The pharmacological treatment of lupus revolves around four considerations1:
1. Is there organ-threatening disease (cardiopulmonary, hepatic, renal, hematological, central nervous system) that requires corticosteroids and immunosuppressive therapy?
2. Is there non-organ-threatening disease (constitutional, musculoskeletal, cutaneous, serositis) warranting disease-modifying therapy?
3. Should organ-specific measures (e.g., treatment of a rash) be implemented?
4. Which adjunctive treatments (e.g., bisphosphonates, angiotensin-converting enzyme inhibitors) are appropriate for the patient?
The principles of drug therapy for lupus state that organ-threatening disease should be managed aggressively with moderate to high doses of corticosteroids, often followed by the institution of steroid-sparing measures in the form of immunosuppressives. Antimalarials are usually introduced as well. Non-organ-threatening disease is managed with nonsteroidal anti-inflammatory drugs (NSAIDs), antimalarials, and low doses of steroids if necessary.
Nonsteroidal Anti-inflammatory Agents and Salicylates
The safest NSAID from a cardioprotective standpoint is naproxen, with or without a proton-pump inhibitor. All other NSAIDs are acceptable in lupus, but with certain caveats: celecoxib is gentler on the stomach and safer in patients on warfarin but has a sulfa component, ibuprofen is associated with infrequent aseptic meningitis, and others (e.g., piroxicam) are sun-sensitizing. These agents are useful for headaches, fevers, serositis, arthralgia, arthritis, myalgias, and generalized pain. They do not have disease-modifying properties. NSAIDs are as efficacious as, and easier to use than, salicylates.
Antimalarials
Chloroquine, hydroxychloroquine, and quinacrine (available from compounding pharmacists) prevent the activation of Toll receptors 7 and 9 and raise cellular pH, which turns off receptor activation sites. They have been used in lupus for over 50 years and are approved by the Food and Drug Administration for this indication. Hydroxychloroquine is the agent of choice. It can diminish the risk of non-organ dissemination in mild disease, decrease the rate of disease flares, and prevent damage accrual; it is approved for use in rheumatoid arthritis (RA) and thus treats synovitis, and it has ameliorative effects on all aspects of organ-threatening disease (especially cutaneous) (Fig. 11.1). Given in doses of 5 to 7 mg/kg, hydroxychloroquine (Plaquenil) begins working in 6 to 12 weeks but does not attain its maximal effects for up to 6 months.2 Recent work suggests that antimalarials also lower cholesterol levels, inhibit platelet aggregation, and improve sicca symptoms associated with Sjögren’s syndrome. Retrospecive studies have associated hydroxychloroquine with less damage accrual, prolonged survival, better renal and skin outcomes, delay in disease onset, less vascular damage, fewer infections and thromboembolic events, and lower blood pressure in lupus patients.7
Ten percent report flu-like symptoms, gastrointestinal distress, or a headache with hydroxychloroquine; this rate is lower when generic preparations are not prescribed. Of those who take the drug for 10 years, 3% develop a reversible maculopathy. Annual ophthalmological examinations are advised after an initial evaluation and at five years in individuals with specific risk factors.8
Chloroquine is very effective for severe cutaneous disease in doses of 500 mg/day for 30 days followed by 250 mg/day for 3 months. Commonly used in developing countries due to its minimal cost, it is more retinotoxic than other treatments (10% develop changes in 10 years, and these may not always be reversible). Most patients who respond to chloroquine are transitioned to hydroxychloroquine for maintenance.
Quinacrine is synergistic with the chloroquines, is effective for cutaneous lupus, and diminishes fatigue. It is not toxic to the eyes. It produces a yellowish stain, and 30% of patients taking it develop mild diarrhea. Quinacrine is dosed at 50 to 100 mg/day, and a complete blood count and basic metabolic panel should be obtained quarterly (Table 11.1).
Figure 11.1 The Canadian Cooperative Trial documentation of the efficacy of hydroxychloroquine (Plaquenil) in preventing lupus flares. Source: N Engl J Med. 1991;324:150-154. ©1991 Massachusetts Medical Society. All rights reserved.
Corticosteroids
The use of corticosteroids is a critical intervention in managing systemic lupus. Patients with organ-threatening disease are usually prescribed 1 mg/kg/day prednisone equivalent for 4 to 6 weeks followed by tapering by 10% per week. Flares of synovitis, rashes, fevers, or serositis are managed with lower doses for days to weeks. Patients with non-organ-threatening disease rarely require maintenance doses of greater than 15 mg/day. The long-term use of corticosteroids is associated with premature atherogenesis, hyperlipidemia, hyperglycemia, cataracts, glaucoma, emotional lability, bone demineralization, ecchymosis, peptic ulcer disease, and avascular necrosis (Table 11.2).
Immunosuppressive Regimens
If patients with organ-threatening lupus demonstrate active disease on 10 mg of prednisone equivalent or less, an immunosuppressant is usually introduced. The same concept applies to patients on lower doses if there are additional risk factors present such as diabetes or difficulty tolerating corticosteroid therapy. The principal immunosuppressants used in SLE are discussed next.
Methotrexate is an antimetabolite that inhibits dehydrofolate reductase and promotes adenosine release. It is effective for synovitis and some constitutional and cutaneous manifestations of SLE but is not helpful for organ involvement. The dosing is similar to that used in RA (10 to 20 mg weekly with 1 mg/day of folic acid).
Table 11.1 Antimalarials for lupus erythematosus
1. Principal relevant effects
a. Inhibits phospholipase A2 and phospholipase C
b. Stabilization of lysosomal membranes
c. Decreased production of estrogen
d. Quinidine-like cardiac effects
e. Antagonism of Toll-like receptors (TLR-7 and 9)
f. Photoprotection
2. Evidence-based clinical effects of hydroxychloroquine
a. Sustained beneficial effect on overall survival, disease-free survival, and damage accrual
b. Delayed onset of SLE and flare rate reduction
c. Protection against thromboembolic events
d. Protective effect against renal damage
e. Decreases in infection rate
f. Lowering of blood sugar and improvement in lipid profiles
Wallace DJ, Gudsoorkar VS, Weisman MH et al. New insights into mechanisms of therapeutic effects of antimalarial agents in SLE. Nature Rev Rheumatol. 2012;8:522–533.
Table 11.2 Corticosteroids for SLE
1. Available preparations:
a. Pulse intravenous methylprednisolone—given for life- or organ-threatening complications and severe flares in doses of 1G daily for 1–5 days. Oral methylprednisolone—preferred in children due to its advantages in an immature liver; does well in adults
b. Prednisone—the gold standard
c. Betamethasone—available intramuscular, intraarticular and topically; crosses the placenta
d. Triamcinolone—available intramuscular and topically
e. Hydrocortisone—available topically, orally (short half-life; used for rapid induction but is salt-retaining; used intravenously in emergency crises as it is effective within 20 minutes)
f. Dexamethasone—available as topical, intraarticular, intramuscular, or oral preparations. May be useful for central nervous system disease
2. Usual regimens for systemic disease:
a. Pulse steroids (see above)
b. High-dose prednisone equivalent (30–100 mg daily), used for at least a month for life- or organ-threatening complications (e.g., nephritis, pneumonitis, central nervous system vasculitis, autoimmune hemolytic anemia, retinitis)
c. Moderate dose prednisone equivalent (7.5–30 mg daily), used for myositis, pleurisy, thrombocytopenia, for example
d. Low dose prednisone equivalent (<7.5 mg daily) is used for arthritis, mild constitutional symptoms, maintenance therapy, rashes, for example.
e. Alternate day prednisone equivalent is used as chronic maintenance therapy where hypothalamic-pituitary-axis sparing is a goal (e.g., membranous nephritis)
Leflunomide is a pyrimidine antagonist. Dosing is 20 mg/day after a 3-day loading dose of 100 mg, and it is used for the same indications as methotrexate.
Azathioprine is an antimetabolite purine antagonist approved by the U.S. Food and Drug Administration, previously approved for RA, and is effective for synovitis. Controlled studies have also demonstrated efficacy for nephritis and hepatic involvement. Case series have demonstrated that it is useful in managing hematological, pulmonary, myositis, and cutaneous manifestations of the disease. Patients are usually started at 50 mg/day for the first week, 100 mg/day for the second week, and 150 mg/day maintenance. Lower doses can be used if there is gastrointestinal intolerance or in patients with stable disease after several years. Ten percent and 1% of patients are heterozygous or homozygous, respectively, for thiopurine S-methyltransferase enzyme activity and may have reactions to the drug. This can be prescreened for with an assay. The drug takes 3 to 4 months to become effective. Blood counts and liver function testing should be monitored every 1 to 3 months. After 3 years of therapy, there is an increased risk for lymphoma.
Mycophenolate mofetil inhibits inosine monophosphate dehydrogenase, which blocks Band T-cell proliferation. It is clearly beneficial for most forms of lupus nephritis. It is generally well tolerated, but up to 20% of patients are have difficulty taking it due to gastrointestinal complaints. Its administration for other manifestations of SLE has not been adequately studied or is not useful (e.g., with synovitis). Most patients are started at 500 mg/day and built up to a maintenance dose of 1500 to 3000 mg/day.
Cyclosporin is an immunosuppressant that inhibits interleukin-2. It is used for membranous nephritis and bone marrow hypoplasias or aplasia. Cyclosporin may be useful in certain refractory rashes seen in SLE. The usual dose is 3 mg/kg/day in divided doses.
Cyclophosphamide is a very powerful alkylating agent that is clearly effective for proliferative and membranous nephritis, central nervous system vasculitis, and serious pulmonary or hematological manifestations of the disease. Best given intravenously in doses of 750 mg/kg monthly for at least 6 months (NIH regimen or EUROLUPUS regimen of 500 mg every two weeks x 6 doses) followed by discontinuation or dosing every 2 to 3 months, this agent produces nausea and cytopenias.3 The 80% risk of infertility in women receiving the drug over the age of 30 can be minimized by leuprolide injections (3.75 mg SC) 2 weeks prior to each dose (Fig. 11.2).
Nitrogen mustard was widely used in the mid 1900s for serious lupus but has been replaced by cyclophosphamide. Chlorambucil is ameliorative for renal disease but is leukemogenic and should not be used. Tacrolimus and sirilimus are transplant rejection drugs that have been safely given to lupus patients, and they are currently being studied for other aspects of the disease.
Figure 11.2 National Institutes of Health randomized study showing the superiority of cyclophosphamide for lupus nephritis over azathioprine or prednisone alone. Source: Balow JE, Austin HA 3rd, Tsokos GC, Antonovych TT, Steinberg AD, Klippel JH. NIH conference. Lupus nephritis. Ann Intern Med. 1987;106:79–94. ©1991 American College of Physicians. Reprinted with permission.
Other niche therapies are discussed earlier in this text under specific organ system manifestations.
Management of Organ- and Symptom-Specific Manifestations of Lupus
Constitutional
Lupus fever is acutely treated with NSAIDs, and corticosteroids if needed. Prednisone is the drug of choice and is usually given every 8 to 12 hours in doses of at least 0.25 kg/day. Hydrocortisone has a more rapid onset of action and can be used intravenously or orally every 6 hours in an emergency setting.
Cutaneous
Topical or Local Regimens
In addition to sunscreens, local measures include corticosteroids and immunosuppressants. Topical steroids include creams, ointments, and lotions and range from low to high potency. Over-the-counter topicals are nonfluorinated and contain hydrocortisone. Fluorinated corticosteroids are more powerful, but chronic use (especially on the face) can lead to cutaneous atrophy and telangiectasias. Facial use should be limited to no more than 2 weeks of treatment at a time. Creams are well tolerated but only 20% absorbed, as opposed to lotions (50%) and ointments (80%). Ointments are the most effective vehicle but are not tolerated as well and tend to be goopy and uncomfortable, especially with certain clothing (see Table 11.2). Where indicated, steroids may be injected intralesionally. On occasion, occlusive corticosteroid dressings are applied to refractory rashes. Pinecrolimus cream and tacrolimus ointments are approved in the United States for eczema, and these immunophylles are modestly effective for cutaneous lupus (see Table 11.3).
Acute Cutaneous Lupus
These lesions respond to systemic steroids, and the length and duration of therapy depend on how active extracutaneous manifestations of the disease are.
Chronic Cutaneous Lupus Erythematosus (Discoid Lupus)
In addition to topical and local regimens (see previous sections), antimalarials represent the gold standard for managing all except the mildest cases. Hydroxychloroquine is initiated in doses of 5 mg/kg/day and has a 6- to 12-week onset of action. More active lesions can be managed with up to 7 mg/kg/day of the drug for the first 3 months, or chloroquine can be substituted (500 mg/day). Upon improvement, these patients can usually be stabilized on 5 mg/kg/day hydroxychloroquine. Quinacrine can be added to the chloroquines and is synergistic (50 to 100 mg/day), or it can be used as monotherapy in individuals who cannot tolerate the chloroquines. Rarely used third-line agents include dapsone, retinoids, lamprene, and topical nitrogen mustard.
Table 11.3 Topical corticosteroids ranked by potency
|
Group |
Generic name |
Brand name |
|
I. Superpotent |
Clobetasol propionate cream, ointment, gel, or emollient, 0.05% |
Temovate Diprolene Psorcon Ultravate |
|
II. Potent |
Amcinonide ointment, 0.1% |
Cyclocort Diprolene Diprolene Topicort Maxiflor Lidex Halog Elocon |
|
III. Midpotent |
Amcinonide cream or lotion, 0.1% |
Cyclocort Diprosone Valisone Maxiflor Lidex-E Cutivate Halog Aristocort A |
|
IV. Midpotent |
Fluocinolone acetonide ointment, 0.025% |
Synalar Cordran Westcort Elocon Kenalog |
|
V. Midpotent |
Betamethasone dipropionate lotion, 0.05% |
Diprosone Valisone Synalar Cordran Cutivate Locoid Westcort Kenalog |
|
VI. Mild |
Alclometasone dipropionate cream or ointment, 0.05% |
Alcovate |
|
VII. Mild |
Betamethasone valerate lotion, 0.05% |
Valisone DesOwen Locorten Synalar Aristocort A |
|
See copyright page of this book for permission to reprint Table 11.3. |
||
Subacute Cutaneous Lupus
This lesion is not as responsive to the chloroquines as is discoid lupus. The addition of a retinoid (e.g., Soriatene, Accutane) for several weeks to months may be necessary.
Mucocutaneous Lesions
Oral ulcers are managed with buttermilk gargles, gargles of hydrogen peroxide diluted in water, or dental pastes containing corticosteroids. Nasal ulcerations are less frequent but need to be distinguished from Wegener’s granulomatosis or the effects of cocaine use. Petroleum jelly (e.g., Vaseline) may be useful. Vaginal ulcerations are observed in 5% of females with SLE at some point in the course of their disease. Cyclosporin can ameliorate chronic aphthous stomatitis.
Alopecia
Reducing inflammation is the best treatment, and alopecia is often the last manifestation of the disease to improve. Intralesional hair follicle injections may be useful. Minoxidil preparations are modestly effective. L-Cysteine-containing shampoos may also be useful.
Other Manifestations
Lupus urticaria responds to steroids, antimalarials, H1 and H2 histamine blockers, and cyclosporine.
Lupus profundus is managed with local injections and antimalarials. Bullous lupus is frequently responsive to dapsone.
Lupus pemphigoid should be treated with mycophenolate mofetil.
Cutaneous vasculitis responds to corticosteroids. Colchicine or dapsone may be helpful.
The first-line treatment for Raynaud’s phenomenon is cold avoidance, biofeedback, and cold-protection measures (e.g., gloves, mittens). Medication is used if the vasospasm is painful or there are skin ulcerations. Calcium channel blockers, especially nifedipine (30 to 90 mg/day), are the intervention of choice. If this class of drugs is not effective or is poorly tolerated, the following classes of drugs can be added to calcium channel blockers or used as monotherapy in the following order: nitroglycerin paste, 5-phosphodiesterase inhibitors (e.g., sildenafil), vasodilators (e.g., minoxidil), and α-blockers (e.g., α-methyldopa). Some angiotensin-converting enzyme inhibitors are minimally effective. Raynaud’s activity does not correlate with disease activity.
Digital vasculitis can lead to gangrene. Patients are given Raynaud’s remedies in addition to corticosteroids and immunosuppressive therapies. Resistant cases also benefit from prostaglandin-blocking agents (e.g., alprostadil infusions) and digital sympathectomy.
Musculoskeletal
Management of the synovitis of lupus arthritis depends on the degree of inflammation and whether or not erosions are present. NSAIDs or salicylates are helpful. Hydroxychloroquine is ameliorative. Most cases respond to 10 mg or less of prednisone daily. In doses similar to those used in RA, methotrexate (10 to 15 mg weekly with 1 mg of folic acid daily) or leflunomide (20 mg/day after a loading dose) is usually effective within 30 days. Tumor necrosis factor inhibitors can be used if erosions are present and patients do not have antibodies to double-stranded DNA. Abatacept, azathioprine, or rituximab represent effective alternative therapies.
Lupus myositis responds to prednisone 20 mg/day for several weeks if serum creatine phosphokinase levels are less than 500 IU. More active myositis is approached with higher doses of corticosteroids in combination with methotrexate, azathioprine, or rituximab.
Pulmonary
Nonscarring pleuritic pain in SLE responds to high-dose NSAIDs or short courses of moderate-dose corticosteroids. Higher doses of corticosteroids with either antimalarial or immunosuppressive maintenance are used in individuals with pleural effusions. Refractory cases can be managed with a pleurodesis or pleurectomy.
Acute lupus pneumonitis is fatal unless patients are given high doses of corticosteroids acutely.
The treatment of interstitial lung disease depends upon its level of activity. If it is deemed to have a reversible component, corticosteroids are usually initiated along with immunosuppressive therapy such as cyclophosphamide or azathioprine.
Pulmonary hemorrhage has a very high mortality rate. Those who have the greatest chance for survival include patients who have received pulse corticosteroids, cyclophosphamide with or without plasmapheresis.
Pulmonary hypertension mandates aggressive vigilance and treatment when pulmonary pressures rise above 50 mmHg. Vasodilators and calcium channel blockers may be useful in mild cases, but progressive pressure elevations usually mandate endothelin receptor antagonists, 5-phosphodiesterase blockers (e.g., sildenafil), or prostaglandin E1/prostacyclin derivatives. Infrequently, pulmonary hypertension is a manifestation of vasculitis and responds to corticosteroids. Heart-lung transplantation may be advisable in advanced, medication-unresponsive patients.
Cardiac
Pericarditis is managed similarly to pleurisy. Pericardial tamponade or hemody-namically compromising effusions are uncommon, but a pericardiocentesis can be of diagnostic and therapeutic value.
Myocardial dysfunction in SLE is treated with inotropic agents, β-blockers, diuretics, and angiotensin-converting enzyme inhibitors. Acute myocarditis responds to 1 mg/kg/day prednisone for several weeks.
Libman-Sacks endocarditis warrants more vigilance than medication therapy. Patients with this manifestation should be on daily low-dose aspirin, have dental prophylaxis, and be considered for platelet antagonists and possibly anticoagulation, depending on their antiphospholipid antibody profile.
Lupus patients with hypertension respond to most antihypertensives, but renal impairment plays a bigger role in this occurrence. Also, some antihypertensives have a sulfa component, which could be problematic.
Microvascular angina is treated with beta blockers and nitrates.
Nervous System
Central nervous system vasculitis is over-diagnosed. When truly present, the best response rates have been reported among those receiving pulse doses of corticosteroids (e.g., 1 g of methylprednisolone intravenously for 3 days) followed by high doses of prednisone for at least a month. Traditionally, patients do well with 750 mg/m2 monthly of intravenous cyclophosphamide for 6 months. Maintenance therapy after this is usually not necessary. Patients who fail to quickly respond often benefit from the addition of a 60 mL/kg plasmapheresis for several days. Recent reports have also suggested that rituximab or intrathecal methotrexate can be beneficial. Antiphospholipid syndromepatients should not be given corticosteroids unless they have the “catastrophic antiphospholipid syndrome” subset or clear-cut evidence for systemic inflammation. Stroke patients should be anticoagulated with heparin followed by warfarin while the source of the process is being worked up.
The management of the dysautonomic syndromes of SLE (e.g., lupus headache, cognitive dysfunction) is similar. Anti-inflammatory medicines are not overly beneficial; anxiety reduction, biofeedback, cognitive-behavioral therapy, psychotropic medications, and antimalarials are the treatments of choice. Vasodilators are useful in selected circumstances. Corticosteroids should be avoided if there is no evidence for vasculitis or inflammation (see Table 11.4).
Nephritis
Renal involvement in SLE is best assessed with a kidney biopsy. Adjunctive measures include monitoring blood pressure; treating nephrosis with diuretics as needed; and low-protein, -salt, or -fat diets as indicated, as well as screening for and managing electrolyte imbalances.4,5
Proliferative nephritis is associated with a high probability for evolving end-stage renal disease at 10 years. The National Institutes of Health protocol used by most lupologists for the past 20 years involves giving 1 mg/kg/day of corticosteroids for 4 to 6 weeks, followed by tapering to a maintenance dose of 10 mg/day for at least 2 years. Concurrently, patients are also given intravenous cyclophosphamide monthly (750/m2) for 6 months followed by retreatment every 1 to 3 months for up to 3 years. One-third have a complete remission on this schedule, one-third respond at first but relapse, and one-third have no response. Recently, many centers have begun adding mycophenolate mofetil or azathioprine at 4 to 6 months in lieu of continuing cyclophosphamide. Infertility associated with cyclophosphamide can be attenuated by the use of leuprolide (Leupron), 3.75 mg subcutaneously (SC), 2 weeks before each chemotherapy dose. A pivotal trial comparing cyclophosphamide with mycophenolate mofetil for induction showed them to be equal in efficacy; however, patients with crescentic, aggressive nephritis were excluded. Pulse steroids or apheresis can be used short term for acute flares Mycophenolate is superior to azathioprine for maintenance or improvement.6 Several biologicals are being studied in clinical trials for proliferative disease. Recent American College of Rheumatology guidelines for managing nephritis have been published and are summarized in Figure 11.3.
Table 11.4 Examples of management options for nervous system lupus
1. Rule out fibromyalgia, infection, or medication reaction-causing symptoms
2. Cerebral vasculitis: High-dose corticosteroids, cyclosphosphamide; rituximab, apheresis for selected cases; anticonvulsants and antipsychotic regimens as needed
3. Thromboembolic event due to antiphospholipid syndrome: Platelet antagonists, anticoagulation
4. Lupus headache/cognitive dysfunction (vasculopathy, not vasculitis): Antimalarials, psychotropics, cognitive-behavioral therapy, anxiety reduction measures, biofeedback, calcium channel blockers
5. Chronic organic brain syndrome: Emotional support, anticonvulsants if needed
6. Cryoglobulinemia or hyperviscosity: Steroids, apheresis, immune suppressive regimens
7. Thrombotic thrombocytopenia purpura: Apheresis, rituximab
8. Peripheral nervous system lupus: Steroids, intravenous immune globulin, gabapentin, rituximab or cyclophosphamide
9. Posterior reversible encephalopathy syndrome: Control blood pressure
10. Pseudotumor cerebri: Lumbar puncture
11. Lupus sclerosis: Multiple sclerosis regimens
Membranous nephritis follows a slower, more indolent course, except that more patients are nephrotic and develop renal vein thrombosis. The above regimens have been used successfully in these circumstances; however, there is evidence that cyclosporine may be effective and that some patients do not need any anti-inflammatory treatment (see Table 11.4).
Figure 11.3 Algorithm for managing proliferative lupus nephritis according to the American College of Rheumatology guidelines.
Hemic-Lymphatic System
Diffuse adenopathy is generally quite responsive to moderate-dose corticosteroids.
Hemolytic anemia responds to high doses of steroids very slowly, and they may have to be given for several months before tapering. Response rates have been disappointing. Cyclophosphamide, azathioprine, or rituximab is usually added to the regimen.
The decision to treat idiopathic thrombocytopenic purpura (ITP) depends on the patient’s platelet counts. No special treatment is required if the count is above 100,000/mm3. Counts between 60,000 and 99,000/mm3 are only treated if there is active inflammation evident outside the hemic-lymphatic system. Patients with counts less than 60,000/mm3 are usually treated with corticosteroids. Cyclophosphamide, azathioprine, danocrine, or rituximab can be quite efficacious corticosteroid adjuncts. Intravenous immunoglobulin transiently raises platelet counts. Splenectomy is curative of ITP in 60% of medication-resistant cases.
Thrombotic thrombocytopenic purpura (TTP) is fatal in up to half of all cases. Plasma exchange is lifesaving; there is some evidence that rituximab is helpful as well.
Most of the agents commonly prescribed in SLE are summarized in Table 11.5.
Alternative and Complementary Medicine
In the United States, 40% of the population uses complementary and alternative medicines, spending $27 billion a year. Lupus patients tend to use four types of approaches3:
1. Manipulative, physical, and manual therapies. These include acupuncture, Pilates, chiropractics, reflexology, tai chi, and yoga. Any technique that strengthens muscles and promotes aerobic conditioning is acceptable, and some diminish pain.
2. Methods that promote relaxation, cognitive improvement, and greater disease understanding. Aromatherapy, biofeedback, cognitive-behavioral therapy, guided imagery, meditation, and prayer are examples of these methods. Evidence-based studies involving lupus have demonstrated that any activity that works with the mind-body connection, decreases anxiety, and promotes restful sleep is usually helpful.
3. Detoxification regimens such as colonic irrigation, magnet therapy, or chelation therapies are unproven in lupus and potentially dangerous.
4. Herbal, dietary, and neutroceutical approaches include homeopathic remedies, lifestyle diets (e.g., elemental, hypoallergenic, fasting, elimination), folk remedies, and vitamin regimens. Some supplements might be beneficial, but the majority are unproven (see Table 11.6).
Table 11.5 Drugs frequently used to manage systemic lupus erythematosus (SLE)
|
1. NSAIDs |
Used for fever, headache, serositis, arthralgia/arthritis, myalgia, fever |
|
2. Antimalarials |
Hydroxychloroquine is FDA approved for SLE and rheumatoid arthritis (RA) |
|
3. Corticosteroids |
Approved by the FDA for SLE |
|
4. Immunosuppressants |
i. Methotrexate: FDA approved for RA, indicated for synovitis and some rashes in RA doses |
|
5. Biologicals |
i. Anti-TNF blockers: FDA approved for RA; can be used in selected lupus patients; issues include disease exacerbation or rash, autoantibody development, infection risk in RA doses |
Table 11.6 Herbs studied for lupus, fibromyalgia, and other rheumatic disorders using evidence-based principles
|
Herb |
Comments |
|
Alfalfa Capsicum Echinacea Gingko biloba Green tea extract L-tryptophan St. John’s wort T wilfordii Valerian root |
L-canavanine in alfalfa sprouts may flare lupus Capsaicin is a proven topical analgesic in osteoarthritis Reports of lupus flares from immune stimulation May help cognitive impairment Reports of improvement in collagen-induced arthritis models Sleep aid; contaminants can cause a scleroderma-like illness A natural serotonin booster Thunder-god vine; used in China for lupus, very potent May improve sleep |
References
1. Wallace DJ, Hahn BH. Section 6: The management of lupus. In: DJ Wallace, BH Hahn, eds. Dubois’ Lupus Erythematosus and related disorders. 78h ed. Philadelphia, PA: Elsevier 2013:582–658.
2. Canadian Cooperative Study Group. A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. The Canadian Hydroxychloroquine Study Group. N Engl J Med. 1991;324:150–154.
3. Balow JE, Austin HA 3rd, Tsokos GC, Antonovych TT, Steinberg AD, Klippel JH. NIH conference. Lupus nephritis. Ann Intern Med. 1987;106:79–94.
4. Ernst E. Musculoskeletal conditions and complementary/alternative medicine. Best Pract Res Clin Rheumatol. 2004;18(4):539–556.
5. Hahn BH, Mc Mahon MA, Wilkinson A, et al, American College of Rheumatology guidelines for screening, treatment and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012;64:797–808.
6. Dooley MA, Jayne D, Ginzler EM, et al. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med. 2011;365:1886–1895.
7. Wallace DJ, Gudsoorkar VS, Weisman MH et al, New insights into mechanisms of therapeutic effects of antimalarial agents in SLE. Nature Rev Rheumatol. 2012;8:522–533.
8. Marmor MF, Kellner U, Lai TY, Lyons JS, et al. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011;118:415–422.