Current and emerging strategies for the management of sarcoidosis

Sarcoidosis is a systemic inflammatory disorder of unknown etiology. Although any organ may be involved, the lungs are most frequently affected. The clinical course of the disease is highly variable, with up to two-thirds of untreated patients experiencing spontaneous remission within 12-24 months of onset of symptoms. When therapy is required, corticosteroids are considered standard, but studies demonstrating their ability to modify the long-term outcome in this disease are lacking. Often, the myriad of adverse side effects of corticosteroids necessitate the addition of immunosuppressants, cytotoxic agents or biologic therapies to maintain disease remission. Unfortunately, optimal therapeutic regimens have not been described. Patients who do not respond to therapy often experience progressive fibrotic changes and end-organ damage, which ultimately may result in significant morbidity or death. Agents commonly used to treat patients with sarcoidosis and emerging therapeutic options are discussed.     

Review article: the limitations of corticosteroid therapy in Crohn's disease

Corticosteroids are highly effective in inducing clinical remission in patients with active Crohn's disease. However, the role of corticosteroids in the treatment of this disease is primarily ameliorative because they are ineffective in maintaining remission or healing mucosal lesions. Nearly half of the patients who initially respond to corticosteroid therapy develop a dependency on corticosteroids or have a relapse within 1 year. In addition, use of these agents is often limited by a relatively high risk of serious adverse effects that can involve nearly every major body system. These effects include: bone loss, which can develop with even short-term and low-dose corticosteroid therapy; metabolic complications such as glucose intolerance and diabetes mellitus; increased intraocular pressure and glaucoma; and potentially lethal infections. To minimize the risk of toxicity, corticosteroids are increasingly recommended for short-term use only at the lowest effective dose to induce remission in patients with moderately to severely active Crohn's disease. Corticosteroid formulations with low systemic bioavailability, such as controlled-release budesonide, may be associated with a lower rate of dermatologic adverse effects but appear to be somewhat less effective than conventional corticosteroids in inducing remission in patients with active Crohn's disease. Immunosuppressive agents such as azathioprine, 6-mercaptopurine, and methotrexate have demonstrated corticosteroid-sparing effects, facilitating the withdrawal of corticosteroids when initiated as maintenance therapy. Infliximab can be used as an alternative to corticosteroids.     

Drug therapy reviews: treatment of sarcoidosis.

Sarcoidosis, the possibility of its spontaneous remission, and its responsiveness to corticosteroid and other drug therapies are discussed. Sarcoidosis is a disease of unknown etiology characterized histologicaly by a granulomatous process with cellular infiltration. The granulomatous changes may remit spontaneously or may develop into fibrosis that, at times, is severe; factors that influence these progressions of the disease are not known. Cellular and humoral immunological abnormalities may be associated with this disease. Any organ can be affected although there is a high frequency of pulmonary involvement. Sarcoidosis may be benign and remit spontaneously in as many as 70% to 80% of cases, but the overall case fatality rate can be as high as 10%. Corticosteroids, the most effective therapy, cause temporary remission of the granulomatous changes but do not influence established fibrosis. Corticosteroids only temporarily influence the natural progression of sarcoidosis; however, corticosteroid therapy can preserve the function of vital organs. Other forms of treatment, such as chloroquine, methotrexate, oxyphenbutazone, allopurinol and levamisole hydrochloride, also produce remissions of the granulomatous infiltrate of sarcoidosis but offer no therapeutic advantages over corticosteroids. The decision to treat is often a difficult one, since corticosteroids and these other therapies have potentially hazardous side effects.     

Anti-tumour necrosis factor therapy for ulcerative colitis: evidence to date

Infliximab, the chimeric monoclonal antibody directed against tumour necrosis factor (TNF)-alpha, has profoundly changed therapy for Crohn's disease (CD). However, for ulcerative colitis (UC), before the publication of ACT 1 and ACT 2 (Active Ulcerative Colitis Trials 1 and 2), there were only a few open-label and controlled trials that evaluated the role of infliximab in the treatment of UC. Results from these earlier studies were equivocal and ambiguous. However, the ACT 1 and ACT 2 trials were large, randomised and placebo-controlled, and have shown that infliximab is significantly more efficacious than placebo in treating both corticosteroid-responsive and -refractory moderate to severe UC. Data from these two studies showed that in patients with moderate to severe UC, treatment with infliximab (5 and 10 mg/kg), compared with placebo, led to significantly higher rates of clinical response, clinical remission and mucosal healing. However, a significant proportion of patients who were receiving oral corticosteroids at the start of the trials, remained on corticosteroids despite infliximab therapy. Additionally, the safety profile of the drug was found to be similar to what has been reported in clinical studies of infliximab in patients with CD.On the basis of currently available data, we use infliximab as a remission-inducing agent in patients who have moderate to severe UC and are either refractory to or intolerant of mesalazine (5-ASA) products and immunomodulators. Moreover, infliximab seems to be a reasonable therapeutic modality for remission maintenance in those patients with UC in whom mesalazine products and immunomodulators have failed. Although data are limited, infliximab may be considered as a remission-inducing agent in patients with moderate to severe UC which is refractory to oral corticosteroids. However, the role of infliximab in the treatment of UC patients who are dependent on oral corticosteroids is still unclear and, therefore, should be considered only in patients who cannot be successfully transitioned to or are intolerant of oral immunomodulators. Furthermore, infliximab may be an alternative to ciclosporin (cyclosporin) in hospitalised patients with severe to moderately severe but not fulminant UC who do not respond to intravenous corticosteroids. At present, there is insufficient evidence to advocate using infliximab as a first-line agent for UC patients with mild or moderate to severe disease. Future randomised, controlled trials with clearly defined patient populations should further help to clarify the definitive role of infliximab in the therapeutic scheme for UC.     

Immunosuppressive drugs in inflammatory bowel disease. A review of their mechanisms of efficacy and place in therapy

Immune effector mechanisms are central to the disease process in inflammatory bowel disease, but it is not clear whether the mucosal or systemic immunological abnormalities are primary phenomena, or are secondary to disease activity. Corticosteroid drugs remain the most effective treatment for active disease, but there is no evidence that they are useful for maintenance therapy. Some patients, however, are dependent on low-dose corticosteroids, and relapse when the drug is withdrawn. These drugs have widespread actions on the immune response, and monocytes are particularly sensitive to corticosteroids. In contrast, sulphasalazine and 5-aminosalicylic acid are effective in maintenance therapy, but do not act primarily by immunosuppressive mechanisms. They are effective in maintenance therapy of ulcerative colitis, and mild relapses of ulcerative colitis and colonic Crohn's disease. New preparations of 5-aminosalicylic acid have reduced side effects, many of which are due to sulphapyridine. Azathioprine and 6-mercaptopurine are used less widely: in Crohn's disease there is reasonable evidence for benefit in chronic active disease unresponsive to corticosteroids, and maintenance of remission. In ulcerative colitis, the position is less clearcut. Overall, trials favour an effect in chronic active disease, and there are pointers to an effect in maintenance of remission. Because of their side effects, in particular marrow suppression, these drugs should be reserved for second-line therapy. Similarly, other cytotoxic drugs are not used because of their side effects. More recently, cyclosporin A, with its selective action on interleukin-2 release and/or synthesis, and inhibition of helper T cell function, has been shown to be helpful in Crohn's disease. At present it should only be used in controlled trials, for patients with unresponsive disease in whom surgery is contraindicated. Renal toxicity may limit long term use. There is little data for cyclosporin A in ulcerative colitis. On the basis that there may be an underlying immune defect in Crohn's disease leading to mucosal inflammation, immunostimulant therapy has been used, but there is no evidence for benefit from treatment with BCG or levamisole in active disease or in maintenance therapy. 7S-Immunoglobulin, plasmapheresis or T-lymphocyte apheresis have been used in acute relapse, but evidence is anecdotal, and does not support their use except as a desperate measure to avoid surgery. Further well-designed controlled trials are needed to define the role of all these drugs, and further research into the mechanism of action on the immune response may shed light on the pathogenesis of inflammatory bowel disease.     

Biological therapy in the management of recent-onset Crohn's disease: why, when and how?

Crohn's disease is a chronic inflammatory bowel disease that may involve any part of the gastrointestinal tract. Conventional therapy consists of corticosteroids, azathioprine or methotrexate, but the clinical management of Crohn's disease is significantly hampered by adverse effects. With the introduction of biological agents (such as infliximab), the goals of therapy have advanced, including induction of remission with bowel healing as well as reduction in the rate of complications, surgeries and mortality. Current therapy for moderate to severe Crohn's disease is based on 'step-up' algorithms, which initiate treatment with corticosteroids followed by immunomodulatory agents, and defer therapy with biological agents until patients become refractory to conventional therapeutics. Recently, it has been shown that induction therapy with infliximab and azathioprine in recent-onset Crohn's disease (i.e. 'top-down' approach) is superior to current step-up algorithms to induce clinical remission. The underlying molecular mechanisms responsible for these differences in clinical outcome remain to be defined. Experimental studies have demonstrated that corticosteroids are able to induce impaired apoptosis of immune cells, including T cells and dendritic cells, resulting in loss of tolerance and subsequent autoimmunity. Further research will have to determine whether corticosteroid therapy augments the mechanism of loss of tolerance in Crohn's disease, which could complicate future clinical management.     

Inflammation and cystic fibrosis pulmonary disease

Inflammation plays a primary role in the pathogenesis of cystic fibrosis (CF)-related lung disease. Controlling the inflammatory process with antiinflammatory therapy may slow the progression of pulmonary disease and thereby decrease morbidity. Despite potential benefits of antiinflammatory therapy, both the decision to treat and selection of the most appropriate therapeutic agent are controversial. Although oral corticosteroids are associated with reduced progression of pulmonary disease, the risk of clinically significant adverse effects limits long-term therapy. Clinical studies with inhaled corticosteroids failed to report positive effects on reducing airway inflammation. Based on available clinical data, routine therapy with these agents should be limited to patients with asthma or steroid-responsive wheezing. High-dosage ibuprofen has a beneficial effect on reducing the annual rate of decline in pulmonary function in patients with mild lung disease. Whereas initial results are encouraging, they do not support routine ibuprofen therapy in all patients with CE However, as advocated by the Cystic Fibrosis Foundation, high-dosage ibuprofen may be considered in children 5-12 years of age with a baseline forced expiratory volume of 60% predicted or greater.     

Recent progress in the pharmacotherapy of Churg-Strauss syndrome

Churg-Strauss syndrome (CSS) is a primary systemic vasculitis occurring primarily in patients with asthma. Unlike other small vessel vasculitides, CSS is characterised by blood and tissue eosinophilia. Corticosteroids are the therapy of first choice for all stages of the disease when active vasculitis needs to be treated rapidly. In patients with severe disease and organ- or life-threatening manifestation, the addition of cyclophosphamide appears to improve the outcome and reduces the incidence of relapses. In cases with an apparently better prognosis and less severe disease, methotrexate can be given as a corticosteroid-sparing agent in order to reduce the cumulative dose of corticosteroids, which is generally high in most cases as long-term administration of corticosteroids is often inevitable in order to control asthma, even if the vasculitis is inactive. In very severe cases of CSS, cyclophosphamide and corticosteroids may be insufficient to induce remission. In these cases, anti-TNF blocking agents such as infliximab or etanercept, may be added for a limited period of time. As this intense immunosuppression increases the risk for infections, a prophylaxis with sulfamethoxazole/trimethoprim is advised. Alternatively, the administration of recombinant IFN-α can be a effective when given on a short-term basis in otherwise refractory cases. Whether a continous administration of immunosuppressive agents in addition to corticosteroids can reduce the frequency of relapses in CSS who are in remission is still unknown. As relapses occur in > 25% of all patients, studies addressing the prevention of relapses in CSS are highly desirable in the future.     

Medical management of mild to moderate Crohn's disease: evidence-based treatment algorithms for induction and maintenance of remission

BACKGROUND: Patients with Crohn's disease alternate between periods of active, symptomatic disease and periods of remission. The treatment goal for Crohn's disease is to induce and then maintain remission of symptoms. AIM: To review evidence from randomized, controlled, clinical trials on medical therapies for inducing and maintaining remission in patients with mild-to-moderate Crohn's disease, and to suggest the best evidence-based approaches for induction and maintenance therapies. METHODS: PubMed search using the following terms: sulfasalazine or salicylazosulfapyridine or aminosalicylate or aminosalicylic acid or mesalamine or mesalazine or corticosteroid or prednisone or prednisolone or methylprednisolone or budesonide or antibiotic or metronidazole or ciprofloxacin or immunosuppressive or azathioprine or mercaptopurine or thiopurine or methotrexate and Crohn's disease. RESULTS: Randomized, controlled trials demonstrated that sulfasalazine, budesonide, and conventional corticosteroids are effective for inducing remission of mild-to-moderate Crohn's disease when administered for a period of 8-16 weeks. An ideal maintenance therapy does not currently exist. CONCLUSIONS: Selection of maintenance therapy is based on a combination of evidence from controlled trials and patient features including disease severity and location, co-morbidities, previous response to treatment, and previous surgical resection. The options for maintenance therapy include therapy cessation and patient observation following successful induction, budesonide, or immunosuppressive therapy.     

Recent progress in the pharmacotherapy of Churg-Strauss syndrome

Churg-Strauss syndrome (CSS) is a primary systemic vasculitis occurring primarily in patients with asthma. Unlike other small vessel vasculitides, CSS is characterised by blood and tissue eosinophilia. Corticosteroids are the therapy of first choice for all stages of the disease when active vasculitis needs to be treated rapidly. In patients with severe disease and organ- or life-threatening manifestation, the addition of cyclophosphamide appears to improve the outcome and reduces the incidence of relapses. In cases with an apparently better prognosis and less severe disease, methotrexate can be given as a corticosteroid-sparing agent in order to reduce the cumulative dose of corticosteroids, which is generally high in most cases as long-term administration of corticosteroids is often inevitable in order to control asthma, even if the vasculitis is inactive. In very severe cases of CSS, cyclophosphamide and corticosteroids may be insufficient to induce remission. In these cases, anti-TNF blocking agents such as infliximab or etanercept, may be added for a limited period of time. As this intense immunosuppression increases the risk for infections, a prophylaxis with sulfamethoxazole/trimethoprim is advised. Alternatively, the administration of recombinant IFN-alpha can be a effective when given on a short-term basis in otherwise refractory cases. Whether a continuous administration of immunosuppressive agents in addition to corticosteroids can reduce the frequency of relapses in CSS who are in remission is still unknown. As relapses occur in > 25% of all patients, studies addressing the prevention of relapses in CSS are highly desirable in the future.     

Pharmacological therapy for Wegener's granulomatosis

Wegener's granulomatosis (WG) is the most common pulmonary granulomatous vasculitis and was a uniformly fatal disease prior to the identification of efficacious pharmacological regimens. The pathogenesis of WG remains elusive but proteinase 3-specific anti-neutrophil cytoplasmic antibodies may be involved. Histologically, WG is defined by the triad of small vessel necrotising vasculitis, 'geographic' necrosis and granulomatous inflammation. Organ involvement characteristically includes the upper and lower respiratory tracts and kidney, but virtually any organ can be involved. The severity of the disease varies, ranging from asymptomatic disease to fulminant, fatal vasculitis. Similarly, the degree of organ involvement is highly variable; WG may be limited to a single organ (typically the lungs or upper respiratory tract), or may be systemic. Currently, a regimen consisting of daily cyclophosphamide and corticosteroids, which induces complete remission in the majority of patients, is considered standard therapy. Since approximately 50% of patients experience a relapse following discontinuation of therapy, alternative regimens designed to maintain remissions after using cyclophosphamide and corticosteroids are usually necessary. This 'induction maintenance' approach to treatment has emerged as a central premise in planning therapy for patients with WG.A number of trials have evaluated the efficacy of less toxic immunosuppressants (e.g. methotrexate, azathioprine, mycophenolate mofetil) and antibacterials (i.e. cotrimoxazole [trimethoprim/sulfamethoxazole]) for treating patients with WG, resulting in the identification of effective alternative regimens to induce or maintain remissions in certain sub-populations of patients. Given the efficacy of methotrexate (for early systemic WG) and cotrimoxazole (in WG limited solely to the upper airways) to induce remissions, and the relatively decreased associated morbidity compared with cyclophosphamide, these alternative regimens are preferred in appropriate patients. Similarly, therapeutic options to maintain disease remission that are less toxic than cyclophosphamide should be offered following induction of remission unless a specific contraindication exists. By following this premise, the development of cyclophosphamide-induced morbidities (e.g. haemorrhagic cystitis, uroepithelial cancers and prolonged myelosuppression) may be minimised. Recent investigation has focussed on other immunomodulatory agents (tumour necrosis factor-alpha inhibitors [infliximab and etanercept] and anti-CD20 antibodies [rituximab]) for treating patients with WG. However, the current data are conflicting and difficult to interpret. As a result, these newer agents cannot be recommended for routine use until vigorous clinical study confirms their efficacy.     

Cost-effectiveness of pharmacotherapy for autoimmune hepatitis

In > 80% of patients with autoimmune hepatitis, steroid therapy alone or in combination with azathioprine results in disease remission. Treatment response results in reversal of fibrosis and excellent long-term survival in many patients, whereas untreated patients may expect a 10-year survival of < 30%. The use of azathioprine monotherapy (2 mg/kg/day) has gained widespread acceptance in maintaining remission in clinical practice. Although all patients with autoimmune hepatitis may not need treatment, particularly those with mild disease, alternative strategies are required in patients who have failed to achieve remission on standard therapy of steroids with or without azathioprine, or patients with azathioprine-induced drug toxicity. In such circumstances, the use of salvage therapy in the form of ciclosporin, tacrolimus or mycophenolate mofetil may be warranted. Liver transplantation is the treatment of choice for patients who present with subacute liver failure or decompensated cirrhosis. Salvage therapy results in an exponential rise in cost with each increment in therapeutic escalation. As an alternative to standard therapy, it has also been suggested that novel therapies such as ciclosporin, tacrolimus or mycophenolate mofetil be initiated to achieve remission. However, a > 10-fold cost differential exists between the charges associated with more potent immunosuppression and standard therapy. Therefore, in evaluating novel immunosuppression in autoimmune hepatitis, it behoves clinicians not only to consider end points pertaining to efficacy, but also end points pertaining to cost-effectiveness. Moreover, the exact role of pharmacogenomics and genotyping of thiopurine methyltransferase in patients with autoimmune hepatitis needs to be fully defined.     

Cost-effectiveness of pharmacotherapy for autoimmune hepatitis

In > 80% of patients with autoimmune hepatitis, steroid therapy alone or in combination with azathioprine results in disease remission. Treatment response results in reversal of fibrosis and excellent long-term survival in many patients, whereas untreated patients may expect a 10-year survival of < 30%. The use of azathioprine monotherapy (2 mg/kg/day) has gained widespread acceptance in maintaining remission in clinical practice. Although all patients with autoimmune hepatitis may not need treatment, particularly those with mild disease, alternative strategies are required in patients who have failed to achieve remission on standard therapy of steroids with or without azathioprine, or patients with azathioprine-induced drug toxicity. In such circumstances, the use of salvage therapy in the form of ciclosporin, tacrolimus or mycophenolate mofetil may be warranted. Liver transplantation is the treatment of choice for patients who present with subacute liver failure or decompensated cirrhosis. Salvage therapy results in an exponential rise in cost with each increment in therapeutic escalation. As an alternative to standard therapy, it has also been suggested that novel therapies such as ciclosporin, tacrolimus or mycophenolate mofetil be initiated to achieve remission. However, a > 10-fold cost differential exists between the charges associated with more potent immunosuppression and standard therapy. Therefore, in evaluating novel immunosuppression in autoimmune hepatitis, it behoves clinicians not only to consider end points pertaining to efficacy, but also end points pertaining to cost-effectiveness. Moreover, the exact role of pharmacogenomics and genotyping of thiopurine methyltransferase in patients with autoimmune hepatitis needs to be fully defined.     

Review article: mild to moderate Crohn's disease--defining the basis for a new treatment algorithm

Previously, clinicians have had few choices in treating mild to moderate Crohn's disease. They currently treat these Crohn's disease patients with oral mesalamine and antibiotics. This treatment approach is based on the safety of these agents, and the perception that they are effective. This perception regarding efficacy may be influenced by publication bias. This review examines the efficacy and safety data of the conventional corticosteroids, mesalamine, sulfasalazine, budesonide and antibiotics for inducing the remission of mild to moderate Crohn's disease from randomized controlled trials, and proposes an evidence-based treatment approach. Sulfasalazine has demonstrated modest efficacy when Crohn's disease is confined to the colon. Mesalamine has no clear benefit over placebo in treating active Crohn's disease. Conventional corticosteroids effectively induce remission but are associated with unwanted adverse effects. Budesonide has similar efficacy to conventional steroids with far fewer adverse effects. Antibiotics have not consistently demonstrated efficacy. We propose a new evidence-based approach which suggests inducing remission of mild to moderate Crohn's disease with budesonide 9 mg/day for patients with ileal and/or right colonic involvement; sulfasalazine for those with disease limited to the colon; and conventional steroids for high disease activity, those who failed budesonide and those with left-sided disease who are allergic or intolerant to sulfasalazine.     

Review article: medical treatment of moderate to severe Crohn's disease

The treatment for patients with Crohn's disease of moderate to severe activity includes traditional drugs, such as corticosteroids, the primary therapy for these forms of disease, able to induce the remission of symptoms in a high percentage of patients. Because of the side-effects produced by systemic steroids, a new glucocorticoid derivative, budesonide, which acts locally in the mucosa, has recently been introduced with positive results. On the assumption that intestinal bacteria play a role in the causing Crohn's disease symptoms, antibiotics are often used in the treatment of active phases, as an alternative to or in association with steroids. The most widely employed antibiotics are metronidazole and ciprofloxacin. Immunosuppressors, such as azathioprine and 6-mercaptopurine, are useful for the treatment of chronic active disease and for maintaining remission, but they have only a marginal role in the therapy of an acute flare-up of Crohn's disease. Methotrexate acts more rapidly and its use in patients with active disease resistant to standard therapy is of interest. The discovery of biological agents represents a new era in the management of patients. To date, infliximab is the more extensively studied biological therapy in the treatment of Crohn's disease and clinical studies have demonstrated its efficacy in inducing remission of refractory disease.     

Adalimumab sustains steroid-free remission after 3 years of therapy for Crohn's disease

Aliment Pharmacol Ther 2011; 34: 306–317

Summary

Background Treatments that achieve sustainable steroid‐free clinical remission in Crohn’s disease are needed; however, long‐term steroid‐sparing efficacy data are limited. Aim To evaluate steroid‐sparing efficacy and the impact of steroid discontinuation on adverse events during treatment of Crohn's disease with adalimumab in the phase III randomised, double‐blind 1‐year CHARM trial and for an additional 2 years in its open‐label extension ADHERE. Methods Steroid‐free remission and response and steroid‐sparing (≥50% steroid dose reduction) remission rates were evaluated over 3 years in patients who were taking corticosteroids at CHARM baseline. Results Of 778 patients randomised in CHARM (including those who did not achieve clinical response to open‐label induction therapy), 313 patients (40%) were on corticosteroids at baseline. In the 206 patients randomised to adalimumab, rates of steroid‐free remission at 1 year and 3 years were 26% and 23% respectively; corresponding rates were 29% and 25% for steroid‐sparing remission and 32% and 28% for steroid‐free response. Although the incidence of serious infections with adalimumab treatment during CHARM was higher in patients taking steroids at baseline than those who were not, the rates of overall adverse events, serious infections and opportunistic infections were lower in patients who were able to discontinue corticosteroids than those who remained on steroids. Conclusion Adalimumab therapy resulted in modest but clinically meaningful rates of steroid‐free remission, sustained over 3 years of treatment, in a heavily pretreated population of patients with Crohn's disease receiving steroids at the start of therapy ( http://www.clinicaltrials.gov number: NCT00077779).     

Review article: treatment algorithms to maximize remission and minimize corticosteroid dependence in patients with inflammatory bowel disease

Background  Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the intestine, which frequently require surgery for complications or failure of medical therapy.
Aim  To seek evidence and provide direction for clinicians on optimal strategies to enable steroid free remission in inflammatory bowel disease.
Methods  Scientific literature was reviewed using MEDLINE with a specific focus on medical therapies for inducing and maintaining remission of CD and UC. The results were discussed at a roundtable meeting to reach a consensus on key issues.
Results  Several therapies have demonstrated efficacy for the treatment of active, moderate-to-severe CD and UC. These include agents, which induce remission [corticosteroids, infliximab and adalimumab (CD only)] or maintain remission and spare corticosteroids [azathioprine, mercaptopurine, methotrexate (CD only), infliximab and adalimumab (CD only)]. Wide variability exists in the use of these agents.
Conclusion  Treatment strategy algorithms are developed for use of these therapies that maximize remission and minimize corticosteroid dependence in patients with moderate-to-severe CD and UC.     

糖皮质激素在社区获得性肺炎治疗中的应用

社区获得性肺炎是临床常见的疾病,虽然有大量抗生素的开发应用,死亡率却无明显下降。肺炎特别是重症肺炎时患者体内可能发生过度炎性反应,导致糖皮质激素相对不足,因此,其作为辅助治疗的作用逐渐被重视,但疗效仍存在一定争议。多数研究者认为糖皮质激素可减少重症肺炎的并发症、降低死亡率,缩短病程,并且没有发现严重不良反应。然而也有研究结果不支持这一结论。不过,对于存在肾上腺皮质功能不全的肺炎患者,中低剂量糖皮质激素可能是安全有效的。如何确定治疗适应证,如何选择适合的剂型、剂量和疗程需要进一步研究。     

Review article: the evidence base for interventions used to maintain remission in Crohn's disease

Background Crohn’s disease is characterised by recurrent flare‐ups alternating with periods of remission. A number of interventions are currently used in clinical practice to try and maintain remission in Crohn’s disease but the evidence base for some of them may be questionable. Aim To review the available evidence on interventions, which are currently used to maintain remission in Crohn’s disease. Methods The Cochrane Library and Medline (Pubmed) were searched for level 1 evidence on specific interventions. Search terms included ‘Crohn’s disease or synonyms’, ‘remission or synonyms’ and the names of specific interventions. Results Azathioprine, infliximab and adalimumab are effective at maintaining remission in Crohn’s disease. Natalizumab is also effective, but there are concerns about its potential association with progressive multifocal leukoencephalopathy. Long‐term enteral nutritional supplementation, enteric‐coated omega‐3 fatty acids and intramuscular methotrexate may also be effective but the evidence for these is based on relatively small studies. The available evidence does not support the use of oral 5‐aminosalicylates agents, corticosteroids, anti‐mycobacterial agents, probiotics or ciclosporin as maintenance therapy in Crohn’s disease. Conclusion A better understanding of the evidence base of existing interventions could result in the use of treatments, which are more likely to lead to improved patient outcomes.     

Neuropsychiatric involvement in systemic lupus erythematosus: current therapeutic approach

The involvement of the central nervous system (CNS) is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients and the less understood aspect of the disease. Its recognition and treatment continue to represent a major diagnostic and therapeutic challenge. Due to the lack of controlled randomized trials, current therapeutic approach is still empirical and based on clinical experience. The therapeutic choice depends on accurate diagnosis, identification of underlying pathogenic mechanism, severity of the presenting neuropsychiatric symptoms, and on prompt identification and management of contributing causes of CNS disease. Mild neuropsychiatric manifestations may need symptomatic treatment only. In more severe CNS disease it is important to distinguish between thrombotic and non-thrombotic mechanisms. Focal CNS manifestations, particularly TIA and stroke, are associated with the presence of antiphospholipid antibodies (aPL). Anticoagulation is warranted in patients with thrombotic disease, particularly in those with the antiphospholipid (Hughes) syndrome (APS). Other CNS manifestations, such as demyelinating syndrome, transverse myelitis, chorea, seizures, migraine and/or cognitive dysfunction, when associated with persistent positivity for aPL, may also benefit from anticoagulation in selected patients. Severe diffuse CNS manifestations, such as acute confusional state, generalised seizures, mood disorders and psychosis, generally require corticosteroids in the first instance. Pulse intravenous cyclophosphamide therapy may help when more severe manifestations are refractory to corticosteroids and other immunosuppressive agents, generally when response is not seen in 3-5 days. Plasmapheresis may also be added in severe cases of symptoms refractory to conventional treatment. Intravenous immunoglobulins, mycophenolate mofetil, rituximab, intratecal methotrexate and dexametasone deserve further studies to confirm their usefulness in the treatment of neuropsychiatric SLE. This article reviews the clinical approach to therapy in patients with SLE and neuropsychiatric involvement.