Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

non-renal SLE: constitutional symptoms or joint manifestations/serositis

1st line – hydroxychloroquine

Back
ONGOING
|
non-renal SLE: constitutional symptoms or joint manifestations/serositis
1st line – 

hydroxychloroquine

Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus (SLE) unless contraindicated.[53]

The beneficial effects of hydroxychloroquine in SLE include the reduction of constitutional symptoms and reduced musculoskeletal manifestations, as well as a reduced risk of mortality.[121]

Concerns exist regarding the development of retinal toxicity.[123][124]​ Risk factors include duration of treatment, higher dose, chronic kidney disease, and pre-existing retinal or macular disease.[124] Retrospective case-control study data suggest that risk of toxic retinopathy is low for doses <5.0 mg/kg (hydroxychloroquine base) for up to 10 years.[123] Ophthalmological screening (by visual field examination and/or spectral domain-optical coherence tomography) is recommended at baseline, after 5 years, and yearly thereafter in the absence of risk factors for retinal toxicity.[53]

Gradual tapering of hydroxychloroquine is recommended for patients who achieve sustained remission.[53] However, it should not be discontinued, in the absence of intolerable adverse effects, due to the increased risk of flare.[53]

Primary options

hydroxychloroquine: 200-400 mg/day orally given in 1-2 divided doses, maximum 5 mg/kg/day (base)

Plus – lifestyle changes, supportive care, and psychological therapies

Back
ONGOING
|
non-renal SLE: constitutional symptoms or joint manifestations/serositis
Plus – 

lifestyle changes, supportive care, and psychological therapies

Treatment recommended for ALL patients in selected patient group

Patients with systemic lupus erythematosus (SLE) should be evaluated for cardiovascular risk. Preventive strategies based on their individual cardiovascular risk profile, as in the general population, may be appropriate (e.g., low-dose aspirin).[94] Although there are no specific interventions to lower the risk of cardiovascular events in patients with SLE, hydroxychloroquine plus the lowest possible corticosteroid dose to reduce disease or maintain low disease activity is recommended to minimise any potential cardiovascular harm.[94]

In patients with SLE, lower blood pressure is associated with lower rates of cardiovascular events and a blood pressure target of <130/80 mmHg should be considered.[94]

Non-pharmacological management of SLE should be individualised to the patients needs, expectations, and preferences, and directed at improving quality of life.[95] Recommended interventions include sun protection (for the prevention of flares), smoking cessation, psychosocial interventions (for anxiety and/or depressive symptoms), and exercise (reducing fatigue and/or depressive symptoms).[95]

People with SLE should be advised to avoid excessive sun exposure and to use a broad-spectrum sunscreen because exposure to ultraviolet light may exacerbate or induce systemic manifestations.[96][97]

In people with SLE, smoking habits should be assessed and cessation strategies implemented. Despite sparse evidence regarding smoking cessation for improving SLE disease activity, international guidelines emphasis the importance of this recommendation.[95] Evidence from clinical and meta-analyses suggests smoking is associated with more active disease, and a significant reduction in the therapeutic effect of hydroxychloroquine.[27][51][98][99]​ Smoking cessation reduces the risk of atherosclerotic vascular disease.

No dietary measures have been shown to alter the course of SLE. However, adherence to a Mediterranean diet has been associated with lower cardiovascular risk, lower disease activity and protection against organ damage.[95] General dietary advice includes eating at least five servings of fruit or vegetables per day, replacing saturated fats with monounsaturates and polyunsaturates, and increasing the amount of oily fish eaten; a diet rich in polyunsaturated fatty acids.[100] Standard advice regarding alcohol consumption should be given.

SLE is associated with inadequate levels of serum vitamin D compared with the general population.[101][102][103] Evidence regarding vitamin D supplementation in patients with SLE is conflicting. Some data suggest that vitamin D supplements reduce disease activity; increase serum levels; and improve levels of inflammatory markers, fatigue, and endothelial function.[103][104][105]​​​​​ However, according to a subsequent systematic review vitamin D supplementation was not associated with a reduction in disease activity.[106]

Evidence demonstrates that omega-3 fatty acid supplementation may reduce SLE disease activity.[104][106][107]​​​​​​[108] Herbal remedies should be avoided as they can interact adversely with drugs and may cause harm.

Patients with stable SLE should be advised to avoid a sedentary lifestyle and to undertake supervised exercise.[100][109] In these patients, adherence to exercise guidelines should be encouraged to maintain optimum cardiovascular fitness. This will typically include ≥30 minutes of moderate physical activity ≥5 times per week; patients are advised to stop exercising if they experience pain or discomfort.

SLE has a significant impact on health-related quality of life, and has been shown to increase suicidal ideation and suicide attempts.[110][111] Literature reviews suggest that psychological interventions such as psychotherapy, cognitive behavioural therapies (CBT), psychoeducation, and mindfulness-based CBT, as adjuncts to medical therapy, improve fatigue, depression, pain, and quality of life for patients with SLE.[112]

People with SLE experience a wide range of symptoms, which extend beyond the manifestations that require immunosuppressive treatment. Symptoms such as fatigue, non-inflammatory pain, mood disturbance, and cognitive dysfunction are among the most commonly referred to by patients.[53] There is a lack of data to support specific recommendations to treat these symptoms.[53] Nevertheless, it is important to determine whether there is any evidence of anaemia, renal impairment, hypothyroidism, depression, interrupted sleep pattern, or deconditioning and treat each symptom accordingly.[114][115][116] There is some evidence to suggest that patients with SLE suffer from poor sleep quality compared with the general population, and may be associated with feelings of depression.[117][118]

Fever can be a manifestation of active disease SLE, infection, or drug reaction.[119][120] Fever due to SLE often resolves with a non-steroidal anti-inflammatory drug (NSAID) or paracetamol. Persisting fever, despite treatment with these drugs, should raise suspicions of an infectious or drug-related aetiology.

Consider – non-steroidal anti-inflammatory drug (NSAID)

Back
ONGOING
|
non-renal SLE: constitutional symptoms or joint manifestations/serositis
Consider – 

non-steroidal anti-inflammatory drug (NSAID)

Additional treatment recommended for SOME patients in selected patient group

NSAIDs are frequently used as a first-line measure in systemic lupus erythematosus (SLE) to control joint stiffness as well as musculoskeletal and serosal pain. Naproxen may be the preferred first-line drug owing to the rare occurrence of aseptic meningitis with ibuprofen.[143][144][145]​​ 

Patients who require an NSAID and who are at high risk of gastrointestinal ulceration should be given a cyclo-oxygenase-2 (COX-2) inhibitor (e.g., celecoxib) if they are at low cardiovascular risk.

NSAIDs are associated with an increased risk of cardiovascular thrombotic events and gastrointestinal toxicity (bleeding, ulceration, perforation). NSAIDs should be used at the lowest effective dose for the shortest effective treatment course.

Blood pressure should be monitored and NSAIDs should be avoided in patients with hypertension or renal disease.

If long-term NSAID therapy is indicated, Helicobacter pylori eradication and the need for gastroprotection are considered. 

Primary options

naproxen: 500 mg orally twice daily when required, maximum 1500 mg/day

Secondary options

celecoxib: 100-200 mg orally twice daily

Consider – corticosteroid

Back
ONGOING
|
non-renal SLE: constitutional symptoms or joint manifestations/serositis
Consider – 

corticosteroid

Additional treatment recommended for SOME patients in selected patient group

An oral or intravenous corticosteroid is recommended, if needed, for short-term use to control active disease of any severity.[53] 

Pulse doses of intravenous methylprednisolone may be considered in patients with moderate-to-severe disease to provide immediate therapeutic effect in systemic lupus erythematosus (SLE) and enable the use of a lower starting dose of oral corticosteroid.[53] However, the recommended dose and route of administration depends on the type and severity of organ involvement.[53]

Gradual tapering of corticosteroid treatment is recommended for patients who achieve sustained remission.[53] For chronic maintenance treatment, the dose of oral corticosteroid should be minimised to ≤5 mg/day (prednisolone or equivalent) and, when possible, withdrawn.[53] Some evidence suggests that continuing low-dose corticosteroids may provide better disease control for patients with SLE with low disease activity, whereas discontinuation slightly increases the risk of disease flare.[139][140]

The long-term adverse effects of corticosteroid therapy are well documented, and patients should be counselled regarding risk of hypertension and atherosclerotic disease, hyperglycaemia, potential skin changes, infection, mood disorders, disorders of bone and muscle (e.g., osteoporosis, osteonecrosis, myopathy), and ophthalmological effects (e.g., cataracts, increased ocular pressure, exophthalmos).[125][126] 

Caution is advised with corticosteroid use in patients with upper gastrointestinal symptoms, especially if also taking non-steroidal anti-inflammatory drugs (NSAIDs). The lowest possible dose to control symptoms should be used for the shortest period of time.

For SLE patients at risk for cardiovascular disease the lowest possible corticosteroid dose should be used to reduce disease or maintain low disease activity, which will help to minimise any potential cardiovascular harm.[94]

Primary options

methylprednisolone sodium succinate: 125-1000 mg intravenously once daily for 1-3 days, followed by oral prednisolone course

and

prednisolone: 0.5 to 2 mg/kg/day orally initially following methylprednisolone course, adjust dose according to response, maximum 40-80 mg/day, taper gradually to target dose ≤5 mg/day

More

OR

prednisolone: 0.5 to 2 mg/kg/day orally initially, adjust dose according to response, maximum 40-80 mg/day, taper gradually to target dose ≤5 mg/day

More

Consider – immunosuppressant

Back
ONGOING
|
non-renal SLE: constitutional symptoms or joint manifestations/serositis
Consider – 

immunosuppressant

Additional treatment recommended for SOME patients in selected patient group

The addition of methotrexate, azathioprine, or mycophenolate may be considered first line for moderate disease or second line for mild disease.[53]​ The choice of drug depends on the prevailing disease manifestation(s) of systemic lupus erythematosus (SLE), the patient’s age and childbearing potential, and safety concerns.[53]

Early or appropriate initiation of immunosuppressants can expedite the tapering/discontinuation of corticosteroids.[53] 

Patients taking methotrexate should have regular haematological and liver function testing. Methotrexate use may increase the risk of infection. Abnormal haematological and/or liver function results may necessitate a reduction in dose.[158] Folinic acid or folic acid (depending on local guidelines) is typically given to counteract the folate-antagonist action of methotrexate.

Primary options

methotrexate: 5 mg orally/subcutaneously once weekly on the same day of each week, increase gradually according to response, maximum 25 mg/week

OR

azathioprine: 2 mg/kg/day orally initially, adjust dose according to response

OR

mycophenolate mofetil: 1 to 1.5 g orally twice daily

Consider – biological therapy

Back
ONGOING
|
non-renal SLE: constitutional symptoms or joint manifestations/serositis
Consider – 

biological therapy

Additional treatment recommended for SOME patients in selected patient group

The addition of belimumab or anifrolumab may be considered first line for moderate disease or second line for mild disease.[53] The use of conventional immunosuppressants is not mandatory for the initiation of belimumab or anifrolumab.[53]

Belimumab may be considered as an add-on treatment for patients whose symptoms do not respond to hydroxychloroquine (alone or in combination with a corticosteroid), or if they are unable to reduce the corticosteroid dose below an acceptable level for chronic use.[53]

In the UK, the National Institute for Health and Care Excellence (NICE) recommends belimumab as an add-on treatment for patients with active autoantibody-positive systemic lupus erythematosus (SLE) with high disease activity despite standard treatment, only if: high disease activity is defined as at least 1 serological biomarker (positive anti-double-stranded DNA or low component) and a SELENA-SLEDAI (Safety of Estrogen in Lupus National Assessment - Systemic Lupus Erythematosus Disease Activity Index) score of greater than or equal to 10; treatment is continued beyond 24 weeks only if the SELENA-SLEDAI score has improved by 4 points or more.[131]​ One Cochrane review concluded that there is moderate- to high-quality evidence that belimumab is associated with clinically meaningful benefit for patients with SLE at 52 weeks compared with placebo. Patients receiving the approved dose showed at least a 4-point reduction in SELENA-SLEDAI score.[132] Belimumab significantly reduced organ damage progression compared with standard care in long-term study (5-year analysis) of patients with SLE.[133][134]

Anifrolumab may be considered as an add-on treatment for patients whose symptoms do not respond to hydroxychloroquine (alone or in combination with a corticosteroid), or if they are unable to reduce the corticosteroid dose below an acceptable level for chronic use.[53]

In randomised placebo-controlled phase 3 trials, anifrolumab reduced oral corticosteroid dose and severity of skin disease, and improved disease response at 52 weeks, in patients with moderate to severe SLE.[135][136]​ Long-term treatment with anifrolumab suggests an acceptable safety profile with sustained improvement in SLE disease activity, health-related quality of life, and serological measures.[137] The most frequently seen adverse effects include upper respiratory tract infection, nasopharyngitis, bronchitis, and herpes zoster.[138]

Primary options

belimumab: 10 mg/kg intravenously every 2 weeks for the first 3 doses, then every 4 weeks thereafter; 200 mg subcutaneously once weekly

More

OR

anifrolumab: 300 mg intravenously every 4 weeks

non-renal SLE: mucocutaneous manifestations

1st line – hydroxychloroquine

Back
ONGOING
|
non-renal SLE: mucocutaneous manifestations
1st line – 

hydroxychloroquine

Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus (SLE), unless contraindicated.[53] 

The beneficial effects of hydroxychloroquine in SLE include reduced mucocutaneous manifestations, as well as a reduced risk of mortality.[121][122]

Concerns exist regarding the development of retinal toxicity.[123][124]​​ Risk factors include duration of treatment, higher dose, chronic kidney disease, and pre-existing retinal or macular disease.[124] Retrospective case-control study data suggest that risk of toxic retinopathy is low for doses <5.0 mg/kg (hydroxychloroquine base) for up to 10 years.[123] Ophthalmological screening (by visual field examination and/or spectral domain-optical coherence tomography) is recommended at baseline, after 5 years, and yearly thereafter in the absence of risk factors for retinal toxicity.[53]

Gradual tapering of hydroxychloroquine is recommended for patients who achieve sustained remission.[53] However, it should not be discontinued, in the absence of intolerable adverse effects, due to the increased risk of flare.[53]

Primary options

hydroxychloroquine: 200-400 mg/day orally given in 1-2 divided doses, maximum 5 mg/kg/day (base)

Plus – topical corticosteroid or calcineurin inhibitor

Back
ONGOING
|
non-renal SLE: mucocutaneous manifestations
Plus – 

topical corticosteroid or calcineurin inhibitor

Treatment recommended for ALL patients in selected patient group

Treatment of skin disease includes the use of topical therapies (e.g., corticosteroids, calcineurin inhibitors such as tacrolimus).[53] 

Topical corticosteroids of different potencies may be used in combination depending on the patient’s symptoms. Potent corticosteroids (e.g., betamethasone valerate 0.1%) and very potent corticosteroids (e.g., clobetasol propionate 0.05%) are often used to treat the trunk and limbs including the hands, as well as the scalp. Moderate-potency corticosteroids (e.g., triamcinolone acetonide 0.1% or betamethasone valerate 0.025%) are used in areas more prone to atrophy such as the face and neck.

Mild-potency corticosteroids (e.g., hydrocortisone 1%) are typically reserved for the eyelids, although may prove insufficient. Scalp involvement may be treated with foam or lotion formulations.

Primary options

hydrocortisone topical: (1%) apply to affected area(s) once or twice daily

More

OR

triamcinolone topical: (0.1%) apply to the affected area(s) once or twice daily

More

OR

betamethasone valerate topical: (0.025%) apply to the affected area(s) once or twice daily

More

OR

betamethasone valerate topical: (0.1%) apply to the affected area(s) once or twice daily

More

OR

clobetasol topical: (0.05%) apply to the affected area(s) twice daily

More

OR

tacrolimus topical: (0.03%, 0.1%) apply to the affected area(s) twice daily

Plus – lifestyle changes, supportive care, and psychological therapies

Back
ONGOING
|
non-renal SLE: mucocutaneous manifestations
Plus – 

lifestyle changes, supportive care, and psychological therapies

Treatment recommended for ALL patients in selected patient group

For patients with symptomatic mucocutaneous manifestations, such as aphthous ulcers, a thorough oral care regime is recommended.[147] Mouthwashes (e.g., chlorhexidine), basic oral hygiene, and regular attendance at a dental practitioner are helpful in the treatment of mouth ulceration. Topical lidocaine may be beneficial for the management of pain secondary to major oral aphthae.[148] Artificial saliva preparations may be required for those with dry mouth.[147] Dry eye disease may be present in up to 16% of patients with systemic lupus erythematosus (SLE), lubricating eye drops are recommended for these patients.[149]

Patients with SLE should be evaluated for cardiovascular risk. Preventive strategies based on their individual cardiovascular risk cardiovascular risk profile, as in the general population, may be appropriate (e.g., low-dose aspirin).[94] Although there are no specific interventions to lower the risk of cardiovascular events in patients with SLE, hydroxychloroquine plus the lowest possible corticosteroid dose to reduce disease or maintain low disease activity is recommended to minimise any potential cardiovascular harm.[94]

In patients with SLE, lower blood pressure is associated with lower rates of cardiovascular events and a blood pressure target of <130/80 mmHg should be considered.[94]

Non-pharmacological management of SLE should be individualised to the patients needs, expectations, and preferences, and directed at improving quality of life.[95] Recommended interventions include sun protection (for the prevention of flares), smoking cessation, psychosocial interventions (for anxiety and/or depressive symptoms), and exercise (reducing fatigue and/or depressive symptoms).[95]

People with SLE should be advised to avoid excessive sun exposure and to use a broad-spectrum sunscreen because exposure to ultraviolet light may exacerbate or induce systemic manifestations.[96][97]​ 

In people with SLE, smoking habits should be assessed and cessation strategies implemented. Despite sparse evidence regarding smoking cessation for improving SLE disease activity, international guidelines emphasis the importance of this recommendation.[95] Evidence from clinical and meta-analyses suggests smoking is associated with more active disease, and a significant reduction in the therapeutic effect of hydroxychloroquine.[27][51][98][99] Smoking cessation reduces the risk of atherosclerotic vascular disease.

No dietary measures have been shown to alter the course of SLE. However, adherence to a Mediterranean diet has been associated with lower cardiovascular risk, lower disease activity and protection against organ damage.[95] General dietary advice includes eating at least 5 servings of fruit or vegetables per day, replacing saturated fats with monounsaturates and polyunsaturates, and increasing the amount of oily fish eaten; a diet rich in polyunsaturated fatty acids.[100] Standard advice regarding alcohol consumption should be given.

SLE is associated with inadequate levels of serum vitamin D compared with the general population.[101][102][103]​​ Evidence regarding vitamin D supplementation in patients with SLE is conflicting. Some data suggest that vitamin D supplements reduce disease activity; increase serum levels; and improve levels of inflammatory markers, fatigue, and endothelial function.[103][104][105]​​ However, according to a subsequent systematic review vitamin D supplementation was not associated with a reduction in disease activity.[106]

Evidence demonstrates that omega-3 fatty acid supplementation may reduce SLE disease activity.[104][106][107]​​​​​​[108] Herbal remedies should be avoided as they can interact adversely with drugs and may cause harm.

Patients with stable SLE should be advised to avoid a sedentary lifestyle and to undertake supervised exercise.[100][109] In these patients, adherence to exercise guidelines should be encouraged to maintain optimum cardiovascular fitness. This will typically include ≥30 minutes of moderate physical activity ≥5 times per week; patients are advised to stop exercising if they experience pain or discomfort.

SLE has a significant impact on health-related quality of life, and has been shown to increase suicidal ideation and suicide attempts.[110][111] Literature reviews suggest that psychological interventions such as psychotherapy, cognitive behavioural therapies (CBT), psychoeducation, and mindfulness-based CBT, as adjuncts to medical therapy, improve fatigue, depression, pain, and quality of life for patients with SLE.[112][113]​​​ 

People with SLE experience a wide range of symptoms, which extend beyond the manifestations that require immunosuppressive treatment. Symptoms such as fatigue, non-inflammatory pain, mood disturbance, and cognitive dysfunction are among the most commonly referred to by patients.[53] There is a lack of data to support specific recommendations to treat these symptoms.[53] Nevertheless, it is important to determine whether there is any evidence of anaemia, renal impairment, hypothyroidism, depression, interrupted sleep pattern, or deconditioning and treat each symptom accordingly.[114][115][116]​​​​ There is some evidence to suggest that patients with SLE suffer from poor sleep quality compared with the general population, and may be associated with feelings of depression.[117][118]​ 

Fever can be a manifestation of active disease SLE, infection, or drug reaction.[119][120]​ Fever due to SLE often resolves with a non-steroidal anti-inflammatory drug (NSAID) or paracetamol. Persisting fever, despite treatment with these drugs, should raise suspicions of an infectious or drug-related aetiology.

Consider – corticosteroid

Back
ONGOING
|
non-renal SLE: mucocutaneous manifestations
Consider – 

corticosteroid

Additional treatment recommended for SOME patients in selected patient group

An oral or intravenous corticosteroid is recommended, if needed, for short-term use to control active disease of any severity.[53] 

Pulse doses of intravenous methylprednisolone may be considered in patients with moderate-to-severe disease to provide immediate therapeutic effect in systemic lupus erythematosus (SLE) and enable the use of a lower starting dose of oral corticosteroid.[53] However, the recommended dose and route of administration depends on the type and severity of organ involvement.[53] 

Gradual tapering of corticosteroid treatment is recommended for patients who achieve sustained remission.[53] For chronic maintenance treatment, the dose of oral corticosteroid should be minimised to ≤5 mg/day (prednisolone or equivalent) and, when possible, withdrawn.[53] Some evidence suggests that continuing low-dose corticosteroids may provide better disease control for patients with SLE with low disease activity, whereas discontinuation slightly increases the risk of disease flare.[139][140]

The long-term adverse effects of corticosteroid therapy are well documented, and patients should be counselled regarding risk of hypertension and atherosclerotic disease, hyperglycaemia, potential skin changes, infection, mood disorders, disorders of bone and muscle (e.g., osteoporosis, osteonecrosis, myopathy), and ophthalmological effects (e.g., cataracts, increased ocular pressure, exophthalmos).[125][126]​ 

For SLE patients at risk for cardiovascular disease the lowest possible corticosteroid dose should be used to reduce disease or maintain low disease activity, which will help to minimise any potential cardiovascular harm.[94]

Primary options

methylprednisolone sodium succinate: 125-1000 mg intravenously once daily for 1-3 days, followed by oral prednisolone course

and

prednisolone: 0.5 to 2 mg/kg/day orally initially following methylprednisolone course, adjust dose according to response, maximum 40-80 mg/day, taper gradually to target dose ≤5 mg/day

More

OR

prednisolone: 0.5 to 2 mg/kg/day orally initially, adjust dose according to response, maximum 40-80 mg/day, taper gradually to target dose ≤5 mg/day

More

Consider – immunosuppressant

Back
ONGOING
|
non-renal SLE: mucocutaneous manifestations
Consider – 

immunosuppressant

Additional treatment recommended for SOME patients in selected patient group

The addition of methotrexate or mycophenolate should be considered for patients with mucocutaneous disease who have symptoms that do not respond to first-line treatment, or patients with moderate severity cutaneous symptoms (i.e., rash on 9% to 18% of their body surface area).[53] The choice of drug depends on the prevailing disease manifestation(s) of systemic lupus erythematosus (SLE), the patient’s age and childbearing potential, and safety concerns.[53]

Early or appropriate initiation of immunosuppressants can expedite the tapering/discontinuation of corticosteroids.[53]  

Patients taking methotrexate should have regular haematological and liver function testing. Methotrexate use may increase the risk of infection. Abnormal haematological and/or liver function results may necessitate reduction in prescribed dose.[158] Folinic acid or folic acid (depending on local guidelines) is given to counteract the folate-antagonist action of methotrexate.

Other options for patients who have symptoms that do not respond to preferred treatments include retinoids (e.g., acitretin), dapsone, cyclophosphamide, azathioprine, or a calcineurin inhibitor (e.g., ciclosporin, tacrolimus). These options should ideally be given with input from a dermatologist who is experienced in the treatment of cutaneous lupus.[53] Thalidomide and lenalidomide should be reserved for patients who have symptoms that have not responded to multiple previous drugs, and with extreme caution in women of reproductive age.[53]

Primary options

methotrexate: 5 mg orally/subcutaneously once weekly on the same day of each week, increase gradually according to response, maximum 25 mg/week

OR

mycophenolate mofetil: 1 to 1.5 g orally twice daily

Secondary options

acitretin: consult specialist for guidance on dose

OR

dapsone: consult specialist for guidance on dose

OR

cyclophosphamide: consult specialist for guidance on dose

OR

azathioprine: consult specialist for guidance on dose

OR

ciclosporin: consult specialist for guidance on dose

OR

tacrolimus: consult specialist for guidance on dose

Tertiary options

thalidomide: consult specialist for guidance on dose

OR

lenalidomide: consult specialist for guidance on dose

Consider – biological therapy

Back
ONGOING
|
non-renal SLE: mucocutaneous manifestations
Consider – 

biological therapy

Additional treatment recommended for SOME patients in selected patient group

The addition of belimumab or anifrolumab should be considered as second-line therapy for patients with mucocutaneous disease who do not respond to first-line treatment, or patients with moderate severity cutaneous symptoms (i.e., rash on 9% to 18% of their body surface area).[53] The use of conventional immunosuppressants is not mandatory for the initiation of belimumab or anifrolumab.[53]

In the UK, the National Institute for Health and Care Excellence (NICE) recommends belimumab as an add-on treatment for patients with active autoantibody-positive systemic lupus erythematosus (SLE) with high disease activity despite standard treatment, only if: high disease activity is defined as at least 1 serological biomarker (positive anti-double-stranded DNA or low component) and a SELENA-SLEDAI (Safety of Estrogen in Lupus National Assessment - Systemic Lupus Erythematosus Disease Activity Index) score of greater than or equal to 10; treatment is continued beyond 24 weeks only if the SELENA-SLEDAI score has improved by 4 points or more.[131]

One Cochrane review concluded that there is moderate- to high-quality evidence that belimumab is associated with clinically meaningful benefit for patients with SLE at 52 weeks compared with placebo.[132] Patients receiving the approved dose were found to have at lease at least a 4-point reduction in SELENA-SLEDAI score.[132] Belimumab has been demonstrated to significantly reduce organ damage progression (5-year analysis), and or significantly increase the risk of adverse effects compared with standard care for patients with SLE.[133][134]

In randomised placebo-controlled phase 3 trials, anifrolumab reduced oral corticosteroid dose and severity of skin disease, and improved disease response at 52 weeks, in patients with moderate to severe SLE.[135][136]​ Long-term anifrolumab treatment suggests an acceptable safety profile with sustained improvement in SLE disease activity, health-related quality of life, and serological measures.[137]

Primary options

belimumab: 10 mg/kg intravenously every 2 weeks for the first 3 doses, then every 4 weeks thereafter; 200 mg subcutaneously once weekly

More

OR

anifrolumab: 300 mg intravenously every 4 weeks

renal SLE (lupus nephritis)

1st line – immunosuppressant induction therapy

Back
ONGOING
|
renal SLE (lupus nephritis)
1st line – 

immunosuppressant induction therapy

Induction therapy is required to achieve complete or partial response, followed by maintenance immunosuppression to maintain the response. Induction therapy is recommended for active renal systemic lupus erythematosus (SLE) (class III/IV/V).

Immunosuppressant options for induction therapy in patients with active proliferative lupus nephritis include mycophenolate or low-dose intravenous cyclophosphamide.[53][86][87]

The American College of Rheumatology (ACR) conditionally recommends mycophenolate-based regimens over cyclophosphamide-based regimens.[86] Evidence from systematic reviews and meta-analyses suggests that mycophenolate is more effective for the initial treatment of lupus nephritis, significantly increasing the levels of serum complement C3 and complete remission, and the reduction of adverse effects compared with cyclophosphamide.[154]

High-dose intravenous cyclophosphamide can be considered in patients at high risk for kidney failure (defined as reduced glomerular filtration rate, histological presence of cellular crescents or fibrinoid necrosis, or severe interstitial inflammation).[53]

Cyclophosphamide should be given with adequate fluid intake and mesna (a uroprotective agent) as there is a risk of uro-epithelial toxicity (e.g., haemorrhagical cystitis). Young women should be advised about the risks of amenorrhoea or premature ovarian failure with cyclophosphamide; gynaecological referral may be required for further in-depth discussion. Male patients should also be counselled regarding possible risk of infertility. The risk of amenorrhoea is lower with mycophenolate, although there are concerns about congenital malformations if it is given during pregnancy.

Primary options

mycophenolate mofetil: 1 to 1.5 g orally twice daily

OR

cyclophosphamide: low-dose regimen: 500 mg intravenously once every 2 weeks for 6 doses; high-dose regimen: 500-1000 mg/square metre of body surface area once monthly for 6 doses, maximum 1000 mg/dose

Plus – hydroxychloroquine

Back
ONGOING
|
renal SLE (lupus nephritis)
Plus – 

hydroxychloroquine

Treatment recommended for ALL patients in selected patient group

All patients with active lupus nephritis should be treated with hydroxychloroquine, unless contraindicated.[53][86][87]

Continued hydroxychloroquine is associated with increased remission rates in patients initially treated with mycophenolate for lupus nephritis.[152]

Concerns exist regarding the development of retinal toxicity.[123][124] Risk factors include duration of treatment, higher dose, chronic kidney disease, and pre-existing retinal or macular disease.[124] Retrospective case-control study data suggest that risk of toxic retinopathy is low for doses <5 mg/kg (hydroxychloroquine base) for up to 10 years.[123] Ophthalmological screening (by visual field examination and/or spectral domain-optical coherence tomography) is recommended at baseline, after 5 years, and yearly thereafter in the absence of risk factors for retinal toxicity.[53]

Gradual tapering of hydroxychloroquine is recommended for patients who achieve sustained remission.[53] However, it should not be discontinued, in the absence of intolerable adverse effects, due to the increased risk of flare.[53]

Primary options

hydroxychloroquine: 200-400 mg/day orally given in 1-2 divided doses, maximum 5 mg/kg/day (base)

Plus – corticosteroid

Back
ONGOING
|
renal SLE (lupus nephritis)
Plus – 

corticosteroid

Treatment recommended for ALL patients in selected patient group

All patients with active lupus nephritis should be treated with an oral or intravenous corticosteroid. Consider pulse doses of an intravenous corticosteroid (with the dose dependent on the severity of disease), followed by oral corticosteroid therapy tapered to target at 6 months.[53][86][87]

Gradual tapering of corticosteroid treatment is recommended for patients who achieve sustained remission.[53] For chronic maintenance treatment, the dose of oral corticosteroid should be minimised to ≤5 mg/day (prednisolone or equivalent) and, when possible, withdrawn.[53] Some evidence suggests that continuing low-dose corticosteroids may provide better disease control for patients with systemic lupus erythematosus (SLE) with low disease activity, whereas discontinuation slightly increases the risk of disease flare.[139][140]

The long-term adverse effects of corticosteroid therapy are well documented, and patients should be counselled regarding risk of hypertension and atherosclerotic disease, hyperglycaemia, potential skin changes, infection, mood disorders, disorders of bone and muscle (e.g., osteoporosis, osteonecrosis, myopathy), and ophthalmological effects (e.g., cataracts, increased ocular pressure, exophthalmos).[125][126]​ 

For SLE patients at risk for cardiovascular disease the lowest possible corticosteroid dose should be used to reduce disease or maintain low disease activity, which will help to minimise any potential cardiovascular harm.[94]

Primary options

methylprednisolone sodium succinate: 125-1000 mg intravenously once daily for 1-3 days, followed by oral prednisolone course

and

prednisolone: 0.5 to 2 mg/kg/day orally initially following methylprednisolone course, adjust dose according to response, maximum 40-80 mg/day, taper gradually to target dose ≤5 mg/day

More

OR

prednisolone: 0.5 to 2 mg/kg/day orally initially, adjust dose according to response, maximum 40-80 mg/day, taper gradually to target dose ≤5 mg/day

More

Plus – lifestyle changes, supportive care, and psychological therapies

Back
ONGOING
|
renal SLE (lupus nephritis)
Plus – 

lifestyle changes, supportive care, and psychological therapies

Treatment recommended for ALL patients in selected patient group

Patients with systemic lupus erythematosus (SLE) should be evaluated for cardiovascular risk. Preventive strategies based on their individual cardiovascular risk profile, as in the general population, may be appropriate (e.g., low-dose aspirin).[94] Although there are no specific interventions to lower the risk of cardiovascular events in patients with SLE, hydroxychloroquine plus the lowest possible corticosteroid dose to reduce disease or maintain low disease activity is recommended to minimise any potential cardiovascular harm.[94]

In patients with SLE, lower blood pressure is associated with lower rates of cardiovascular events and a blood pressure target of <130/80 mmHg should be considered.[94]

Patients with class V lupus nephritis will have high levels of blood, protein, or both in their urine as well as high blood pressure and should be treated with a renin-angiotensin system inhibitor to protect renal function, in addition to blood pressure control.[86]​ In patients with lupus nephritis, ACE inhibitors or angiotensin-II receptor antagonists are recommended for those with urine protein-to-creatinine ratio >500 mg/g or arterial hypertension.[94]

Non-pharmacological management of SLE should be individualised to the patients needs, expectations, and preferences, and directed at improving quality of life.[95] Recommended interventions include sun protection (for the prevention of flares), smoking cessation, psychosocial interventions (for anxiety and/or depressive symptoms), and exercise (reducing fatigue and/or depressive symptoms).[95]

People with SLE should be advised to avoid excessive sun exposure and to use a broad-spectrum sunscreen because exposure to ultraviolet light may exacerbate or induce systemic manifestations.[96][97]

In people with SLE, smoking habits should be assessed and cessation strategies implemented. Despite sparse evidence regarding smoking cessation for improving SLE disease activity, international guidelines emphasis the importance of this recommendation.[95] Evidence from clinical and meta-analyses suggests smoking is associated with more active disease, and a significant reduction in the therapeutic effect of hydroxychloroquine.[27][51][98][99]​​ Smoking cessation reduces the risk of atherosclerotic vascular disease.

No dietary measures have been shown to alter the course of SLE. However, adherence to a Mediterranean diet has been associated with lower cardiovascular risk, lower disease activity, and protection against organ damage.[95] General dietary advice includes eating at least five servings of fruit or vegetables per day, replacing saturated fats with monounsaturates and polyunsaturates, and increasing the amount of oily fish eaten; a diet rich in polyunsaturated fatty acids.[100] Standard advice regarding alcohol consumption should be given.

SLE is associated with inadequate levels of serum vitamin D compared with the general population.[101][102][103]​ Evidence regarding vitamin D supplementation in patients with SLE is conflicting. Some data suggest that vitamin D supplements reduce disease activity; increase serum levels; and improve levels of inflammatory markers, fatigue, and endothelial function.[103][104][105]​​​​​​ However, according to a subsequent systematic review vitamin D supplementation was not associated with a reduction in disease activity.[106]

Evidence demonstrates that omega-3 fatty acid supplementation may reduce SLE disease activity.[104][106][107]​​​​​​​[108] Herbal remedies should be avoided as they can interact adversely with drugs and may cause harm.

Patients with stable SLE should be advised to avoid a sedentary lifestyle and to undertake supervised exercise.[100][109]​ In these patients, adherence to exercise guidelines should be encouraged to maintain optimum cardiovascular fitness. This will typically include ≥30 minutes of moderate physical activity ≥5 times per week; patients are advised to stop exercising if they experience pain or discomfort.

SLE has a significant impact on health-related quality of life, and has been shown to increase suicidal ideation and suicide attempts.[110][111]​ Literature reviews suggest that psychological interventions such as psychotherapy, cognitive behavioural therapies (CBT), psychoeducation, and mindfulness-based CBT, as adjuncts to medical therapy, improve fatigue, depression, pain, and quality of life for patients with SLE.[112]

People with SLE experience a wide range of symptoms, which extend beyond the manifestations that require immunosuppressive treatment. Symptoms such as fatigue, non-inflammatory pain, mood disturbance, and cognitive dysfunction are among the most commonly referred to by patients.[53] There is a lack of data to support specific recommendations to treat these symptoms.[53] Nevertheless, it is important to determine whether there is any evidence of anaemia, renal impairment, hypothyroidism, depression, interrupted sleep pattern, or deconditioning and treat each symptom accordingly.[114][115][116]​ There is some evidence to suggest that patients with SLE suffer from poor sleep quality compared with the general population, and may be associated with feelings of depression.[117][118]

Fever can be a manifestation of active disease SLE, infection, or drug reaction.[119][120]​ Fever due to SLE often resolves with a non-steroidal anti-inflammatory drug (NSAID) or paracetamol. Persisting fever, despite treatment with these drugs, should raise suspicions of an infectious or drug-related aetiology.

Consider – belimumab or voclosporin or tacrolimus

Back
ONGOING
|
renal SLE (lupus nephritis)
Consider – 

belimumab or voclosporin or tacrolimus

Additional treatment recommended for SOME patients in selected patient group

Belimumab may be considered in addition to mycophenolate or low-dose intravenous cyclophosphamide.[53][86][87]​ Regimens that include belimumab may be effective for patients with extrarenal manifestations.[86]

Compared with standard therapy alone, belimumab has been demonstrated to significantly increase the rate of renal response defined as ratio of urinary protein to creatinine of 0.7 or less, an estimated glomerular filtration rate (eGFR) that was no worse than 20% below the pre-flare value or at least 60 mL/minute/1.73 m², and no use of rescue therapy for treatment failure for patients with lupus nephritis.[155]

Alternatively, a calcineurin inhibitor (i.e., voclosporin, tacrolimus) may be considered in addition to mycophenolate.[53][86][87] Regimens that contain a calcineurin inhibitor in addition to mycophenolate may benefit patients with proteinuria ≥3 g/g. For patients with active onset, new onset, or flare of pure class V lupus nephritis and proteinuria ≥1g/g, the American College of Rheumatology (ACR) recommends a calcineurin inhibitor in addition to mycophenolate.[86] In the UK, NICE recommends voclosporin (plus mycophenolate) as treatment option for adults with class 3 to 5 (including mixed class 3 and 5, and 4 and 5) lupus nephritis.[153]

In a phase 3 randomised controlled trial (RCT) of patients with lupus nephritis, voclosporin in combination with mycophenolate and a low-dose corticosteroid led to a clinically significant superior complete renal response at week 52 compared with mycophenolate and a low-dose corticosteroid alone (73 [41%] of 179 patients vs. 40 [23%] of 178 patients, respectively).[156] Long-term follow up data from these patients demonstrated the continued efficacy and safety of voclosporin at 3 years.[157]

Primary options

belimumab: 10 mg/kg intravenously every 2 weeks for the first 3 doses, then every 4 weeks thereafter; 400 mg subcutaneously once weekly for the first 4 doses, then 200 mg once weekly thereafter

More

OR

voclosporin: 23.7 mg orally twice daily, adjust dose according to eGFR

OR

tacrolimus: consult specialist for guidance on dose

Plus – immunosuppressant maintenance therapy

Back
ONGOING
|
renal SLE (lupus nephritis)
|
response to induction therapy
Plus – 

immunosuppressant maintenance therapy

Treatment recommended for ALL patients in selected patient group

​Maintenance treatment should continue for at least 3 years post renal response.[53][86][87]

Maintenance immunosuppressant therapy will depend on the initial treatment regimen used, for example: patients initially treated with mycophenolate (alone or in combination with belimumab or a calcineurin inhibitor) should remain on these drugs for maintenance therapy; patients initially treated with intravenous cyclophosphamide (alone or in combination with belimumab) should be switched to mycophenolate or azathioprine for maintenance therapy; patients initially treated with triple therapy should remain on the same regimen for maintenance.[53][86]

Corticosteroid dose should be tapered to the lowest possible dose during maintenance therapy. Discontinuation can be considered after patients have maintained a complete renal response for 12 months.[87]

If relapse of lupus nephritis occurs after a partial or complete response has been achieved, the patient should be treated with the same induction therapy used to achieve the original response, or an alternative recommended induction regimen.[87]

Consult a specialist for guidance on selection of the most appropriate regimen

Plus – treatment escalation

Back
ONGOING
|
renal SLE (lupus nephritis)
|
non-responsive or refractory disease
Plus – 

treatment escalation

Treatment recommended for ALL patients in selected patient group

​Treatment escalation may be considered for patients with any class of lupus nephritis who have not achieved at least a partial renal response by 6-12 months, once doses and patient adherence have been assessed.[86]

If treated initially with dual therapy, escalation to triple therapy is recommended. For patients treated with triple therapy initially, an alternative triple therapy regimen, or the addition of rituximab as the second immunosuppressive drug should be considered.[86] Rituximab is recommended especially after failure with cyclophosphamide-based regimens, or an extended course of intravenous cyclophosphamide may be considered for patients with persistent disease activity or inadequate response to initial treatment.[53][87]

For patients who experience treatment failure with two standard therapy courses, a more intensive regimen is recommended, including the addition of rituximab, or triple therapy with three non-corticosteroid immunosuppressive drugs (i.e., mycophonate, belimumab, and a calcineurin inhibitor), or patients can be referred for investigational therapy.[86]

Consult a specialist for guidance on selection of the most appropriate regimen.

non-renal SLE: neuropsychiatric manifestations

1st line – immunosuppressant

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory only
1st line – 

immunosuppressant

Distinction between the two pathophysiological processes (inflammatory and atherothrombotic/antiphospholipid-related manifestations) may be difficult in practice. The two processes could co-exist in the same patient.

For patients with active neuropsychiatric disease attributed to systemic lupus erythematosus (SLE), an immunosuppressant is recommended for inflammatory manifestations.[53]

The choice of immunosuppressant (e.g., azathioprine, mycophenolate, methotrexate) will depend on individual cases, as the neuropsychiatric manifestations can be varied. For severe inflammatory manifestations (e.g., myelopathy, acute confusional state), potent immunosuppressants (e.g., cyclophosphamide, rituximab) are preferred.[53]

Patients taking methotrexate should have regular haematological and liver function testing. Methotrexate use may increase the risk of infection. Abnormal haematological and/or liver function results may necessitate a reduction in dose.[158] ​Folinic acid or folic acid (depending on local guidelines) is typically given to counteract the folate-antagonist action of methotrexate.

Primary options

methotrexate: 5 mg orally/subcutaneously once weekly on the same day of each week, increase gradually according to response, maximum 25 mg/week

OR

azathioprine: 2 mg/kg/day orally initially, adjust dose according to response

OR

mycophenolate mofetil: 1 to 1.5 g orally twice daily

Secondary options

cyclophosphamide: consult specialist for guidance on dose

OR

rituximab: consult specialist for guidance on dose

Plus – hydroxychloroquine

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory only
Plus – 

hydroxychloroquine

Treatment recommended for ALL patients in selected patient group

​Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus (SLE), unless contraindicated.[53]

The beneficial effects of hydroxychloroquine in SLE include a reduced risk of mortality.[121][122]

Concerns exist regarding the development of retinal toxicity.[123][124] Risk factors include duration of treatment, higher dose, chronic kidney disease, and pre-existing retinal or macular disease.​[124] Retrospective case-control study data suggest that risk of toxic retinopathy is low for doses <5 mg/kg (hydroxychloroquine base) for up to 10 years.[123] Ophthalmological screening (by visual field examination and/or spectral domain-optical coherence tomography) is recommended at baseline, after 5 years, and yearly thereafter in the absence of risk factors for retinal toxicity.[53]

Gradual tapering of hydroxychloroquine is recommended for patients who achieve sustained remission.[53] However, it should not be discontinued, in the absence of intolerable adverse effects, due to the increased risk of flare.[53]

Primary options

hydroxychloroquine: 200-400 mg/day orally given in 1-2 divided doses, maximum 5 mg/kg/day (base)

Plus – corticosteroid

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory only
Plus – 

corticosteroid

Treatment recommended for ALL patients in selected patient group

Treatment of systemic lupus erythematosus (SLE)-related neuropsychiatric disease includes corticosteroids for manifestations considered to reflect an inflammatory process.[53]​ Initial therapy with pulse doses of intravenous methylprednisolone is encouraged.[53]

Gradual tapering of corticosteroid treatment is recommended for patients who achieve sustained remission.[53] For chronic maintenance treatment, the dose of oral corticosteroid should be minimised to ≤5 mg/day (prednisolone or equivalent) and, when possible, withdrawn.[53] Some evidence suggests that continuing low-dose corticosteroids may provide better disease control for patients with SLE with low disease activity, whereas discontinuation slightly increases the risk of disease flare.[139][140]

The long-term adverse effects of corticosteroid therapy are well documented, and patients should be counselled regarding risk of hypertension and atherosclerotic disease, hyperglycaemia, potential skin changes, infection, mood disorders, disorders of bone and muscle (e.g., osteoporosis, osteonecrosis, myopathy), and ophthalmological effects (e.g., cataracts, increased ocular pressure, exophthalmos).[125][126]​ 

For SLE patients at risk for cardiovascular disease the lowest possible corticosteroid dose should be used to reduce disease or maintain low disease activity, which will help to minimise any potential cardiovascular harm.[94] 

Primary options

methylprednisolone sodium succinate: 125-1000 mg intravenously once daily for 1-3 days, followed by oral prednisolone course

and

prednisolone: 0.5 to 2 mg/kg/day orally initially following methylprednisolone course, adjust dose according to response, maximum 40-80 mg/day, taper gradually to target dose ≤5 mg/day

More

OR

prednisolone: 0.5 to 2 mg/kg/day orally initially, adjust dose according to response, maximum 40-80 mg/day, taper gradually to target dose ≤5 mg/day.

More

Plus – lifestyle changes, supportive care, and psychological therapies

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory only
Plus – 

lifestyle changes, supportive care, and psychological therapies

Treatment recommended for ALL patients in selected patient group

Patients with systemic lupus erythematosus (SLE) should be evaluated for cardiovascular risk. Preventive strategies based on their individual cardiovascular risk profile, as in the general population, may be appropriate (e.g., low-dose aspirin).[94] Although there are no specific interventions to lower the risk of cardiovascular events in patients with SLE, hydroxychloroquine plus the lowest possible corticosteroid dose to reduce disease or maintain low disease activity is recommended to minimise any potential cardiovascular harm.[94]

In patients with SLE, lower blood pressure is associated with lower rates of cardiovascular events and a blood pressure target of <130/80 mmHg should be considered.[94]

Non-pharmacological management of SLE should be individualised to the patients needs, expectations, and preferences, and directed at improving quality of life.[95] Recommended interventions include sun protection (for the prevention of flares), smoking cessation, psychosocial interventions (for anxiety and/or depressive symptoms), and exercise (reducing fatigue and/or depressive symptoms).[95]

People with SLE should be advised to avoid excessive sun exposure and to use a broad-spectrum sunscreen because exposure to ultraviolet light may exacerbate or induce systemic manifestations.[96][97]

In people with SLE, smoking habits should be assessed and cessation strategies implemented. Despite sparse evidence regarding smoking cessation for improving SLE disease activity, international guidelines emphasis the importance of this recommendation.[95] Evidence from clinical and meta-analyses suggests smoking is associated with more active disease, and a significant reduction in the therapeutic effect of hydroxychloroquine.[27][51][98][99]​​ Smoking cessation reduces the risk of atherosclerotic vascular disease.

No dietary measures have been shown to alter the course of SLE. However, adherence to a Mediterranean diet has been associated with lower cardiovascular risk, lower disease activity and protection against organ damage.[95] General dietary advice includes eating at least five servings of fruit or vegetables per day, replacing saturated fats with monounsaturates and polyunsaturates, and increasing the amount of oily fish eaten; a diet rich in polyunsaturated fatty acids.[100] Standard advice regarding alcohol consumption should be given.

SLE is associated with inadequate levels of serum vitamin D compared with the general population.[101][102][103]​ Evidence regarding vitamin D supplementation in patients with SLE is conflicting. Some data suggest that vitamin D supplements reduce disease activity; increase serum levels; and improve levels of inflammatory markers, fatigue, and endothelial function.[103][104][105]​​​​​​ However, according to a subsequent systematic review vitamin D supplementation was not associated with a reduction in disease activity.[106]

Evidence demonstrates that omega-3 fatty acid supplementation may reduce SLE disease activity.[104][106][107]​​​​​​​[108] Herbal remedies should be avoided as they can interact adversely with drugs and may cause harm.

Patients with stable SLE should be advised to avoid a sedentary lifestyle and to undertake supervised exercise.[100][109]​ In these patients, adherence to exercise guidelines should be encouraged to maintain optimum cardiovascular fitness. This will typically include ≥30 minutes of moderate physical activity ≥5 times per week; patients are advised to stop exercising if they experience pain or discomfort.

SLE has a significant impact on health-related quality of life, and has been shown to increase suicidal ideation and suicide attempts.[110][111]​ Literature reviews suggest that psychological interventions such as psychotherapy, cognitive behavioural therapies (CBT), psychoeducation, and mindfulness-based CBT, as adjuncts to medical therapy, improve fatigue, depression, pain, and quality of life for patients with SLE.[112]

People with SLE experience a wide range of symptoms, which extend beyond the manifestations that require immunosuppressive treatment. Symptoms such as fatigue, non-inflammatory pain, mood disturbance, and cognitive dysfunction are among the most commonly referred to by patients.[53] There is a lack of data to support specific recommendations to treat these symptoms.[53] Nevertheless, it is important to determine whether there is any evidence of anaemia, renal impairment, hypothyroidism, depression, interrupted sleep pattern, or deconditioning and treat each symptom accordingly.[114][115][116]​ There is some evidence to suggest that patients with SLE suffer from poor sleep quality compared with the general population, and may be associated with feelings of depression.[117][118]

Fever can be a manifestation of active disease SLE, infection, or drug reaction.[119][120]​ Fever due to SLE often resolves with a non-steroidal anti-inflammatory drug (NSAID) or paracetamol. Persisting fever, despite treatment with these drugs, should raise suspicions of an infectious or drug-related aetiology.

Consider – intravenous immunoglobulin (IVIG)

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory only
Consider – 

intravenous immunoglobulin (IVIG)

Additional treatment recommended for SOME patients in selected patient group

IVIG may be used as adjunctive therapy when initial treatment is inadequate, but the quality of evidence supporting its use is poor (small cohort studies).[150] IVIG can be effective in the treatment of systemic lupus erythematosus-associated peripheral neuropathies. 

Primary options

normal immunoglobulin human: consult specialist for guidance on dose

Consider – plasmapheresis

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory only
Consider – 

plasmapheresis

Additional treatment recommended for SOME patients in selected patient group

Plasmapheresis may be considered as an adjunctive treatment.[150] The aim of the treatment is to remove circulating auto-antibodies. Recommended if there are clinical and investigative findings consistent with cerebral vasculitis, and may be used when earlier treatments are inadequate.[150] 

Consider – targeted symptomatic pharmacotherapy

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory only
Consider – 

targeted symptomatic pharmacotherapy

Additional treatment recommended for SOME patients in selected patient group

Targeted symptomatic pharmacotherapy is indicated according to the type of neuropsychiatric manifestation.[53] 

Antidepressants, anticonvulsants, antipsychotics, or antimigraine therapies should be prescribed on the advice of relevant specialist on an individual patient basis.

1st line – antiplatelet agent or anticoagulation

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
atherothrombotic/antiphospholipid-related manifestations only
1st line – 

antiplatelet agent or anticoagulation

Distinction between the two pathophysiological processes (inflammatory and atherothrombotic/antiphospholipid-related manifestations) may be difficult in practice. The two processes could co-exist in the same patient.

Treatment of systemic lupus erythematosus (SLE)-related neuropsychiatric disease includes antiplatelet/anticoagulant therapy for atherothrombotic/antiphospholipid-related manifestations (e.g., warfarin, aspirin) after the first arterial or unprovoked attack. Low-dose aspirin should be considered in patients with SLE/without APS with a high-risk aPL profile. The treatment of SLE-a/APS should follow the same principles of therapy as primary APS.

Consult a haematologist for guidance on specific antiplatelet/anticoagulant treatment regimens.

Plus – hydroxychloroquine

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
atherothrombotic/antiphospholipid-related manifestations only
Plus – 

hydroxychloroquine

Treatment recommended for ALL patients in selected patient group

​Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus (SLE), unless contraindicated.[53]

The beneficial effects of hydroxychloroquine in SLE include a reduced risk of mortality.[121][122]

Concerns exist regarding the development of retinal toxicity.[123][124] Risk factors include duration of treatment, higher dose, chronic kidney disease, and pre-existing retinal or macular disease.​[124] Retrospective case-control study data suggest that risk of toxic retinopathy is low for doses <5 mg/kg (hydroxychloroquine base) for up to 10 years.[123] Ophthalmological screening (by visual field examination and/or spectral domain-optical coherence tomography) is recommended at baseline, after 5 years, and yearly thereafter in the absence of risk factors for retinal toxicity.[53]

Gradual tapering of hydroxychloroquine is recommended for patients who achieve sustained remission.[53] However, it should not be discontinued, in the absence of intolerable adverse effects, due to the increased risk of flare.[53]

Primary options

hydroxychloroquine: 200-400 mg/day orally given in 1-2 divided doses, maximum 5 mg/kg/day (base)

Plus – lifestyle changes, supportive care, and psychological therapies

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
atherothrombotic/antiphospholipid-related manifestations only
Plus – 

lifestyle changes, supportive care, and psychological therapies

Treatment recommended for ALL patients in selected patient group

Patients with systemic lupus erythematosus (SLE) should be evaluated for cardiovascular risk. Preventive strategies based on their individual cardiovascular risk profile, as in the general population, may be appropriate (e.g., low-dose aspirin).[94] Although there are no specific interventions to lower the risk of cardiovascular events in patients with SLE, hydroxychloroquine plus the lowest possible corticosteroid dose to reduce disease or maintain low disease activity is recommended to minimise any potential cardiovascular harm.[94]

In patients with SLE, lower blood pressure is associated with lower rates of cardiovascular events and a blood pressure target of <130/80 mmHg should be considered.[94]

Non-pharmacological management of SLE should be individualised to the patients needs, expectations, and preferences, and directed at improving quality of life.[95] Recommended interventions include sun protection (for the prevention of flares), smoking cessation, psychosocial interventions (for anxiety and/or depressive symptoms), and exercise (reducing fatigue and/or depressive symptoms).[95]

People with SLE should be advised to avoid excessive sun exposure and to use a broad-spectrum sunscreen because exposure to ultraviolet light may exacerbate or induce systemic manifestations.[96][97]

In people with SLE, smoking habits should be assessed and cessation strategies implemented. Despite sparse evidence regarding smoking cessation for improving SLE disease activity, international guidelines emphasis the importance of this recommendation.[95] Evidence from clinical and meta-analyses suggests smoking is associated with more active disease, and a significant reduction in the therapeutic effect of hydroxychloroquine.[27][51][98][99]​​ Smoking cessation reduces the risk of atherosclerotic vascular disease.

No dietary measures have been shown to alter the course of SLE. However, adherence to a Mediterranean diet has been associated with lower cardiovascular risk, lower disease activity and protection against organ damage.[95] General dietary advice includes eating at least five servings of fruit or vegetables per day, replacing saturated fats with monounsaturates and polyunsaturates, and increasing the amount of oily fish eaten; a diet rich in polyunsaturated fatty acids.[100] Standard advice regarding alcohol consumption should be given.

SLE is associated with inadequate levels of serum vitamin D compared with the general population.[101][102][103]​ Evidence regarding vitamin D supplementation in patients with SLE is conflicting. Some data suggest that vitamin D supplements reduce disease activity; increase serum levels; and improve levels of inflammatory markers, fatigue, and endothelial function.[103][104][105]​​​​​​ However, according to a subsequent systematic review vitamin D supplementation was not associated with a reduction in disease activity.[106]

Evidence demonstrates that omega-3 fatty acid supplementation may reduce SLE disease activity.[104][106][107]​​​​​​​[108] Herbal remedies should be avoided as they can interact adversely with drugs and may cause harm.

Patients with stable SLE should be advised to avoid a sedentary lifestyle and to undertake supervised exercise.[100][109]​ In these patients, adherence to exercise guidelines should be encouraged to maintain optimum cardiovascular fitness. This will typically include ≥30 minutes of moderate physical activity ≥5 times per week; patients are advised to stop exercising if they experience pain or discomfort.

SLE has a significant impact on health-related quality of life, and has been shown to increase suicidal ideation and suicide attempts.[110][111]​ Literature reviews suggest that psychological interventions such as psychotherapy, cognitive behavioural therapies (CBT), psychoeducation, and mindfulness-based CBT, as adjuncts to medical therapy, improve fatigue, depression, pain, and quality of life for patients with SLE.[112]

People with SLE experience a wide range of symptoms, which extend beyond the manifestations that require immunosuppressive treatment. Symptoms such as fatigue, non-inflammatory pain, mood disturbance, and cognitive dysfunction are among the most commonly referred to by patients.[53] There is a lack of data to support specific recommendations to treat these symptoms.[53] Nevertheless, it is important to determine whether there is any evidence of anaemia, renal impairment, hypothyroidism, depression, interrupted sleep pattern, or deconditioning and treat each symptom accordingly.[114][115][116]​ There is some evidence to suggest that patients with SLE suffer from poor sleep quality compared with the general population, and may be associated with feelings of depression.[117][118]

Fever can be a manifestation of active disease SLE, infection, or drug reaction.[119][120]​ Fever due to SLE often resolves with a non-steroidal anti-inflammatory drug (NSAID) or paracetamol. Persisting fever, despite treatment with these drugs, should raise suspicions of an infectious or drug-related aetiology.

Consider – intravenous immunoglobulin (IVIG)

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
atherothrombotic/antiphospholipid-related manifestations only
Consider – 

intravenous immunoglobulin (IVIG)

Additional treatment recommended for SOME patients in selected patient group

IVIG may be used as adjunctive therapy when initial treatment is inadequate, but the quality of evidence supporting its use is poor (small cohort studies).[150] IVIG can be effective in the treatment of systemic lupus erythematosus-associated peripheral neuropathies.

Primary options

normal immunoglobulin human: consult specialist for guidance on dose

Consider – plasmapheresis

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
atherothrombotic/antiphospholipid-related manifestations only
Consider – 

plasmapheresis

Additional treatment recommended for SOME patients in selected patient group

Plasmapheresis may be considered as an adjunctive treatment.[150] The aim of the treatment is to remove circulating auto-antibodies. Recommended if there are clinical and investigatory findings consistent with cerebral vasculitis, and may be used when earlier treatments are inadequate.[150]

Consider – targeted symptomatic pharmacotherapy

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
atherothrombotic/antiphospholipid-related manifestations only
Consider – 

targeted symptomatic pharmacotherapy

Additional treatment recommended for SOME patients in selected patient group

Targeted symptomatic pharmacotherapy is indicated according to the type of neuropsychiatric manifestation.[53] 

Antidepressants, anticonvulsants, antipsychotics, or antimigraine therapies should be prescribed on the advice of relevant specialist on an individual patient basis.

1st line – immunosuppressant

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory and atherothrombotic/antiphospholipid-related manifestations
1st line – 

immunosuppressant

Distinction between the two pathophysiological processes (inflammatory and atherothrombotic/antiphospholipid-related manifestations) may be difficult in practice. The two processes could co-exist in the same patient.

The combination of an immunosuppressant and antiplatelet/anticoagulant therapy may be considered in these patients.[53] Consult a specialist for guidance on choice of immunosuppressant regimen. 

Plus – antiplatelet agent or anticoagulation

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory and atherothrombotic/antiphospholipid-related manifestations
Plus – 

antiplatelet agent or anticoagulation

Treatment recommended for ALL patients in selected patient group

Treatment of systemic lupus erythematosus (SLE)-related neuropsychiatric disease includes antiplatelet/anticoagulant therapy for atherothrombotic/antiphospholipid-related manifestations (e.g., warfarin, aspirin), after the first arterial or unprovoked attack. Low-dose aspirin should be considered in patients with SLE/without APS with a high-risk aPL profile. The treatment of SLE-a/APS should follow the same principles of therapy as primary APS. Consult a haematologist for guidance on specific antiplatelet/anticoagulant regimens.

Plus – hydroxychloroquine

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory and atherothrombotic/antiphospholipid-related manifestations
Plus – 

hydroxychloroquine

Treatment recommended for ALL patients in selected patient group

Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus (SLE), unless contraindicated.[53]

The beneficial effects of hydroxychloroquine in SLE include a reduced risk of mortality.[121][122]

Concerns exist regarding the development of retinal toxicity.[123][124] Risk factors include duration of treatment, higher dose, chronic kidney disease, and pre-existing retinal or macular disease.​[124] Retrospective case-control study data suggest that risk of toxic retinopathy is low for doses <5 mg/kg (hydroxychloroquine base) for up to 10 years.[123] Ophthalmological screening (by visual field examination and/or spectral domain-optical coherence tomography) is recommended at baseline, after 5 years, and yearly thereafter in the absence of risk factors for retinal toxicity.[53]

Gradual tapering of hydroxychloroquine is recommended for patients who achieve sustained remission.[53] However, it should not be discontinued, in the absence of intolerable adverse effects, due to the increased risk of flare.[53]

Primary options

hydroxychloroquine: 200-400 mg/day orally given in 1-2 divided doses, maximum 5 mg/kg/day (base)

Plus – lifestyle changes, supportive care, and psychological therapies

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory and atherothrombotic/antiphospholipid-related manifestations
Plus – 

lifestyle changes, supportive care, and psychological therapies

Treatment recommended for ALL patients in selected patient group

Patients with systemic lupus erythematosus (SLE) should be evaluated for cardiovascular risk. Preventive strategies based on their individual cardiovascular risk profile, as in the general population, may be appropriate (e.g., low-dose aspirin).[94] Although there are no specific interventions to lower the risk of cardiovascular events in patients with SLE, hydroxychloroquine plus the lowest possible corticosteroid dose to reduce disease or maintain low disease activity is recommended to minimise any potential cardiovascular harm.[94]

In patients with SLE, lower blood pressure is associated with lower rates of cardiovascular events and a blood pressure target of <130/80 mmHg should be considered.[94]

Non-pharmacological management of SLE should be individualised to the patients needs, expectations, and preferences, and directed at improving quality of life.[95] Recommended interventions include sun protection (for the prevention of flares), smoking cessation, psychosocial interventions (for anxiety and/or depressive symptoms), and exercise (reducing fatigue and/or depressive symptoms).[95]

People with SLE should be advised to avoid excessive sun exposure and to use a broad-spectrum sunscreen because exposure to ultraviolet light may exacerbate or induce systemic manifestations.[96][97]

In people with SLE, smoking habits should be assessed and cessation strategies implemented. Despite sparse evidence regarding smoking cessation for improving SLE disease activity, international guidelines emphasis the importance of this recommendation.[95] Evidence from clinical and meta-analyses suggests smoking is associated with more active disease, and a significant reduction in the therapeutic effect of hydroxychloroquine.[27][51][98][99]​​ Smoking cessation reduces the risk of atherosclerotic vascular disease.

No dietary measures have been shown to alter the course of SLE. However, adherence to a Mediterranean diet has been associated with lower cardiovascular risk, lower disease activity and protection against organ damage.[95] General dietary advice includes eating at least five servings of fruit or vegetables per day, replacing saturated fats with monounsaturates and polyunsaturates, and increasing the amount of oily fish eaten; a diet rich in polyunsaturated fatty acids.[100] Standard advice regarding alcohol consumption should be given.

SLE is associated with inadequate levels of serum vitamin D compared with the general population.[101][102][103]​ Evidence regarding vitamin D supplementation in patients with SLE is conflicting. Some data suggest that vitamin D supplements reduce disease activity; increase serum levels; and improve levels of inflammatory markers, fatigue, and endothelial function.[103][104][105]​​​​​​ However, according to a subsequent systematic review vitamin D supplementation was not associated with a reduction in disease activity.[106]

Evidence demonstrates that omega-3 fatty acid supplementation may reduce SLE disease activity.[104][106][107]​​​​​​​[108] Herbal remedies should be avoided as they can interact adversely with drugs and may cause harm.

Patients with stable SLE should be advised to avoid a sedentary lifestyle and to undertake supervised exercise.[100][109]​ In these patients, adherence to exercise guidelines should be encouraged to maintain optimum cardiovascular fitness. This will typically include ≥30 minutes of moderate physical activity ≥5 times per week; patients are advised to stop exercising if they experience pain or discomfort.

SLE has a significant impact on health-related quality of life, and has been shown to increase suicidal ideation and suicide attempts.[110][111]​ Literature reviews suggest that psychological interventions such as psychotherapy, cognitive behavioural therapies (CBT), psychoeducation, and mindfulness-based CBT, as adjuncts to medical therapy, improve fatigue, depression, pain, and quality of life for patients with SLE.[112]

People with SLE experience a wide range of symptoms, which extend beyond the manifestations that require immunosuppressive treatment. Symptoms such as fatigue, non-inflammatory pain, mood disturbance, and cognitive dysfunction are among the most commonly referred to by patients.[53] There is a lack of data to support specific recommendations to treat these symptoms.[53] Nevertheless, it is important to determine whether there is any evidence of anaemia, renal impairment, hypothyroidism, depression, interrupted sleep pattern, or deconditioning and treat each symptom accordingly.[114][115][116]​ There is some evidence to suggest that patients with SLE suffer from poor sleep quality compared with the general population, and may be associated with feelings of depression.[117][118]

Fever can be a manifestation of active disease SLE, infection, or drug reaction.[119][120]​ Fever due to SLE often resolves with a non-steroidal anti-inflammatory drug (NSAID) or paracetamol. Persisting fever, despite treatment with these drugs, should raise suspicions of an infectious or drug-related aetiology.

Consider – intravenous immunoglobulin (IVIG)

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory and atherothrombotic/antiphospholipid-related manifestations
Consider – 

intravenous immunoglobulin (IVIG)

Additional treatment recommended for SOME patients in selected patient group

IVIG may be used as adjunctive therapy when initial treatment is inadequate, but the quality of evidence supporting its use is poor (small cohort studies).[150] IVIG can be effective in the treatment of systemic lupus erythematosus-associated peripheral neuropathies. 

Primary options

normal immunoglobulin human: consult specialist for guidance on dose

Consider – plasmapheresis

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory and atherothrombotic/antiphospholipid-related manifestations
Consider – 

plasmapheresis

Additional treatment recommended for SOME patients in selected patient group

Plasmapheresis may be considered as an adjunctive treatment.[150] The aim of the treatment is to remove circulating auto-antibodies. Recommended if there are clinical and investigative findings consistent with cerebral vasculitis, and may be used when earlier treatments are inadequate.[150]

Consider – targeted symptomatic pharmacotherapy

Back
ONGOING
|
non-renal SLE: neuropsychiatric manifestations
|
inflammatory and atherothrombotic/antiphospholipid-related manifestations
Consider – 

targeted symptomatic pharmacotherapy

Additional treatment recommended for SOME patients in selected patient group

Targeted symptomatic pharmacotherapy is indicated according to the type of neuropsychiatric manifestation.[53]

Antidepressants, anticonvulsants, antipsychotics, or antimigraine therapies should be prescribed on the advice of relevant specialist on an individual patient basis.

non-renal SLE: haematological manifestations

1st line – immunosuppressant

Back
ONGOING
|
non-renal SLE: haematological manifestations
1st line – 

immunosuppressant

Haematological manifestations that require anti-inflammatory/immunosuppressive treatment in patients with systemic lupus erythematosus (SLE) include thrombocytopenia and autoimmune haemolytic anaemia. A platelet count of 20,000 to 30,000/mm³ is typically used as the cut-off; platelet counts below this number require treatment[53] 

Treatment of significant lupus thrombocytopenia and autoimmune haemolytic anaemia consists of an immunosuppressant (e.g., azathioprine, mycophenolate, ciclosporin) as a corticosteroid-sparing agent (i.e., used in combination with a corticosteroid).[53]

This is followed by maintenance therapy with azathioprine, mycophenolate, or ciclosporin (these drugs are continued if used first line, or switched to if intravenous treatment is required for initial therapy).[53]

Primary options

azathioprine: 2 mg/kg/day orally initially, adjust dose according to response

OR

mycophenolate mofetil: 1 to 1.5 g orally twice daily

OR

ciclosporin: consult specialist for guidance on dose

Plus – hydroxychloroquine

Back
ONGOING
|
non-renal SLE: haematological manifestations
Plus – 

hydroxychloroquine

Treatment recommended for ALL patients in selected patient group

​Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus (SLE), unless contraindicated.[53] 

The beneficial effects of hydroxychloroquine in SLE include a reduced risk of mortality.[121][122]

Concerns exist regarding the development of retinal toxicity.[123][124]​​​ Risk factors include duration of treatment, higher dose, chronic kidney disease, and pre-existing retinal or macular disease.[124] Retrospective case-control study data suggest that risk of toxic retinopathy is low for doses <5.0 mg/kg (hydroxychloroquine base) for up to 10 years.[123] Ophthalmological screening (by visual field examination and/or spectral domain-optical coherence tomography) is recommended at baseline, after 5 years, and yearly thereafter in the absence of risk factors for retinal toxicity.[53]

Gradual tapering of hydroxychloroquine is recommended for patients who achieve sustained remission.[53] However, it should not be discontinued, in the absence of intolerable adverse effects, due to the increased risk of flare.[53]

Primary options

hydroxychloroquine: 200-400 mg/day orally given in 1-2 divided doses, maximum 5 mg/kg/day (base)

Plus – corticosteroid

Back
ONGOING
|
non-renal SLE: haematological manifestations
Plus – 

corticosteroid

Treatment recommended for ALL patients in selected patient group

Treatment of significant lupus thrombocytopenia and autoimmune haemolytic anaemia includes high-dose systemic corticosteroids (including pulse doses of intravenous methylprednisolone).[53]

Gradual tapering of corticosteroid treatment is recommended for patients who achieve sustained remission.[53] For chronic maintenance treatment, the dose of oral corticosteroid should be minimised to ≤5 mg/day (prednisolone or equivalent) and, when possible, withdrawn.[53] Some evidence suggests that continuing low-dose corticosteroids may provide better disease control for patients with systemic lupus erythematosus (SLE) with low disease activity, whereas discontinuation slightly increases the risk of disease flare.[139][140]

The long-term adverse effects of corticosteroid therapy are well documented, and patients should be counselled regarding risk of hypertension and atherosclerotic disease, hyperglycaemia, potential skin changes, infection, mood disorders, disorders of bone and muscle (e.g., osteoporosis, osteonecrosis, myopathy), and ophthalmological effects (e.g., cataracts, increased ocular pressure, exophthalmos).[125][126]

For SLE patients at risk for cardiovascular disease the lowest possible corticosteroid dose should be used to reduce disease or maintain low disease activity, which will help to minimise any potential cardiovascular harm.[94]

Primary options

methylprednisolone sodium succinate: 125-1000 mg intravenously once daily for 1-3 days, followed by oral prednisolone course

and

prednisolone: 0.5 to 2 mg/kg/day orally initially following methylprednisolone course, adjust dose according to response, maximum 40-80 mg/day, taper gradually to target dose ≤5 mg/day.

More

OR

prednisolone: 0.5 to 2 mg/kg/day orally initially, adjust dose according to response, maximum 40-80 mg/day, taper gradually to target dose ≤5 mg/day

More

Plus – lifestyle changes, supportive care, and psychological therapies

Back
ONGOING
|
non-renal SLE: haematological manifestations
Plus – 

lifestyle changes, supportive care, and psychological therapies

Treatment recommended for ALL patients in selected patient group

Patients with systemic lupus erythematosus (SLE) should be evaluated for cardiovascular risk. Preventive strategies based on their individual cardiovascular risk profile, as in the general population, may be appropriate (e.g., low-dose aspirin).[94] Although there are no specific interventions to lower the risk of cardiovascular events in patients with SLE, hydroxychloroquine plus the lowest possible corticosteroid dose to reduce disease or maintain low disease activity is recommended to minimise any potential cardiovascular harm.[94]

In patients with SLE, lower blood pressure is associated with lower rates of cardiovascular events and a blood pressure target of <130/80 mmHg should be considered.[94]

Non-pharmacological management of SLE should be individualised to the patients needs, expectations and preferences, and directed at improving quality of life.[95] Recommended interventions include sun protection (for the prevention of flares), smoking cessation, psychosocial interventions (for anxiety and/or depressive symptoms), and exercise (reducing fatigue and/or depressive symptoms).[95]

People with SLE should be advised to avoid excessive sun exposure and to use a broad-spectrum sunscreen because exposure to ultraviolet light may exacerbate or induce systemic manifestations.[96][97]

In people with SLE, smoking habits should be assessed and cessation strategies implemented. Despite sparse evidence regarding smoking cessation for improving SLE disease activity, international guidelines emphasis the importance of this recommendation.[95] Evidence from clinical and meta-analyses suggests smoking is associated with more active disease, and a significant reduction in the therapeutic effect of hydroxychloroquine.[27][51][98][99]​​​​ Smoking cessation reduces the risk of atherosclerotic vascular disease.

No dietary measures have been shown to alter the course of SLE. However, adherence to a Mediterranean diet has been associated with lower cardiovascular risk, lower disease activity, and protection against organ damage.[95] General dietary advice includes eating at least five servings of fruit or vegetables per day, replacing saturated fats with monounsaturates and polyunsaturates, and increasing the amount of oily fish eaten; a diet rich in polyunsaturated fatty acids.[100] Standard advice regarding alcohol consumption should be given.

SLE is associated with inadequate levels of serum vitamin D compared with the general population.[101][102][103]​​ Evidence regarding vitamin D supplementation in patients with SLE is conflicting. Some data suggest that vitamin D supplements reduce disease activity; increase serum levels; and improve levels of inflammatory markers, fatigue, and endothelial function.[103][104][105]​​​​​​​ However, according to a subsequent systematic review vitamin D supplementation was not associated with a reduction in disease activity.[106]

Evidence demonstrates that omega-3 fatty acid supplementation may reduce SLE disease activity.[104][106][107]​​​​​​​​[108] Herbal remedies should be avoided as they can interact adversely with drugs and may cause harm.

Patients with stable SLE should be advised to avoid a sedentary lifestyle and to undertake supervised exercise.[100][109]​​ In these patients, adherence to exercise guidelines should be encouraged to maintain optimum cardiovascular fitness. This will typically include ≥30 minutes of moderate physical activity ≥5 times per week; patients are advised to stop exercising if they experience pain or discomfort.

SLE has a significant impact on health-related quality of life, and has been shown to increase suicidal ideation and suicide attempts.[110][111]​​ Literature reviews suggest that psychological interventions such as psychotherapy, cognitive behavioural therapies (CBT), psychoeducation, and mindfulness-based CBT, as adjuncts to medical therapy, improve fatigue, depression, pain, and quality of life for patients with SLE.[112]

People with SLE experience a wide range of symptoms, which extend beyond the manifestations that require immunosuppressive treatment. Symptoms such as fatigue, non-inflammatory pain, mood disturbance, and cognitive dysfunction are among the most commonly referred to by patients.[53] There is a lack of data to support specific recommendations to treat these symptoms.[53] Nevertheless, it is important to determine whether there is any evidence of anaemia, renal impairment, hypothyroidism, depression, interrupted sleep pattern, or deconditioning and treat each symptom accordingly.[114][115][116]​​ There is some evidence to suggest that patients with SLE suffer from poor sleep quality compared with the general population, and may be associated with feelings of depression.[117][118]

Fever can be a manifestation of active disease SLE, infection, or drug reaction.[119][120]​​ Fever due to SLE often resolves with a non-steroidal anti-inflammatory drug (NSAID) or paracetamol. Persisting fever, despite treatment with these drugs, should raise suspicions of an infectious or drug-related aetiology.

Consider – intravenous immunoglobulin (IVIG)

Back
ONGOING
|
non-renal SLE: haematological manifestations
Consider – 

intravenous immunoglobulin (IVIG)

Additional treatment recommended for SOME patients in selected patient group

IVIG may be considered in the acute phase, in cases of inadequate response to high-dose corticosteroids or to avoid corticosteroid-related infectious complications.[53]

Primary options

normal immunoglobulin human: consult specialist for guidance on dose

2nd line – rituximab or cyclophosphamide

Back
ONGOING
|
non-renal SLE: haematological manifestations
2nd line – 

rituximab or cyclophosphamide

In patients with organ-or life-threatening disease, intravenous cyclophosphamide may be considered. In refractory cases, rituximab may be considered. Rituximab may also be used earlier in this setting.[53]

This is followed by maintenance therapy with oral treatment with azathioprine, mycophenolate, or ciclosporin, or continuation of rituximab.[53] 

Primary options

rituximab: consult specialist for guidance on dose

OR

cyclophosphamide: consult specialist for guidance on dose

Consider – corticosteroid

Back
ONGOING
|
non-renal SLE: haematological manifestations
Consider – 

corticosteroid

Additional treatment recommended for SOME patients in selected patient group

​Treatment of significant lupus thrombocytopenia and autoimmune haemolytic anaemia includes high-dose systemic corticosteroids (including pulse doses of intravenous methylprednisolone).[53]

Gradual tapering of corticosteroid treatment is recommended for patients who achieve sustained remission.[53] For chronic maintenance treatment, the dose of oral corticosteroid should be minimised to ≤5 mg/day (prednisolone or equivalent) and, when possible, withdrawn.[53] Some evidence suggests that continuing low-dose corticosteroids may provide better disease control for patients with systemic lupus erythematosus (SLE) with low disease activity, whereas discontinuation slightly increases the risk of disease flare.[139][140]

The long-term adverse effects of corticosteroid therapy are well documented, and patients should be counselled regarding risk of hypertension and atherosclerotic disease, hyperglycaemia, potential skin changes, infection, mood disorders, disorders of bone and muscle (e.g., osteoporosis, osteonecrosis, myopathy), and ophthalmological effects (e.g., cataracts, increased ocular pressure, exophthalmos).[125][126]​ 

For SLE patients at risk for cardiovascular disease the lowest possible corticosteroid dose should be used to reduce disease or maintain low disease activity, which will help to minimise any potential cardiovascular harm.[94]

Primary options

methylprednisolone sodium succinate: 125-1000 mg intravenously once daily for 1-3 days, followed by oral prednisolone course

and

prednisolone: 0.5 to 2 mg/kg/day orally initially following methylprednisolone course, adjust dose according to response, maximum 40-80 mg/day, taper gradually to target dose ≤5 mg/day

More

OR

prednisolone: 0.5 to 2 mg/kg/day orally initially, adjust dose according to response, maximum 40-80 mg/day, taper gradually to target dose ≤5 mg/day

More

Consider – lifestyle changes, supportive care, and psychological therapies

Back
ONGOING
|
non-renal SLE: haematological manifestations
Consider – 

lifestyle changes, supportive care, and psychological therapies

Additional treatment recommended for SOME patients in selected patient group

Patients with systemic lupus erythematosus (SLE) should be evaluated for cardiovascular risk. Preventive strategies based on their individual cardiovascular risk profile, as in the general population, may be appropriate (e.g., low-dose aspirin).[94] Although there are no specific interventions to lower the risk of cardiovascular events in patients with SLE, hydroxychloroquine plus the lowest possible corticosteroid dose to reduce disease or maintain low disease activity is recommended to minimise any potential cardiovascular harm.[94]

In patients with SLE, lower blood pressure is associated with lower rates of cardiovascular events and a blood pressure target of <130/80 mmHg should be considered.[94]

Non-pharmacological management of SLE should be individualised to the patients needs, expectations, and preferences, and directed at improving quality of life.[95] Recommended interventions include sun protection (for the prevention of flares), smoking cessation, psychosocial interventions (for anxiety and/or depressive symptoms), and exercise (reducing fatigue and/or depressive symptoms).[95]

People with SLE should be advised to avoid excessive sun exposure and to use a broad-spectrum sunscreen because exposure to ultraviolet light may exacerbate or induce systemic manifestations.[96][97]

In people with SLE, smoking habits should be assessed and cessation strategies implemented. Despite sparse evidence regarding smoking cessation for improving SLE disease activity, international guidelines emphasis the importance of this recommendation.[95] Evidence from clinical and meta-analyses suggests smoking is associated with more active disease, and a significant reduction in the therapeutic effect of hydroxychloroquine.[27][51][98][99]​​​ Smoking cessation reduces the risk of atherosclerotic vascular disease.

No dietary measures have been shown to alter the course of SLE. However, adherence to a Mediterranean diet has been associated with lower cardiovascular risk, lower disease activity, and protection against organ damage.[95] General dietary advice includes eating at least five servings of fruit or vegetables per day, replacing saturated fats with monounsaturates and polyunsaturates, and increasing the amount of oily fish eaten; a diet rich in polyunsaturated fatty acids.[100] Standard advice regarding alcohol consumption should be given.

SLE is associated with inadequate levels of serum vitamin D compared with the general population.[101][102][103]​​ Evidence regarding vitamin D supplementation in patients with SLE is conflicting. Some data suggest that vitamin D supplements reduce disease activity; increase serum levels; and improve levels of inflammatory markers, fatigue, and endothelial function.[103][104][105]​​​​​​​ However, according to a subsequent systematic review vitamin D supplementation was not associated with a reduction in disease activity.[106]

Evidence demonstrates that omega-3 fatty acid supplementation may reduce SLE disease activity.[104][106][107]​​​​​​​​[108] Herbal remedies should be avoided as they can interact adversely with drugs and may cause harm.

Patients with stable SLE should be advised to avoid a sedentary lifestyle and to undertake supervised exercise.[100][109]​​ In these patients, adherence to exercise guidelines should be encouraged to maintain optimum cardiovascular fitness. This will typically include ≥30 minutes of moderate physical activity ≥5 times per week; patients are advised to stop exercising if they experience pain or discomfort.

SLE has a significant impact on health-related quality of life, and has been shown to increase suicidal ideation and suicide attempts.[110][111]​​ Literature reviews suggest that psychological interventions such as psychotherapy, cognitive behavioural therapies (CBT), psychoeducation, and mindfulness-based CBT, as adjuncts to medical therapy, improve fatigue, depression, pain, and quality of life for patients with SLE.[112]

People with SLE experience a wide range of symptoms, which extend beyond the manifestations that require immunosuppressive treatment. Symptoms such as fatigue, non-inflammatory pain, mood disturbance, and cognitive dysfunction are among the most commonly referred to by patients.[53] There is a lack of data to support specific recommendations to treat these symptoms.[53] Nevertheless, it is important to determine whether there is any evidence of anaemia, renal impairment, hypothyroidism, depression, interrupted sleep pattern, or deconditioning and treat each symptom accordingly.[114][115][116]​​ There is some evidence to suggest that patients with SLE suffer from poor sleep quality compared with the general population, and may be associated with feelings of depression.[117][118]

Fever can be a manifestation of active disease SLE, infection, or drug reaction.[119][120]​​ Fever due to SLE often resolves with a non-steroidal anti-inflammatory drug (NSAID) or paracetamol. Persisting fever, despite treatment with these drugs, should raise suspicions of an infectious or drug-related aetiology.

3rd line – thrombopoietin agonist or splenectomy

Back
ONGOING
|
non-renal SLE: haematological manifestations
3rd line – 

thrombopoietin agonist or splenectomy

If patients have symptoms which are refractory to initial treatments, a thrombopoietin receptor agonist (e.g., eltrombopag, romiplostim) or splenectomy can be considered.[53]​ It should be noted that thrombopoietin agonists have been associated with a higher risk of thromboembolic events. Thrombopoietin agonists are not recommended in patients with autoimmune haemolytic anaemia.[53]

Primary options

eltrombopag: consult specialist for guidance on dose

OR

romiplostim: consult specialist for guidance on dose

Consider – lifestyle changes, supportive care, and psychological therapies

Back
ONGOING
|
non-renal SLE: haematological manifestations
Consider – 

lifestyle changes, supportive care, and psychological therapies

Additional treatment recommended for SOME patients in selected patient group

Patients with systemic lupus erythematosus (SLE) should be evaluated for cardiovascular risk. Preventive strategies based on their individual cardiovascular risk profile, as in the general population, may be appropriate (e.g., low-dose aspirin).[94] Although there are no specific interventions to lower the risk of cardiovascular events in patients with SLE, hydroxychloroquine plus the lowest possible corticosteroid dose to reduce disease or maintain low disease activity is recommended to minimise any potential cardiovascular harm.[94]

In patients with SLE, lower blood pressure is associated with lower rates of cardiovascular events and a blood pressure target of <130/80 mmHg should be considered.[94]

Non-pharmacological management of SLE should be individualised to the patients needs, expectations, and preferences, and directed at improving quality of life.[95] Recommended interventions include sun protection (for the prevention of flares), smoking cessation, psychosocial interventions (for anxiety and/or depressive symptoms), and exercise (reducing fatigue and/or depressive symptoms).[95]

People with SLE should be advised to avoid excessive sun exposure and to use a broad-spectrum sunscreen because exposure to ultraviolet light may exacerbate or induce systemic manifestations.[96][97]

In people with SLE, smoking habits should be assessed and cessation strategies implemented. Despite sparse evidence regarding smoking cessation for improving SLE disease activity, international guidelines emphasis the importance of this recommendation.[95] Evidence from clinical and meta-analyses suggests smoking is associated with more active disease, and a significant reduction in the therapeutic effect of hydroxychloroquine.[27][51][98][99]​​​ Smoking cessation reduces the risk of atherosclerotic vascular disease.

No dietary measures have been shown to alter the course of SLE. However, adherence to a Mediterranean diet has been associated with lower cardiovascular risk, lower disease activity, and protection against organ damage.[95] General dietary advice includes eating at least five servings of fruit or vegetables per day, replacing saturated fats with monounsaturates and polyunsaturates, and increasing the amount of oily fish eaten; a diet rich in polyunsaturated fatty acids.[100] Standard advice regarding alcohol consumption should be given.

SLE is associated with inadequate levels of serum vitamin D compared with the general population.[101][102][103]​​ Evidence regarding vitamin D supplementation in patients with SLE is conflicting. Some data suggest that vitamin D supplements reduce disease activity; increase serum levels; and improve levels of inflammatory markers, fatigue, and endothelial function.[103][104][105]​​​​​​​ However, according to a subsequent systematic review vitamin D supplementation was not associated with a reduction in disease activity.[106]

Evidence demonstrates that omega-3 fatty acid supplementation may reduce SLE disease activity.[104][106][107]​​​​​​​​[108] Herbal remedies should be avoided as they can interact adversely with drugs and may cause harm.

Patients with stable SLE should be advised to avoid a sedentary lifestyle and to undertake supervised exercise.[100][109]​​ In these patients, adherence to exercise guidelines should be encouraged to maintain optimum cardiovascular fitness. This will typically include ≥30 minutes of moderate physical activity ≥5 times per week; patients are advised to stop exercising if they experience pain or discomfort.

SLE has a significant impact on health-related quality of life, and has been shown to increase suicidal ideation and suicide attempts.[110][111]​​ Literature reviews suggest that psychological interventions such as psychotherapy, cognitive behavioural therapies (CBT), psychoeducation, and mindfulness-based CBT, as adjuncts to medical therapy, improve fatigue, depression, pain, and quality of life for patients with SLE.[112]

People with SLE experience a wide range of symptoms, which extend beyond the manifestations that require immunosuppressive treatment. Symptoms such as fatigue, non-inflammatory pain, mood disturbance, and cognitive dysfunction are among the most commonly referred to by patients.[53] There is a lack of data to support specific recommendations to treat these symptoms.[53] Nevertheless, it is important to determine whether there is any evidence of anaemia, renal impairment, hypothyroidism, depression, interrupted sleep pattern, or deconditioning and treat each symptom accordingly.[114][115][116]​​ There is some evidence to suggest that patients with SLE suffer from poor sleep quality compared with the general population, and may be associated with feelings of depression.[117][118]

Fever can be a manifestation of active disease SLE, infection, or drug reaction.[119][120]​​ Fever due to SLE often resolves with a non-steroidal anti-inflammatory drug (NSAID) or paracetamol. Persisting fever, despite treatment with these drugs, should raise suspicions of an infectious or drug-related aetiology.

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