Systemic lupus erythematosus medical therapy: Difference between revisions

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** 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.
** 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 =====
===== Fever management =====
* NSAIDs
* NSAIDs
* Acetaminophen 1000 mg every 6 hours; maximum daily dose: 3000 mg daily '''AND/OR''' 
* Acetaminophen 1000 mg every 6 hours; maximum daily dose: 3000 mg daily '''AND/OR''' 
* Low to moderate doses of glucocorticoids 
* Low to moderate doses of glucocorticoids 
===== Chronic pain management =====
* Moderate pain should be treated with mild prescription opiates such as:
** Dextropropoxyphene
** Co-codamol
* Moderate to severe chronic pain should be treated with stronger opioids such as:
** Hydrocodone
** Oxycodone
** MS Contin
** Methadone.
** 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


===== Considerations =====
===== Considerations =====
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** Vitamin D and calcium supplements for preventing osteoporosis in patients using corticosteroids
** Vitamin D and calcium supplements 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.
* 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.  
[[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]].
 
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.
 
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.


====Contraindicated medications====
====Contraindicated medications====

Revision as of 17:11, 3 July 2017

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

Overview

As lupus erythematosus is a chronic disease with no known cure, treatment is restricted to dealing with the 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.

Medical Therapy

Non-pharmacologic therapy:
  • Sun protection: Use of sun-cream with high SPF to prevent skin flares
  • Exercise
  • Smoking cessation: Smoking has been associated with more severe disease
  • Immunizations: Patients should receive appropriate immunizations prior to the institution of immunosuppressive therapies
  • Treating comorbid conditions:
    • 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
  • NSAIDs
  • Acetaminophen 1000 mg every 6 hours; maximum daily dose: 3000 mg daily AND/OR 
  • Low to moderate doses of glucocorticoids 
Chronic pain management
  • Moderate pain should be treated with mild prescription opiates such as:
    • Dextropropoxyphene
    • Co-codamol
  • Moderate to severe chronic pain should be treated with stronger opioids such as:
    • Hydrocodone
    • Oxycodone
    • MS Contin
    • Methadone.
    • 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
Considerations
  • Treatment recommendations are mostly based on the following:[1]
    • 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.

Contraindicated medications

all patients with SLE with any degree and type of disease activity should be treated with hydroxychloroquine or chloroquine, unless these agents are contraindicated=

Cutaneous lupus erythematosus Photoprotection: broad spectrum sunscreens and sun protective clothing

Avoidance of exacerbating drugs

Smoking cessation

LOCAL THERAPY :

Topical corticosteroids: first-line therapies for patients with DLE or SCLE / twice daily application of a super high potency or high potency topical corticosteroid / clobetasol propionate : first-line therapy for acute flares of DLE / inimal disease activity on the face,:  hydrocortisone 1% or 2.5% /  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

18797893: pimecrolimus 1% cream and as tacrolimus 0.03% or 0.1% ointment / more expensive than topical corticosteroids, and may be slower-acting

Patients with focal lesions that do not respond to topical corticosteroids or topical calcineurin inhibitors can be treated with intralesional corticosteroid injections

16966017

SYSTEMIC THERAPY

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 /

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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.

●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.)

●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.)

●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 In patients who do not respond adequately to a calcium channel blocker (CCB) alone, we suggest the addition of a phosphodiesterase (PDE) inhibitor (eg, sildenafil) rather than another orally administered vasodilator or topical nitrate (Grade 2B). Sildenafil is begun at 20 mg once or twice daily

In patients with an inadequate response to a CCB and for whom a PDE inhibitor is not available, effective, or well-tolerated, we suggest the addition of topical nitroglycerin (NTG) 

intravenous (IV) infusions of a prostaglandin (PG) for extremely severe patients

antiplatelet therapy with low-dose aspirin (75 or 81 mg/day) in all patients with secondary RP

use of bosentan, an orally administered endothelin-1 inhibitor, as the next step rather than other oral agents or sympathectomy in very severe un-responsive

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.

For initial therapy in patients with diffuse or focal proliferative LN, we recommend immunosuppressive therapy with glucocorticoids plus either intravenous (or oral) cyclophosphamide or mycophenolate mofetil, rather than other immunosuppressive regimens such as glucocorticoid monotherapy or azathioprine

In patients with severe active disease (eg, acute kidney injury, crescentic glomerulonephritis, severe extrarenal 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. In patients without severe active disease, we use conventional doses of oral glucocorticoids (eg, 0.5 to 1 mg/kg per day of prednisone) without a pulse. There is no consensus about the best oral glucocorticoid regimen. One option is 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. 

If cyclophosphamide is used instead of mycophenolate mofetil as initial therapy, most experts give intravenous cyclophosphamide, 500 mg every two weeks for a total of six doses. 

If 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.

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

SLE complication treatment

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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  

References

  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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