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


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


==Overview==
==Overview==
As lupus erythematosus is a chronic disease with no known cure, treatment is restricted to dealing with the [[Symptomatic treatment|symptoms]]; essentially this involves preventing flares and reducing their severity and duration when they occur. There are several means of preventing and dealing with flares, including drugs, alternative medicine and lifestyle changes.
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==
Due to the variety of symptoms and organ system involvement with Lupus patients, the severity of the SLE in a particular patient must be assessed in order to successfully treat SLE.  Mild or remittent disease can sometimes be safely left untreated. If required, [[non-steroidal anti-inflammatory drug]] and anti-malarials may be used.<ref> [http://www.merck.com/mmpe/sec04/ch032/ch032g.html#sec04-ch032-ch032g-205 Merck manual discussion of Lupus] </ref>
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
*** 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
 
== 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<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 
 
==== 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>
 
===== 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
 
===== 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 
 
===== 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


[[Disease-modifying antirheumatic drug]]s (DMARDs) are used preventively to reduce incidence of flares, the process of the disease, and lower the need for steroid use; when flares occur, they are treated with corticosteroids.  DMARDs commonly in use are anti-malarials and immunosupressants (e.g. [[methotrexate]] and [[azathioprine]]). [[Hydroxychloroquine]] (trade name Plaquenil) is an FDA approved anti-malarial used for constitutional, cutaneous, and articular manifestations, while [[Cyclophosphamide]] (trade names Cytoxan and Neosar) is used for severe glomerulonephritis or other organ-damaging complications, and in 2005, [[mycophenolic acid|CellCept]] became accepted for treatment of [[lupus nephritis]].
* Diffuse or focal proliferative LN:
** 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: [[Immunosuppressive therapy]] with [[glucocorticoids]] plus IV [[cyclophosphamide]] 500 mg every two weeks for a total of six doses


In more severe cases, medications that modulate the [[immune system]] (primarily [[corticosteroid]]s and [[Immunosuppresive drug|immunosuppressant]]s) are used to control the disease and prevent re-occurrence of symptoms (known as flares).  Patients who require steroids frequently may develop [[obesity]], [[diabetes mellitus|diabetes]] and [[osteoporosis]]. Depending on the dosage, corticosteroids can cause other side effects such as a puffy face, an unusually large appetite and difficulty sleeping. Those side effects can subside if and when the large initial dosage is reduced, but long term use of even low doses can cause elevated blood pressure and cataracts. Due to these side effects, steroids are avoided if possible.
* Severe active disease: 
** 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 


Since a large percentage of Lupus patients suffer from varying amounts of chronic pain, stronger prescription analgesics may be used if over-the-counter drugs, mainly [[non-steroidal anti-inflammatory drug]] do not provide effective relief. Moderate pain in Lupus patients if typically treated with mild prescription opiates such as Dextropropoxyphene (trade name Darvocet), and Co-codamol (trade name Tylenol #3). Moderate to severe chronic pain is treated with stronger opioids such as Hydrocodone (trade names Lorcet, Lortab, Norco, Vicodin, Vicoprofen) or longer-acting continuous release opioids such as Oxycodone (trade names OxyContin), MS Contin, or Methadone. The Fentanyl Duragesic Transdermal patch is also a widely-used treatment option for chronic pain due to Lupus complications because of its long-acting timed release and easy usage. When opioids are used for prolonged periods drug tolerance, chemical dependency and (rarely) addiction may occur. Opiate addiction is not typically a concern for Lupus patients, since the condition is not likely to ever completely disappear. Thus, lifelong treatment with opioids is fairly common in Lupus patients that exhibit chronic pain symptoms; accompanied by periodic increased titration that is typical of any long-term opioid regimen.
===== 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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