Just who is at risk for organ damage? What factors contribute to it? How does it impact patients and their lives? And, most importantly, what treatment strategies can slow its progress? 

 

Patients at Risk

How many of your patients with SLE could be at risk for developing permanent organ damage?

Organ damage begins to accrue early, with as many as 50% of patients showing evidence of irreversible damage* within 5 years of SLE diagnosis7-9

* Based on Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) measurements

Percentage of patients with permanent organ damage7,8

Chart showing the percentage of patients with permanent organ damage (by SDI) at 1 Year and 5 Years
Chart showing the percentage of patients with permanent organ damage (by SDI) at 1 Year and 5 Years

Damage is defined as an irreversible tissue injury occurring after SLE diagnosis and lasting at least 6 months.9 SDI is the internationally agreed and validated measure of organ damageA limitation of the SDI is that it may also capture damage that may not be related to SLE specifically.

Assessing Organ Damage via SDI9

While typically employed in clinical studies, the SDI may prove useful in assessing organ damage in your patients with SLE.  

SDI measures permanent, irreversible damage in a lupus patient. Items should be present for at least 6 months, except manifestations such as myocardial infarction and stroke, which are recorded once they occur.

It is important to note that an increase of even one point in a patient’s SDI can correlate with serious health issues (eg, myocardial infarction, cerebrovascular accident, or cataracts).

Damage is defined for
12 organs/systems:
Ocular
Neuropsychiatric
Renal
Pulmonary
Cardiovascular
Peripheral vascular
Gastrointestinal
Musculoskeletal
Skin
Premature gonadal failure
Diabetes (regardless of treatment)
Malignancy

Damage over time can only be stable or increase, theoretically, to a maximum of 47 points.

Patient Burden

Which organs can be affected?

Several organ systems are commonly involved in SLE and should be carefully monitored for disease activity. Commonly involved organ systems include the following: central nervous; renal; gastrointestinal; mucous membranes; cardiovascular; mucocutaneous; hematologic; musculoskeletal; and, pulmonary.4

Severity of the disease can vary from mild to potentially fatal, due to detrimental organ damage.10 

  • Kidneys

    Renal damage is one of the most serious complications of SLE.16 Usually manifesting during the early stage of SLE, renal disease has consistently been shown to be a major cause of mortality in patients with SLE.16

    • Urinalysis abnormalities or renal dysfunction exist in 35% of patients early in the course of the disease.17
    • Up to 60% of adults with SLE develop renal abnormalities over the course of their disease.18
  • Bones

    Patients with SLE are 5 times more likely to have a bone fracture than age-matched controls.19

    This is primarily due to the prolonged use of steroids in their treatment and age at SLE diagnosis.

    • The relative risk of osteoporotic fractures is increased 1.9-fold with a cumulative dose of 36.5 g of corticosteroids.20
  • Skin

    Mucocutaneous involvement is almost universal in SLE. Manifestations include11:

    • rashes
    • photosensitivity
    • nasal and oral ulcers
    • alopecia
  • Brain

    Neuropsychiatric syndromes can affect many patients with SLE.12 They range from mild to severe. The most common manifestations include:

    • cognitive dysfunction
    • headache
    • depression
    • anxiety
  • Eyes

    SLE may affect almost any part of the eye and the visual pathway. If a patient has ophthalmic issues, he or she should be referred to an ophthalmologist. The following symptoms may be a sign of potential complications13:

    • blurriness
    • dry eyes
    • loss of vision
    • pain
  • Heart

    Risks of coronary heart disease (CHD) and stroke are significantly higher for patients with SLE compared to general population.14,15

    • Patients with SLE are at 2- to 10- times increased risk of CHD.

How can permanent organ damage affect your patients?

Icon: Organ Damage leads to the risk of additional damage and increased mortality

leads to the risk of additional damage and increased mortality8,21,22

Long-Term Considerations

Patients with SLE now live longer, with survival rates improving significantly over the last 50 years.16 This improved longevity has created a situation where SLE patients accrue more organ damage over time. Evidence also indicates that clinicians should be particularly vigilant during the early course of SLE.

Once organ damage occurs, the risk of additional damage and mortality are increased.8,21,22 Patients at risk for further damage should be monitored closely for adverse effects of medication and the development of co-morbidities and complications of SLE.8  

Even with low/moderate disease activity, patients still accrue organ damage. Multiple factors may contribute to damage accrual, including the chronic use of corticosteroids.4,7 In particular, the risk of prolonged cumulative steroid dose may be more important to consider than duration of exposure.23

Icon: No Clinical Symptoms

Hidden Damage

There is also a risk of organ damage accrual while the patient is completely unaware. For example, osteonecrosis may be asymptomatic in patients with SLE.24 Cardiovascular disease may also be subclinical in patients with SLE—prevalence of plaques in internal carotid arteries is 3 times higher, and endothelial dysfunction, an early marker of atherosclerosis, is 2 times as common compared to the control group.25,26 

Contributing Factors

What factors contribute to organ damage?

Persistent disease activity is linked to increased organ damage, which, in turn, is predictive of increased damage and mortality.

Currently, no consensus exists on how to assess patient outcomes and measure disease activity. Tools,27-29 including SELENA-SLEDAI, BILAG, and PGA, have been developed for use in clinical trials, but their use in real-world practice is limited.

The changeable nature of SLE may make it difficult to predict when disease activity—in the form of flares—will occur.2

Patterns of SLE Disease Activity

Disease activity in SLE may appear in different patterns—relapsing-remitting (RR), chronically active (CA), and long-quiescent.1,2

A study of the Hopkins Lupus Cohort found that while RR was the most common disease pattern observed, over a 3-year perspective, less than half of patients maintained their original pattern.30

The charts below are for illustrative purposes only and represent activity over any three-year period.

RR was the most prevalent pattern type.

80%-94% of patients with SLE had RR and/or CA patterns.30

(M-SLEDAI: 66% n=1244, CA 14.6% n = 275; PGA: RR 56.7% n= 1069, CA 37.8% n = 712)

Chart showing 3 patterns of SLE disease activity across relapsing-remitting (RR) patients, chronically active (CA) patients, and long-quiescent patients
Chart showing 3 patterns of SLE disease activity across relapsing-remitting (RR) patients, chronically active (CA) patients, and long-quiescent patients

 

Drug-related side effects can also result in the accrual of organ damage.3

  • Chronic corticosteroid use is associated with cataracts, diabetes mellitus, atherosclerotic heart disease, osteoporosis and osteonecrosis, and fluid retention17
  • Opportunistic infections and certain malignancies can develop, most often in patients receiving chronic immunosuppressive therapy31
  • Long-term use of NSAIDs is associated with GI bleeding and kidney damage10
  • There is evidence for multiple beneficial effects of antimalarials in SLE; however, patients should be monitored for potential retinal toxicities.32

 

Prevention and Management

How can organ damage be prevented or managed?

Minimize disease activity and flares

  • Persistent disease activity can result in ongoing organ damage4
    • Since damage predicts subsequent damage and death, prevention of the damage accrual should be a major therapeutic goal in SLE33
  • Prevention of flares (especially severe flares) is a realistic target in SLE and should be a therapeutic goal33

EULAR treatment recommendations highlight the importance of controlling disease activity and flares while also limiting steroid dose.27

EULAR=European League Against Rheumatism

Chart showing the irreversible damage accrual that may occur in SLE patients with long-term persistent disease activity

Graphical representation of a hypothetical disease course of a patient with SLE.

Reduce glucocorticoid use as much as possible

  • Glucocorticoids are invaluable in the treatment of SLE; however, their chronic use has consistently shown to increase irreversible damage in patients with lupus, a major predictor of morbidity and mortality34
    • In general, the risk of organ damage increases at 7.5 mg/day35

Glucocorticoids ≥7.5 mg/day

1.7x greater risk of
developing any
new organ damage

  • Dosage should be reduced to the minimum needed to control disease, or eliminated if possible.33,34,36 

Monitor for subclinical activity

  • Regular monitoring should be undertaken to detect "silent variables"37 
    • At 3-4-month intervals for patients with mild or inactive disease.

More Information

more-information
more-information

DON'T LEAVE LUPUS TO SMOLDER

Can you do more to decrease disease activity and prevent flares with the lowest possible dose of glucocorticoids?3,27,33

References: 1. Steiman AJ, Urowitz MB, Ibanez D, et al. Prolonged clinical remission in patients with systemic lupus erythematosus. J Rheumatol. 2014;41(9):1808-1816. 2. Barr S, Zonana-Nacach A, Magder LS, Petri M. Patterns of disease activity in systemic lupus erythematosus. Arthritis Rheum. 1999;42(12):‍2682-2688. 3. Doria A, Gatto M, Zen M, et al. Optimizing outcome in SLE: treating-to-target and definition of treatment goals. Autoimmun Rev. 2014;13(7):770-777. 4. Lopez R, Davidson JE, Beeby MD, et al. Lupus disease activity and the risk of subsequent organ damage and mortality in a large lupus cohort. Rheumatology (Oxford). 2012;51(3):491-498. 5. Gladman D, Urowitz M, Rahman P, et al. Accrual of damage over time in patients with systemic lupus erythematosus. J Rheumatol. 2003;30(9):1955-1959. 6. Stoll T, Sutcliffe N, Mach J, et al. Analysis of the relationship between disease activity and damage in patients with systemic lupus erythematosus—a 5-yr prospective study. Rheumatology (Oxford). 2004;43(8):1039-1044. 7. Urowitz MB, Gladman DD, Ibañez D, et al. Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort. Arthritis Care Res (Hoboken). 2012;64(1):132-137. 8. Chambers SA, Allen E, Rahman A, Isenberg D. Damage and mortality in a group of British patients with systemic lupus erythematosus followed up for over 10 years. Rheumatology (Oxford). 2009;48(6):673-675. 9. Gladman D, Ginzler E, Goldsmith C, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum. 1996;39(3):363-369. 10. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis Rheum. 1999;42(9):1785-1796. 11. Bertsias G, Cervera R, Boumpas DT. Systemic lupus erythematosus: pathogenesis and clinical features. In: EULAR Textbook on Rheumatic Diseases. Geneva, Switzerland: European League Against Rheumatism. 2012:476-505. Available at: http://www.eular.org/myUploadData/files/sample%20chapter20_mod%2017.pdf. Accessed April 7, 2020. 12. Brey RL, Holliday SL, Saklad AR, et al. Neuropsychiatric syndromes in lupus: prevalence using standardized definitions. Neurology. 2002;58(8):1214-1220. 13. Sivaraj RR, Durrani OM, Denniston AK, Murray PI, Gordon C. Ocular manifestations of systemic lupus erythematosus. Rheumatology (Oxford). 2007;46(12):1757-1762. 14. Schoenfield S, Kasturi S, Costenbader KH. The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: a systematic review. Semin Arthritis Rheum. 2013;43(1):77-95. 15. Magder LS, Petri M. Incidence of and risk factors for adverse cardiovascular patients with systemic lupus erythematosus. Am J Epidemiol. 2012;176(8):708-719. 16. Mak A, Cheung MWL, Chiew HJ, Chun-man Ho R. Global trend of survival and damage of systemic lupus erythematosus: meta-analysis and meta-regression of observational studies from the 1950s to 2000s. Semin Arthritis Rheum. 2012;41(6):830-839. 17. Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012;64(6):797-808. 18. Saxena et al. Lupus nephritis: current update. Arthritis Research & Therapy 2011, 13:240. http://arthritisresearch. com/content/13/5/240. 19. Ramsey-Goldman R, Dunn JE, Huang CF, et al. Frequency of fractures in women with systemic lupus erythematosus: comparison with United States population data. Arthritis Rheum. 1999;42(5):882-890. 20. Zonana-Nacach A, Barr SG, Magder LS, Petri M. Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum. 2000;43(8):1801-1808. 21. Rahman P, Gladman DD, Urowitz MB, et al. Early damage as measured by the SLICC/ACR Damage Index is a predictor of mortality in systemic lupus erythematosus. Lupus 2001;10:93-96. 22. Nossent J, Cikes N, Kiss E, et al. Current causes of death in systemic lupus erythematosus in Europe, 2000–2004: relation to disease activity and damage accrual. Lupus 2007;16:309-317. 23. Davidson JE, Fu Q, Rao S, et al. Quantifying the burden of steroid-related damage in SLE in the Hopkins Lupus Cohort. Lupus Sci Med. 2018;5(1):e000237. doi:10.1136/lupus-2017-000237. 24. Houssiau FA, N’Zeusseu Toukap A, Depresseux G, et al. Magnetic resonance imaging detected avascular osteonecrosis in systemic lupus erythematosus: lack of correlation with antiphospholipid antibodies. Br J Rheumatol. 1998;37(4):448-453. 25. Ahmad Y, Shelmerdine J, Bodill H, et al. Subclinical atherosclerosis in systemic lupus erythematosus (SLE): the relative contribution of classic risk factors and the lupus phenotype. Rheumatology (Oxford). 2007;46:983-988. 26. El-Magadmi M, Bodill H, Ahmad Y, et al. Systemic lupus erythematosus: an independent risk factor for endothelial dysfunction in women. Circulation. 2004;110:399-404. 27. Fanouriakis A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736-745. 28. Doria A, et al. Value and goals of treat-to-target in systemic lupus erythematosus: knowledge and foresight. Lupus. 2015;24(4-5):507-515. 29. van Vollenhoven RF, et al. A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann Rheum Dis. 2017;76(3):554-561. 30. Györi N, Giannakou I, Chatzidionysiou K, et al. Disease activity patterns over time in patients with SLE: analysis of the Hopkins Lupus Cohort. Lupus Science & Medicine. 2017;4:e000192. doi:10.1136/lupus-016-00019231. 31. Bartels M, Diamond H. Systemic lupus erythematosus (SLE) treatment & management. Medscape. 2017. Available at: https://emedicine.medscape.com/article/332244-treatment#showall. Accessed August 7, 2020. 32. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, et al. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010;69:20-28. 33. van Vollenhoven RF, Mosca M, Bertsias G, et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis. 2014;73(6):958-967. 34. Ruiz-Irastorza G, Danza A, Khamashta M. Glucocorticoid use and abuse in SLE. Rheumatology (Oxford). 2012;51(7):1145-1153. 35. Al Sawah S, Zhang X, Zhu B, et al. Effect of corticosteroid use by dose on the risk of developing organ damage over time in systemic lupus erythematosus—the Hopkins Lupus Cohort. Lupus Science & Medicine. 2015;2:e000066. doi:10.1136/lupus-2014-000066. 36. Thamer M, Hernán MA, Zhang Y, Cotter D, Petri M. Prednisone, Lupus Activity, and Permanent Organ Damage. J Rheumatol. 2009;36(3):560-564.  37. Gladman DD, Ibañez D, Ruiz I, et al. Recommendations for frequency of visits to monitor systemic lupus erythematosus in asymptomatic patients: data from an observational cohort study. J Rheumatol. 2013;40(5):630-633.