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08.08.2014

Alternative medicine for lupus disease, functional medicine doctors in massachusetts - Plans Download

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Although many medications are used for the management of systemic lupus erythematosus (SLE) and its complications, only aspirin, corticosteroids, and the antimalarial drug hydroxychloroquine (HCQ) are specifically approved by the FDA.1 Most other medications used for SLE treatment are commercially available off label (Table 1), usually borrowed from cancer or transplant regimens.
H Hashimoto, S Hirose, S Kano, et al1992Studies on clinical subsets and severity of systemic lupus erythematosus based on a 1987 questionnaire conducted in Japan-Clinical analysis of the outcome and treatments in clinical subsets. M Seki, C Ushiyama, N Seta, et al1998Apoptosis of lymphocytes induced glucocorticoids and relationship to therapeutic efficacy in patients with systemic lupus erythematosus. S Hirohata, Y Kanai, A Mitsuo, et al2009Accuracy of cerebrospinal fluid IL-6 testing for diagnosis of lupus psychosis. In some cases, medications have been approved for a specific clinical manifestation seen in both idiopathic disease and SLE, such as bosentan for pulmonary hypertension. These include medications with less toxicity or a better adverse effect profile that can prevent disease flares and accrual of damage resulting from the pathological changes of SLE itself or adverse effects of treatment (eg, corticosteroid-induced osteoporosis, diabetes mellitus, osteonecrosis). Remission rate of lupus nephritis according the WHO classification type and degree of proteinuria3.2. IntroductionSystemic lupus erythematosus (SLE), which is an inflammatory disease of unknown cause, is a representative autoimmune disease. In addition, long-term complications, such as premature atherosclerosis, must be recognized and prevented.Instead of targeting the entire immune system with the general immunosuppressive agents currently available, medications should be developed to target specific immunological dysfunction and specific disease features, and agents should be identified that have differential efficacy and toxicity in specific racial and ethnic groups.
L Dubois, 1987Prognostic subsets, natural course, and causes of death in systemic lupus erythematosus, In: Wallace DJ, Dubois EL editors.
C Roberts, 1975The heart in systemic lupus erythematosus and the changes induced in it by corticosteroid therapyA study of 36 necropsy patients.
Identification of biomarkers to predict outcomes and drug efficacy also is essential.In this article, we review the drugs currently available for SLE and the newer therapeutic agents in clinical trials for lupus in general or particular disease manifestations. E Gallacher, et al2011Efficacy and safety of belimumab in patients with active systemic lupus eryhematosus: a randomized, placebo-controlled, phase 3 trial. We also discuss drugs used off label for the manifestations of SLE and management options for the complications of SLE.FDA-approved medications for SLECorticosteroids often are used as the first-line agent for patients with most manifestations of SLE because of their powerful anti-inflammatory actions. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Instituting corticosteroid-sparing agents should be considered somewhat quickly, especially in the case of corticosteroid dependency or frequent exacerbations of disease activity.HCQ was the last medication approved by the FDA for lupus in 1955. This drug has long been recognized as a valuable agent for managing fatigue, as well as cutaneous and musculoskeletal manifestations, and preventing lupus flares.2 More recently, evidence has shown that HCQ improves long-term survival of patients with SLE and protects against irreversible organ damage, thrombosis, and bone mass loss.
However, potent NSAIDs (eg, ketorolac, indomethacin, diclofenac) are relatively contraindicated for patients with SLE because they increase the risk of acute renal failure and congestive heart failure. NSAIDs should be prescribed with particular caution in patients with lupus nephritis (LN) or renal impairment.Medications in clinical trialsBiologic agents currently being studied for SLE have been designed to target various immunological processes, such as B-cell and T-cell functions, including production of cytokines (Table 2).
Clinical findings One thousand one hundred and twenty-five SLE patients fulfilling four or more of the revised ACR (American College of Rheumatology) criteria [2] were examined and treated at the Department of Internal Medicine and Rheumatology in Juntendo University School of Medicine between 1955 and 2002. In children and adults over the age of 50, the incidence of SLE demonstrated only a slight female predominance, however, for those in their twenties, thirties and forties, close to 90% of patients were women. Treatment according to disease severity Clinical subsets of SLE were divided into three groups according to disease severity that related to prognosis [7].
The nephritis trial for atacicept was terminated early because of an unexpected incidence of infectious complications.
Belimumab, the anti-BLyS monoclonal antibody, showed a reduction in anti-dsDNA titers correlating with SLE disease activity. Moderate disease: lupus nephritis without renal failure, pleuritis, pericarditis, meningitis, hemolytic anemia, thrombocytopenic purpura, etc.
Although this agent is FDA-approved for rheumatoid arthritis (RA), clinical trials of preventing flares of generalized SLE did not meet primary or secondary end points. Anti–TNF-? agents also are in trials for treatment of patients with LN and cutaneous lupus.


The initial dose of steroids was usually determined according to the severity and activity of the disease. However, given the case reports of drug-induced lupus in patients with RA who were treated with TNF-? inhibitors, patients with SLE need to be monitored closely when these drugs are administered.Lupuzor is a novel immune modulator. After gaining approval for the management of plaque psoriasis and being studied for cutaneous lupus, efalizumab was withdrawn from the market because of reports of progressive multifocal leukoencephalopathy.Managing organ-specific manifestationsWe have several suggestions for the management of organ-specific manifestations of SLE. Lupus erythematosus tumidus: response to antimalarial treatment in 36 patients with emphasis on smoking. AZA is used as a corticosteroid-sparing agent for mild to moderate generalized lupus features, rash, and arthritis and as maintenance therapy for LN.•Cutaneous lupus. Recently, belimumab (anti-BLyS antibody), the first targeted biological drug, was approved for treatment of SLE by the FDA [10]. Antimalarials should be added to the treatment regimen as early as possible, along with oral corticosteroids, for moderate to severe cutaneous lupus. If other causes of the lesions are suspected, referral to a dermatologist for biopsy is needed.Use of antimalarials other than HCQ, such as quinacrine and chloroquine, may be considered to control cutaneous lupus, but these agents carry an increased risk of retinal toxicity and rheumatologists do not use them frequently. If there is a poor response to the initial therapies, dapsone and colchicine may be added to the regimen.Thalidomide has been very useful for refractory cutaneous lupus because of its antiangiogenic effects.
The causes of death were renal failure (30%), cerebrovascular diseases (23%), infection (19%), and others. However, this agent requires special regulation and close monitoring for pregnancy and neuropathy.Therapeutic agents currently in trials for cutaneous lupus are topical pimecrolimus, betamethasone, thalidomide and, systemically administered, etanercept (a TNF-? blocker) and lenalidomide (a thalidomide derivative). Oral prednisone, antimalarials, NSAIDs, and celecoxib often are used as first-line agents for the management of synovitis in SLE.
Disease-modifying antirheumatic drugs (eg, MTX and leflunomide) may be added in patients with arthritis in SLE, and they are useful in clinical practice. Abatacept and rituximab may be considered for the treatment of patients with refractory "rhupus," ie, patients with SLE who also have erosive, deforming arthritis or chronic synovitis. However, questions remain about the appropriate dosage and duration of maintenance therapy after remission has been achieved.AZA may be used for class II LN or for patients who cannot tolerate MMF, but it has not been shown to be as effective as MMF or IV CYC for induction regimens. During the maintenance phase, corticosteroids usually are discontinued while only the immunosuppressive agent—MMF or AZA—is continued.Pulse intravenous corticosteroids, IV CYC, and IV gammaglobulin may be considered for patients with severe nephritis that is unresponsive to MMF and corticosteroids. Short-term hemodialysis may be an option for some patients in whom acute renal failure and fluid overload develop.Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) should be added and titrated as much as possible to aid in decreasing proteinuria, along with aggressive management of hypertension and dyslipidemia.
Drugs in clinical trials for LN are abatacept, TRU-015, rituximab, fludarabine, ocrelizumab, infliximab, etanercept, AMG 811 (anti–IFN-?), sirolimus, tacrolimus, and leflunomide.•Neuropsychiatric manifestations of SLE (NPSLE).
Vasculitis may be managed with the immunosuppressive agents described above for other manifestations in combination with corticosteroids. Thalidomide and rituximab also may be useful for the management of vasculitis in SLE.Raynaud phenomenon may be managed with calcium channel blockers, cilostazol, ticlopidine, topical nitrates, phosphodiesterase inhibitors (eg, sildenafil), and endothelin receptor antagonists (eg, bosentan) as needed to avoid digital gangrene.
The success of pregnancy depends on the duration of well-controlled lupus before conception; longer duration correlates with better outcomes.
If secondary antiphospholipid antibody syndrome is present with a history of previous pregnancy losses, heparin may be used for prophylaxis.Medications used to prevent and manage complications of SLEThe leading causes of death in SLE are infections and atherosclerotic events (Table 3). Accelerated atherosclerosis—cardiovascular, cerebrovascular, or peripheral vascular disease—has been well documented in SLE. In the patients with DPGN or RPGN, intravenous pulse therapy of cyclophosphamide (IVCY) (500-750mg, monthly for 3 to 6 months), as immunosuppressive agent, was used. Alternative induction therapies included combined therapies with steroids and immunosuppressive agents such as daily oral cyclophosphamide, azathioprine, tacrorimus, mizoribine, and cyclosporine, etc.
Apart from counteracting dyslipidemia, statins may have anti-inflammatory effects and are being explored in a clinical trial for the management of general lupus. Agents that may be used for pulmonary arterial hypertension include calcium channel blockers, bosentan, sildenafil, and inhaled iloprost.Corticosteroid-induced osteoporosis contributes to significant morbidity because of fractures.


For discussions of other important considerations, see the Boxes, "Recommendations for treating patients with lupus" and "Medication interactions and adverse effects in lupus" above.SummaryPatients with SLE currently have an improved prognosis because of earlier diagnosis and aggressive management of active disease manifestations and complications.
Because SLE is phenotypically heterogeneous, focused research is required on therapeutic agents for the management of organ-specific manifestations and for patient subsets based on individual characteristics. Figure 1.Remission rate of lupus nephritis according the WHO classification type and degree of proteinuriaFigure 1 shows the remission rate after onset according to the WHO classification type and degree of proteinuria. The remission rates of patients with Type IV (DPGN) and profuse peroteiniria or nephrotic syndrome tended to decrease during the course of the disease, while the remission rates of patients with Type II and persistent proteinuria tended to increase. Patients with Type V (MGN) had a low remission rate through out the course of the disease, but no decrease in the remission rate was observed until later on.
This fact suggests that the underlying disease types had a greater influence on the remission rate than the treatment method. Table 4.Frequencies of neuropsychiatric manifestations (NPLE) in 1125 lupus patientsThe American College of Rheumatology (ACR) proposed new criteria for the classification of neuropsychiatric syndrome of systemic lupus erythematosus (NPSLE) in 1999 [16].
Many NPLE cases were considered to be caused by lupus itself, excluding obvious causes such as antiphospholipid antibody syndrome (APS), necrotizing angiitis, and complications.NPLE is one of the diseases that influence the prognosis of SLE as well as LN.
Especially, patients with acute confusional state or organ brain syndrome (OBS), cognitive dysfunction, recurrent seizure, and cerebrovascular disease, etc., had poor prognosis. PleuritisPleuritis is by far the most common pulmonary manifestation, occurring at some time in the course in 40 to 50% of lupus patients. The majority of patients were hypoxic, requiring supplemental oxygen or intubation for assisted ventilation. Myocardial infarction and coronary artery diseaseCoronary artery disease due to arteriosclerotic changes is more common in SLE patients.
Death from myocardial infarction late in the course of the disease is one of the most frequent causes of death after 10 to 30 years of SLE [28]. Death from myocardial infarction due to inflammation of the coronary arteries has been reported in SLE patients dying early in the course of their disease, but this is a rare event [28]. In cases associated with bowel infarction or perforation, treatment for infection was also needed. Steroids were the mainstay of the treatment for AIHA and a response was achieved in about 75% of patients. TTP has been reported in association with various other diseases, including SLE, most of which are characterized by some degree of vasculitis of the small vessels and circulating immune complexes [30]. Moreover, even if the patient had active disease, pregnancy was allowed after the disease improved with treatment. Treatment and management during pregnancy It was important for the physician and the gynecologist to be in close communication for the treatment and management during pregnancy. Prevention of exacerbationThe mother was hospitalized prior to the expected delivery date for management of the mother and fetus.
However, it is unclear whether this reflects pro-atherogenic effects of the underlying disease process or adverse metabolic effects associated with steroid use [36].
Table 5 shows the frequencies of these complications at the time of occurence in 97 SLE patients who had been observed for over 20 years.
ConclusionIn this paper, steroid therapy for SLE based on the clinical analysis of 1,125 cases, especially for principal organ involvement that required large doses of steroids, was evaluated.



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