Moderate Doses Of Corticosteroids Research Articles

Paradoxical tuberculous reaction to anti-tnfα discontinuation: a complex case of miliary tuberculosis and macrophagic activation syndrome with hepatic manifestations

Tuberculosis reactivation during anti-TNF-alpha therapy paradoxically worsened following reconstitution of pathogen-specific immune responses after cessation of TNFα antagonist treatment and initiation of anti-bacillary therapy. We report the case of a 46-year-old woman who was prescribed a tumor necrosis factor blocker (anti-TNF) for a relapse of Behçet's disease. The patient developed pulmonary miliary tuberculosis following the reactivation of latent tuberculosis, despite a normal pre-therapeutic work-up. Discontinuation of anti-TNF and initiation of anti-bacillary drugs triggered a paradoxical tubercular reaction (PTR). The diagnosis of paradoxical reaction to anti-tuberculosis drugs was evoked by the clinical and biological deterioration and the appearance of miliary cerebral tuberculosis and cerebral venous thrombosis after a period of clinical improvement. Although this phenomenon has been documented, it represents a major challenge for clinicians. The peculiarity of this case lies in its association with a macrophagic activation syndrome (MAS) with hepatic involvement, retained on clinical-biological and histological criteria. The overlap between MAS and PTR makes it difficult to diagnose these two entities with certainty. The patient responded favorably to moderate-dose systemic corticosteroid therapy with progressive degression, and the reintroduction of anti-tuberculosis drugs.This work aims to highlight the importance of close monitoring of TB patients on anti-TNFα therapy for early diagnosis and management of complications to improve the prognosis of these complex patients.

MO136: Histological Findings in Checkpoint Inhibitor-Induced Nephropathy

Abstract BACKGROUND AND AIMS Immune checkpoint inhibitors (CPIs)—a landmark in cancer therapy—has been occasionally associated with immune-related nephropathy [1]. Acute interstitial nephritis is considered to be the most common underlying histological entity, according to recent literature [2]. METHOD We report on six patients, 58–73 years old, three women and three men who presented with acute kidney disease, while on immunotherapy with CPIs. Five of them carried the diagnosis of non-small cell lung carcinoma (NSCLC) and one the diagnosis of renal cell carcinoma. All received proton pump inhibitors and experienced one or more of immune-related adverse events (dermatitis, arthritis, colitis, hepatitis and pneumonitis), prior to nephropathy. All underwent kidney biopsy. RESULTS Two female patients, both with NSCLC, developed heavy nephrotic syndrome (serum albumin: 1.7–1.8 mg/dL and 24-h urine protein: 12–16 g), after 23–28 months on pembrolizumab monotherapy, which was withdrawn. In the first patient, kidney biopsy demonstrated histology consistent with a lupus like membranous nephropathy (Figure 1). She received corticosteroids with partial recovery. Rechallenge with pembrolizumab was attempted and well tolerated. Renal biopsy of the second patient demonstrated a secondary AA (+) amyloidosis (Figure 2). She showed increased levels of SAA (114 mg/L) and IL-1b (22.9 pg/mL). She received colchicine and moderate dose of corticosteroids with partial remission. Two other patients, with NSCLC and clear cell renal carcinoma respectively, demonstrated renal biopsy findings consistent with acute interstitial nephritis (serum creatinine 1.5–1.6 mg/dL). The first one was on pembrolizumab along with cisplatin and pemetrexed, while the second one was on pembrolizumab along with axitinib. Both received prednisolone (10–20 mg for 3 months approximately). Pembrolizumab was restarted thereafter. Their renal function remained stable. Finally, two patients with NSCLC, both men, disclosed acute renal failure (serum creatinine: 3.6- 5 mg/dL) without considerable albuminuria. Acute tubular injury (ATI) was the predominant histological finding (along with focal and mild interstitial inflammation). Both were on combined chemo- and immune- therapy. One on ipilimumab and nivolumab along with platinum and pemetrexed and the other on pembrolizumab and pemetrexed. ATI was attributed most probably to pemetrexed which was withdrawn. Corticosteroids were promptly stopped in the first patient. The second patient showed gradual improvement of his renal function without corticosteroid therapy. CONCLUSION CPIs can induce nephropathy other than acute interstitial nephritis. Renal biopsy showed diverse and unusual histological findings. Renal biopsy along with the clinical setting was helpful in choosing appropriate therapy and deciding on CPI's continuation or withdrawal.

497. Moderate Versus High Dose Corticosteroids in Adult Patients with Severe COVID-19: Less Is More

BackgroundThe early administration of corticosteroids (CS) in patients with severe COVID-19 (hospitalized with need for supplemental oxygen) has been the only therapy to improve survival. However, the optimal dosing of CS remains unclear. Beginning March 2020 methylprednisolone (MP) in a dose of 40mg twice daily (high dose CS - HDC) was adopted at our institution. Based on emerging trials, this dose of MP was reduced to 16mg twice daily (moderate dose CS – MDC) in November 2020. The study aims to evaluate the outcome difference in patients receiving HDC versus MDC. MethodsThis pre-post quasi-experimental study was done at Henry Ford Hospital, an 877-bed tertiary care hospital in Detroit, Michigan. Consecutive patients in the HDC group from September 1, 2020 to November 15, 2020 were compared to the MDC group from November 30, 2020 to January 20, 2021. Only hospitalized patients with severe COVID-19 were included. The primary outcome was 28-day mortality. Secondary outcomes included progression to mechanical ventilation, length of hospital stay, discharge on supplemental oxygen and CS-associated adverse events. Patient demographics were evaluated using descriptive statistics. Bivariate and multivariable logistic regression analysis was planned to test the association between primary outcome and exposure. Results470 patients were evaluated, 218 and 252 in the HDC and MDC groups respectively. Clinical characteristics and severity of illness on admission were comparable in both groups (Table 1). Among comorbidities - lung disease, cardiovascular disease and hypertension were higher in MDC. Antibiotic and tocilizumab use were lower in MDC. Significantly more patients in MDC group received oral CS. There was no difference in mortality between HDC and MDC through bivariate and multivariate analysis (14.7% and 13.5%, p < 0.712, adjusted OR 0.913 [0.514-1.619]) (Table 2,3). Median length of hospital stay was 5 and 6 days in HDC and MDC respectively (p < 0.001). There was no difference in CS-associated adverse events. ConclusionThe survival in severe COVID-19 patients treated with MDC is comparable to HDC. Oral corticosteroids are an equally effective option.Disclosures Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)

Comparative efficacy and safety of mycophenolate mofetil and azathioprine in combination with corticosteroids in the treatment of lymphocytic myocarditis

Aim. To study the efficacy and safety of mycophenolate mofetil (MM) in combination with corticosteroids in the treatment of lymphocytic myocarditis in comparison with a standard combination of corticosteroids and azathioprine.Material and methods. The study included 46 patients aged 18 years and older with severe and moderate lymphocytic myocarditis (men, 34; women 12; mean age, 53,5±13,0 years). The diagnosis was verified using endomyocardial biopsy. Symptom duration averaged 9,5 [4; 20.25] months. All patients had class 3 [2,75; 3] heart failure (HF). The main group included 29 patients who received MM 2 g/day, including six patients — instead of azathioprine, which was canceled due to cytopenia (n=3) or insufficient effect (n=3). The comparison group included 17 patients who received azathioprine 150 [100; 150] mg/day. Patients of both groups also received methylprednisolone at a starting dose of 24 [24; 32] and 24 [24; 24] mg/day and standard HF therapy. In 7/2 patients, the parvovirus B19 genome was detected in the myocardium. In all cases, an increase in anticardiac antibody titers was evidence of immune activity. The average follow-up period was 24 [12; 54] months (at least 6 months).Results. The groups were completely comparable in age, initial characteristics and standard drug therapy. In both groups, a comparable significant increase in the ejection fraction (EF) was noted as follows: from 31,2±7,6 to 44,7±8,3% and from 29±9,1 to 46±11,9% (p&lt;0,001). An excellent response to treatment (an increase in EF by 10% or more) was noted in 68,2% and 66,7% of patients, a good response (by 9-5%) — in 27,3% and 14,3%, a poor response (an increase in less than 5% or a decrease in EF) — in 4,5% and 19,0%, respectively. In both groups, we noted the same significant (p&lt;0,01) decrease in pulmonary artery systolic pressure (36,3±12 to 28,1±6,1 mm Hg in the MM group and from 44,1±8,5 to 30,7±12,1 mm Hg in the azathioprine group), left ventricular (LV) end-diastolic dimension (from 6,4±0,6 to 6±0,7 cm and from 6,2±0,5 to 5,8±0,6 cm), LV end-diastolic volume (from 188,7±55,2 to 178,8±57,1 ml and from 167,8±47,5 to 163,3±61,8 ml), LV end-systolic volume (from 130,3±44,1 to 98,4±32 ml and from 118,1±39 to 94,1±46 ml), left atrial volume (from 98,3±30,3 to 86,7±32,6 ml and from 105±27,4 to 91,2±47,3 ml, p&lt;0,05), as well as mitral regurgitation grade. The incidence of deaths was 2 (6,9%) and 2 (8,7%), transplantation — 1 (3,4%) and 1 (4,3%) patients, death+transplantation end point — 3 (10,3%) and 2 (11,8%) without significant differences between the groups. The presence of the parvovirus B19 genome did not affect the results of treatment. The incidence of infectious complications was comparable in both groups (in one case, MM was completely canceled), no new cytopenia cases were noted during the follow-up period.Conclusion. In patients with moderate and severe virus-negative (except for parvovirus B19) lymphocytic myocarditis, the combination of moderate-dose corticosteroids with mycophenolate mofetil 2 g/day is at least no less effective than the standard regimen of immunosuppressive therapy. There was a tendency towards a more pronounced decrease in anticardiac antibody titers in combination with better tolerance (no cases of cytopenia) in MM group. MM in combination with corticosteroids can be recommended as an alternative treatment regimen for lymphocytic myocarditis.

Corticosteroids, COVID-19 pneumonia, and acute respiratory distress syndrome.

Although corticosteroids dampen the dysregulated immune system and sometimes are prescribed as an adjunctive treatment for pneumonia, their effectiveness in the treatment of coronavirus disease 2019 (COVID-19) remains controversial. In this issue of the JCI, Liu and Zhang et al. evaluated corticosteroid treatment in more than 400 patients with severe COVID-19. The authors assessed subjects retrospectively for cardiac and liver injury, shock, ventilation, mortality, and viral clearance. Corticosteroids in severe COVID-19-related acute respiratory distress syndrome (ARDS) were associated with increased mortality and delayed viral clearance. Here, we consider how to reconcile the negative effects of corticosteroids revealed by Liu and Zhang et al. with the favorable effects (reduced mortality) that were described in the RECOVERY trial. We posit that treatment timing, dosage, and COVID-19 severity determine immune response and viral outcome. Patients with moderate-to-severe COVID-19 pneumonia are likely to benefit from moderate-dose corticosteroid treatment when administered relatively late in the disease course.

Diagnosing EVALI in the Time of COVID-19

Diagnosing EVALI in the Time of COVID-19

Acthar Gel (repository corticotropin injection) for persistently active SLE: study design and baseline characteristics from a multicentre, randomised, double-blind, placebo-controlled trial

ObjectiveSLE is a chronic inflammatory autoimmune disease characterised by the excessive production of autoantibodies, immune complexes and proinflammatory cytokines. Repository corticotropin injection (RCI) is a naturally sourced complex mixture of...

Repository corticotropin injection in patients with persistently active SLE requiring corticosteroids: post hoc analysis of results from a two-part, 52-week pilot study.

ObjectivePost hoc analyses evaluated the effectiveness and safety of repository corticotropin injection (RCI) in patients with persistently active SLE over 52 weeks.MethodsPatients were initially randomised to 40 U daily or 80 U every other day RCI (n=26) or placebo (n=12) for the 8-week double-blind period. Completers entered the open-label extension (OLE; n=33) receiving 16, 40 or 80 U RCI 1–3 times/week and were followed through week 52. Outcomes included proportion of responders based on a novel index (resolution of joint or skin activity using hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) without any worsening British Isles Lupus Assessment Group (BILAG) scores in other organ systems) or revised novel index (using SLE Responder Index (SRI) definition of BILAG worsening (1A or 2B)), proportion of responders by SRI and changes in total hSLEDAI and BILAG scores. Adverse events and laboratory values were assessed.ResultsAt week 52, 12.0% (3/25) RCI/RCI patients and 36.4% (4/11) placebo/RCI patients were responders using the novel index. The revised novel responder index demonstrated response rates of 48.0% (12/25) and 54.5% (6/11) in the RCI/RCI and placebo/RCI groups, respectively. Proportions of SRI responders were 40.0% (10/25) and 54.5% (6/11). In the RCI/RCI group, total hSLEDAI and BILAG scores declined from 10.0 and 15.7 at week 0 to 3.5 and 4.6 at week 52, respectively. Reductions in the placebo/RCI group on switching were observed (mean hSLEDAI: 9.1–3.3; BILAG: 13.5–2.6). Other disease activity endpoints also improved in both groups. No new safety signals were observed during the OLE.ConclusionsRCI demonstrated durable effectiveness in patients with persistently active SLE despite moderate-dose corticosteroid therapy. Switching from placebo resulted in reduced disease activity during the OLE. These data provide the foundation for evaluation of RCI in a robustly powered study.

Efficacy and tolerability of repository corticotropin injection in patients with persistently active SLE: results of a phase 4, randomised, controlled pilot study

ObjectiveTo evaluate the efficacy of a prolonged-release formulation of a porcine adrenocorticotropic hormone analogue (repository corticotropin injection (RCI)) added to standard of care in patients requiring moderate-dose corticosteroids for symptomatic...

Efficacy and Safety of Methotrexate Combined with Low- to Moderate-Dose Corticosteroids for Severe Alopecia Areata

Background: In severe alopecia areata (AA), spontaneous recovery is unlikely, and treatment is not standardized. Objective: To evaluate the efficacy and safety of methotrexate (MTX) used alone or combined with low- to moderate-dose oral corticosteroids (OC) for treating severe AA (totalis, universalis and severe multifocal). Methods: Retrospective monocentric study of all consecutive patients receiving this treatment between 2006 and 2012. Efficacy was defined as achieving a total regrowth of terminal hair. Results: 26 patients were included (17 with AA universalis or totalis and 9 with severe multifocal AA). Total regrowth was noted in 15/26 patients. After 3 months of treatment, hair regrowth >80% was associated with further complete regrowth, and hair regrowth <30% was associated with later treatment failure (p = 0.0014). When treatment was tapered, 11/15 patients with initial complete efficacy experienced AA relapse. Conclusion: MTX combined with low- to moderate-dose OC may be an efficient and well-tolerated treatment for severe AA. However, long-term maintenance treatment is usually required.

62-Year-Old Man With Persistent Postoperative Nausea and Vomiting

dicine, te ester, visor tant in linic, .). A 62-year-old man with a history of type 2 diabetes mellitus, hypogonadotropic hypogonadism (diagnosed 6 months before presentation), stage 3 chronic kidney disease, and coronary artery disease was admitted to the hospital for treatment ofmitral valve endocarditis. Broad-spectrum antibiotics, including vancomycin and rifampin, were initiated, and in addition, he underwent mitral valve replacement because of vegetations causing severe valvular stenosis. On hospital admission and initiation of broad-spectrum antibiotics, progressive nausea, vomiting, fatigue, and anorexia developed. These symptoms persisted for up to 15 days postoperatively. The symptoms were constant and not necessarily postprandial. He also had fevers and chills, but these symptoms resolved with antibiotic therapy. He reported no abdominal pain and had no history of abdominal surgery. His bowel movements remained regular. The patient had no symptoms of gastroesophageal reflux, headaches, or vertigo. His diabetes was recently diagnosed and was controlled with diet. His symptoms continued despite maximum doses of antiemetics. He had not had similar symptoms before the current episode. Vital signs on evaluation included a temperature of 37.1 C, heart rate of 65 beats/ min, blood pressure of 138/73 mm Hg, and oxygen saturation of 96% while breathing room air. On physical examination, the patient was cachexic and had generalized nonfocal weakness. His body mass index was 19 kg/m. His abdomen was soft, nondistended, and nontender, and normal bowel sounds were present. He had no rashes or lower extremity edema.

Pharmacological interventions in acute respiratory distress syndrome.

Pharmacological interventions are commonly considered in acute respiratory distress syndrome (ARDS) patients. Inhaled nitric oxide (iNO) and neuromuscular blockers (NMBs) are used in patients with severe hypoxemia. No outcome benefit has been observed with the systematic use of iNO. However, a sometimes important improvement in oxygenation can occur shortly after starting administration. Therefore, its ease of use and its good tolerance justify iNO optionally combined with almitirne as a rescue therapy on a trial basis. Recent data from the literature support the use of a 48-h infusion of NMBs in patients with a PaO2 to FiO2 ratio <120 mmHg. No strong evidence exists on the increase of ICU-acquired paresis after a short course of NMBs. Fluid management with the goal to obtain zero fluid balance in ARDS patients without shock or renal failure significantly increases the number of days without mechanical ventilation. On the other hand, patients with hemodynamic failure must receive early and adapted fluid resuscitation. Liberal and conservative fluid strategies therefore are complementary and should ideally follow each other in time in the same patient whose hemodynamic state progressively stabilizes. At present, albumin treatment does not appear to be justified for limitation of pulmonary edema and respiratory morbidity. Aerosolized β2-agonists do not improve outcome in patients with ARDS and one study strongly suggests that intravenous salbutamol may worsen outcome in those patients. The early use of high doses of corticosteroids for the prevention of ARDS in septic shock patients or in patients with confirmed ARDS significantly reduced the duration of mechanical ventilation but had no effect or even increased mortality. In patients with persistent ARDS after 7 to 28 days, a randomized trial showed no reduction in mortality with moderate doses of corticosteroids but an increased PaO2 to FiO2 ratio and thoracopulmonary compliance were found, as well as shorter durations of mechanical ventilation and of ICU stay. Conflicting data exist on the interest of low doses of corticosteroids (200 mg/day of hydrocortisone) in ARDS patients. In the context of a persistent ARDS with histological proof of fibroproliferation, a corticosteroid treatment with a progressive decrease of doses can be proposed.

Severe immunosuppression in inflammatory bowel disease: opening the floodgates to opportunists?

Dear editor: Ulcerative colitis is a primarily non-infectious, chronic inflammatory bowel disease that typically affects the rectum and may involve the whole colon in an uninterrupted pattern. The disease has a high impact on the patients' health-related quality of life and is prone to repetitive hospitalisation. Therapeutic options primarily include lifestyle alterations, medical management and surgical interventions. Medical as well as surgical therapy may be associated with lifethreatening complications, which may require intensive care unit (ICU) admission. Here, we report on a female patient suffering from ulcerative colitis, whose medical therapy was complicated by toxic megacolon, and later on pulmonary aspergillosis and disseminated herpes zoster. A 55-year old woman with ulcerative colitis suffered from purulent haemorrhagic diarrhoea and weight loss of 9 kg within 2 weeks and was treated in a community general hospital for 6 weeks. Azathioprine (2.5 mg kg d p.o.) was administered for a total of 15 days and had been discontinued due to severe leukopenia. At that time, the patient had a high erythrocyte thiopurine methyl thiopurine methyltransferase (TPMT) activity (38 nmol h− gHb−; normal >23, intermediate 10–23, low <10 nmol h− gHb−), which represents the detoxifyfing enzyme for azathioprine. In addition, TPMT genotyping was performed and confirmed the absence of clinically relevant enzyme polymorphisms. Furthermore, toxic 6-thioguanine nucleotides (6-TGN) were undetectable in the patient's blood. Persistent bowel inflammation was treated with high doses of topical and systemic corticosteroids (prednisolone up to 2 mg kg− per day) and intravenous cyclosporine (3 mg kg− as continuous infusion over 24 h) in combination with antimicrobial therapy. Cyclosporine was discontinued after 6 days as leukopenia deteriorated, and subsequent immunomodulatory therapy consisted of mesalazine and regressive doses of prednisolone. At transferal to our university hospital, the patient presented the full clinical picture of toxic megacolon, which required emergency subtotal colectomy, blind closure of the rectum and percutaneous ileostomy. Following surgery, the patient was transferred to the intermediate care unit and treated with antimicrobial therapy (cefuroxime and metronidazole) and moderate doses of corticosteroids (prednisolone 1 mg kg per day). On postoperative day 3, she developed acute cholecystitis, which required urgent cholecystectomy and escalation of antimicrobial therapy (meropenem and vancomycin). Throughout the early clinical course, the patient remained leukopenic with white blood cell counts between 950 and 2,840 cells per microliter. Fractional lymphocyte count persisted below 10%. Filgrastim treatment (recombinant-methionyl human granulocyte colony-stimulating factor; r-metHuG-CSF; Christian Ertmer and Wolf A. Mardin equally contributed to this work.

Constrictive Pericarditis Due to Graft-vs-Host Disease

A 29-year-old man experienced a diffuse lichenoid rash that extended to his palms (panel A) and soles, peripheral blood eosinophilia, blurry vision, and recalcitrant generalized edema 2 weeks after donor lymphocyte infusion (DLI) for relapsed T-cell acute lymphoblastic leukemia. Skin biopsy revealed vacuolar interface inflammation consistent with graft-vs-host disease (GVHD). The rash improved with topical corticosteroids; however, the edema gradually worsened during the ensuing weeks, and the patient gained 23 kg. A thorough endocrine/metabolic evaluation for causes of anasarca was unremarkable. Transthoracic echocardiography, which had been completely normal 2 weeks before DLI, revealed a thickened pericardium, paroxysmal ventricular septal motion (supplemental video online linked to this article), high medial mitral annular velocity (panel B), and phasic respiratory changes of mitral valve inflow (E wave velocity; panel C). Cardiac magnetic resonance imaging demonstrated abnormal concentric delayed pericardial enhancement (arrow, panel D). The patient's condition was unresponsive to oral colchicine of 1 month's duration. Because his symptoms attributable to constrictive pericarditis occurred in the setting of GVHD development in other organs after DLI, the patient was treated with a moderate dose of corticosteroids (prednisone, 0.5 mg/kg/d). The anasarca rapidly improved. Six weeks after initiation of prednisone and 6 months after DLI, the patient remained in remission from T-cell acute lymphoblastic leukemia. His symptoms due to chronic GVHD were manageable; however, he died of infectious complications of profound immunosuppression. Pericarditis is an uncommon manifestation of chronic GVHD,1 and, to our knowledge, has been reported after DLI only once previously.2

Role of corticosteroids in the management of acute respiratory distress syndrome

Background: Evidence exploring the use of corticosteroids for acute respiratory distress syndrome (ARDS) has targeted various stages of disease progression, from preventing ARDS in high-risk patients to halting disease evolution once ARDS has developed. Objective: The aim of this review was to evaluate randomized, controlled trials describing the role of corticosteroids in preventing and treating ARDS. Methods: English-language randomized, controlled trials were identified using MEDLINE via PubMed and EMBASE searches (key terms: acute respiratory distress syndrome, acute lung injury, and corticosteroids; years: 1968-January 2008). Results: A total of 10 trials were found and included in this analysis. Trials describing the role of high-dose corticosteroids compared with controls in preventing ARDS found no benefit, with the range of occurrence of ARDS in at-risk populations from 14% to 64% and absolute increases in mortality from 4% to 31%. Conflicting evidence was found for treating late-phase ARDS with corticosteroids, with 13% hospital mortality among patients receiving corticosteroids versus 63% with controls ( P = 0.03) in one small study, but no significant difference was found when evaluating 60-day mortality (corticosteroid group, 29.2% vs control, 28.6%) in another investigation. The use of highdose corticosteroids for the treatment of early phase ARDS was not associated with significant differences in 45-day mortality (methylprednisolone, 60% vs control, 63%).However,onetrialfoundthatmethylprednisolone taper for early ARDS was associated with significant improvement in lung function or extubation (69.8% vs 35.7%; P = 0.002), fewer days on mechanical ventilation (median, 5.0 vs 9.5; P = 0.002), higher intensive care unit survival (79.4% vs 57.4%; P = 0.03), but similar rates of hospital survival (methylprednisolone, 76.2% vs control, 57.1%; P = NS). Conclusions: Data from clinical trials did not support the use of short-course, high-dose corticosteroids for preventing ARDS or for the treatment of early ARDS. Longer-course corticosteroids have not conclusively been associated with improved survival in the treatment of late-phase ARDS but have provided some benefits in other markers of disease severity in this setting and in early phase ARDS. Published trials support the administration of low- to moderate-dose corticosteroids in the treatment of early (<7 days) and late-phase (days 7\\2-14) ARDS, but this evidence is controversial.

Corticosteroids for community-acquired pneumonia: time to act!

The use of corticosteroids for the treatment of community-acquired pneumonia has been reported for almost 50 years. A recent systematic analysis of the relevant literature suggested that corticosteroids reduce the critical illness associated with community-acquired pneumonia. There is little doubt that a prolonged administration of a moderate dose of corticosteroids may alleviate the systemic inflammatory response and subsequent organ dysfunction in severe infection. Whether these favorable effects on morbidity may translate into better survival and quality of life needs to be addressed in additional adequately powered randomized controlled trials.

Steroid therapy in clinically stable but serologically active systemic lupus erythematosus prevents severe disease flares

Evaluation of: Tseng CE, Buyon JP, Kim M et al. The effect of moderate-dose corticosteroids in preventing severe flares in patients with serologically active, but clinically stable, systemic lupus erythematosus: findings of a prospective, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 54, 3623–3632 (2006).Systemic lupus erythematosus is an autoimmune disease of unknown origin. Flares and remissions are commonly seen in clinical settings. These clinical flares can have several degrees of severity, some of which require intensive immunosuppressive treatment and/or hospitalization. Clinicians treating these patients have looked at different strategies for prevention, early detection and prompt treatment of a lupus flare. Clinical information and laboratory findings have been proposed to reach these goals and preventive steroid adjustment has even been used in some cases without convincing results. This paper presents results from a controlled, multicenter, double-blind clinical trial evaluating the effectiveness of short-term corticosteroid treatment for preventing severe flares in which elevations of C3a by 50% were accompanied by a 25% increase in the anti-double-stranded DNA titer in patients with inactive or stable/active systemic lupus erythematosus. Results suggest that this strategy can prevent severe lupus flares.

Steroid Therapy for ARDS, Revisited

In a recent clinical trial, moderate-dose corticosteroids were not beneficial for patients with acute respiratory distress syndrome (ARDS; Journal

Pleural dissemination of thymoma showing tumor regression after combined corticosteroid and tacrolimus therapy

We present the case of an elderly woman with myasthenia gravis who had pleural dissemination of thymoma reduced by treatments with a moderate dose of corticosteroids and a conventional dose of tacrolimus. A maintenance dose of prednisolone for myasthenia gravis could not shrink the size of the disseminated thymoma, but prednisolone (> 30 mg daily) succeeded in reducing the size of the tumor. Moreover, a combination with tacrolimus enabled the daily dose of prednisolone to be tapered off without recurrence of myasthenia gravis, and the disseminated thymoma almost disappeared. A moderate or higher dosage of corticosteroids with tacrolimus may, in some cases, be an effective procedure for pleural dissemination of thymoma. Treatment should be undertaken on a trial basis for patients not indicated for surgery, radiotherapy, or chemotherapy.

Diagnosis and treatment of vasculitis of the central nervous system in a patient with systemic lupus erythematosus

A 23-year-old white woman with a 3-year history of systemic lupus erythematosus and a 15-month history of lupus nephritis and retinal vasculitis was successfully treated with antibiotics for Pseudomonas aeruginosa pneumonia while on moderate doses of corticosteroids. Even though her pneumonia had improved, she developed acute changes in her mental status that rapidly progressed to encephalopathy with coma. Physical examination, fundoscopic examination, laboratory tests for metabolic abnormalities, cerebrospinal fluid analysis, microbiology and serologic testing, electroencephalogram, tests for IgM and IgG anticardiolipin antibodies, neuroimaging including CT of the brain and T1-weighted MRI before and after gadolinium contrast, and flow-attenuated inversion recovery MRI. Vasculitis of the central nervous system associated with systemic lupus erythematosus. Intravenous methylprednisolone 1,000 mg/day for 3 days, one dose of intravenous pulse cyclophosphamide 750 mg/m(2), intravenous immunoglobulin 400 mg/kg/day for 4 days, plasmapheresis on alternate days for five cycles, and prednisone 40 mg/day. She continued monthly doses of intravenous pulse cyclophosphamide and intravenous pulse methylprednisolone for 6 months, followed by maintenance infusions every 3 months over 2 years. Prednisone was tapered over 18 months. Cyclophosphamide was discontinued after 2 years because of poor bone-marrow tolerance, and was replaced with mycophenolate mofetil 3,000 mg/ day and ciclosporin 50 mg twice daily.