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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. [[Pharmacology|Pharmacologic]] medical therapies for SLE include [[hydroxychloroquine]], [[Non-steroidal anti-inflammatory drug|NSAIDs]] like [[celecoxib]], and [[glucocorticoids]] like [[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==
Treatment goals in systemic lupus erythematosus (SLE):
Treatment goals in systemic lupus erythematosus (SLE) include:
* Ensure long-term survival
* Ensure long-term survival
* Achieve the lowest possible disease activity
* Achieve the lowest possible disease activity
* Prevent organ damage
* Prevent organ damage
* Minimize drug toxicity
* Minimize [[drug toxicity]]
* Improve quality of life
* Improve quality of life


===== General treatment =====
===== General treatment =====
* Preferred regiemen:  Hydroxychloroquine (oral): 200 to 400 mg daily as a single daily dose or in 2 divided doses
* [[Hydroxychloroquine]]: 200 to 400 mg daily as a single daily dose or in 2 divided doses.
** Generally all the patients with any type of SLE manifestation should be treated with hydroxychloroquine despie the level of their disease.
** 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.
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 ==
== 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
===== Pharmacological therapy for severe presentation of SLE =====
* 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
* Preferred regimen 1: Hydroxychloroquine (oral): 200 to 400 mg daily as a single daily dose or in 2 divided doses
* Alternative regimen (2): [[Mycophenolate]]
* Preferred regimen 2: Celecoxib for fever management even in SLE patients, even in those with “sulfa” allergy. Dosing: 100 to 200 mg twice daily
** For induction: 1 g twice daily for 6 months in combination with a [[glucocorticoid]]
* Preferred regimen 3: 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
** For maintenance: 0.5-3 g daily or 1 g twice daily
** Alternative regiemen: Prednisone oral; 40-60 mg/day
*** Initial period of intensive [[immunosuppressive therapy]] (induction therapy) to control the disease and halt tissue injury
* Preferred 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 (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
** Initial period of intensive immunosuppressive therapy (induction therapy) to control the disease and halt tissue injury
* 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
*** Alternative regimen 1: 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 2: 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 ==
== Less Severe (mild and moderate) disease ==
* Preferred regimen 1: Hydroxychloroquine (oral): 200 to 400 mg daily as a single daily dose or in 2 divided doses
* Preferred regimen (1): [[Hydroxychloroquine]] PO 200 to 400 mg daily as a single daily dose or in 2 divided doses
* Preferred regimen 2: Celecoxib 100 to 200 mg twice daily
* Preferred regimen (2): [[Prednisone]] PO low doses of 10 mg/d or less for a short term therapy
** For fever management even in SLE patients with “sulfa” allergy
* Preferred regimen 3: Prednisone low doses of 10 mg/d or less for a short term therapy
** For milder SLE
** For milder SLE
** For treatment of cutaneous and musculoskeletal symptoms not responding to other therapies
** For treatment of [[cutaneous]] and musculoskeletal symptoms not responding to other therapies
** It should be tapered once hydroxychloroquine or chloroquine has taken effect
** It should be tapered once [[hydroxychloroquine]] has taken effect
* Alternative regiemen 1: Azathioprine oral; initial 2 mg/kg/day; may reduce to 1.5 mg/kg/day after 1 month
* 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
** Can be used to control symptoms
* Alternative regiemen 2:  Methotrexate oral; initial therapy with 7.5 mg once weekly; may increase by 2.5 mg increments weekly
* 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
** Can be used to control symptoms


== Other organ specific treatments ==
== Other organ specific treatments ==


===== Cutaneous lupus erythematosus =====
===== 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 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: [[Celecoxib]] PO 100 to 200 mg twice daily
** Hydrocortisone 1% or 2.5% for minimal disease activity on the face 
** For [[fever]] management even in SLE patients with [[Sulfa allergy|“sulfa” allergy]]
** Triamcinolone acetonide 0.1% cream or fluocinonide 0.05% cream: trunk, extremity, or scalp disease 
* Alternative regimen: [[Acetaminophen]] 1000 mg every 6 hours; maximum daily dose: 3000 mg daily 
** Clobetasol propionate first-line therapy for acute flares of DLE 
 
** Discontinue treatment in the absence of disease activity 
==== 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> ====
* Alternative regimen 1: topical calcineurin inhibitor such as tacrolimus 0.1% ointment or pimecrolimus 1% cream 
* Preferred regimen (1): [[Calcium channel blocker]] ([[nifedipine]]) 10 to 30 mg 3 times daily  
* Preferred regimen 2: intralesional corticosteroid injections for DLE or SCLE if an acute flare of DLE or SCLE doesn't respond to topical corticosteroid therapy for two to four week 
* Preferred regimen (2): Antiplatelet therapy with low-dose [[aspirin]] (75 or 81 mg/day) in all patients with secondary [[Raynaud phenomenon]]
* Alternative regimen 2: fail of local therapy or extensive disease manifestation are the indications of systemic medications like hydroxychloroquine 200 to 400 mg/day for at least six weeks, after improvement it should be decreased to 200 mg/day for maintenance therapy 
* Alternative regimen (1): [[Phosphodiesterase inhibitors|Phosphodiesterase (PDE) inhibitor]] ([[sildenafil]]) 20 mg once or twice daily
* Alternative regimen 3: If antimalarial drugs are unsuccessful, add quinacrine 100 mg/day 
** 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>
 
===== 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> =====
* 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


<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>
===== 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> =====
<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>
* Preferred regimen (1): Super high potency or high potency [[Steroid|topical steroid]] twice daily for patients with DLE or SCLE
<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>
** [[Hydrocortisone]] 1% or 2.5% for facial involvement 
<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>
** [[Triamcinolone acetonide]] 0.1% cream or [[fluocinonide]] 0.05% cream: [[trunk]], extremity, or scalp disease 
<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>
** [[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 


===== Lupus nephritis treatment =====
===== 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
* 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
* In patients with [[proteinuria]], antiproteinuric therapy with blockade of the [[renin-angiotensin system]] include [[ACEIs]] and [[ARBs]]:
* Lipid lowering with statin therapy
** [[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


* Diffuse or focal proliferative LN:
* Diffuse or focal proliferative LN:
** Preferred regimen: Immunosuppressive therapy with glucocorticoids plus either intravenous or oral mycophenolate mofetil: 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
** 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
** Alternative regimen: IV cyclophosphamide instead of mycophenolate mofetil  500 mg every two weeks for a total of six doses
** Alternative regimen: [[Immunosuppressive therapy]] with [[glucocorticoids]] plus IV [[cyclophosphamide]] 500 mg every two weeks for a total of six doses


* Severe active disease: 
* 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  
** 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  
** 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 
** 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 


===== Raynaud phenomenon treatment =====
===== Considerations<ref name="pmid25778500" /> =====
* 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: 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
 
===== 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:
* Appropriate adjunct therapy:
** Vitamin D and calcium supplements for preventing osteoporosis in patients using corticosteroids
** [[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
** [[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.
* Adverse effects: Cutaneous [[atrophy]] is a potential side effect of the long-term use of [[Topical steroid|topical steroids]]
===== Adverse effects: =====
* Cutaneous atrophy is a potential side effect of the long-term use of topical corticosteroids
 
==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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