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Systemic Lupus Erythematosus: A review of the disease and treatment options
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Systemic Lupus Erythematosus: A review of the disease and treatment options
Author Page
Samuel L. Gurevitz, PharmD, CGP
Assistant Professor
Physician Assistant Program
College of Pharmacy and Health Sciences
Butler University
Address:
4600 Sunset Avenue
Indianapolis, IN 46208
Fax: (317) 940-6172
Tel: (317) 940-6542
Email: [email protected]
Jennifer A. Snyder, PA-C, DFAAPA
Associate Professor
Physician Assistant Program
College of Pharmacy and Health Sciences
Butler University
Eric K. Wessel, PA-S
Physician Assistant Program
College of Pharmacy and Health Sciences
3
Butler University
Julianne Frey, MS, RCEP, PA-S
Physician Assistant Program
College of Pharmacy and Health Sciences
Butler University
Bridgett A. Williamson, PA-S
Physician Assistant Program
College of Pharmacy and Health Sciences
Butler University
Disclosures: No funding was received for this study or the development of the manuscript.
The authors report no potential conflicts of interest.
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Systemic Lupus Erythematosus: A review of the disease and treatment options
Abstract
Objective: To provide an up-to-date review of the etiology, epidemiology, clinical features,
diagnostic findings, and treatment options for systemic lupus erythematosus.
Data Sources: A PubMed search of English language using a combination of words: elderly,
systemic lupus erythematosus*, late onset systemic lupus erythematosus*, etiology, screening,
diagnosis, or treatment to identify original studies, guidelines, and reviews on systemic lupus
erythematosus, SLE, late onset systemic lupus erythematosus published between 2000 - present.
Study Selection and Data Extraction: Overall original studies, clinical reviews, references, and
guidelines were obtained and evaluated on their clinical relevance.
Data Synthesis: The literature included guidelines and considerations for the etiology,
diagnosis, screening, and management of systemic lupus erythematosus*, and late onset systemic
lupus erythematosus.
Conclusion: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder whereby the
exact etiology is unknown. SLE predominately affects younger women; however, it is reported
to occur in up to 20% of patients 50 years or older. In patients with SLE, nearly every system in
the body is affected with varying degrees of severity ranging from subclinical to fatal. The
hallmark feature of SLE is the production of auto-antibodies directed primarily against nuclear
antigens, but also against cytoplasmic components of cells. The diagnosis of SLE is based on
criteria set by the American College of Rheumatology. Management is individualized and
depends on presenting symptoms and reducing the likelihood of permanent damage to organs
and tissues.
5
Key Words: Elderly, Geriatrics, Late onset Systemic Lupus Erythematosus, Systemic Lupus
Erythematosus, Treatment.
Abbreviations
ACEI = Angiotensin Converting Enzyme Inhibitor, ACR = American College of Rheumatology,
ALT= Alanine Transaminase, ANA = Antinuclear antibodies, Anti-DNA = Anti-
deoxyribonucleic acid, Anti-dsDNA = Anti-double stranded deoxyribonucleic acid, Anti-La/
SSB = Anti-La sjögren syndrome type B, Anti-RNP antibodies = Anti-ribonucleoprotein, Anti-
Ro/SSA = Anti-Ro/Sjögren syndrome type A, Anti-Sm antibodies = Anti-Smith antibodies, AST
= Aspartate Transaminase, CBC = Complete Blood Count, CH50=50% hemolytic complement,
COX-1= Cyclooxygenase-1, COX-2 = Cyclooxygenase-2, EULAR = European League Against
Rheumatism, GI = Gastrointestinal, IV = Intravenous, MTX = Methotrexate, NSAIDs = Non-
Steroidal Anti-inflammatory Drugs, RF= Rheumatoid Factor, SLE = Systemic Lupus
Erythematosus, SLICC = Systemic Lupus International Collaborating Clinic
6
Systemic Lupus Erythematosus: A review of the disease and treatment options
Introduction
Systemic lupus erythematosus (SLE) or lupus is a chronic, progressive, autoimmune disorder
that affects multiple organ systems, with a broad range of clinical and laboratory
manifestations.1-3
The term lupus means wolf in Latin and is named as such due to facial lesions
found in the disease process that are reminiscent of a wolf's bite.4 This review will provide up-to-
date information regarding the etiology, environmental and genetic influences, clinical features,
diagnostic findings, and treatment options for SLE.
Etiology
While the etiology is unknown, there are several factors associated with the development of SLE
(Table 1).1, 2, 5-8
Unexplainably, SLE patients do not clear apoptotic cells appropriately.2, 9
These
cells release auto-antigens that may help drive the defective immune process.9 The complex
interaction between environment and immunologic factors in genetically susceptible individuals
leads to continued deregulation of the innate and adaptive immune pathways with evidence of
auto-antibody secreting plasma cells and auto-antigen, hyper-reactive, memory B-cells.1, 7, 10-13
Auto-antibodies often form long before clinical manifestations result in chronic, widespread
tissue and organ damage.2, 6, 14, 15
Patients with SLE experience acute exacerbations and
remissions resulting in protean clinical and serologic manifestations.16,17
SLE may develop as a result of exposure to medications. It is estimated that 10% of patients
diagnosed with SLE may have drug induced lupus, and over 80 drugs (Table 2) have been
implicated in the disease development.7, 16, 18-21
Epidemiology
7
SLE is most often initially diagnosed in young women of reproductive age but does affect those
50 years of age or older.17,18, 22
Early diagnosis and treatment are important. The average time to
reach a diagnosis is 2 years.7 However, in the late onset population, the average time to establish
the diagnosis is often as long as 5 years.23
Improvements in diagnostic techniques as well as
more intensive treatment methods have enhanced survival rates dramatically in recent years.24
The survival rate has improved from a 4 year survival rate of 50% in the 1950’s to the present
day 20 year survival rate of approximately 80%.25-27
The prevalence of SLE in the United States population is 14.6-68 /100,000.7 About 10 - 20% of
patients will be diagnosed with late onset SLE (first diagnosed age 50 years or older) and will
often have more mild manifestations of the disease that may result in a delayed diagnosis.18, 23, 28
The female predominance may not be as significant in the late-onset populations.23
Systemic
lupus erythematosus is 2 to 4 times more common among African Americans and other non-
white populations.17, 22
Clinical Manifestations
Lupus often follows a characteristic pattern of relapse and remissions and typically develops
over an extended period of time.3, 5, 29
It takes careful observation to make the diagnosis. The
clinical presentation of SLE may be comprised of both systemic symptoms as well as specific
signs of organ-system dysfunction.3, 29
The incidence of clinical findings of early and late-onset
SLE may vary (Table 3).18, 28, 30
Common presenting findings of patients with SLE are fatigue, malaise, fever, anorexia, and
weight loss. They may present with an signs of systemic infection.5, 29
Patients may also present
with a number of dermatologic findings, including discoid and malar lesions, photosensitivity,
8
alopecia, periungual erythema, nailfold infarcts, and splinter hemorrhages.3,5,29
Thirty-five
percent of patients with
SLE will have some form of glomerulonephritis or nephrotic syndrome symptoms and signs on
clinical examination, predicting a worse outcome.31
A renal biopsy is often suggested in patients
with renal complications to fully understand the extent of its severity.7
Myalgias and muscle weakness are common. Up to 90% of patients with SLE present with
symmetrical joint pain, that is typically a migratory polyarthropathy, distinguished from
rheumatoid arthritis by its lack of joint destruction.3,5,29
The pathophysiology behind
osteoporosis and the occurrence of fractures in SLE is multifactorial. It involves both disease
and non-disease related factors, including complications of the treatment itself.32
The most common cardiac findings are pericarditis and pericardial effusion.3, 5, 29, 33
Valvular
abnormalities are frequent in patients with SLE, especially the mitral valve. Screening with
transthoracic echocardiography may be indicated in patients with SLE, especially for those with
identified risk factors such as corticosteroid use.33
SLE is also associated with an increased risk
of coronary disease due to atherosclerosis.34
The mechanism for neuronal damage is consistent with the autoimmune nature of SLE. Anti-
neuronal antibodies attack neurons causing damage and neurologic symptoms such as stroke,
seizures and peripheral neuropathy.5 Cognitive dysfunction is a common neuropsychiatric
manifestation of SLE as it is found in up to 80% of patients to a variable extent.35
Higher rates of
anxiety and depression are found in patients with SLE.36
Depression occurs more commonly
with changes in appearance and physical limitations due to complications or medication side
effects.36
Health care providers should be alert for these manifestations.
Diagnosis
9
The clinical heterogeneity of SLE resulted in the development of classification criteria in 1982,
and revised in 1997, by the American College of Rheumatology (ACR).37
The revision resulted
in the establishment of 11 equally weighted criteria (Table 4), with 4 needing to be present for
the formal diagnosis of SLE.12, 38, 39
A subspecialist in rheumatology or nephrology may
diagnose a patient with only 3 criteria, if at least one is serologic and one is clinical.7 A patient
can be described as having “latent” or “incomplete” lupus with as few as one criterion and
additional common symptoms, such as fatigue, fever, alopecia or Raynaud’s phenomenon.7, 40-42
Upon initial suspicion of SLE, the most important laboratory screening measure is the blood test
for antinuclear antibodies (ANA).7, 39
However, ANA is found in conditions other than
SLE; therefore, more specific tests are needed to help confirm the diagnosis, such as anti-dsDNA
(anti-double stranded DNA), anti-Sm (anti-Smith) and antiphospholipid antibodies.38, 43
The anti-
dsDNA and anti-Sm serological tests are considered definitive for lupus.7 Recent support has
been given to monitoring specific B-cell subsets as biomarkers of disease activity.13
In 2009, the Systemic Lupus International Collaborating Clinic (SLICC) revised the ACR’s
classification criteria for SLE. The proposed classification “had better sensitivity than the ACR
(94% vs. 86%), and roughly equal specificity (92% vs. 93%), and resulted in significantly fewer
misclassifications (p = .0082).”44
If validated, the SLICC criteria may become the standard in the
diagnosis of this disease.
Treatment
There is no cure for SLE so early diagnosis and treatment to control dysfunction and
complications are important. Management is individualized, depends on symptoms, and is
directed at reducing the likelihood of permanent damage to organs and tissues. Treatment
strategies in late onset SLE do not differ widely from those seen in younger patients.18
The
10
disease course in late onset SLE is usually mild requiring less use of cytotoxic/
immunosuppressive drugs and high dose corticosteroids for disease control.18,30
Guidelines were
developed in 1999 by the ACR and in 2008 by the European League Against Rheumatism
(EULAR) Task Force (Table 5).45,46
A major challenge in treating SLE is to inhibit clinically
active disease without causing long term consequences.18
Clinicians should be aware of drug
interactions and adverse reactions are possible. This is especially true in the older patient as they
are more likely to be affected by multiple disease states and taking several medications. In
addition, the pharmacokinetics and pharmacodynamics of drugs are often altered in the older
patient. The safety profiles and monitoring recommendations for medications used in SLE are
provided (Table 6).15, 41, 45, 47- 51
Non-pharmacologic Management
Both the ACR and EULAR recommend non-pharmacologic treatment in the management of
SLE. Patients should be counseled on lifestyle modifications, such as smoking cessation, weight
control, and increasing exercise to limit co-morbidities of atherosclerosis, hypertension, and
diabetes.45, 46
Patients should minimize sun exposure by wearing appropriate clothing, applying
topical sunscreens, and avoiding tanning beds. Screening for bone loss should be instituted and
treatment commenced as needed.32
Patient education and psychosocial support are an important
aspect of management. Information about SLE and specific problems of living with the disease
should be combined with medical therapy to help alleviate depression and anxiety.52
Unfortunately, challenges remain in increasing a patient’s quality of life.2, 36
Clinicians should be
alert to changes in psychosocial functioning and treated and/or referred for appropriate
counseling as indicated.
Pharmacologic Management
11
Nonsteroidal Anti-inflammatory Drugs
Nonsteroidal Anti-inflammatory drugs (NSAIDs) are commonly used to relieve arthralgia,
inflammation, serositis, and fever in patients with SLE. They can be used with or without low
doses of steroids or antimalarial agents.41, 46, 47
NSAIDs inhibit the production of
cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2).53
The inhibition of COX-1
decreases the production of prostaglandins that protect the lining of the gastrointestinal tract. The
inhibition of COX-2 mediates the production of prostaglandins which moderates inflammation
and pain. Therefore, NSAIDs that are selective COX-2 inhibitors, such as celecoxib, have
reduced the occurrence of adverse gastrointestinal bleeding.53
In a study of 50 SLE patients with
predominance of musculoskeletal complaints and less severe organ involvement, celecoxib was
found to be effective and safe.54
Regardless of their cyclooxygenase selectivity, NSAIDs may cause renal impairment, fluid
retention, and interstitial nephritis.47
Lupus nephritis is a risk factor for NSAID induced acute
renal failure55
; therefore, NSAIDs should be used for the shortest effective period of time
especially in patients with renal involvement, hypertension, or heart disease.46, 56
Hydroxychloroquine
Hydroxychloroquine, an antimalarial drug, is frequently used as a first line treatment option for
patients with mild SLE. It is effective in preventing the occurrence of new mild SLE
manifestations.15
A systematic review found antimalarials reduced lupus activity by more than
50% in pregnant and non-pregnant patients and a greater than 50% improvement in mortality.51
Hydroxychloroquine also has been shown to have a beneficial effect on dyslipidemia.57
Hydroxychloroquine inhibits Toll-like receptors that cause a down regulation of interferon-α and
decreases the antigen processing for auto-antigen presentation.58
The safety profile for
12
hydroxychloroquine is good. Retinal toxicity and macular damage can occur due to accumulation
of the drug in ocular tissue;41, 47
therefore, the ACR recommends patients undergo a baseline eye
examination before treatment and every 6 to 12 months thereafter.45
Hydroxychloroquine may be
used during pregnancy.46
Glucocorticoids
Systemic glucocorticoids are usually unnecessary in mild SLE, but low doses of prednisone 10
mg/day or less are used if the patient has cutaneous and musculoskeletal symptoms not
responding to other therapies.45
Systemic glucocorticoids are used alone or in combination with
other immunosuppressive agents for patients with significant organ involvement or refractory
symptoms.41, 47
Due to the long term adverse effects of glucocorticoid treatment, the shortest effective duration
should be used.41, 47
Patients requiring long term glucocorticoid therapy should be monitored for
the complications of hypertension, diabetes, myopathy, psychosis, and cataracts.
Methotrexate
Methotrexate (MTX), an antifolate, may be preferred in the management of resistant arthritis and
cutaneous SLE.15
Methotrexate provides a significant advantage in patients with moderately
active lupus by allowing lower steroid doses, and slightly decreasing lupus disease activity.59
In a
recent prospective open label study, low dose MTX appears to be as effective as the antimalarial
chloroquine, in patients with articular and cutaneous manifestations of SLE.60
Cyclophosphamide
Cyclophosphamide, an alkylating agent, is the standard of care for lupus nephritis and is usually
used in conjunction with corticosteroids.41, 61
It is also used with corticosteroids in patients with
severe neuropsychiatric involvement.15, 62
13
Mycophenolate
Mycophenolate exerts its immunosuppressive effect by inhibiting B- and T-cell proliferation.47
In a systematic review and meta-analysis, mycophenolate in combination with corticosteroids
was shown to be as effective as cyclophosphamide in the treatment of lupus nephritis and had
less risk of leukopenia.63
Maintenance therapy, either with azathioprine or mycophenolate, is
required for periods of remission and prevention of relapse after the initial control of lupus
nephritis. In a 36-month, randomized, double-blind, double-dummy, trial comparing oral
mycophenolate mofetil and oral azathioprine, mycophenolate mofetil was superior to
azathioprine in maintaining a renal response to treatment and in preventing relapse in patients
with lupus nephritis who had a response to induction.64
Azathioprine
Azathioprine inhibits DNA synthesis and prevents lymphocyte proliferation in the immune
system.15, 41, 47
It is used as a steroid-sparing agent in moderate to severe lupus and in the
maintenance phase of lupus nephritis.15, 47
Belimumab
Belimumab, a human monoclonal antibody, blocks the biologic activity of B lymphocyte
stimulator (BLyS/BAFF). This decreases the antibody levels in the body which may help reduce
the autoimmune activity of SLE.41
Belimumab was approved by the FDA in 2011 for use in
adults.7 In two phase III trials, BLISS-52 and BLISS-76, belimumab showed noteworthy
improvements in patients with SLE after 52 weeks, but the advances were not statistically
maintained at week 76.15
Belimumab demonstrated a steroid-sparing effect in these trials as well
as a decreased rate of disease flares.65
To be included in the trial, patients had to meet the ACR
criteria for SLE, and they had to have active disease. Patients also had to demonstrate a positive
14
ANA and be on a stable regimen of prednisone, NSAIDs, antimalarials, or immunosuppressive
drugs for 30 days prior to the start of the trial. Exclusion criteria included severe active lupus
nephritis, CNS lupus, and pregnancy. Exclusion criteria also included prior therapy within the
last 3 months of IV cyclophosphamide, IV immunoglobulin, IV prednisone, or drugs that target
B-lymphocytes.65
The safety profile for belimumab is good. Safety data from the BLISS trials demonstrated an
adverse effect profile and infection rate similar to that of placebo in patients with a mean age of
40 +/- 12 years.7, 65, 66
There is no efficacy data in older patients. Patients on belimumab should
not receive live vaccines 30 days before, or during treatment due to a decreased ability to mount
an immune response.49
Rituximab
Rituximab is a humanized chimeric mouse/human monoclonal antibody that targets the B-cell-
specific antigen CD20. It leads to depletion of auto-reactive B-cells in the circulation of patients
with SLE.15, 47
Although not FDA approved, it is often used off label for severe refractory SLE.
Unfortunately, placebo controlled trials in SLE failed to improve clinical outcomes.15, 67, 68
Pharmacist’s Role
Review the patient’s medications for drug induced lupus or for drug interactions (Table 2
7, 16,18-21 and Table 7)
48- 50, 69, 70
Monitor for adverse reactions and therapeutic response
Ensure the patient is current on inactivated influenza and pneumococcal vaccines45
Monitor vitamin D levels and bone mineral density 71, 72
15
o The majority of patients with SLE have insufficient levels of vitamin D. This
may be due in part to less sun exposure, and medications used for the treatment of
SLE.
o Patients on long-term glucocorticoids should receive sufficient daily calcium and
vitamin D and/or a bisphosphonate to minimize the degree of bone loss.73
Review patient’s history to determine increased risk of NSAID-induced ulcers
o The addition of a proton pump inhibitor or histamine-2 receptor blocker may be
indicated
Ensure that the patient is receiving daily supplemental folic acid to reduce side effects
related to the gastrointestinal system74
Confirm and make recommendations to ensure medications are administered correctly
with regard to meals and in relation to other medications.
Conclusion
SLE is a chronic autoimmune disorder whereby the exact etiology of which is unknown. SLE
predominately affects younger women; however, it is reported to occur in up to 20% of patients
50 years or older. In patients with SLE, nearly every system in the body is affected with varying
degrees of severity ranging from subclinical to fatal. The hallmark feature of SLE is the
production of hyper-reactive, memory B-cells. Auto-antibodies are directed primarily against
nuclear antigens, but also against cytoplasmic components of cells. The diagnosis of SLE is
based on criteria set by the ACR. The management of SLE is largely a suppression of the
immune response, but should be individualized and dependent on presenting symptoms and
disease progression.
16
17
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Table 1. Factors Associated with the Development or Exacerbation of SLE
Sun exposure Genetic influence
Smoking Female hormones
Virus exposure (e.g. Epstein–Barr virus) Immunizations
Stress Occupational exposure (silica, mercury, etc.)
Diet
Sources: References 1, 2, 5-8.
Abbreviations: SLE = Systemic Lupus Erythematosus
Table 2. Medications that May Lead to the Development of SLE
Drug Classification Very Low Risk Low to Moderate Risk High Risk
Antiarrhythmic Propafenone Quinidine Procainamide
Antibiotic Nitrofurantoin Isoniazid, Minocycline
Antiepileptic Phenytoin, Primidone
Ethosuximide
Carbamazepine
Antihypertensive Enalapril, Clonidine,
Labetalol, Atenolol,
Chlorthalidone,
Hydrochlorthiazide
Captopril, Methyldopa Hydralazine
Anti-inflammatory Sulfasalazine
Antipsychotic Perphenazine, Lithium Chlorpromazine
Antithyroid Propylthiouracil
Miscellaneous Lovastatin, Levodopa
Timolol ophthalmic
drops
Biologic
Infliximab, Etanercept,
Adalimumab, Interferons
Sources: References 7, 16, 18-21.
Abbreviations: SLE = Systemic Lupus Erythematosus
26
Sources: References 18, 28, 30.
Abbreviations: ANA = Antinuclear antibodies, Anti-La /SSB = Anti-La /Sjogren syndrome type
B, Anti- RNP antibodies = Anti-ribonucleoprotein, Anti-Ro/SSA = Anti/Ro Sjogren syndrome
type A, Sm antibodies = Anti-Smith antibodies, CH50=50% hemolytic complement, RF=
Rheumatoid Factor, SLE = Systemic Lupus Erythematosus
Table 3. Clinical findings of early and late-onset SLE
Early Onset SLE (age < 50 y) Late Onset SLE (age ≥ 50 y)
Physical Findings
Malar rash Pulmonary manifestations
Photosensitivity Serositis
Arthritis Pericarditis
Alopecia Pleurisy
Purpura / Cutaneous vasculitis Sjögren’s syndrome
Raynaud’s phenomenon
Neuropsychiatric manifestations
Fever and lymphadenopathy
Nephritis / Nephrotic syndrome
Hematologic derangements
Serological Findings
Increased frequency of anti-RNP antibodies
and anti-Sm antibodies;
low CH50
Increased frequency of RF and ANA
positivity;
Increased frequency of the anti-nuclear
autoantibodies, anti-Ro/SSA and anti-La/SSB
positivity
27
Table 4 American College of Rheumatology Criteria for Diagnosis of SLE*
Malar rash – butterfly shaped rash over the nose and cheeks; can be flat or raised
Discoid rash – a rash that appears as red, raised, disk-shaped patches
Photosensitivity – unusual reaction to sun or light that causes a rash to appear
Oral ulcers – sores, usually painless, appearing in the mouth or nasopharynx
Non-erosive arthritis – joint pain and swelling of two or more joints
Serositis – Pleuritis (inflammation around the lungs) or Pericarditis (inflammation around the
heart)
Renal disorder – persistent protein (>0.5 gram/day) or any cellular casts in the urine
Neurological disorder – seizures or psychosis in the absence of offending drugs or known
metabolic conditions
Hematologic disorder – hemolytic anemia, leukopenia, lymphopenia, or thrombocytopenia
Immunologic disorder – anti-DNA, Anti-Smith antibodies, or positive antiphospholipid
antibodies on testing
Positive antinuclear antibody at any point in time in the absence of medications/drugs
*Four of 11 criteria are needed for the formal diagnosis of SLE
Sources: References 12, 38, 39.
Abbreviations: Anti-DNA = Anti-deoxyribonucleic acid, SLE = Systemic Lupus Erythematosus
28
Table 5 Treatment Recommendations Overview of SLE
American College of Rheumatology
Committee
European League Against Rheumatism
Task Force
Mild SLE
Nonsteroidal anti-inflammatory Drugs
Antimalarials (Hydroxychloroquine)
Oral glucocorticoids (low dose)
SLE without major manifestations
Antimalarials
Glucocorticoids
Nonsteroidal anti-inflammatory Drugs
(used judiciously)
Serious, Life Threatening, or Organ
Threatening SLE
High dose glucocorticoids
Immunosuppresive/cytotoxic agents
(azathioprine, cyclophosphamide, and
methotrexate)
Non-responsive patients or unable to
reduce steroid dose
Immunosuppressive agents
(azathioprine, mycophenolate, and
methotrexate)
Lupus Nephritis
Glucocorticoid in combination with
immunosuppressive agents
(cyclophosphamide and mycophenolate)
Sources: References 45, 46.
Abbreviations: SLE = Systemic Lupus Erythematosus
29
Table 6 Summary of adverse effects and recommended monitoring for medications used in the
treatment of SLE
Medication Adverse effects Monitor
NSAIDs Gastrointestinal bleeding,
hepatic toxicity, renal
toxicity, hypertension
CBC, creatinine,
AST, ALT, blood
pressure, monitor for
bleeding
Glucocorticoids Hypertension,
hyperglycemia,
hyperlipidemia,
hypokalemia, osteoporosis,
cataracts, fluid retention,
glaucoma, infections
Blood pressure,
cholesterol, glucose,
potassium, bone
mineral density
Hydroxychloroquine Retinal and macular
damage
Fundoscopic and
visual fields, visual
changes
Azathioprine GI side effects, infections,
Myelosuppression,
hepatotoxicity,
lymphoproliferative
disorders
CBC, differential and
platelet count, AST
or ALT
Cyclophosphamide Myelosuppression,
malignancy, hemorrhagic
cystitis,
immunosuppression,
severe infections, nausea,
vomiting, reversible hair
loss
CBC, differential and
platelet count,
urinalysis
Methotrexate Myelosuppression, hepatic
toxicity, pulmonary
infiltrates or fibrosis,
stomatitis
CBC, Hepatitis B and
C serology in high
risk patients, AST,
albumin, bilirubin,
creatinine, chest
radiograph
Mycophenolate Anemia, leukopenia,
thrombocytopenia,
infections, diarrhea,
pancreatitis
CBC, differential and
platelet count
Belimumab Infections, bradycardia,
hypotension, depression,
leukopenia
CBC with differential
Sources: References 15, 41, 45, 47-51.
Abbreviations: ALT = Alanine Transaminase, AST = Aspartate Transaminase, CBC =
Complete Blood Count, GI = Gastrointestinal, NSAIDs – Nonsteroidal Anti-inflammatory
Drugs, SLE = Systemic Lupus Erythematosus
30
Table 7. Summary of drug interactions used in the treatment of SLE
Medication Drug Interaction
NSAIDs Lithium, Diuretics, Beta blockers, ACEI,
Angiotensin Receptor Blockers
Glucocorticoids No significant drug interactions
Hydroxychloroquine No significant drug interactions
Azathioprine Allopurinol, Febuxostat, Mesalamine, ACEI,
Trimethoprim-sulfamethoxazole
Cyclophosphamide No significant drug interactions
Methotrexate Trimethoprim-sulfamethoxazole, NSAIDs
Mycophenolate Cholestyramine, Antacids, and Phosphate
Binders should not be administered at the same
time
Belimumab Drug interactions have not been formally
studied
Sources: References 48-50, 69, 70.
Abbreviations: ACEI =Angiotensin Converting Enzyme Inhibitor, NSAIDs = Non-Steroidal
Anti-inflammatory Drugs, SLE = Systemic Lupus Erythematosus
