes the cell to undergo programmed cell death (apoptosis) and die.1,12,17 Small apoptotic bodies circulate and expose the inside of a cell and nucleus to the rest of the body. The immune system incorrectly identifies the nucleus components of the cell such as DNA, histones, cardiolipin, and other proteins as antigens and begins an immune attack. Because these components originate from the nucleus, they are called nuclear antigens. Inefficient clearance of apoptotic bodies also results in an abundance of nuclear antigens. B-lymphocytes begin to produce antibodies against components of the nucleus, called antinuclear antibodies (ANAs), and mediate inflammation with proinflammatory cytokines (proteins), predominantly interferon-alpha (IF-alpha).1,12,17 The antibodies produced incorrectly identify normal proteins (self-proteins or autoantibodies) as being foreign and harmful to the person. ANAs are present in 95% of people with SLE.18,19 T-lymphocytes regulate B-lymphocyte responses and potentiate inflammation by dysregulation of proinflammatory interleukins (ILs), including IL-2, IL-17, and IL-21.1,12,17-19 These nuclear antibodies bind to nuclear antigens, forming immune complexes (one antibody + one antigen together) that deposit into blood vessels and body tissues, initiating local inflammation and damage by activating the complement system. The complement system is made up of more than 30 proteins released by the liver in abundance with acute inflammation and infection to rid the body of antigens.1,9,12,17-19 Abnormally low complement levels, particularly complement-3 (C3) and complement-4 (C4), indicate that chronic inflammation is consuming proteins. Low C3 and C4 are markers of active disease.20

 

Clinical presentation

The clinical presentation of SLE differs dramatically among patients. Some have mild disease, whereas others rapidly progress to life-threatening stages.21-23 The most common initial presentations are fatigue, fever, nonerosive arthritis, arthralgia, weight loss, and cutaneous manifestations. The most common arthritis symptoms in patients with SLE are aching and stiffness.21-23 Deforming joint abnormalities manifested in rheumatoid arthritis rarely occur in patients with SLE.9,21 A decreased red blood cell (RBC) count may indicate anemia secondary to chronic inflammation.9,21 Hemolytic anemia may occur when the immune system attacks RBCs. Decreased white blood cells, particularly neutrophils (neutropenia), results from treatment with immunosuppressive medications or an immune-mediated attack on the bone marrow. Reduction in platelets (thrombocytopenia) may indicate an immune-mediated attack on the bone marrow. Renal studies may be abnormal.9,21

 

For example, a patient with high serum creatinine, low estimated glomerular filtration rate, proteinuria, low serum proteins, edema, and hypertension may indicate lupus nephritis (LN), a life-threatening complication of SLE. A renal biopsy is required to confirm a diagnosis of LN. Decreased C3 and C4 levels, elevated erythrocyte sedimentation rate, and elevated C-reactive protein reflect active inflammation and should be correlated with antibodies associated with SLE and other autoimmune diseases.9,20,21 Combining broad ANA detection with specific antigenic ANA testing is a common practice.18,19,24 For example, patients with a positive ANA may be tested for antibodies against histones and DNA and extractable nuclear antigens. Individual antibodies may indicate a specific clinical presentation (see Antibodies in SLE and related autoimmune diseases).18,19,24

  
Antibodies in SLE an... - Click to enlarge in new windowAntibodies in SLE and related autoimmune diseases

Mucocutaneous manifestations are common SLE features encompassing lupus-specific and nonspecific rashes and lesions. The first image features a lupus-specific malar rash sparing the nasolabial folds that may be flat or raised.13,21,25

 

The second sidebar illustrates a lupus-specific papulosquamous subacute cutaneous lupus erythematosus, sometimes called "psoriasiform" because it resembles psoriasis.13,21,25 The rashes in acute cutaneous lupus erythematosus (ACLE) malar rash and lupus-specific papulosquamous subacute cutaneous occur secondary to exposure to the sun and indoor lighting. Other specific lesions include chronic cutaneous lupus erythematosus and discoid lupus erythematosus (DLE), which may exist without systemic manifestations. Nonspecific mucosal and skin lesions, including nonscarring alopecia, vasculitis (inflammation of blood vessels in the skin), and urticaria, are common in SLE. Rashes and lesions cause pain, discomfort, and body image disturbances and may indicate inflammation in body organs and tissues.13,21,25

 

Neuropsychiatric syndromes in SLE include headache, cognitive dysfunction, anxiety, depression, mood disorder, aseptic meningitis, stroke, seizure, polyneuropathy, Guillain-Barre syndrome, and myasthenia gravis.9,21 Abdominal pain, anorexia, nausea, vomiting, and diarrhea may occur secondary to medications to treat SLE or complications of SLE, including peritonitis, pancreatitis, and vasculitis of the mesentery and bowel.9,21 Elevated liver enzymes are rarely caused directly by SLE, but likely result from the medications to treat the disease or autoimmune hepatitis. SLE can affect the eye in many ways. The most common eye symptom is keratoconjunctivitis sicca, manifested by itching, burning, and blurring eyes.9,21 A chest X-ray may show pleural effusion. An echocardiogram may reveal valvular disease and pericardial effusion and may reveal conduction disturbances causing dysrhythmias.9,21

  
Figure. Acute cutane... - Click to enlarge in new windowFigure. Acute cutaneous lupus erythematosus malar rash (also known as butterfly rash)
 
Figure. Subacute cut... - Click to enlarge in new windowFigure. Subacute cutaneous lupus erythematosus (papulosquamous subtype)

The American College of Rheumatology (ACR) revised the 1982 criteria for the classification of SLE in 1997 (see Revised criteria for the classification of SLE). A person meeting 4 of the 11 criteria simultaneously or serially indicates SLE.21,26,27 The ACR and European League for Rheumatism developed criteria to identify early-stage SLE (see 2019 Classification for SLE). Patients must have a positive ANA to be eligible to use the classification system. Each criterion is assigned a number. Only the highest numbered criterion in a domain is counted toward the total score. A total score of 10 or more plus one criterion met is classified as SLE. A person must meet criteria simultaneously or serially. Both classification systems are tools that providers use to correlate complex clinical features in SLE, exclude differential diagnoses, and manage the patient.21,26,27

  
Revised criteria for... - Click to enlarge in new windowRevised criteria for the classification of SLE

Management

Medication treatment is the standard intervention to manage inflammation in SLE. Medication classifications include corticosteroids (CS), disease-modifying antirheumatic drugs (DMARDs), and biological response modifiers (BRMs).9,28-34 (See Common SLE medications and priority assessments.)28-34

 

Selected nursing interventions

1. Physical assessment. Conduct a head-to-toe physical assessment. Mood changes may be related to fatigue, medications, and depression from chronic illness. Changes in cognition, speech, and motor movement may indicate inflammation of the central nervous system. Assess joints for redness, swelling, pain, and limitation in range of motion. Erythema, rashes, and mucosal lesions may indicate inflammation in the body's vital organs. Assess respiratory rate, depth, rhythm, and oxygen saturation. Auscultate the lungs for pleural friction rubs and crackles. Assess cardiac rate and rhythm. Auscultate the heart valves for murmurs from valvular dysfunction and pericardial friction rubs. Assess the abdomen for bowel sounds, pain, or distension. Assess for infections, pain level, and quality of life.9,21,29

 

2. Lab and imaging. Correlate any physical assessment findings with lab indicators of inflammation. For example, elevated C-reactive protein and erythrocyte sedimentation rate and low RBCs, C3, and C4. Imaging studies also indicate inflammation. For example, ultrasound and MRI show inflammation and damage to joints and soft tissues without synovitis and bone erosion.9,21,29

  
2019 Classification ... - Click to enlarge in new window2019 Classification for SLE

3. Medication responses. Systemic medications control inflammation. The efficacy of these medications is measured with improved symptoms and minimal to no adverse reactions (see Common SLE medications and priority assessments). Nurses should teach patients to report adverse reactions to medications, including but not limited to an increase in pain or discomfort, the onset of fever (infection and increased inflammation), bleeding from anywhere in the body, weight gain or loss, changes in mental status, abdominal pain or discomfort, and skin rashes and lesions. Nurses should teach patients to apply a sun protection factor greater than 30 to protect the skin from harmful light sources when taking azathioprine and have sufficient hydration when taking cyclophosphamide to avoid hemorrhagic cystitis.28-34

 

4. Nutrition. Foods with anti-inflammatory properties should be encouraged, including fish, vegetables, fruit, beans, legumes, seeds, whole grain bread, oats, olive oil, and tofu. Overweight and obesity proinflammatory cytokines that can worsen SLE. Patients should consult a dietitian to help them with healthy food choices.9,29,35

 

5. Health promotion. Patients with SLE may have challenges coping with chronic illness and comorbidities unrelated to SLE. Strategies to promote quality of life include (1) adhering to the treatment plan, (2) receiving vaccinations as indicated, (3) avoiding people who are sick, (4) wearing an N95 or KN95 mask if receiving immunosuppressive medications, (5) sun protection such as wide-brimmed hats, wearing sunglasses, and applying sun protection factor greater than or equal to 30, (6) wearing comfortable clothing, (7) getting plenty of sleep, (8) resting at intervals, (9) being physically active, (10) getting a hobby, (11) avoiding smoking and excessive alcohol consumption, and (12) engaging in support groups.9,29,35

 

Conclusions

The primary goals in managing SLE are controlling inflammation to protect body organs and tissues from damage, reducing pain and discomfort, and promoting quality of life. Research continues to result in new medications to treat SLE. Thankfully, medication therapy and lifestyle modification have substantially improved morbidity and mortality in patients with SLE since the 1950s. In all, SLE is a complex illness that requires the nurse to use critical thinking and clinical reasoning to manage the patient safely.

 

INSTRUCTIONS Selected nursing interventions for systemic lupus erythematosus

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