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Overview of the management and prognosis of systemic lupus erythematosus in adults

Author: Daniel J Wallace, MD

Section Editors: David S Pisetsky, MD, PhD, Peter H Schur, MD
Deputy Editor: Monica Ramirez Curtis, MD, MPH

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2018. | This topic last updated: Jan 24, 2018.

INTRODUCTION — Systemic lupus erythematosus (SLE) is a chronic, occasionally life-threatening, multisystem

disorder. Patients may present with a wide array of symptoms, signs, and laboratory findings and have a variable
prognosis that depends upon the disease severity and type of organ involvement. Establishing the diagnosis of
SLE may be challenging, and the approach to the diagnosis and differential diagnosis of SLE is presented
separately. (See "Diagnosis and differential diagnosis of systemic lupus erythematosus in adults".)

Due to the variable disease course, effective management of SLE requires regular clinical and laboratory
monitoring to assess disease activity; guide therapy to alleviate symptoms and prevent and treat relapses;
assess side effects related to drug therapy; encourage adherence with medications; and coordinate care with the
patient's other providers.

This topic will review the general issues related to the management of patients with SLE. The treatment of
specific organ involvement is discussed in separate topic reviews. (See appropriate topic reviews.)

OVERVIEW OF TREATMENT — The goals of therapy for patients with systemic lupus erythematosus (SLE) are to
ensure long-term survival, achieve the lowest possible disease activity, prevent organ damage, minimize drug
toxicity, improve quality of life, and educate patients about their role in disease management [1,2].

Treatment of SLE is individualized based upon patient preferences [3], clinical manifestations, disease activity
and severity, and comorbidities. Patients require monitoring at regular intervals by a rheumatologist to optimize
both nonpharmacologic and pharmacologic therapies, and achieve treatment goals. Patients often have
multiorgan system involvement and may require multidisciplinary care.

Our management strategy for SLE is generally consistent with guidelines developed by professional
organizations, including the European League Against Rheumatism [2] and the British Society for Rheumatology
[4,5]. Specific guidelines for the management of lupus nephritis are discussed separately in the relevant topics.

ASSESSMENT OF DISEASE ACTIVITY AND SEVERITY — Determining the appropriate therapeutic regimen

requires an accurate assessment of both disease activity and severity and a clear understanding of the patient's
response to previous and ongoing therapeutic interventions [6-10]. It is also important to assess for the wide
range of disease manifestations. Disease activity refers to the manifestations of the underlying inflammatory
process at a point in time in terms of magnitude and intensity. The disease severity refers to the type and level of
organ dysfunction and its consequences, often described as mild, moderate, and severe. The degree of
irreversible organ dysfunction has been referred to as damage [11]. (See "Overview of the clinical manifestations
of systemic lupus erythematosus in adults", section on 'Clinical manifestations'.)
When evaluating the patient and assessing disease activity, there are generally three patterns of disease to
consider:

● Intermittent disease flares (or relapsing and remitting disease with periods of disease quiescence in
between flares)

● Chronically active disease in terms of patterns of organ involvement

● Quiescent disease

In clinical practice, disease activity and severity are assessed using a combination of clinical history, physical
examination, laboratory and serologic studies as well as organ-specific tests [6-10,12-14].

Clinical evaluation — Given the heterogeneity of disease presentation and clinical course among patients with
SLE, an assessment of disease activity should be performed at each clinic visit. Furthermore, features
attributable to active SLE must be distinguished from chronic damage, drug toxicities, and other conditions such
as infection. As an example, marked proteinuria and a reduced glomerular filtration rate may result from either
active inflammation or scarred glomeruli. Differentiating between these two possibilities has significant
therapeutic implications, since immunosuppressive therapy should not be escalated in the latter setting.
Similarly, joint pain may be related to active synovitis for which glucocorticoids may be indicated, or it may be
due to avascular necrosis which is a side effect of treatment with glucocorticoids.

As part of the clinical and laboratory evaluation, all organ systems must be reviewed since almost any organ can
be involved in SLE. If specific symptoms are present, patients should also be asked about any potential triggers
such as sun exposure, infection, or discontinuation of therapy.

The physical examination should be extensive (complete) and include examination of the skin (including scalp
and mucous membranes) and lymph nodes, as well as respiratory, cardiovascular, abdominal, musculoskeletal,
and neurologic systems. A more detailed discussion of all of the clinical manifestations associated with SLE is
presented separately. (See "Overview of the clinical manifestations of systemic lupus erythematosus in adults".)

A variety of validated indices have been developed primarily for research purposes to measure disease activity or
damage; however, their incorporation into clinical practice is often limited by the time needed to complete them.
(See 'Research tools' below.)

Laboratory evaluation — In addition to obtaining a detailed clinical history and performing a thorough physical
exam, laboratory tests may be used to help assess disease activity and monitor organ-specific complications
(such as renal or hematological) [15]. Since there is no single marker of disease activity, clinicians must interpret
the laboratory results in the appropriate clinical context.

We typically check the following laboratory tests when monitoring disease activity in all patients with SLE:

● Complete blood count (CBC) – Leukopenia is common and may reflect active disease. Anemia and
thrombocytopenia may also be observed with active disease. Cytopenias may also result from drug
toxicities. (See "Hematologic manifestations of systemic lupus erythematosus".)

● Acute phase reactants (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]) – Increases in
acute phase reactants are commonly observed in patients with SLE, and therefore may not be as reliable for
detecting disease activity as is the case with other inflammatory diseases [16-19]. Nonetheless, an elevated
ESR can be associated with increased disease activity and accrued damage [19,20]. Similarly, elevations in
CRP can also be associated with disease activity. There are conflicting data on the diagnostic value of a
markedly elevated CRP in distinguishing active lupus from infection; however, an elevated CRP should raise
the suspicion for infection in a patient with SLE [21,22].
 ● Urinalysis with examination of urinary sediment – Proteinuria or cellular casts and hematuria may be due to
lupus involving the kidney. (See "Diagnosis and classification of renal disease in systemic lupus
erythematosus".)

● Spot urine protein-to-creatinine ratio – Quantification of proteinuria helps assess the severity of glomerular
disease [23].

● Serum creatinine and estimated glomerular filtration rate (eGFR) – Elevations in serum creatinine may
reflect lupus nephritis.

● Anti-double-stranded deoxyribonucleic acid (dsDNA) – Titers of anti-dsDNA antibodies often fluctuate with
disease activity, particularly in patients with active glomerulonephritis. (See "Antibodies to double-stranded
(ds)DNA, Sm, and U1 RNP".)

● Complement levels (C3 and C4) – Low C3 and C4 and/or elevated C3 and C4 activation products often
indicate active lupus, particularly lupus nephritis. (See "Diagnosis and classification of renal disease in
systemic lupus erythematosus".)

With the exception of anti-dsDNA antibodies, we do not repeatedly check antinuclear antibodies (ANAs) or other
specific antibodies (eg anti-Smith [Sm], Ro/SSA, La/SSB and U1 ribonucleoprotein [RNP]). It has been noted that
some SLE patients have ANAs that decrease in titer over time; however, the clinical utility of this observation
remains unclear.

Additional studies — Monitoring for specific SLE-related organ involvement typically requires additional studies.
Depending on the organ system in question, appropriate investigations such as electrocardiogram, lung function
tests, x-rays, computed tomography (CT) scans, and renal or other organ (eg, skin) biopsies may be required to
further evaluate the abnormalities detected on clinical assessment.

Monitoring frequency — The frequency with which monitoring laboratory tests are performed is tailored to each
patient. Factors that should be taken into account when determining the frequency of visits include the history of
the patient's prior symptoms, current disease activity status, disease severity, and frequency and severity of prior
disease flares. As an example, a patient with active lupus nephritis may require laboratory tests every one to two
weeks to monitor and guide therapy. By contrast, another patient with previously active nephritis, but whose SLE
is quiescent, may be tested every three to four months.

Although expert groups recommend that SLE patients with stable disease be monitored less frequently (eg, at up
to six-month intervals), there is evidence that these patients benefit from closer follow-up at three- to four-month
intervals [15,24]. A study including over 500 SLE patients with mild or inactive disease found that one in four
patients followed over a two-year period will have a clinically silent laboratory abnormality (eg, low complement
or hematuria) that could lead to a change in management [25]. The average length of time between visits in the
aforementioned study was 3.8 months, highlighting the importance of regular patient monitoring.

Research tools

● Laboratory tests – Numerous laboratory tests assessing disease activity have been reported; however, their
utility is limited because they are either unconfirmed or not accessible for routine clinical care. Some of
these investigational markers that have been shown to correlate with disease activity include vitamin D
receptors, urinary interleukin (IL)-6, and complement activation markers [14,26-29].

● Disease activity indices – A number of disease activity measures or indices have been developed and are
generally used for research purposes. These measures are often used in observational and clinical trials to
evaluate outcomes, differences among SLE groups, and their responses to therapeutic interventions. All of
 the indices use a combination of history, examination, and laboratory data; they may have general
applicability to clinical practice if simplified.

Examples of scoring systems for global disease activity include the Systemic Lupus Erythematosus Disease
Activity Index-2K (SLEDAI-2K), the Revised Systemic Lupus Activity Measure (SLAM-R), the European
Consensus Lupus Activity Measurement (ECLAM) [10,30-33]. Other assessment scales that assess disease
activity in a single organ include the British Isles Lupus Assessment Group-2004 (BILAG-2004) [34]. While
the BILAG can assess single organs, it provides information on multiple systems and can be used in a
composite form.Clinical trials are also using combinations of indices to create composite assessment
measures for determining trial outcomes. Examples include the SRI (Systemic Lupus Erythematosus
Response Index), used in the pivotal belimumab trials; and the BICLA (BILAG-based Combined Lupus
Assessment), used in a trial of epratuzumab [35,36].

● Damage indices – A damage index score is a measure for chronic damage and is typically used in clinical
research for its prognostic value [37]. Damage can reflect the effects of either disease activity or treatment.
The systemic lupus international collaborating clinics American College of Rheumatology damage index
(SLICC/ACR-DI) is used to measure accumulated damage that has occurred since disease onset [11,38].

Flares

Definition — The clinical course of SLE is variable and may be characterized by unpredictable disease flares
and remissions. There is no consensus on what constitutes a disease flare, but most definitions have
incorporated a combination of results from serologic measures and disease activity indices. Flares are generally
categorized by severity, with moderate or severe flares being the most clinically significant. Most clinicians agree
that a moderate or severe flare refers to a measurable increase in disease activity that is clinically meaningful
enough to result in a change in therapy [39-41]. A challenge in clinical practice is to stratify patients at risk for
disease flares. We use serologic measures of disease activity in the context of the clinical presentation and
organ domain involvement to evaluate for a disease flare. (See 'Laboratory evaluation' above.)

Since almost any organ system can be involved in a lupus flare, there are myriad combinations of signs and
symptoms that could constitute a lupus flare. Some examples of lupus exacerbations that range in severity from
mild to severe, in patients with previously quiescent or stable disease, are presented below [42]:

● Mild SLE flare – A patient who develops new onset low-grade fevers, a malar rash, and arthralgias, and who
also feels increasingly fatigued. Laboratory evaluation is notable for a mild leukopenia. This patient may
require no treatment. Alternatively, the patient may require the addition of hydroxychloroquine or the
equivalent of prednisone 7.5 mg per day or less.

● Moderate SLE flare – A patient with SLE who develops pleuritic chest pain and a swelling of the wrists.
Laboratory evaluation reveals elevated acute phase reactants. A chest radiograph is notable for a right-sided
pleural effusion. The patient may require a short course of prednisone.

● Severe SLE flare – A patient with SLE who develops new onset renal insufficiency and significant proteinuria
due to lupus nephritis. Laboratory evaluation is notable for a low C3, C4, elevated dsDNA antibodies, and
elevated acute phase reactants. The patient may require high doses of glucocorticoids (eg, 1 to 2 mg/kg/day
of prednisone or equivalent or intermittent intravenous "pulses" of methylprednisolone), additional
immunosuppressive therapy (eg, cyclophosphamide, azathioprine, or mycophenolate mofetil), and/or
hospitalization.

Predictors — The most useful laboratory tests to predict an SLE flare (particularly lupus nephritis) are the
onset of an increased serum titer of anti-dsDNA antibodies and a fall in complement levels (especially CH50, C3,
and C4) [43-49]. Persistently low serum levels of complement C1q are also associated with activity of lupus
nephritis [50,51].

However, not all patients with these serologic markers have active disease, and these markers do not necessarily
predict disease exacerbation or "flares" (see 'Definition' above) [48]. In one study, for example, 12 percent of
patients with hypocomplementemia and elevated anti-DNA antibody titers had no clinical evidence of active
disease [52].

There are also clinical features that are associated with an increased risk of SLE flare. These include diagnosis of
SLE before age 25 as well as patients who have renal, vasculitic, or neurologic involvement [49,53].

Thus, we favor an approach in which such patients are closely monitored, and therapy is adjusted if there are
signs of clinical worsening of the disease.

NONPHARMACOLOGIC AND PREVENTIVE INTERVENTIONS — Several nonpharmacologic measures and other

medical interventions are important in the comprehensive management of systemic lupus erythematosus (SLE),
in addition to the specific medication regimens. (See 'Pharmacologic therapies' below.)

Sun protection — Exposure to ultraviolet (UV) light may exacerbate or induce systemic manifestations of SLE
[54]. Thus, patients should avoid exposure to direct or reflected sunlight, and other sources of UV light (eg,
fluorescent and halogen lights). Sunscreens that block both UV-A and UV-B, and have a sun protection factor
(SPF) ≥55, are suggested. Medications that can cause photosensitivity should also be avoided in patients with
SLE (table 1). (See "Overview of cutaneous lupus erythematosus", section on 'Management'.)

Diet and nutrition — Limited data exist concerning the effect of dietary modification in SLE. However, a
conservative approach is to recommend a balanced diet consisting of carbohydrates, proteins, and fats.
Additional considerations regarding diet and nutrition in patients with SLE include the following:

● Patients with active inflammatory disease and fever may require an increase in caloric intake.

● Glucocorticoids can enhance appetite, resulting in potentially significant weight gain. One of the authors has
found that antacids, proton pump inhibitors, and/or histamine H2 blockers may be helpful in diminishing
appetite.

● Vitamins are rarely needed when patients eat a balanced diet. However, a daily multivitamin should be taken
by patients who are not able to obtain an adequate diet.

● The majority of patients with SLE have low serum levels of 25-hydroxyvitamin D (calcidiol) [55], probably due,
at least in part, to avoidance of sun exposure and/or use of sunscreen products. Vitamin D levels should be
monitored periodically and patients with low vitamin D levels should be treated with supplemental vitamin D.
(See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment".)

● Herbal remedies are of unproven benefit and may cause harm [56].

● In patients with hypertension and/or nephritis, dietary measures such as salt restriction may be required.
(See "Salt intake, salt restriction, and primary (essential) hypertension" and "Diet in the treatment and
prevention of hypertension".)

Exercise — Inactivity produced by acute illness causes a rapid loss of muscle mass, bone demineralization, and
loss of stamina resulting in a sense of fatigue. This can usually be managed with isometric and graded exercise
[57,58].
Smoking cessation — Patients should be counseled against cigarette smoking, since it has been associated with
more active disease [59,60]. Smoking adds to the baseline increased risk of accelerated atherosclerosis with
coronary heart disease in those with SLE [61,62]. There is also evidence to suggest that smoking diminishes the
efficacy of hydroxychloroquine [63,64].

Immunizations — We advise that patients should receive appropriate immunizations prior to the institution of
immunosuppressive therapies (table 2), with a few caveats. Influenza vaccine and pneumococcal vaccines are
safe, but resultant antibody titers are somewhat less in patients with SLE than in controls [65-67]. The
quadrivalent human papilloma virus (HPV) vaccine has also been shown to be safe and reasonably effective in
patients with stable SLE, without increasing disease activity or flares [68]. Hepatitis B vaccine also appears to be
safe in patients with stable SLE [69]. Use of glucocorticoids, such as prednisone, or other immunosuppressive
agents may contribute to the blunted antibody response. (See "Glucocorticoid effects on the immune system",
section on 'Impact on vaccination'.)

Live attenuated vaccines (eg, measles, mumps, rubella, polio, varicella, zoster, and vaccinia [smallpox]) can lead
to complications in patients on immunosuppressive therapy. Recommendations for vaccination of patients with
chronic inflammatory diseases receiving immunosuppressive medications are summarized in the following table
(table 2) [65].

Treating comorbid conditions — Accelerated atherosclerosis, pulmonary hypertension, and antiphospholipid

syndrome, as well as osteopenia or osteoporosis, are among the comorbid conditions which can be treated and
for which screening tests are appropriately used. These comorbid disorders, for which patients with SLE have an
increased risk, include [3]:

● Accelerated atherosclerosis – Modifiable risk factors for coronary heart disease can be addressed using
guidelines for the general population such as for smoking cessation, weight loss through dietary
modification and exercise, use of statins, and optimal blood pressure control. (See "Coronary heart disease
in systemic lupus erythematosus", section on 'Prevention and treatment'.)

● Pulmonary hypertension – If pulmonary hypertension is documented, management is similar to the patient

with idiopathic pulmonary hypertension. (See "Treatment of pulmonary hypertension in adults".)

● Antiphospholipid syndrome – The indications for therapy and specific management issues are the same in
patients with antiphospholipid syndrome with or without concurrent SLE. (See "Treatment of
antiphospholipid syndrome".)

● Osteopenia or osteoporosis – Osteoporosis or osteopenia is a significant problem in patients with SLE,

particularly in patients receiving therapy with glucocorticoids. The treatment of this condition is discussed
separately. (See "Musculoskeletal manifestations of systemic lupus erythematosus".)

Issues with specific medications and therapies — Specific medications, such as sulfonamide containing
antibiotics, have been associated with SLE exacerbations and should be avoided. [70,71]. Furthermore, up to 30
percent of patients with SLE have an allergy to sulfonamide antibiotics which includes sulfamethoxazole (in
trimethoprim-sulfamethoxazole [TMP-SMX]) and other less commonly used antimicrobials (table 3) [71]. (See
"Sulfonamide allergy in HIV-uninfected patients", section on 'Types of sulfonamides'.)

By contrast, medications that cause drug-induced lupus, such as procainamide and hydralazine, do not cause
exacerbations of idiopathic SLE. This observation is a presumed reflection of the pathogenetic differences
between the two disorders. However, while we use most other agents that may cause drug-induced lupus, we
avoid the use of minocycline in patients with established (idiopathic) SLE. (See "Drug-induced lupus".)
Radiation therapy for the treatment of malignancy should not be withheld or avoided in patients with SLE. In the
past, several case reports of increased toxicity following therapeutic radiation in patients with systemic
rheumatic diseases made radiation oncologists wary of treating patients with SLE [72-75]. However, additional
studies found that radiation therapy in patients with SLE is not associated with an increased risk of toxicity. The
following studies are illustrative:

● A case-control study including 38 patients with systemic rheumatic diseases, 21 of whom had SLE, found no
significant difference in the incidence of acute or late complications from radiation [76]. However, there was
a higher incidence of radiation complications, particularly radiation dermatitis, among patients with
systemic sclerosis (SSc).

● A small observational study which included four SLE patients who received radiation therapy did not report
any unusual toxicities associated with the treatment [77].

● Two observational series have included 19 patients with SLE among those with "collagen vascular diseases"
receiving radiation therapy for cancer [78,79]. No unusually severe local reactions in the skin or
subcutaneous tissues in the radiation portal were noted in those with lupus.

However, patients with SLE who also have overlapping features of SSc may be at increased risk of induction of
pulmonary fibrosis, and treatment decisions should be made on an individual basis with careful consideration of
the potential risks and benefits of therapy.

Pregnancy and contraception — Pregnancy should be avoided during active disease (especially with significant
organ impairment) due to the high risk of miscarriage and exacerbation of SLE. Women with SLE should be
counseled not to become pregnant until the disease has been quiescent for at least six months. A detailed
discussion on pregnancy in patients with SLE is presented separately. (See "Pregnancy in women with systemic
lupus erythematosus".)

Issues related to contraception in patients with SLE are discussed separately. (See "Approach to contraception in
women with systemic lupus erythematosus".)

PHARMACOLOGIC THERAPIES — The choice of therapy for systemic lupus erythematosus (SLE) is highly
individualized and depends on the predominant symptoms, organ involvement, response to previous therapy, and
disease activity and severity. Adverse effects of individual therapeutic agents and patient preferences must also
be taken into consideration when determining therapy.

Approach to drug therapy — Given the clinical heterogeneity of SLE and the unpredictable disease course, the
therapeutic approach is highly variable and is generally guided by the predominant disease manifestations.
However, there are some general principles of drug therapy that apply to all patients.

In general, all patients with SLE with any degree and type of disease activity should be treated with
hydroxychloroquine or chloroquine, unless these agents are contraindicated [80,81]. The benefits of
hydroxychloroquine or chloroquine in SLE are broad and include relief of constitutional symptoms,
musculoskeletal manifestations, and mucocutaneous manifestations [80]. In addition, a few small randomized
trials and mostly observational evidence suggest that hydroxychloroquine may reduce flare rates, thrombotic
events, organ damage accrual, and mortality [81-86]. A discussion on the use of antimalarial drugs in the
treatment of SLE, along with the potential adverse effects, is presented elsewhere. (See "Antimalarial drugs in the
treatment of rheumatic disease".)

Additional therapy is based upon the severity of disease and the combination of manifestations:
 ● Patients with mild lupus manifestations (eg, skin, joint, and mucosal involvement) may be treated with
hydroxychloroquine or chloroquine, with and without nonsteroidal antiinflammatory drugs (NSAIDs), and/or
short-term use of low-dose glucocorticoids (eg, ≤ 7.5 mg prednisone equivalent per day).

● Patients with moderate lupus involvement are defined as having significant but non-organ-threatening
disease (eg, constitutional, cutaneous, musculoskeletal, or hematologic). Patients usually respond to
hydroxychloroquine or chloroquine plus short-term therapy with 5 to 15 mg of prednisone (or equivalent)
daily. Prednisone is usually tapered once hydroxychloroquine or chloroquine has taken effect. A steroid-
sparing immunosuppressive agent (eg, azathioprine or methotrexate) is often required to control symptoms.

● Patients with severe or life-threatening manifestations secondary to major organ involvement (eg, renal and
central nervous system) generally require an initial period of intensive immunosuppressive therapy
(induction therapy) to control the disease and halt tissue injury. Patients are usually treated for a short
period of time with high doses of systemic glucocorticoids (eg, intravenous "pulses" of methylprednisolone,
0.5 to 1 g/day for three days in acutely ill patients, or 1 to 2 mg/kg/day in more stable patients) used alone
or in combination with other immunosuppressive agents. There is a paucity of data to support the use of
intravenous "pulse" versus daily oral glucocorticoids [87]. One of the major advantages of glucocorticoid
therapy is that it rapidly reduces inflammation, thereby helping to achieve disease control. However,
attempts to minimize exposure must always be made, given the long-term adverse effects. (See "Major side
effects of systemic glucocorticoids".)

Examples of other immunosuppressive agents that may be used include mycophenolate, azathioprine,
cyclophosphamide, or rituximab. This initial therapy is subsequently followed by a longer period of less
intensive, and ideally less toxic, maintenance therapy to consolidate remission and prevent flares. During
this phase of treatment, the dose of prednisone or equivalent is reduced while monitoring clinical and
laboratory measures of disease activity.

Some additional agents are generally reserved for use in patients with SLE resistant to more well-established
therapeutic approaches in the treatment of non-renal SLE. An example of such an agent is belimumab.

Treatment for specific SLE manifestations — There is limited evidenced-based literature for managing organ-
specific manifestations outside of the kidney and skin manifestations. Despite this, the choice of therapy is
generally guided by the predominant symptoms and organ involvement. A general approach to treating the
predominant symptomatology and/or organ-system involvement in SLE is presented in this section.

Constitutional symptoms — Constitutional symptoms such as fatigue and fever are common among patients
with SLE:

● Fatigue among patients with lupus is often caused by a host of possibilities not directly associated with
lupus. These include depression, deconditioning, disordered sleep, fibromyalgia, and iron-deficiency anemia.
Once these causes of fatigue have been excluded or addressed, fatigue in patients who do not have organ-
threatening lupus involvement may be reduced by low-dose glucocorticoids and hydroxychloroquine or
chloroquine [88].

● An underlying infection may be the cause of fever in a patient with lupus, particularly among those receiving
significant immunosuppressive agents. After an infection has been excluded, fever associated with lupus
activity should respond to NSAIDs, acetaminophen, and/or low to moderate doses of glucocorticoids. Fever
that does not respond to such therapy further raises the suspicion of an infectious and/or drug-related
etiology. (See "Overview of the clinical manifestations of systemic lupus erythematosus in adults", section
on 'Constitutional symptoms'.)
 Specific organ system involvement — The management of patients with involvement of the dermatologic,
musculoskeletal, kidney, gastrointestinal, pulmonary, cardiovascular, hematologic, and neurologic systems is
discussed separately in the following topic reviews:

● (See "Overview of cutaneous lupus erythematosus" and "Initial management of discoid lupus and subacute
cutaneous lupus" and "Management of refractory discoid lupus and subacute cutaneous lupus".)

● (See "Initial treatment of the Raynaud phenomenon" and "Treatment of the Raynaud phenomenon resistant
to initial therapy".)

● (See "Treatment and prognosis of diffuse or focal proliferative lupus nephritis" and "Therapy of resistant or
relapsing diffuse or focal proliferative lupus nephritis" and "Clinical features and therapy of lupus
membranous nephropathy" and "End-stage renal disease due to lupus nephritis".)

● (See "Gastrointestinal manifestations of systemic lupus erythematosus".)

● (See "Pulmonary manifestations of systemic lupus erythematosus in adults".)

● (See "Non-coronary cardiac manifestations of systemic lupus erythematosus in adults" and "Coronary heart
disease in systemic lupus erythematosus".)

● (See "Hematologic manifestations of systemic lupus erythematosus".)

● (See "Neurologic manifestations of systemic lupus erythematosus" and "Neuropsychiatric manifestations of

systemic lupus erythematosus".)

OTHER THERAPIES — Several agents have been used in patients with systemic lupus erythematosus (SLE) who
are resistant to more well-established therapeutic approaches. Examples of such agents include those targeting
B-cell pathways, such as belimumab and rituximab. Belimumab has been approved by the US Food and Drug
Administration (FDA) for use in SLE patients, whereas use of rituximab is considered off-label use.

Belimumab — Belimumab is a human monoclonal antibody that inhibits the soluble form of a B-cell survival
factor (known as BLyS or BAFF). Levels of BLyS are elevated in some patients with SLE, and it may play a role in
the pathogenesis of lupus by promoting the formation and survival of memory B cells and plasmablasts making
autoantibodies [89-95]. (See "The humoral immune response", section on 'TACI, BAFF, and APRIL' and
"Epidemiology and pathogenesis of systemic lupus erythematosus", section on 'Immune abnormalities'.)

Based upon the available data as well as our clinical experience, we suggest limiting the use of belimumab to
patients with active musculoskeletal or cutaneous disease that is unresponsive to standard therapy with
glucocorticoids or other immunosuppressive agents. Benefits with belimumab were noted in such patients in the
two major trials of safety and efficacy [91,92]. We do not recommend its use for the purpose of treating severe
active lupus nephritis or severe active central nervous system (CNS) lupus until sufficient efficacy has been
shown for these indications [96]. There have been anecdotal reports of belimumab being helpful for a variety of
other complications of SLE, and in view of its favorable safety profile, its implementation should be decided on a
case-by-case basis in patients resistant to standard approaches. (See "Musculoskeletal manifestations of
systemic lupus erythematosus" and "Overview of cutaneous lupus erythematosus".)

Belimumab is approved for active autoantibody-positive patients with SLE in terms of antinuclear antibodies
(ANA) and/or anti-DNA. This approval raises the question about the ANA status of patients at the time that the
medication may be used, especially if ANA can change over time.

Rituximab — The role of rituximab, a B-cell-depleting chimeric monoclonal antibody, in the treatment of patients
with SLE remains controversial. Several uncontrolled observational studies have reported efficacy of rituximab in
the treatment of SLE patients with and without lupus nephritis who have failed to respond to standard treatment
[97-101]. In addition, a systematic review of SLE patients with active disease refractory to steroids and/or
immunosuppressive drugs assessed the efficacy and safety of rituximab on non-renal outcomes and found
short-term improvements in measures of disease activity, immunologic parameters (eg, complement levels and
dsDNA), arthritis, and thrombocytopenia, as well as a steroid-sparing effect [102]. By comparison, the EXPLORER
and LUNAR trials, which were both randomized trials, found that rituximab did not provide any significant benefit
compared with controls [103,104]. However, limitations in the study design of the both the EXPLORER and LUNAR
trials may have prevented a determination of benefit. In each of the trials, both comparator groups were receiving
high doses of glucocorticoids in addition to immune suppression; thus, it was not possible to determine the
efficacy of rituximab.

The use of rituximab in patients with lupus nephritis is discussed in detail separately. (See "Treatment and
prognosis of diffuse or focal proliferative lupus nephritis", section on 'Rituximab' and "Therapy of resistant or
relapsing diffuse or focal proliferative lupus nephritis", section on 'Rituximab for cyclophosphamide and MMF
resistance'.)

For patients without significant renal disease, we reserve the administration of rituximab to those with serious
organ involvement that has not responded to standard therapies.

Cyclosporine — Cyclosporine (or ciclosporin) inhibits the transcription process that is normally associated with
T-cell activation (see "Pharmacology of cyclosporine and tacrolimus", section on 'Mechanism of action').
Cyclosporine is sometimes used for lupus membranous nephropathy, refractory skin involvement, and bone
marrow hypoplasia. (See "Clinical features and therapy of lupus membranous nephropathy" and "Management of
refractory discoid lupus and subacute cutaneous lupus" and "Hematologic manifestations of systemic lupus
erythematosus".)

Cyclosporine is also used as a steroid-sparing agent. This approach is more commonly used in Europe.

Other agents in clinical trials — A number of other therapeutic approaches have been tried or are under
investigation in SLE. These include B-cell-targeted therapy (such as atacicept and blisibimod), anti-Jak/stat or
tyrosine kinases (inhibition of the BTK pathway), anti-IL-6 receptor, interferon-alpha and -gamma inhibitors such
as sifalimumab, and T-cell costimulation blocker (abatacept) [35,105-120]. Information concerning ongoing trials
in the United States of agents for patients with SLE can be found at www.clinicaltrials.gov.

PROGNOSIS — Systemic lupus erythematosus (SLE) can run a varied clinical course, ranging from a relatively
benign illness to a rapidly progressive disease with fulminant organ failure and death. The five-year survival rate
in SLE has dramatically increased since the mid-20th century, from approximately 40 percent in the 1950s to
greater than 90 percent since 1980s [121-125]. The improvement in patient survival is probably due to multiple
factors including increased disease recognition with more sensitive diagnostic tests [126], earlier diagnosis or
treatment, the inclusion of milder cases, increasingly judicious therapy, and prompt treatment of complications
[127]. Despite these improvements, patients with SLE still have mortality rates ranging from two to five times
higher than that of the general population [128]. In addition, other factors such as sex, race, and geographic
region may have independent effects on mortality in SLE patients. In a large population-based study in the United
States, mortality risk was higher among women, African Americans, and residents of the South [129].

Prognostic factors — Poor prognostic factors in SLE include [122,123,130-138]:

● Renal disease (especially diffuse proliferative glomerulonephritis)

● Hypertension

● Male sex
 ● Young age

● Older age at presentation

● Low socioeconomic status

● Black race, which may primarily reflect low socioeconomic status

● Presence of antiphospholipid antibodies

● Antiphospholipid antibody syndrome

● High overall disease activity

Causes of death — The major causes of death in the first few years of illness are active disease (eg, central
nervous system [CNS] and renal disease) or infection due to immunosuppression, while causes of late death
include complications of SLE (eg, endstage renal disease), treatment complications, and cardiovascular disease
[127,131,139-144]. The frequency of the different causes of death is best illustrated by a 2014 meta-analysis of
12 studies which included 27,123 patients with SLE (4993 observed deaths) [145]. This analysis reported an
overall threefold increased risk of death in patients with SLE (standardized mortality rate [SMR] 2.98, 95% CI
2.32-3.83) when compared with the general population. The risks of death due to cardiovascular disease,
infection, and renal disease were significantly increased. Mortality due to malignancy was not found to be
increased, while patients with renal disease were found to have the highest mortality risk (SMR 7.90, 95% CI 5.5-
11.0).

Morbidity — Despite a reduction in the risk of premature death, patients with SLE are at risk for significant
morbidity due both to active disease and to the side effects of drugs such as glucocorticoids and cytotoxic
agents [146]. Glucocorticoid-induced avascular necrosis of the hips and knees, osteoporosis, fatigue, and
cognitive dysfunction have become particularly important problems as patients live longer with their illness with
a concomitant increase in total glucocorticoid exposure [147]. (See "Major side effects of systemic
glucocorticoids" and "Prevention and treatment of glucocorticoid-induced osteoporosis".)

Factors that may be associated with a shorter delay between disease onset and organ damage include [148]:

● Hispanic ethnicity

● Greater disease activity

● A history of thrombotic events

● Glucocorticoid use of less than 10 mg per day

Glucocorticoid use at doses equivalent to prednisone ≥10 mg/day has been associated with a longer time from
SLE onset to organ damage, but, as noted above, long-term use of higher doses of glucocorticoids has
significant risks that must be considered. However, the relationship between glucocorticoid dose and organ
damage is not well-defined, and there are conflicting results. A cohort of 525 SLE patients from a single
academic medical center was followed for up to 10 years on varying doses of prednisone, and the findings
suggested that low doses of prednisone do not result in a substantially increased risk of irreversible organ
damage [149].

Is cancer risk increased? — Although the overall risk of death due to malignancy does not appear to be increased
in SLE patients, the risk of death due to specific malignancies, particularly non-Hodgkin lymphoma, is
significantly increased among SLE patients when compared with the general population [142,150-158]. Non-
Hodgkin lymphoma in patients with SLE is often an aggressive histologic subtype, especially diffuse large B-cell
lymphoma [159,160]. There also appears to be an increased risk of cancers of the vulva, lung, thyroid, and
possibly liver [158].

Clinical remission — After appropriate therapy, some patients go into a clinical remission, requiring no treatment
[161-163]. However, remission is uncommon, and, when it is achieved, it is often not sustained. The frequency of
clinical remission has been addressed in the following studies [161,163,164]:

● In one study of 667 patients, approximately 25 percent had at least one treatment-free clinical remission
lasting for at least one year [161]. The mean duration of remission was 4.6 years, which represents an
underestimate since one-half of the patients were still in remission at the end of follow-up. A long history of
SLE or the presence of renal or neuropsychiatric disease did not preclude remission. Among the 48 percent
of patients who relapsed after achieving remission, one-half did not achieve a subsequent remission.

● In a second study of 703 patients, 46 achieved complete clinical remission of at least one-year duration
[164]. However, of these, only 12 were still in remission after five years.

● In another study of 224 Caucasian patients with SLE, only 7 percent of patients achieved prolonged
complete remission, which was defined as no clinical or serological disease activity off immunosuppressive
therapy during a five-year consecutive period [163].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries
and regions around the world are provided separately. (See "Society guideline links: Systemic lupus
erythematosus".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and
"Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond
the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written
at the 10th to 12th grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these
topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on
"patient info" and the keyword(s) of interest.)

● Basics topic (see "Patient education: Lupus (The Basics)")

● Beyond the Basics topics (see "Patient education: Systemic lupus erythematosus (SLE) (Beyond the Basics)"
and "Patient education: Systemic lupus erythematosus and pregnancy (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● The goals of therapy for systemic lupus erythematosus (SLE) patients are to ensure long-term survival,
achieve the lowest possible disease activity, prevent organ damage, minimize drug toxicity, improve quality
of life, and educate patients about their role in disease management. (See 'Overview of treatment' above.)

● Determining the appropriate therapeutic regimen requires an accurate assessment of both disease activity
and severity, and a clear understanding of the patient's response to ongoing and previous therapeutic
interventions. The three general patterns of disease to consider when assessing disease activity include
intermittent disease flares (or relapsing and remitting disease), chronically active disease, and quiescent
disease. (See 'Assessment of disease activity and severity' above.)
● In clinical practice, disease activity and severity are assessed using a combination of clinical history,
physical examination, laboratory and imaging studies for specific organs, and serologic tests. A number of
disease activity and damage indices are also available, but they are primarily used for research purposes.
(See 'Assessment of disease activity and severity' above and 'Research tools' above and 'Clinical evaluation'
above.)

● We typically check the following laboratory tests when monitoring disease activity in patients with SLE:
complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), spot urine
protein and creatinine, serum creatinine, estimated glomerular filtration rate (eGFR), anti-double-stranded
deoxyribonucleic acid (dsDNA), and complement levels (C3 and C4). The frequency with which monitoring
laboratory tests are performed is tailored to each patient. Monitoring for specific SLE-related organ
involvement requires additional studies depending on the organ system in question. (See 'Laboratory
evaluation' above and 'Monitoring frequency' above and 'Additional studies' above.)

● Several nonpharmacologic and preventive interventions important in the management of SLE include sun
protection, diet and nutrition, exercise, smoking cessation, maintenance of appropriate immunizations,
treatment of comorbid conditions, avoidance of certain medications, and pregnancy and contraception
counseling. (See 'Nonpharmacologic and preventive interventions' above.)

● The therapeutic approach to SLE is highly individualized and is guided by the predominant disease
manifestations. However, some general principles of drug therapy for all SLE patients are as follows (see
'Approach to drug therapy' above and 'Treatment for specific SLE manifestations' above and 'Other therapies'
above):

• Among patients with SLE with any degree and type of disease activity, we suggest administering
hydroxychloroquine or chloroquine (Grade 2B), unless a contraindication exists.

• Additional therapy is based upon the severity of disease and the combination of manifestations:

- Patients with mild lupus manifestations (eg, skin, joint, and mucosal involvement) are administered
hydroxychloroquine or chloroquine, with or without nonsteroidal antiinflammatory drugs (NSAIDs),
and/or short-term use of low-dose glucocorticoids (eg, ≤7.5 mg prednisone equivalent per day).

- Patients with moderate lupus involvement are defined as having significant but non-organ-
threatening disease (eg, constitutional, cutaneous, musculoskeletal, or hematologic). Patients
usually respond to hydroxychloroquine or chloroquine plus short-term therapy with 5 to 15 mg of
prednisone (or equivalent) daily. Prednisone is usually tapered once hydroxychloroquine or
chloroquine has taken effect. A steroid-sparing immunosuppressive agent (eg, azathioprine or
methotrexate) is often required to control symptoms.

- Patients with severe or life-threatening manifestations secondary to major organ involvement (eg,
renal and central nervous system) generally require an initial period of intensive
immunosuppressive therapy (induction therapy) to control the disease and halt tissue injury.
Patients are usually treated for a short period of time with high doses of systemic glucocorticoids
(eg, 1 to 2 mg/kg/day of prednisone or equivalent or intermittent intravenous "pulses" of
methylprednisolone) used alone or in combination with other immunosuppressive agents (eg,
mycophenolate, cyclophosphamide, or rituximab). This initial therapy is subsequently followed by a
longer period of less intensive and, ideally, less toxic maintenance therapy to consolidate remission
and prevent flares. During this phase of treatment, the dose of prednisone or equivalent is reduced
while monitoring clinical and laboratory measures of disease activity.
● SLE can run a varied clinical course, ranging from a relatively benign illness to a rapidly progressive disease
with fulminant organ failure and death. Clinical remission after appropriate therapy is uncommon, and, when
it is achieved, it is often not sustained. (See 'Prognosis' above and 'Clinical remission' above.)

● Poor prognostic factors for survival in SLE include renal disease (especially diffuse proliferative
glomerulonephritis), hypertension, male sex, younger or older age at presentation, low socioeconomic
status, black race, presence of antiphospholipid antibodies, and high overall disease activity. (See
'Prognostic factors' above.)

● Patients with SLE have mortality rates ranging from 2 to 5 times higher than that of the general population.
The major causes of death in the first few years of illness are active disease (eg, central nervous system
[CNS] and renal) or infection due to immunosuppression, while causes of late death include complications
of SLE (eg, endstage renal disease), treatment complications, and cardiovascular disease. Patients are also
at risk for significant morbidity due to both active disease and the side effects of drugs such as
glucocorticoids and cytotoxic agents. (See 'Causes of death' above and 'Prognosis' above.)

● Although the overall risk of death due to malignancy does not appear to be increased in SLE patients, the
risk of death due to specific malignancies, particularly non-Hodgkin lymphoma, is significantly increased
among SLE patients when compared with the general population. (See 'Is cancer risk increased?' above.)

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2005; 32:1467.

Topic 4675 Version 38.0

GRAPHICS

Some agents that may cause photosensitivity reactions

Anticancer drugs Antipsychotic drugs Sunscreens

Dacarbazine Chlorpromazine* Aminobenzoic acids*

Fluorouracil Fluphenazine Avobenzone

Flutamide Haloperidol Benzophenonones*

Methotrexate Perphenazine Cinnamates

Vinblastine Prochlorperazine* Homosalate

Antidepressants Thioridazine Menthyl anthranilate

Amitriptyline Thiothixene PABA esters*

Amoxapine Trifluoperazine Antihistamine

Clomipramine Triflupromazine Cyproheptadine

Desipramine Diuretics Diphenhydramine

Doxepin Acetazolamide Anthypertensives

Imipramine Amiloride Captopril
Maprotiline Bendroflumethiazide Diltiazem
Phenelzine Benzthiazide Methyldopa
Protriptyline Chlorthiazide* Minoxidil
Trazodone Furosemide* Nifedipine
Trimipramine Hydrochlorothiazide*
Others
Antimicrobials Hydroflumethiazide
Alpazolam
Ciprofloxacin Methyclothiazide
Amantadine
Clofazimine Metolazone
Amiodarone*
Dapsone Polythiazide
Benzocaine
Demeclocycline* Trimterene
Benzyl peroxide
Doxycycline* Trichlormethiazide
Bergamol oil, oils of citron, lavender, lime, sandalwood, cedar*
Enoxacin Hypoglycemics Carbamazepine
Flucytosine Acetohexamide Chlordiazepoxide
Griseofulvin Chlorpropamide Clofibrate
Lomefloxacin* Glipizide Desoximetasone
Minocycline Glyburide Disopyramide
Nalidixic acid* Tolazamide Etretinate
Norfloxacin Tolbutamide* Fluoroscein
Ofloxacin NSAIDs Gold salts
Oxytetracycline Difluisal Hexachlorophene
Pyrazinamide Ibuprofen Isotretinoin
Sulfonamides Indomethacin 6-methylcoumRIN*
Tetracycline Ketoprofen Musk ambrette*
Trimethopterin Nabumetone Oral contraceptives

Antiparasitic drugs Naproxen Promethazine*

 Chloroquine Phenylbutazone Quinidine sulfate

Quinine Piroxicam* Tretinoin

Sulindac Trimeprazine

* Reactions which occur more frequently

Adapted from The Medical Letter 1995; 37:35.

Graphic 62152 Version 1.0

Vaccination of persons with chronic inflammatory diseases on immunosuppressive medications

Planned Low-level High-level

immunosuppression immunosuppression* immunosuppression*
Vaccine
Strength, Strength, Strength,
Recommendation evidence Recommendation evidence Recommendation evidence
quality quality quality

Haemophilus influenzae U Strong, U Strong, low U Strong, low

b conjugate moderate

Hepatitis A U Strong, U Strong, low U Strong, low

moderate

Hepatitis B U Strong, U Strong, low U Strong, low

moderate

Diphtheria toxoid, U Strong, U Strong, low U Strong, low

tetanus toxoid, moderate
acellular pertussis;
tetanus toxoid, reduced
diphtheria toxoid;
tetanus toxoid, reduced
diphtheria toxoid, and
reduced acellular
pertussis

Human papillomavirus U: 11 to 26 years Strong, U: 11 to 26 years Strong, low U: 11 to 26 years Strong, very
moderate low

Influenza-inactivated U Strong, U Strong, U Strong,

(inactivated influenza moderate moderate moderate
vaccine)

Influenza live- X Weak, very X Weak, very X Weak, very

attenuated (live- low low low
attenuated influenza
vaccine)

Measles, mumps, and U¶ Strong, X Weak, very X Weak, very

rubella-live moderate low low

Measles, mumps, and U¶ Strong, low X Weak, very X Strong, very

rubella-varicella-live low low

Meningococcal U Strong, U Strong, U Strong, low

conjugate moderate moderate

Pneumococcal RΔ Strong, U: <6 years Strong, low U: <6 years Strong, low
conjugate (PCV13) moderate R: ≥6 years Δ Strong, very R: ≥6 years Δ Strong, very
low low

Pneumococcal R: age ≥2 years Strong, low R: age ≥2 years Strong, low R: age ≥2 years Strong, very
polysaccharide low
(PPSV23)

Polio-inactivated U Strong, U Strong, U Strong, low

(inactivated poliovirus moderate moderate
vaccine)

Rotavirus-live U Strong, X Weak, very X Weak, very

moderate low low

Varicella-live U¶ Strong, X◊ Weak, very X Strong,

moderate low moderate

Zoster-live R: age 50 to 59 Weak, low R: age 50 to 59 Weak, very X Weak, very

§ §
 years § Strong, low years § low low
U: age ≥60 years U: age ≥60 years Strong, very
low

U: usual - administer if patient not current with recommendations for dose(s) of vaccine for immunocompetent persons in risk and age
categories; X: contraindicated; R: recommended - administer if not previously administered or not current (such patients may be at increased risk
for this vaccine-preventable infection); ACIP: Advisory Committee on Immunization Practices; CDC: United States Centers for Disease Control
and Prevention.
* Low-level immunosuppression includes treatment with <20 mg/day prednisone equivalents (or <2 mg/kg per day for patients who weigh <10
kg) for <14 days, methotrexate ≤0.4 mg/kg per week, azathioprine ≤3 mg/kg per day, or 6-mercaptopurine ≤1.5 mg/kg per day. High-level
immunosuppression regimens include treatment with doses higher than those listed for low-dose immunosuppression and biologic agents such
as tumor necrosis factor-alpha antagonists or rituximab.
¶ Administer only if patient is nonimmune, not severely immunosuppressed, and the timing is ≥4 weeks prior to initiation of immunosuppressive
medications.
Δ For patients aged ≥19 years who have received PPSV23, PCV13 should be administered after an interval of ≥1 year after the last PPSV23 dose
(weak, low).
◊ Administration of varicella vaccine can be considered for non-varicella-immune patients treated for chronic inflammatory disease who are
receiving long-term low-dose immunosuppression (weak, very low). This recommendation deviates from recommendations of the ACIP, CDC.
§ This recommendation deviates from recommendations of the ACIP, CDC [1].

References:
1. Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization
Practices (ACIP). MMWR Recomm Rep 2008; 57:1–30.
From: Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis
2013; 58:e44. By permission of the Infectious Disease Society of America. Copyright © 2013 Oxford University Press.

Graphic 91884 Version 16.0

Sulfonamide antimicrobials (sulfonylarylamines)

  G6PD risk* Description

Systemic agents ¶

Sulfadiazine Low As single agent or in combination with

pyrimethamine

Sulfadoxine   As single agent or in combination with

pyrimethamine; long-acting ◊

Sulfaguanidine Δ Low Gastrointestinal antimicrobial

Sulfamerazine Δ Low In combination with other sulfonamides or

trimethoprim

Sulfamethizole Δ   Urinary tract antimicrobial

Sulfamethazine (sulfadimidine) Δ High As single agent or in combination with other

sulfonamides

Sulfamethoxazole Variable In combination with trimethoprim or as

single agent

Sulfametopyrazine Δ   In combination with pyrimethamine; long-

acting ◊

Sulfamoxole Δ   In combination with trimethoprim

Sulfapyridine Δ   Rarely used due to crystalluria risk

Sulfasalazine (salazosulfapyridine, High Rheumatologic/gastrointestinal agent

salazopyrin) (nonantimicrobial); releases sulfapyridine in
contact with gut flora

Sulfisoxazole (sulfafurazole) High As single agent or in combination with

erythromycin

Topical and ophthalmic agents

Mafenide   Topical solution or cream

Silver sulfadiazine Low Topical cream or ointment

Sulfacetamide High As single agent ophthalmic solution,

ointment, various topicals, vaginal or in
combination with sulfabenzamide,
sulfathiazole, or prednisolone

Sulfanilamide High As single agent vaginal or in combination

with other antimicrobials

G6PD: glucose-6-phosphate dehydrogenase.

* Risk in G6PD deficiency may vary by type. See: www.g6pd.org/.
¶ The human immunodeficiency virus (HIV) protease inhibitors darunavir, fosamprenavir, and tipranavir, as well as the hepatitis C virus (HCV)
protease inhibitor simeprevir contain sulfonamide moieties but lack one or both essential functional groups implicated in sulfonamide antibiotic
hypersensitivity (ie, N4 arylamine or N-containing ring substitution at N1) and do not appear to cross-react. Refer to text.
Δ Not available commercially in United States.
◊ Long-acting sulfonamides may be more frequently implicated in allergic reactions and are cleared slowly upon discontinuation.

Graphic 82011 Version 7.0