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{{Systemic lupus erythematosus}}
{{Systemic lupus erythematosus}}


{{CMG}}; {{AE}} {{RT}}
{{CMG}}; {{AE}} {{MIR}} {{RT}}


==Overview==
==Overview==
The mainstay of therapy for systemic lupus erythematosus (SLE) is to control disease activity and prevent organ damage. Pharmacologic medical therapies for SLE include hydroxychloroquine, NSAIDs like celecoxib, and glucocorticoids (prednisone). Hydroxychloroquine is the drug of choice to treat SLE. All organ related complications of SLE should be treated seperately.
The mainstay of therapy for systemic lupus erythematosus (SLE) is to control disease activity and prevent organ damage. The treatment of choice for systemic lupus erythematosus (SLE) varies based on the severity of the disease and symptoms. Generally, all the patients with any type of SLE manifestation should be treated with [[hydroxychloroquine]] regardless of the level of their disease. Other [[Pharmacology|pharmacologic]] medical therapies for SLE include [[glucocorticoids]] like oral [[prednisone]] or [[Intravenous therapy|intravenous]] [[methylprednisolone]], [[Non-steroidal anti-inflammatory drug|NSAIDs]] like [[celecoxib]], and [[immunosuppressive therapy]] with [[mycophenolate]], [[cyclophosphamide]], or [[rituximab]], particularly in severe cases. Cutaneous lupus erythematosus (CLE), if presented separately without any other system involvement, can be treated with [[Topical steroid|topical corticosteroids]]. Other organ-related complications of SLE should be treated separately.
 
==Medical Therapy==
==Medical Therapy==
=====Non-pharmacologic therapy=====
Treatment goals in systemic lupus erythematosus (SLE) include:
* Sun protection: Use of sun-cream with high SPF to prevent skin flares
* Ensure long-term survival
* Exercise
* Achieve the lowest possible disease activity
* Smoking cessation: Smoking has been associated with more severe disease
* Prevent organ damage
* Immunizations: Patients should receive appropriate immunizations prior to the institution of immunosuppressive therapies
* Minimize [[drug toxicity]]
* Treating comorbid conditions:
* Improve quality of life
** Accelerated atherosclerosis: Smoking cessation, weight loss through dietary modification and exercise, use of statins, and optimal blood pressure control
** Pulmonary hypertension
** Antiphospholipid syndrome
** Osteopenia or osteoporosis: It is a significant problem in patients with SLE, particularly in patients receiving therapy with glucocorticoids
* Decrease or eliminate use of contraceptives and hormone replacement therapy
 
===== Pharmacological therapy for constitutional SLE =====
* Preferred regimen 1: Hydroxychloroquine (oral): 200 to 400 mg daily as a single daily dose or in 2 divided doses
* Preferred regimen 2: Celecoxib for fever management even in SLE patients, even in those with “sulfa” allergy. Dosing: 100 to 200 mg twice daily
* Preferred regimen 3: Prednisone high doses of 40 to 60 mg/d for patients with severe SLE, and doses of 10 mg/d or less for milder SLE and treatment of cutaneous and musculoskeletal symptoms not responding to other therapies
* Alternative regimen 1: Mycophenolate for induction 1 g twice daily for 6 months in combination with a glucocorticoid or 2-3 g daily for 6 months in combination with glucocorticoids and for maintenance 0.5-3 g daily or 1 g twice daily or 1-2 g daily
* Alternative regimen 2: Cyclophosphamide (more for lupus nephritis)  IV: 500 mg once every 2 weeks for 6 doses or 500 to 1,000 mg/m2 once every month for 6 doses or 500 to 1,000 mg/m2 every month for 6 months, then every 3 months for a total of at least 2.5 years
* Alternative regimen 3: Rituximab IV: 375 mg/m2 once weekly for 4 doses or 1,000 mg (flat dose) on days 0 and 15 or 500 to 1,000 mg on days 1 and 15
* Alternative regimen 4: Methotrexate Oral: Initial therapy with 7.5 mg once weekly; may increase by 2.5 mg increments weekly
* Alternative regimen 5: Azathioprine Oral: Initial 2 mg/kg/day; may reduce to 1.5 mg/kg/day after 1 month. It is usually used for nephritis treatment
 
===== Treatment regimen based on the SLE manifestations =====
* Mild lupus manifestations:
** Hydroxychloroquine with and without nonsteroidal antiinflammatory drugs (NSAIDs), and/or short-term use of low-dose glucocorticoids (eg, ≤ 7.5 mg prednisone equivalent per day)
 
* Moderate lupus manifestations:
** Defined as having significant but non-organ-threatening disease
** Hydroxychloroquine plus short-term therapy with 5 to 15 mg of prednisone (or equivalent) daily. Prednisone is usually tapered once hydroxychloroquine has taken effect.
** A steroid-sparing immunosuppressive agent like azathioprine or methotrexate is often required to control symptoms.
 
* Severe or life-threatening manifestations:
** Secondary to major organ involvement
** An initial period of intensive immunosuppressive therapy (induction therapy) to control the disease and halt tissue injury.
** A short period of time treatment of high doses of systemic glucocorticoids (eg, intravenous “pulses” of methylprednisolone, 0.5 to 1 g/day for three days in acutely ill patients, or 1 to 2 mg/kg/day in more stable patients) alone or in combination with other immunosuppressive agents.
 
===== Fever management =====
* Preferred regimen: NSAIDs especially celecoxib with a dosing: 100 to 200 mg twice daily
* Alternative regimen 1: Acetaminophen 1000 mg every 6 hours; maximum daily dose: 3000 mg daily '''AND/OR''' 
* Alternative regimen 2: Low to moderate doses of glucocorticoids 
 
===== Chronic pain management =====
* Moderate pain should be treated with mild prescription opiates such as:
** Preferred regimen: Dextropropoxyphene
** Alternative regimen: Co-codamol (Acetaminophene+opioid): Acetaminophen (300 to 1,000 mg/dose)/codeine (15 to 60 mg/dose) every 4 hours as needed; adjust dose according to severity of pain and response of patient (maximum: acetaminophen 4,000 mg/codeine 360 mg per 24 hours)
* Moderate to severe chronic pain should be treated with stronger opioids such as:
** Preferred regimen 1: Hydrocodone: Single doses >40 mg or >60 mg with a total daily dose ≥80 mg
** Preferred regimen 2: Oxycodone: 5 to 15 mg every 4 to 6 hours as needed
** Alternative regimen 1:MS Contin: Opioid naive patients can have 5 to 10 mg every 4 hours as needed; usual dosage range between 5 to 15 mg every 4 hours as needed. Patients with prior opioid exposure may require higher initial doses.
** Alternative regimen 2: Methadone: Maximum initial dose 30 mg
** Alternative regimen 3: Fentanyl Duragesic Transdermal patch: A convenient treatment option for lupus chronic pain. It has a long lasting effect as well
 
===== Considerations =====
* Treatment recommendations are mostly based on the following:<ref name="pmid25778500">{{cite journal |vauthors=Tunnicliffe DJ, Singh-Grewal D, Kim S, Craig JC, Tong A |title=Diagnosis, Monitoring, and Treatment of Systemic Lupus Erythematosus: A Systematic Review of Clinical Practice Guidelines |journal=Arthritis Care Res (Hoboken) |volume=67 |issue=10 |pages=1440–52 |year=2015 |pmid=25778500 |doi=10.1002/acr.22591 |url=}}</ref>
** Ensuring long-term survival
** Preventing organ damage
** Controlling disease activity
** Minimizing comorbidities
** Minimizing drug toxicity
* Treatment targets:
** Remission and prevention of flares 
* Appropriate adjunct therapy:
** Vitamin D and calcium supplements for preventing osteoporosis in patients using corticosteroids
** Antihypertensive drugs and statins were also recommended in patients using corticosteroids
* Patients with more severe manifestations of the disease whom are not responsive to first line therapy like antimalarials or glucocorticoids should be considered for treatment with immunosuppressive agents like cyclophosphamide, azathioprine, mycophenolate mofetil, and methotrexate.
{| class="wikitable"
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|Cutaneous lupus erythematosus
|Photoprotection: broad spectrum sunscreens and sun protective clothing
Avoidance of exacerbating drugs
 
Smoking cessation
|LOCAL THERAPY :
Topical corticosteroids: 
 
Preferred regimen 1: twice daily application of a super high potency or high potency topical corticosteroid as the first-line therapies for patients with DLE or SCLE 
 
Preferred regimen 2: clobetasol propionate : first-line therapy for acute flares of DLE 
 
Preferred regimen 3: hydrocortisone 1% or 2.5% for minimal disease activity on the face 
 
Preferred regimen 4: triamcinolone acetonide 0.1% cream or fluocinonide 0.05% cream: trunk, extremity, or scalp disease/ lowest-potency agent that maintains disease control should be utilized. When all signs of disease activity (eg, scale or erythema) are absent, treatment can be discontinued / a topical calcineurin inhibitor or intralesional corticosteroid therapy: If an acute flare of DLE or SCLE doesn't respond to corticosteroid therapy for two to four week / Cutaneous atrophy is a potential side effect of the long-term use of topical corticosteroids  14162995 
 
13971327


Topical calcineurin inhibitors
===== General treatment =====
* [[Hydroxychloroquine]]: 200 to 400 mg daily as a single daily dose or in 2 divided doses.
** Generally, all patients with any type of SLE manifestation should be treated with [[hydroxychloroquine]] regardless of the severity of the disease.
The treatment choice for systemic lupus erythematosus (SLE) is varied based on the severity of the disease and symptoms:
* Mild cases are defined as disease pattern with one or two organ involvement.
* Moderate cases are defined as more than 2 organ involvement during disease flares with low grade of involvement and complications or one or two organ involvement with more extensive involvements.
* Severe cases are defined as presentation of the disease with life threatening complications and multiple (more than 2) organ involvements.


18797893: pimecrolimus 1% cream and as tacrolimus 0.03% or 0.1% ointment / more expensive than topical corticosteroids, and may be slower-acting
== Severe disease ==
* Preferred regimen (1): [[Hydroxychloroquine]] PO 200 to 400 mg daily as a single daily dose or in 2 divided doses '''AND''' [[methylprednisolone]] as [[intravenous]] "pulse"; 0.5 to 1 g/day for three days in acutely ill patients, or 1 to 2 mg/kg/day in more stable patients
* Alternative regimen(1): [[Hydroxychloroquine]] PO 200 to 400 mg daily as a single daily dose or in 2 divided doses '''AND''' [[prednisone]] oral; 40-60 mg/day
* Alternative regimen (2): [[Mycophenolate]]
** For induction: 1 g twice daily for 6 months in combination with a [[glucocorticoid]]
** For maintenance: 0.5-3 g daily or 1 g twice daily
*** Initial period of intensive [[immunosuppressive therapy]] (induction therapy) to control the disease and halt tissue injury
* Alternative regimen (3): [[Cyclophosphamide]] IV 500 mg once every 2 weeks for 6 doses or 500 to 1,000 mg/m2 once every month for 6 doses or 500 to 1,000 mg/m2 every month for 6 months, then every 3 months for a total of at least 2.5 years
* Alternative regimen (4): [[Rituximab]] IV: 375 mg/m2 once weekly for 4 doses or 1,000 mg (flat dose) on days 0 and 15 or 500 to 1,000 mg on days 1 and 15


Patients with focal lesions that do not respond to topical corticosteroids or topical calcineurin inhibitors can be treated with intralesional corticosteroid injections
== Less Severe (mild and moderate) disease ==
* Preferred regimen (1): [[Hydroxychloroquine]] PO 200 to 400 mg daily as a single daily dose or in 2 divided doses
* Preferred regimen (2): [[Prednisone]] PO low doses of 10 mg/d or less for a short term therapy
** For milder SLE
** For treatment of [[cutaneous]] and musculoskeletal symptoms not responding to other therapies
** It should be tapered once [[hydroxychloroquine]] has taken effect
* Alternative regimen (1): [[Azathioprine]] PO initial 2 mg/kg/day; may reduce to 1.5 mg/kg/day after 1 month
** Can be used to control symptoms
* Alternative regimen (2):  [[Methotrexate]] PO initial therapy with 7.5 mg once weekly; may increase by 2.5 mg increments weekly
** Can be used to control symptoms


16966017
== Other organ specific treatments ==


SYSTEMIC THERAPY
===== Fever management<ref name="pmid27529058">{{cite journal |vauthors=Jordan N, D'Cruz D |title=Current and emerging treatment options in the management of lupus |journal=Immunotargets Ther |volume=5 |issue= |pages=9–20 |year=2016 |pmid=27529058 |pmc=4970629 |doi=10.2147/ITT.S40675 |url=}}</ref><ref name="pmid24830791">{{cite journal |vauthors=Cobo-Ibáñez T, Loza-Santamaría E, Pego-Reigosa JM, Marqués AO, Rúa-Figueroa I, Fernández-Nebro A, Cáliz Cáliz R, López Longo FJ, Muñoz-Fernández S |title=Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: a systematic review |journal=Semin. Arthritis Rheum. |volume=44 |issue=2 |pages=175–85 |year=2014 |pmid=24830791 |doi=10.1016/j.semarthrit.2014.04.002 |url=}}</ref> =====
* Preferred regimen: [[Celecoxib]] PO 100 to 200 mg twice daily
** For [[fever]] management even in SLE patients with [[Sulfa allergy|“sulfa” allergy]]
* Alternative regimen: [[Acetaminophen]] 1000 mg every 6 hours; maximum daily dose: 3000 mg daily 


Antimalarials are the first-line systemic therapy for the treatment of DLE and SCLE/ Antimalarials — Hydroxychloroquine, chloroquine, and quinacrine / hydroxychloroquine (200 to 400 mg/day) for at least six weeks / after improvement, decreased the dosage to 200 mg/day for maintenance therapy /
==== Raynaud's phenomenon treatment<ref name="pmid3691593">{{cite journal |vauthors=Challenor VF, Waller DG, Francis DA, Francis JL, Mani R, Roath S |title=Nisoldipine in primary Raynaud's phenomenon |journal=Eur. J. Clin. Pharmacol. |volume=33 |issue=1 |pages=27–30 |year=1987 |pmid=3691593 |doi= |url=}}</ref> ====
* Preferred regimen (1): [[Calcium channel blocker]] ([[nifedipine]]) 10 to 30 mg 3 times daily
* Preferred regimen (2): Antiplatelet therapy with low-dose [[aspirin]] (75 or 81 mg/day) in all patients with secondary [[Raynaud phenomenon]]
* Alternative regimen (1): [[Phosphodiesterase inhibitors|Phosphodiesterase (PDE) inhibitor]] ([[sildenafil]]) 20 mg once or twice daily
** Inadequate response to a [[CCB]]
* Alternative regimen (2): Addition of [[Nitroglycerin (Topical ointment)|topical nitroglycerin (NTG)]]
** Inadequate response to a [[CCB]]
** A [[Sildenafil|PDE inhibitor]] is not available, effective, or well-tolerated
* Alternative regimen (3): Intravenous (IV) infusions of a [[Prostaglandin|prostaglandin (PG)]] especially [[Prostacyclin|prostacyclin (PGI2) analogue]] for extremely severe patients with [[Raynaud's phenomenon|raynaud's phenomenon]]<ref name="pmid6890719">{{cite journal |vauthors=Pardy BJ, Hoare MC, Eastcott HH, Miles CC, Needham TN, Harbourne T, Ellis BW |title=Prostaglandin E1 in severe Raynaud's phenomenon |journal=Surgery |volume=92 |issue=6 |pages=953–65 |year=1982 |pmid=6890719 |doi= |url=}}</ref>


359493
===== Chronic pain management<ref name="pmid24938194">{{cite journal |vauthors=Di Franco M, Guzzo MP, Spinelli FR, Atzeni F, Sarzi-Puttini P, Conti F, Iannuccelli C |title=Pain and systemic lupus erythematosus |journal=Reumatismo |volume=66 |issue=1 |pages=33–8 |year=2014 |pmid=24938194 |doi= |url=}}</ref> =====
|For patients with DLE or SCLE, we suggest the use of topical agents as first-line therapy (algorithm 1) (Grade 2B). We suggest treatment with topical corticosteroids over topical calcineurin inhibitors as initial therapy (Grade 2C). The relatively rapid onset of topical corticosteroids is beneficial.
* Moderate pain should be treated with mild prescription [[opiates]] such as:
** Preferred regimen: [[Dextropropoxyphene]] 600 mg maximum daily dosage divided into 2 or 3 doses
** Alternative regimen: [[Co-codamol|Co-codamol (Acetaminophene+opioid)]]: [[Acetaminophen]] (300 to 1,000 mg/dose)/[[codeine]] (15 to 60 mg/dose) every 4 hours as needed; adjust dose according to severity of pain and response of patient (maximum: [[acetaminophen]] 4,000 mg/[[codeine]] 360 mg per 24 hours)
* Moderate to severe [[chronic pain]] should be treated with stronger [[Opioid|opioids]] such as:
** Preferred regimen (1): [[Hydrocodone]]: Single doses >40 mg or >60 mg with a total daily dose ≥80 mg
** Preferred regimen (2): [[Oxycodone]]: 5 to 15 mg every 4 to 6 hours as needed
** Alternative regimen (1): [[MS Contin|MS Contin:]] Opioid naive patients can have 5 to 10 mg every 4 hours; usual dosage range between 5 to 15 mg every 4 hours
*** Higher initial doses in patients with prior [[opioid]] exposure
** Alternative regimen (2): [[Methadone]]: Maximum initial dose 30 mg
** Alternative regimen (3): [[Fentanyl]] Duragesic Transdermal patch: A convenient treatment option for [[Systemic lupus erythematosus|lupus]] chronic pain. It has a long lasting effect as well


●If topical corticosteroid therapy is not effective, we suggest treatment with a topical calcineurin inhibitor such as tacrolimus 0.1% ointment or pimecrolimus 1% cream (Grade 2C). Topical calcineurin inhibitors also may be useful for long-term therapy for lesions in areas of the skin where the risk of corticosteroid-induced atrophy is a concern. (See 'Topical corticosteroids' above and 'Topical calcineurin inhibitors' above.)
===== Cutaneous lupus erythematosus<ref name="pmid14162995">{{cite journal |vauthors=DOEGLAS HM |title=CHRONIC DISCOID LUPUS ERYTHEMATOSUS TREATED WITH TRIAMCINOLONE AND PLASTIC OCCLUSION |journal=Dermatologica |volume=128 |issue= |pages=384–6 |year=1964 |pmid=14162995 |doi= |url=}}</ref><ref name="pmid16966017">{{cite journal |vauthors=Rothfield N, Sontheimer RD, Bernstein M |title=Lupus erythematosus: systemic and cutaneous manifestations |journal=Clin. Dermatol. |volume=24 |issue=5 |pages=348–62 |year=2006 |pmid=16966017 |doi=10.1016/j.clindermatol.2006.07.014 |url=}}</ref><ref name="pmid18797893">{{cite journal |vauthors=Sárdy M, Ruzicka T, Kuhn A |title=Topical calcineurin inhibitors in cutaneous lupus erythematosus |journal=Arch. Dermatol. Res. |volume=301 |issue=1 |pages=93–8 |year=2009 |pmid=18797893 |doi=10.1007/s00403-008-0894-6 |url=}}</ref><ref name="pmid13971327">{{cite journal |vauthors=BJORNBERG A, HELLGREN L |title=Treatment of chronic discoid lupus erythematosus with fluocinolone acetonide ointment |journal=Br. J. Dermatol. |volume=75 |issue= |pages=156–60 |year=1963 |pmid=13971327 |doi= |url=}}</ref><ref name="pmid359493">{{cite journal |vauthors=Ritschel WA, Hammer GV, Thompson GA |title=Pharmacokinetics of antimalarials and proposals for dosage regimens |journal=Int J Clin Pharmacol Biopharm |volume=16 |issue=9 |pages=395–401 |year=1978 |pmid=359493 |doi= |url=}}</ref> =====
* Preferred regimen (1): Super high potency or high potency [[Steroid|topical steroid]] twice daily for patients with DLE or SCLE
** [[Hydrocortisone]] 1% or 2.5% for facial involvement 
** [[Triamcinolone acetonide]] 0.1% cream or [[fluocinonide]] 0.05% cream: [[trunk]], extremity, or scalp disease 
** [[Clobetasol propionate]] for acute flares of DLE
*** Discontinue treatment in the absence of disease activity 
* Alternative regimen (1): [[Calcineurin inhibitor|Topical calcineurin inhibitor]] such as [[tacrolimus]] 0.1% ointment or [[pimecrolimus]] 1% cream
* Preferred regimen (2): Intralesional [[corticosteroid]] injections for DLE or SCLE if an acute flare of DLE or SCLE doesn't respond to [[Topical steroid|topical steroid therapy]] for two to four week 
* Alternative regimen (2): Systemic medications; [[hydroxychloroquine]] 200 to 400 mg/day for at least six weeks
** After improvement it should be decreased to 200 mg/day for maintenance therapy
** Administered in the case of failure of local therapy or extensive disease manifestation 
* Alternative regimen (3): [[Quinacrine]] 100 mg/day
** In case of [[Antimalarial drug|antimalarial drugs]] failure 


●For patients with focal lesions of DLE or SCLE that fail to respond to topical therapy, we suggest treatment with intralesional corticosteroid injections (Grade 2C). (See 'Intralesional corticosteroids' above.)
===== Lupus nephritis treatment<ref name="pmid25014039">{{cite journal |vauthors=Schwartz N, Goilav B, Putterman C |title=The pathogenesis, diagnosis and treatment of lupus nephritis |journal=Curr Opin Rheumatol |volume=26 |issue=5 |pages=502–9 |year=2014 |pmid=25014039 |pmc=4221732 |doi=10.1097/BOR.0000000000000089 |url=}}</ref><ref name="pmid23328501">{{cite journal |vauthors=Hogan J, Appel GB |title=Update on the treatment of lupus nephritis |journal=Curr. Opin. Nephrol. Hypertens. |volume=22 |issue=2 |pages=224–30 |year=2013 |pmid=23328501 |doi=10.1097/MNH.0b013e32835d921c |url=}}</ref><ref name="pmid25778500">{{cite journal |vauthors=Tunnicliffe DJ, Singh-Grewal D, Kim S, Craig JC, Tong A |title=Diagnosis, Monitoring, and Treatment of Systemic Lupus Erythematosus: A Systematic Review of Clinical Practice Guidelines |journal=Arthritis Care Res (Hoboken) |volume=67 |issue=10 |pages=1440–52 |year=2015 |pmid=25778500 |doi=10.1002/acr.22591 |url=}}</ref> =====
* Aggressive [[antihypertensive therapy]] with [[blood pressure]] goal of 130/85
* In patients with [[proteinuria]], antiproteinuric therapy with blockade of the [[renin-angiotensin system]] include [[ACEIs]] and [[ARBs]]:
** [[ACE inhibitor|ACE inhibitors]]; [[captopril]] PO 25 mg 3 times daily
*** Antiproteinuric effect 
** [[ARBs]]; [[losartan]] PO initial: 50 mg once daily; can be increased to 100 mg once daily based on [[blood pressure]] response
*** Slowing progression of [[GFR]] decline;
* [[Lipid]] lowering with [[statin therapy]] with the goal of [[LDL]]< 130


●Patients who fail local therapy or who have extensive disease that makes topical or intralesional therapy impractical may benefit from systemic medications. We suggest treating these patients with hydroxychloroquine (Grade 2B). If therapy with hydroxychloroquine is unsuccessful, we suggest adding quinacrine 100 mg/day (Grade 2C). Switching from hydroxychloroquine to chloroquine is an additional therapeutic option. (See 'Antimalarials' above.)
|-
|Raynaud phenomenon
|
|
* Preferred regimen 1: Channel blocker (CCB) alone
* Preferred regimen 2: Antiplatelet therapy with low-dose aspirin (75 or 81 mg/day) in all patients with secondary RP
* Alternative regimen 1: Add phosphodiesterase (PDE) inhibitor (eg, sildenafil) if there was no answer to CCBs. Sildenafil is begun at 20 mg once or twice daily
* Alternative regimen 2: Addition of topical nitroglycerin (NTG) in patients with an inadequate response to a CCB and for whom a PDE inhibitor is not available, effective, or well-tolerated
* Alternative regimen 3: Intravenous (IV) infusions of a prostaglandin (PG) for extremely severe patients
|
|-
|Lupus nephritis
|Aggressive antihypertensive and, in patients with proteinuria, antiproteinuric therapy with blockade of the renin-angiotensin system (eg, angiotensin-converting enzyme [ACE] inhibitor or angiotensin II receptor blocker [ARB])
Lipid lowering with statin therapy, since chronic kidney disease is a risk factor for cardiovascular morbidity and mortality.
|
* Diffuse or focal proliferative LN:
* Diffuse or focal proliferative LN:
** Immunosuppressive therapy with glucocorticoids plus either intravenous (or oral) cyclophosphamide or mycophenolate mofetil
** Preferred regimen: [[Immunosuppressive therapy]] with [[glucocorticoids]] plus either [[Intravenous therapy|intravenous]] or oral [[Mycophenolate sodium|mycophenolate mofetil]]: 0.5 g of [[Mycophenolate sodium|mycophenolate mofetil]] twice daily for the first week, then 1 g twice daily for the second week, and thereafter increase the dose to 1.5 g twice daily
** mycophenolate mofetil is used instead of cyclophosphamide as initial therapy, we give 0.5 g of mycophenolate mofetil twice daily for the first week, then 1 g twice daily for the second week, and thereafter increase the dose to 1.5 g twice daily
** Alternative regimen: [[Immunosuppressive therapy]] with [[glucocorticoids]] plus IV [[cyclophosphamide]] 500 mg every two weeks for a total of six doses
** Alternative regimen: Intravenous cyclophosphamide, 500 mg every two weeks for a total of six doses


* Severe active disease: 
* Severe active disease: 
** glucocorticoid therapy is initiated with intravenous pulse methylprednisolone (250 mg to 1000 mg given over 30 minutes daily for three days) to induce a rapid immunosuppressive effect, followed by conventional doses.  
** Preferred regimen: [[Glucocorticoid|Glucocorticoid therapy]] is initiated with [[Intravenous therapy|intravenous]] pulse [[methylprednisolone]] (250 mg to 1000 mg given over 30 minutes daily for three days) to induce a rapid [[immunosuppressive]] effect, followed by conventional doses  
** Conventional doses of oral glucocorticoids (eg, 0.5 to 1 mg/kg per day of prednisone) without a pulse.Oral prednisolone at a dose of 60 mg/day, tapered every two weeks by 10 mg/day until 40 mg/day is reached, then tapered by 5 mg/day until 10 mg/day is reached. 
** Alternative regimen: Conventional doses of oral [[glucocorticoids]] (eg, 0.5 to 1 mg/kg per day of prednisone) without a pulse.
 
*** Oral [[prednisolone]] at a dose of 60 mg/day, tapered every two weeks by 10 mg/day until 40 mg/day is reached, then tapered by 5 mg/day until 10 mg/day is reached 
|Prednisone:
 
Lupus nephritis, induction (off-label dose): Oral:
 
Class III-IV lupus nephritis: 0.5 to 1 mg/kg/day (after glucocorticoid pulse) tapered after a few weeks to lowest effective dose, in combination with an immunosuppressive agent (Hahn 2012).
 
Class V lupus nephritis: 0.5 mg/kg/day for 6 months in combination mycophenolate mofetil; if not improved after 6 months, use 0.5 to 1 mg/kg/day (after a glucocorticoid pulse) for an additional 6 months in combination with cyclophosphamide (Hahn 2012).
|-
|Gastro-intestinal manifestation
|proton pump inhibitor for accompanies peptic ulcer
 
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|}
 
The benefits of hydroxychloroquine or chloroquine in SLE are broad and include relief of constitutional symptoms, musculoskeletal manifestations, and mucocutaneous manifestations  


===== Considerations<ref name="pmid25778500" /> =====
* Appropriate adjunct therapy:
** [[Vitamin D]] and [[calcium supplement|calcium supplements]]<nowiki/> for preventing [[osteoporosis]] in patients using [[corticosteroids]]
** [[Antihypertensive drugs]] and [[statins]] were also recommended in patients using [[corticosteroids]]
* Adverse effects: Cutaneous [[atrophy]] is a potential side effect of the long-term use of [[Topical steroid|topical steroids]]
==References==
==References==
{{reflist|2}}
{{reflist|2}}

Latest revision as of 18:39, 23 August 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2] Raviteja Guddeti, M.B.B.S. [3]

Overview

The mainstay of therapy for systemic lupus erythematosus (SLE) is to control disease activity and prevent organ damage. The treatment of choice for systemic lupus erythematosus (SLE) varies based on the severity of the disease and symptoms. Generally, all the patients with any type of SLE manifestation should be treated with hydroxychloroquine regardless of the level of their disease. Other pharmacologic medical therapies for SLE include glucocorticoids like oral prednisone or intravenous methylprednisolone, NSAIDs like celecoxib, and immunosuppressive therapy with mycophenolate, cyclophosphamide, or rituximab, particularly in severe cases. Cutaneous lupus erythematosus (CLE), if presented separately without any other system involvement, can be treated with topical corticosteroids. Other organ-related complications of SLE should be treated separately.

Medical Therapy

Treatment goals in systemic lupus erythematosus (SLE) include:

  • Ensure long-term survival
  • Achieve the lowest possible disease activity
  • Prevent organ damage
  • Minimize drug toxicity
  • Improve quality of life
General treatment
  • Hydroxychloroquine: 200 to 400 mg daily as a single daily dose or in 2 divided doses.
    • Generally, all patients with any type of SLE manifestation should be treated with hydroxychloroquine regardless of the severity of the disease.

The treatment choice for systemic lupus erythematosus (SLE) is varied based on the severity of the disease and symptoms:

  • Mild cases are defined as disease pattern with one or two organ involvement.
  • Moderate cases are defined as more than 2 organ involvement during disease flares with low grade of involvement and complications or one or two organ involvement with more extensive involvements.
  • Severe cases are defined as presentation of the disease with life threatening complications and multiple (more than 2) organ involvements.

Severe disease

  • Preferred regimen (1): Hydroxychloroquine PO 200 to 400 mg daily as a single daily dose or in 2 divided doses AND methylprednisolone as intravenous "pulse"; 0.5 to 1 g/day for three days in acutely ill patients, or 1 to 2 mg/kg/day in more stable patients
  • Alternative regimen(1): Hydroxychloroquine PO 200 to 400 mg daily as a single daily dose or in 2 divided doses AND prednisone oral; 40-60 mg/day
  • Alternative regimen (2): Mycophenolate
    • For induction: 1 g twice daily for 6 months in combination with a glucocorticoid
    • For maintenance: 0.5-3 g daily or 1 g twice daily
  • Alternative regimen (3): Cyclophosphamide IV 500 mg once every 2 weeks for 6 doses or 500 to 1,000 mg/m2 once every month for 6 doses or 500 to 1,000 mg/m2 every month for 6 months, then every 3 months for a total of at least 2.5 years
  • Alternative regimen (4): Rituximab IV: 375 mg/m2 once weekly for 4 doses or 1,000 mg (flat dose) on days 0 and 15 or 500 to 1,000 mg on days 1 and 15

Less Severe (mild and moderate) disease

  • Preferred regimen (1): Hydroxychloroquine PO 200 to 400 mg daily as a single daily dose or in 2 divided doses
  • Preferred regimen (2): Prednisone PO low doses of 10 mg/d or less for a short term therapy
    • For milder SLE
    • For treatment of cutaneous and musculoskeletal symptoms not responding to other therapies
    • It should be tapered once hydroxychloroquine has taken effect
  • Alternative regimen (1): Azathioprine PO initial 2 mg/kg/day; may reduce to 1.5 mg/kg/day after 1 month
    • Can be used to control symptoms
  • Alternative regimen (2): Methotrexate PO initial therapy with 7.5 mg once weekly; may increase by 2.5 mg increments weekly
    • Can be used to control symptoms

Other organ specific treatments

Fever management[1][2]

Raynaud's phenomenon treatment[3]

Chronic pain management[5]
  • Moderate pain should be treated with mild prescription opiates such as:
  • Moderate to severe chronic pain should be treated with stronger opioids such as:
    • Preferred regimen (1): Hydrocodone: Single doses >40 mg or >60 mg with a total daily dose ≥80 mg
    • Preferred regimen (2): Oxycodone: 5 to 15 mg every 4 to 6 hours as needed
    • Alternative regimen (1): MS Contin: Opioid naive patients can have 5 to 10 mg every 4 hours; usual dosage range between 5 to 15 mg every 4 hours
      • Higher initial doses in patients with prior opioid exposure
    • Alternative regimen (2): Methadone: Maximum initial dose 30 mg
    • Alternative regimen (3): Fentanyl Duragesic Transdermal patch: A convenient treatment option for lupus chronic pain. It has a long lasting effect as well
Cutaneous lupus erythematosus[6][7][8][9][10]
Lupus nephritis treatment[11][12][13]
  • Severe active disease: 
    • Preferred regimen: Glucocorticoid therapy is initiated with intravenous pulse methylprednisolone (250 mg to 1000 mg given over 30 minutes daily for three days) to induce a rapid immunosuppressive effect, followed by conventional doses  
    • Alternative regimen: Conventional doses of oral glucocorticoids (eg, 0.5 to 1 mg/kg per day of prednisone) without a pulse.
      • Oral prednisolone at a dose of 60 mg/day, tapered every two weeks by 10 mg/day until 40 mg/day is reached, then tapered by 5 mg/day until 10 mg/day is reached 
Considerations[13]

References

  1. ↑ Jordan N, D'Cruz D (2016). "Current and emerging treatment options in the management of lupus". Immunotargets Ther. 5: 9–20. doi:10.2147/ITT.S40675. PMC 4970629. PMID 27529058.
  2. ↑ Cobo-Ibáñez T, Loza-Santamaría E, Pego-Reigosa JM, Marqués AO, Rúa-Figueroa I, Fernández-Nebro A, Cáliz Cáliz R, López Longo FJ, Muñoz-Fernández S (2014). "Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: a systematic review". Semin. Arthritis Rheum. 44 (2): 175–85. doi:10.1016/j.semarthrit.2014.04.002. PMID 24830791.
  3. ↑ Challenor VF, Waller DG, Francis DA, Francis JL, Mani R, Roath S (1987). "Nisoldipine in primary Raynaud's phenomenon". Eur. J. Clin. Pharmacol. 33 (1): 27–30. PMID 3691593.
  4. ↑ Pardy BJ, Hoare MC, Eastcott HH, Miles CC, Needham TN, Harbourne T, Ellis BW (1982). "Prostaglandin E1 in severe Raynaud's phenomenon". Surgery. 92 (6): 953–65. PMID 6890719.
  5. ↑ Di Franco M, Guzzo MP, Spinelli FR, Atzeni F, Sarzi-Puttini P, Conti F, Iannuccelli C (2014). "Pain and systemic lupus erythematosus". Reumatismo. 66 (1): 33–8. PMID 24938194.
  6. ↑ DOEGLAS HM (1964). "CHRONIC DISCOID LUPUS ERYTHEMATOSUS TREATED WITH TRIAMCINOLONE AND PLASTIC OCCLUSION". Dermatologica. 128: 384–6. PMID 14162995.
  7. ↑ Rothfield N, Sontheimer RD, Bernstein M (2006). "Lupus erythematosus: systemic and cutaneous manifestations". Clin. Dermatol. 24 (5): 348–62. doi:10.1016/j.clindermatol.2006.07.014. PMID 16966017.
  8. ↑ Sárdy M, Ruzicka T, Kuhn A (2009). "Topical calcineurin inhibitors in cutaneous lupus erythematosus". Arch. Dermatol. Res. 301 (1): 93–8. doi:10.1007/s00403-008-0894-6. PMID 18797893.
  9. ↑ BJORNBERG A, HELLGREN L (1963). "Treatment of chronic discoid lupus erythematosus with fluocinolone acetonide ointment". Br. J. Dermatol. 75: 156–60. PMID 13971327.
  10. ↑ Ritschel WA, Hammer GV, Thompson GA (1978). "Pharmacokinetics of antimalarials and proposals for dosage regimens". Int J Clin Pharmacol Biopharm. 16 (9): 395–401. PMID 359493.
  11. ↑ Schwartz N, Goilav B, Putterman C (2014). "The pathogenesis, diagnosis and treatment of lupus nephritis". Curr Opin Rheumatol. 26 (5): 502–9. doi:10.1097/BOR.0000000000000089. PMC 4221732. PMID 25014039.
  12. ↑ Hogan J, Appel GB (2013). "Update on the treatment of lupus nephritis". Curr. Opin. Nephrol. Hypertens. 22 (2): 224–30. doi:10.1097/MNH.0b013e32835d921c. PMID 23328501.
  13. ↑ 13.0 13.1 Tunnicliffe DJ, Singh-Grewal D, Kim S, Craig JC, Tong A (2015). "Diagnosis, Monitoring, and Treatment of Systemic Lupus Erythematosus: A Systematic Review of Clinical Practice Guidelines". Arthritis Care Res (Hoboken). 67 (10): 1440–52. doi:10.1002/acr.22591. PMID 25778500.

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