Systemic lupus erythematosus medical therapy
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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
- 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[1][2]
- Preferred regimen: Celecoxib PO 100 to 200 mg twice daily
- For fever management even in SLE patients with “sulfa” allergy
- Alternative regimen: Acetaminophen 1000 mg every 6 hours; maximum daily dose: 3000 mg daily
Raynaud's phenomenon treatment[3]
- 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 (PDE) inhibitor (sildenafil) 20 mg once or twice daily
- Inadequate response to a CCB
- Alternative regimen (2): Addition of topical nitroglycerin (NTG)
- Inadequate response to a CCB
- A PDE inhibitor is not available, effective, or well-tolerated
- Alternative regimen (3): Intravenous (IV) infusions of a prostaglandin (PG) especially prostacyclin (PGI2) analogue for extremely severe patients with raynaud's phenomenon[4]
Chronic pain management[5]
- 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 (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; 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]
- Preferred regimen (1): Super high potency or high potency 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): 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 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 drugs failure
Lupus nephritis treatment[11][12][13]
- 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 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;
- ACE inhibitors; captopril PO 25 mg 3 times daily
- Lipid lowering with statin therapy with the goal of LDL< 130
- 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
- Alternative regimen: Immunosuppressive therapy with glucocorticoids plus IV cyclophosphamide 500 mg every two weeks for a total of six doses
- 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]
- 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
- Adverse effects: Cutaneous atrophy is a potential side effect of the long-term use of topical steroids
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ DOEGLAS HM (1964). "CHRONIC DISCOID LUPUS ERYTHEMATOSUS TREATED WITH TRIAMCINOLONE AND PLASTIC OCCLUSION". Dermatologica. 128: 384–6. PMID 14162995.
- ↑ 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.
- ↑ 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.
- ↑ BJORNBERG A, HELLGREN L (1963). "Treatment of chronic discoid lupus erythematosus with fluocinolone acetonide ointment". Br. J. Dermatol. 75: 156–60. PMID 13971327.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 13.0 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.