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Keywords:

  • SLE;
  • genetics;
  • lupus;
  • SLE treatment;
  • SLE management

Abstract

  1. Top of page
  2. Abstract
  3. Pathogenesis of SLE
  4. Genetic linkage
  5. Incidence and prevalence
  6. Diagnostic criteria
  7. Precipitating factors
  8. Prognosis
  9. Management
  10. Disease progression
  11. General recommendations
  12. Case presentation
  13. Conclusion
  14. References

Purpose: To review the symptom presentation, genetic aspects, and available treatment options for individuals diagnosed with systemic lupus erythematosus (SLE). Primary care providers should be vigilant in identifying symptoms, which may be related to SLE, perform adequate assessment, and diagnostic testing in order to arrive at an early diagnosis.

Data sources: Extensive literature review of textbook, clinical, medical, and nursing journals.

Conclusions: Lupus is a multigenic autoimmune disease, which requires the clinician to be hypervigilant by collecting a thorough family history and performing a complete physical assessment of the patient. There is an array of treatment modalities, both experimental and proven therapies, which improve signs and symptoms associated with SLE. Numerous medications are available for symptom management: anti-inflammatory agents for patients with musculoskeletal presentation, and steroids or antimalarials for those with more extensive organ involvement.

Implications for practice: In SLE, the overall aim of management is to determine the extent of disease and prevent extensive organ involvement. Therefore, when diagnosed in a timely manner, most patients will survive and are able to manage their disease.

Systemic lupus erythematosus (SLE) is a connective tissue, autoimmune-mediated disorder, marked by a wide array of organ system dysfunction. Observable symptoms include fever, fatigue, arthritis, anemia, and rash, which are manifested when antibody–antigen complexes are deposited in capillaries of tissues (arthritis, rash) or with the occurrence of autoantibody-mediated destruction of host cells (e.g., anemia, fever; Arbuckle et al., 2003; Rigby & Vinuesa, 2008). SLE is a multifactorial, chronic, multisystem, and occasionally life-threatening disease with environmental, genetic, and hormonal origins. In the 13th century, the physician Rogerius first described the characteristic “butterfly rash” located on the cheeks and nose, which has become known as the malar rash of lupus (Tierney, 2005). However, it was Kaposi who in 1872 described systemic features associated with disseminated disease such as arthritis and psychosis (Smith & Cyr, 1988). SLE is marked by disease remission, flares, and progression. A flare is an exacerbation of previous symptoms, while progression is the worsening of new symptoms with or without the presentation of new disease features. Prognosis depends on the degree of organ impairment, with skin and musculoskeletal having the best outcomes, and central nervous system (CNS) and renal disease having the worst outcomes. Males who are diagnosed with SLE tend to have more severe symptoms, renal and CNS involvement, and a higher 1-year death rate than females (Kasitanon, Magder, & Petri, 2006).

Pathogenesis of SLE

  1. Top of page
  2. Abstract
  3. Pathogenesis of SLE
  4. Genetic linkage
  5. Incidence and prevalence
  6. Diagnostic criteria
  7. Precipitating factors
  8. Prognosis
  9. Management
  10. Disease progression
  11. General recommendations
  12. Case presentation
  13. Conclusion
  14. References

The precise etiology of lupus is unknown; however, genes play a major role in disease susceptibility, with environmental factors such as ultraviolet (UV) exposure and hormonal factors such as pregnancy or stress contributing to disease presentation. SLE is a disorder of the immune system, with excessive B-cell activity and abnormal T-cell function resulting in defects in programmed cell death, and atypical production of regulatory proteins (Ramos et al., 2006). Symptoms associated with SLE occur because of the presence of antibodies directed against ribonucleoproteins, chromatin (chromosomal material), and phospholipids (Arbuckle et al., 2003; Rigby & Vinuesa, 2008). Autoantibody production precedes clinical manifestations and is likely responsible for end-organ disease (Arbuckle et al., 2003; Rigby & Vinuesa, 2008).

SLE is manifested by a broad array of phenotypic features such as renal, dermatologic, neurological, and hematologic involvement. Common renal manifestations include proteinuria, hematuria, fluid retention, and mild elevation in blood pressure. Dermatologic disease is seen in patients who present with a butterfly rash or cutaneous lesions such as fingertip lesions, nail fold infarcts, and splinter hemorrhages (Tierney, 2005). When symptoms are limited to the skin the condition is usually referred to as cutaneous lupus erythematosus (CLE). However, CLE can occur in the presence or absence of systemic manifestations of SLE. In fact, two to three times more patients have CLE than have SLE. Active lesions are typically erythematous macules, papules, or plaques that typically have adherent, crusty scales with follicular blockage, which typically resolve with scarring and dyspigmentation (Lin, Dutz, Sontheimer, & Werth, 2007). Neurological complications of SLE may include psychosis, seizures, peripheral, and cranial neuropathies. Hemolytic anemia, the untimely destruction of red blood cells, is associated with poor survival if present at any point in the course of disease (Kasitanon et al., 2006). Individuals with hemolytic anemia are twice as likely to die, independent of other disease manifestations such as age, gender, ethnicity, or income (Kasitanon et al., 2006; Table 1).

Table 1.  Symptoms and presentation of SLE
SymptomPercent at onsetPercent at any time
  1. aVon Feldt (1995); bChng (2001); cGill et al. (2003); dOzbek, sert et al. (2003); eLahita (2004); fBautista et al. (2008); gJallouli et al. (2008); hAdelowo and Aguntona (2009); iAl Arfaj and Khalil (2009); jStoller (2009).

Fatigue, fever, weight loss20–10040–100a
Arthritis or arthralgia62–98h,a83–95
Hematological (e.g., clotting, hemolytic anemia, nosebleeds)36–82.7c,i30–80e
Skin rash (malar or generalized)7380–91
Renal insufficiency8.6–47.9c,d,i15–75k
Malar rash (butterfly rash over cheeks and bridge of nose)28–47.9i48–54
Raynaud's phenomenon8.7–33i22–71
Photosensitivity2941–60a
Neuropsychiatric symptoms (e.g., psychosis)27.615–52
Alopecia45h21.2–47.6g,i
Gastrointestinal (e.g., hepatomegaly, nausea, vomiting, ascites)18c6.1–53b,i
Mucous membrane lesion10–2127–52a
Lymphadenopathy7–1621–50a
Cardiac (e.g., pericarditis)0.8–15c,d30–50e
Central nervous system (e.g., seizures, numbness, and tingling)14f25–75a
Pulmonary (e.g., pleurisy)2–1224–98a
Splenomegaly520–59a

Because SLE is a multisystemic disease, one hypothesis is that the phenotypic diversity seen in SLE is a reflection of underlying genetic heterogeneity (Bautista, Kelly, Harley, & Gray-McGuire, 2008). Disease expression among family members may be estimated from the ratio of the risk to siblings of patients with the disease to the risk in the general population. When this ratio (λ) approaches 1.0, there is no evidence of familial amalgamation. Nevertheless, most autoimmune diseases have λ values, which significantly surpass 1.0 (Shai et al., 1999; Vyse & Todd, 1996). The λ value for SLE is estimated to be 20.0 (Hochberg, 1987; Shai et al., 1999; Vyse & Todd, 1996) as evidenced by at least 10% of SLE sufferers having an affected family member, with an increased likelihood between identical twins (Sestak, Nath, Sawalha, & Harley, 2007). In addition, there is SLE familial clustering with other autoimmune diseases, such as rheumatoid arthritis, Sjögren's syndrome, antiphospholipid antibody syndrome, scleroderma, and autoimmune thyroid disease. Studies have shown that 10%–20% of lupus probands (i.e., the index case) have at least one first- or second-degree relative affected by an autoimmune disease besides lupus (Nath, Kilpatrick, & Harley, 2004).

Genetic linkage

  1. Top of page
  2. Abstract
  3. Pathogenesis of SLE
  4. Genetic linkage
  5. Incidence and prevalence
  6. Diagnostic criteria
  7. Precipitating factors
  8. Prognosis
  9. Management
  10. Disease progression
  11. General recommendations
  12. Case presentation
  13. Conclusion
  14. References

On chromosome 6, there is a region called the major histocompatibility complex (MHC), which consists of at least 100 different genes that exert an effect on the functioning of the immune system. The MHC region is divided into three subgroups called MHC class I, MHC class II, and MHC class III. Approximately 40% of the MHC genes provide instruction with regards to immunomodulatory function, thereby exerting the strongest effect on lupus susceptibility. The MHC I and II encode cell-surface antigen-presenting proteins called human leukocyte antigen (HLA) proteins, which are responsible for antigen presentation to T cells, thereby initiating an immune response (Fernando et al., 2007; Horton et al., 2004). The MHC class II alleles HLA-DR2 and HLA-DR3 have been routinely linked with SLE.

HLA-DRB1*0301-DQB1*0201/HLA-DRB1*1501-DQB1*0602 are considered high-risk genotypes, while HLA-DRB1*0301-DQB1*0201-containing genotypes demonstrate a dose-dependent effect in increasing lupus susceptibility (Fernando et al., 2007).

Complement, which is a cascade of 20 proteins in the humoral immune system, defends the host against infection but can cause injury and destruction when triggered in an unrestrained manner (Lappegard et al., 2009). The complement system can be activated by antigen–antibody complexes, by products released from bacteria, and by components of other plasma protein systems (Huether & Kathryn 2000). Deficiencies in complement proteins and receptors such as C1q, C1r, C1s, C3, and C4 have been reported in SLE, thereby, placing patients at risk for infection because of impaired phagocytosis (Kang & Park, 2003; Vratsanos, Jung, Park, & Craft, 2001; Walport, 1993).

Traditionally, CH50 (which measures total complement activity) and C1–C9 are complement proteins that have been used to monitor disease activity. However, they have low sensitivity and specificity because blood levels reflect ongoing complement synthesis and consumption, both of which are elevated during inflammation (Illei, Tackey, Lapteva, & Lipsky, 2004). Furthermore, genotypic markers of SLE may differ based on ethnicity, in addition to certain genes being responsible for the prominence of certain phenotypic characteristics (Table 2).

Table 2.  Genes with associated linkages by ethnicity
Major linkageAssociated geneMajor ethnicity
  1. Note. AA, African American; EA, European American; EU, European; HIS, Hispanic; IC, Icelandic; MEX, Mexican; SW, Swedish.

  2. aGaffney et al. (1998); bMoser et al. (1998); cLindqvist and Alarcon-Riquelme (1999); dShai et al. (1999); eGray-McGuire et al. (2000); fNath et al. (2001); gEdberg et al. (2002); hGraham et al. (2002); iKelly et al. (2002); jNamjou et al. (2002); kProkunina et al. (2002); lQuintero-del-Rio et al. (2004).

1q23b,fFcγRIIA, FcγRIIIAAA, EA
1p36dDIS468MEX
1q44dDIS2785MEX
1q41gNot knownEA, HIS
2q34lNot knownAA
2q37kPD-1EU, MEX
4p16e,fNot knownEA
5p15f,jNot knownEA, AA, HIS
6p11–21f,hHLA-DREA
10q22f,lNot knownEA
11q14iNot knownAA
11q23cD11S1998SW
11q25bD11S915EA
12p11–12bD12S1042EA
12q24fNot knownHIS, EA
13q32bD13S779AA, EA
16q13aD16S415EA, AA, HIS
17p12fNot knownEA
19p13cD19S247, D19S246IC

Genes located at 1q23 and 11p13 play a key role in the manifestation of thrombocytopenia. Approximately 10%–25% of SLE patients experience thrombocytopenia, which is associated with poorer outcomes in contrast to families without the propensity for thrombocytopenia (Alarcon et al., 2002; Scofield et al., 2003; Tan et al., 1982). Thrombocytopenia can be classified into two subgroups; first, it may be a chronic condition, which is present without disease activity or it may occur acutely with severe, multisystem SLE disease flares (Scofield et al., 2003; Figure 1).

image

Figure 1. Major genetic linkage with associated symptom presentation.

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Ro(SSA) is a ribonucleoprotein particle; Anti-Ro(SSA) autoantibody is a positive marker in 30%–50% of lupus patients (Frank, McArthur, Harley, & Fujisaku, 1990; Harley et al., 1986; Reichlin, 1986). In SLE patients, Ro(SSA) antibodies are associated with lymphopenia, photosensitive dermatitis, and pulmonary disease (Frank et al., 1990; Hamilton et al., 1988; Smolen et al., 1985).

SLE biologic markers are used to diagnose the presence of disease, assess end-organ damage, treatment response, and or simply to assess inflammation during an acute flare. Potential biomarkers for SLE may be considered as follows: double-stranded DNA antibody (anti-dsDNA) and C3, C4, C3a, C5a, C3d, and C4d, which are serum complement and activation products, may be used to monitor disease activity. C-reactive protein (CRP) and ferritin are measured during acute disease. Renal involvement may be monitored using anti-dsDNA, anti-C1q, anti-nucleosome, urinary soluble vascular cell adhesion molecule (sVCAM), and monocyte chemoattractant protein-1 (MCP-1) levels.

Incidence and prevalence

  1. Top of page
  2. Abstract
  3. Pathogenesis of SLE
  4. Genetic linkage
  5. Incidence and prevalence
  6. Diagnostic criteria
  7. Precipitating factors
  8. Prognosis
  9. Management
  10. Disease progression
  11. General recommendations
  12. Case presentation
  13. Conclusion
  14. References

Annual SLE rates are reported to be 2.5–4.0 and 8.1–11.5 per 100,000 in Caucasian and African–American women, respectively. Rates in men tend to be significantly lower and are reported to be 0.3–0.9 and 0.7–2.5 per 100,000 in Caucasian and African–American men, respectively (Parker & Bruce, 2007). Prevalence rates are estimated to be 40–50 cases per 100,000 in the United States and 40–70 cases per 100,000 in China (Parker & Bruce, 2007). Approximately, half of lupus patients will exhibit an erratic relapsing–remitting disease pattern (Ho, Barr, Magder, & Petri, 2001).

Diagnostic criteria

  1. Top of page
  2. Abstract
  3. Pathogenesis of SLE
  4. Genetic linkage
  5. Incidence and prevalence
  6. Diagnostic criteria
  7. Precipitating factors
  8. Prognosis
  9. Management
  10. Disease progression
  11. General recommendations
  12. Case presentation
  13. Conclusion
  14. References

The diagnosis of SLE is made based on the presence of four or more of the 11 criteria listed below. The antinuclear antibody (ANA) is the sole criteria, which must be positive in order to support the diagnosis of SLE. As determined by the American College of Rheumatology (ACR), at least four of the following criteria must be exhibited for a definitive diagnosis of SLE: (a) malar rash, (b) discoid rash on the cheeks, (c) photosensitivity to sunlight, (d) painless mucocutaneous ulcers, (e) nonerosive arthritis of at least two joints, (f) renal dysfunction evidenced as proteinuria or cellular casts, (g) positive serum ANA, (h) neurologic disorder such as seizure or psychosis, (i) serositis as evidenced by pleuritis or pericarditis, (j) hematologic disorders (anemia, thrombocytopenia, or leukopenia), and (k) immunologic dysfunction (positive anti-sm antibody, anti-ds DNA, or antiphospholipid antibody). If fewer than four criteria are present this cannot be diagnosed as SLE, or may be considered incomplete SLE (ISLE) based on symptom presentation (Gill, Quisel, Rocca, & Walters, 2003).

To definitively diagnose SLE for patients presenting with symptoms manifesting in two or more organs, ANA testing should be one of the first laboratory tests done. If the ANA titer is negative (< 1:40), then an alternate explanation for the organ system manifestation should be pursued. If no explanation is found, consider referral to a rheumatologist if question of SLE or ISLE remains. In the absence of SLE, the most common reason for a positive ANA test is the presence of another connective tissue disease. Connective tissue diseases that often are associated with a positive ANA test include Sjögren's syndrome, scleroderma, and rheumatoid arthritis (Gill et al., 2003).

Conversely, if the ANA titer is positive (>1:40), in addition to an elevated serum antibody titer (e.g., anti-dsDNA, anti-sm, anti-RoSSa), consider referring to a rheumatologist for full SLE evaluation. Diagnostic lab tests should include complete blood count (CBC), urinalysis, serum creatinine level, and antiphospholipid antibodies. Differential diagnosis for SLE symptom presentation include but are not limited to Lyme disease, antiphospholipid syndrome, polyarteritis nodosa, rheumatoid arthritis, scleroderma, thrombotic thrombocytopenic purpura, and undifferentiated and mixed connective-tissue disease.

Precipitating factors

  1. Top of page
  2. Abstract
  3. Pathogenesis of SLE
  4. Genetic linkage
  5. Incidence and prevalence
  6. Diagnostic criteria
  7. Precipitating factors
  8. Prognosis
  9. Management
  10. Disease progression
  11. General recommendations
  12. Case presentation
  13. Conclusion
  14. References

SLE may be activated by a combination of biological and environmental factors. The following are considered to be common lupus triggers. (a) Exposure to the sun and other sources of UV light that may cause exacerbations or induce the first signs of lupus (Nived, Johansen, & Sturfelt, 1993). (b) Infections (Duffy, Duffy, & Gladman, 1991; Hess, 1994), (c) stress, (d) surgery, and (e) pregnancy can cause an exacerbation or even trigger the first symptoms of lupus. With pregnancy, a relapse is more likely to occur in the immediate postpartum period (Ruiz-Irastorza, Egurbide, Olivares, Martinez-Berriotxoa, & Aguirre, 2008).

Prognosis

  1. Top of page
  2. Abstract
  3. Pathogenesis of SLE
  4. Genetic linkage
  5. Incidence and prevalence
  6. Diagnostic criteria
  7. Precipitating factors
  8. Prognosis
  9. Management
  10. Disease progression
  11. General recommendations
  12. Case presentation
  13. Conclusion
  14. References

Five-year survival has increased from 40% in the 1950s to greater than 90% in the 21st century (Urowitz, Gladman, Tom, Ibanez, & Farewell, 2008). Life expectancy rates for SLE patients are generally reduced because of long-term medication side effect and disease course; consequently, 10% of patients will die within 5 years of diagnosis (Aringer, Smolen, & Graninger, 1998; Smolen, 2002; Urowitz & Gladman, 2000). The course of SLE is varied, and ranges from a nonprogressive illness to rapidly advancing organ failure. The disease has periods of exacerbation and remission, which is commonly controlled by steroids. Poor prognosis is associated with renal disease, hypertension, male gender, young age of diagnosis, older age at presentation, poor socioeconomic status, Afro-American/Afro-Caribbean, presence of antiphospholipid antibodies or antiphospholipid syndrome, and high disease activity.

Management

  1. Top of page
  2. Abstract
  3. Pathogenesis of SLE
  4. Genetic linkage
  5. Incidence and prevalence
  6. Diagnostic criteria
  7. Precipitating factors
  8. Prognosis
  9. Management
  10. Disease progression
  11. General recommendations
  12. Case presentation
  13. Conclusion
  14. References

Because of the complex nature of SLE, consultation between primary care providers and specialty providers is recommended for optimal management of SLE. The most commonly involved specialists are rheumatologists, nephrologists, dermatologists, and hematologists. The treatment spectrum is broad and includes steroids, topical agents, nonsteroidal antiinflammatory drugs (NSAIDs), antimalarials, and cytotoxic medications that exert antiinflammatory effects.

Corticosteroids are the foundation of SLE therapy. Dosage and method of administration depend on disease severity and organ involvement (Zonana-Nacach, Barr, Magder, & Petri, 2000). Patients with significant renal or CNS disease are usually treated with systemic glucocorticoids with or without the addition of immunosuppressive agents (Parker & Bruce, 2007). Therefore, clinical disease expression usually directs treatment modalities for both children and adults (Carreno, Lopez-Longo, Gonzalez, & Monteagudo, 2002).

Topical steroid preparations may be utilized for localized problems such as skin lesions of cutaneous or discoid lupus erythematosus. NSAIDs are usually effective for musculoskeletal pain and mild serositis. Antimalarials are most useful for dermatologic symptoms and for musculoskeletal pain that does not satisfactorily respond to NSAIDs. Antimalarials (e.g., chloroquine and hydroxychloroquine) are widely used in SLE patients because of their regulatory effects on the immune system; however, they are not usually used as first line therapy in patients with renal and CNS involvement. Antimalarials are effective because of their ability to control SLE activity and prevent flares, assisting with lipid profile management, and reducing thrombotic and cardiovascular events (Shinjo, 2009).

Immunosuppressive drugs (e.g., cyclophosphamide [CYC], methotrexate, azathioprine) are usually prescribed to patients with severe organ dysfunction or if they partially respond to glucocorticoids. Azathioprine is used in patients with lupus nephritis (LN) owing to its ability to stabilize renal function and reduce proteinuria (Chan et al., 1995; Felson & Anderson, 1984; Goldblatt & Isenberg, 2005). CYC, despite being extremely toxic, is efficacious in the treatment of severe LN and other acute manifestations of SLE (Ginzler & Moldovan, 2004). Common CYC toxicities include infection, reproductive failure, malignancy, cytopenias, and hemorrhagic cystitis (Petri, 2004).

Mycophenolate mofetil (MMF), which was originally developed for organ transplantation, acts by inhibiting lymphocyte replication and T-cell dependent antibody responses. MMF is usually used as induction treatment in proliferative nephritis or as long-term treatment in severe SLE. Moreover, MMF has a milder side effect profile in terms of lower risk for infection and leukopenia than CYC in SLE patients (Allison & Eugui, 2000; Gescuk & Davis, 2002).

Autologous hematopoietic stem cell transplant (HSCT) is generally administered to patients with hematological manifestations or pervasive organ dysfunction in spite of aggressive mainstream therapy (Goldblatt & Isenberg, 2005). HSCT involves chemotherapeutic destruction of unregulated cells, thereby allowing for regeneration of the bone marrow with healthy stem cells (Goldblatt & Isenberg, 2005; Jayne & Tyndall, 2004).

Immunoablation without SCT is the destruction of the patient's circulating immune system without stem cell transplant. One approach is to induce aplasia of the blood lines using CYC, followed by granulocyte-colony stimulating factor therapy, to stimulate hematopoietic reconstitution without HSCT (Jayne & Tyndall, 2004).

Disease progression

  1. Top of page
  2. Abstract
  3. Pathogenesis of SLE
  4. Genetic linkage
  5. Incidence and prevalence
  6. Diagnostic criteria
  7. Precipitating factors
  8. Prognosis
  9. Management
  10. Disease progression
  11. General recommendations
  12. Case presentation
  13. Conclusion
  14. References

Despite advances in determining genetic linkages, disease detection, and treatment, lupus has a fairly high mortality rate and significant long-term morbidity. Deaths related to renal disease have declined with time, while mortality because of circulatory disease has remained constant (Bernatsky et al., 2006). Common causes of morbidity are related to complications because of chronic immune suppression and steroid therapy, osteoporosis or avascular necrosis of the hips and knees because of long-term steroid use, and severe fatigue because of SLE exacerbation. Osteoporosis may be caused by long-term steroid used as well as vitamin D deficiency. Vitamin D is essential for bone metabolism, in addition to exerting inhibitory effects on T cells, B cells, and dendritic cells (Kamen & Aranow, 2008).

Long-term steroid therapy has been linked to hypertension, diabetes mellitus, hyperlipidemia, and obesity, which increases one's risk for atherosclerosis. The major causes of mortality include cardiac complications, coronary disease, acute renal failure, end-stage renal disease, infection, non-Hodgkin lymphoma (NHL), and lung cancer. The primary genetic aberration between SLE and NHL are unknown. A significant peculiarity of NHL is the translocation of an oncogene with a gene important for immune cell function (Baecklund et al., 2003; Bernatsky et al., 2005). Such chromosomal abnormalities may be the common link between SLE and lymphoproliferative malignancies, especially because the same tumor-forming factors involved in NHL may have a functional role in the uncontrolled lymphocyte proliferation of lupus (Bernatsky et al., 2005). In SLE, there is amplified B-cell activation and poor immune regulation, which is also evident in malignancies (Bernatsky, Clarke, & Ramsey-Goldman, 2002).

General recommendations

  1. Top of page
  2. Abstract
  3. Pathogenesis of SLE
  4. Genetic linkage
  5. Incidence and prevalence
  6. Diagnostic criteria
  7. Precipitating factors
  8. Prognosis
  9. Management
  10. Disease progression
  11. General recommendations
  12. Case presentation
  13. Conclusion
  14. References

Sun protection

Protection from direct or reflected sunlight and other sources of UV light must be emphasized with lupus patients as well as the use of sunscreens, which blocks both UVA and UVB protection. The majority of lupus patients are photosensitive, and have an increased risk of nonmelanoma skin cancer because of immunosuppressive therapy (Lindelof, Sigurgeirsson, Gabel, & Stern, 2000; Obermoser & Zelger, 2008). Because lupus patients are encouraged to avoid excessive sun exposure, they have an elevated risk for vitamin D deficiency, in which case supplementation is recommended (Barnes & Bucknall, 2004; Thudi, Yin, Wandstrat, Li, & Olsen, 2008).

Medications that induce SLE-like symptoms

Drugs that are known to induce lupus-like symptoms include hydralazine, methyldopa, procainamide, quinidine, isoniazid, and chlorpromazine (Tierney, 2005). Semisynthetic penicillins may exacerbate symptoms, while skin eruptions from sulfa antibiotics or sulfamethoxazole-trimethoprim are significantly more common in SLE patients (Pope, Jerome, Fenlon, Krizova, & Ouimet, 2003). Consequently, clinicians should take a detailed personal and family history of allergies while treating patients with SLE and inflammatory arthritis (Pope et al., 2003).

Blood pressure control and nutrition

Elevated systolic blood pressure is a major risk factor for mortality, coronary disease, heart failure, and cerebrovascular accidents in the general population. Furthermore, the recognition of these risk factors in the lupus population is imperative for the most favorable outcome, because strict blood pressure control prevents rapid disease progression.

Manzi et al. (1999) reported that premenopausal women with SLE, a population unaffected by the risks of coronary artery disease, had a 50 times greater likelihood of a deadly vascular event when compared with controls matched for age and gender (Manzi et al., 1999; Stanic et al., 2006).

Smoking cessation

Cigarette smoking may increase the risk of developing SLE, and smokers have been shown to have more active disease. Ghaussy et al. (2003) found that current smokers scored higher on the SLE Disease Activity Index (SLEDAI) when compared to ex-smokers and non-smokers (Ghaussy, Sibbitt, Bankhurst, & Qualls, 2003).

Exercise

Major psychological problems generally develop as a consequence of impaired physical mobility; consequently, participation in physical exercise reduces one's sense of disability and improves overall health rating for SLE patients. Aerobic activities such as walking, swimming, or cycling have been found to create a sense of well-being as well as decrease depression levels in SLE patients (Ayan & Martin, 2007; Daltroy, Robb-Nicholson, Iversen, Wright, & Liang, 1995; Tench, McCarthy, McCurdie, White, & D’Cruz, 2003).

Immunizations

Annual influenza and routine pneumococcal vaccine should be offered (Petri, 2004). However, it is not prudent to vaccinate immunosuppressed SLE patients with live vaccines such as measles mumps rubella, varicella (VZV), or smallpox. The British Society for Rheumatology guidelines state that after vaccination with a live virus, a waiting period of at least 4 weeks is recommended before initiating immunosuppressive treatment. Secondly, steroid therapy is deemed immunosuppressive if taken for more than 2 weeks at a dose of at least 20 mg per day; therefore, caution should be taken when considering vaccination for such patients (Millet, Decaux, Perlat, Grosbois, & Jego, 2009).

Case presentation

  1. Top of page
  2. Abstract
  3. Pathogenesis of SLE
  4. Genetic linkage
  5. Incidence and prevalence
  6. Diagnostic criteria
  7. Precipitating factors
  8. Prognosis
  9. Management
  10. Disease progression
  11. General recommendations
  12. Case presentation
  13. Conclusion
  14. References

R.M. is a 38-year-old Hispanic female who presents to the primary care provider with complaints of pain in the knees, wrists, and shoulders over the course of 2 weeks. In addition, she reports poor appetite, hair loss, photosensitivity, nausea, dry mouth, hoarse voice, “puffiness in feet,” and joint pain and morning stiffness lasting 45 min to 1 h. Also, she complains of feeling “down” and has trouble initiating and maintaining sleep.

Past medical history is significant for asthma, hyperlipidemia, seasonal allergies, obesity, and varicella (during childhood). Daily medication regimen includes simvastatin 40 mg, montelukast 10 mg, and loratadine 10 mg. She is currently unemployed, has a seventh grade education, and denies illicit drug use.

Physical exam revealed muscle strength 5/5, positive diffuse symmetrical joint tenderness (wrists, proximal interphalangeals, metacarpophalangeals, shoulders, ankles, and metatarsophalangeal joints). Cranial nerves II–XII intact and +3 edema bilaterally in the feet.

R.M. is prescribed ibuprofen 600 mg twice daily as needed, encouraged to elevate extremities, and maintain a low salt diet. Routine labs drawn included erythrocyte sedimentation rate (ESR), comprehensive metabolic profile, lipid profile, thyroid stimulating hormone, ANA, CBC with differential (CBC with diff), and urinalysis.

One week after the initial visit, lab results reveal ANA 1:320 (homogenous pattern), ESR 43 (0–20 mm/h normal range), urinalysis negative for protein and blood, total cholesterol 246 (120–200 mg/dL), and LDL 174 (70–130 mg/dL).

Additional diagnostic labs are drawn in light of a positive ANA, which include creatine kinase (CK), CRP, Smith autoantibodies, double-stranded DNA autoantibodies (dsDNA), single-stranded A/Ro (SS-A/Ro), SS-B/La autoantibodies, and ribonuclear protein autoantibodies (RNP). Results of diagnostic testing reveal anti-dsDNA is 174 IU/mL (normal range <25 IU/mL). R.M. was diagnosed with SLE and polyarthritis and referred to rheumatologist for consultation and further management. Ibuprofen was discontinued and she was prescribed hydroxychloroquine 200 mg and meloxicam 15 mg once daily.

Providers may encounter patients with SLE, but simply disregard the importance of obtaining a family pedigree. If we analyze the genogram, it becomes evident that this family has a strong genetic disposition for autoimmune conditions. The proband's sister is afflicted with rheumatoid arthritis, her mother with SLE, and brother with arthritis (Figure 2). By obtaining a genogram, the health dynamics of family members are brought into focus, thereby allowing the provider to make recommendations for health promotion or screening for susceptible genetic diseases.

image

Figure 2. Family pedigree: Puerto Rican Ancestry. No consanguinity.

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For example, the proband's younger sibling who is 25 years old may be offered genetic counseling and testing for SLE and rheumatoid arthritis because both conditions are present in the familial lineage, share similar genetic loci, and tend to manifest in women during their reproductive years.

Of importance is the proband's daughter, who has a diagnosis of bipolar disorder and schizophrenia. This diagnosis may simply be an inherited mental disorder from her paternal lineage or it could also be a sign of SLE, manifested as psychosis/neuropsychiatric disorder. Therefore, the proband's daughter should also be offered genetic counseling and testing for SLE. If it were discovered that she has SLE and her presenting symptom was neuropsychiatric, then treatment modalities could be tailored accordingly.

In SLE, the overall aim of management is to determine the extent of disease with prevention of major organ involvement. Appropriate levels of therapy are then instituted to control or eliminate inflammation, prevent end-organ dysfunction, and maintain satisfactory quality of life (Parker & Bruce, 2007).

Conclusion

  1. Top of page
  2. Abstract
  3. Pathogenesis of SLE
  4. Genetic linkage
  5. Incidence and prevalence
  6. Diagnostic criteria
  7. Precipitating factors
  8. Prognosis
  9. Management
  10. Disease progression
  11. General recommendations
  12. Case presentation
  13. Conclusion
  14. References

Finally, lupus is a multigenic autoimmune disease, which requires the clinician to be hypervigilant by collecting a thorough family history and performing a complete physical assessment of the patient. When diagnosed in a timely manner, most patients will survive and are able to manage their disease. Patients should be adequately counseled on preventing flare-ups and how to maintain a state of remission because they are the gatekeepers to their own health.

References

  1. Top of page
  2. Abstract
  3. Pathogenesis of SLE
  4. Genetic linkage
  5. Incidence and prevalence
  6. Diagnostic criteria
  7. Precipitating factors
  8. Prognosis
  9. Management
  10. Disease progression
  11. General recommendations
  12. Case presentation
  13. Conclusion
  14. References