Mycophenolate Mofetil with Steroid, a Reasonable Alternative to Current First-line Therapy, for Idiopathic Membranous Nephropathy in Resource-constrained Settings: A Randomized, Open-label Study.

BACKGROUND: The modified Ponticelli regimen (mPR) is a first-line therapy in patients with idiopathic membranous nephropathy (IMN); however, it has a less favorable safety profile. Though mycophenolate mofetil (MMF) + steroid (S) is not recommended by Kidney Disease Improving Global Outcomes guidelines, it can be used as an alternative to mPR due to higher tolerability and steroid-sparing effect. Thus, we compared the safety and effectiveness of MMF + S and mPR regimens in patients with IMN. METHODS: This randomized, open-label study enrolled patients with adult-onset nephrotic syndrome (NS) and biopsy-proven IMN. Forty-two patients were allocated to MMF + S group (MMF 1 gm twice daily + oral prednisolone 0.5 mg/kg/day; n = 21) and mPR group [methylprednisolone (1 gm intravenous) for 3 days followed by alternating monthly cycles of oral prednisolone (0.5 mg/kg/day) for the next 27 days and cyclophosphamide (2 mg/kg/day) for 6 months; n = 21]. The primary outcome measure was change in urinary protein creatinine ratio (UPCR). RESULTS: At 6 months, both groups demonstrated a significant increase in serum albumin levels and estimated glomerular filtration rate (eGFR) (both p-values <0.0001) as well as a decrease in 24-hour proteinuria (MMF + S group: p-value = 0.003, and mPR group: p-value <0.0001) and UPCR (both p-values <0.0001). However, the groups did not differ in any of these parameters at any of the monthly follow-up visits. Moreover, the groups did not differ significantly in terms of the composite remission rates (61.91% for MMF + S group and 71.43% for mPR group). CONCLUSION: MMF + S and mPR had comparable tolerability and effectiveness, with MMF-associated advantage of reduced steroid exposure.

Favourable effect of a 'second hit' after 13 weeks in early RA non-responders: the Amsterdam COBRA treat-to-target randomized trial.

OBJECTIVE: The aim of this study was to investigate the effect of treat-to-target combination therapy with intensification at 13 weeks in early RA. METHODS: Early RA patients were classified as being at high or low risk of worsening RA based on disease activity and prognostic factors. High-risk patients received COBRA-light (prednisolone 30 mg/day tapered to 7.5 mg/day, MTX increasing to 25 mg/week), and low-risk patients received MTX monotherapy increasing to 25 mg/week. The primary outcome (target) was DAS44 < 1.6 or EULAR good response at 26 weeks. At 13 weeks, non-responders were randomized to (open-label) intensification [high-risk patients: prednisolone 60 mg/day tapered to 7.5 mg/day, addition of SSZ (2 g/day) and HCQ (400 mg/day); low-risk patients: prednisolone 30 mg/day tapered to 7.5 mg/day] or continuation. RESULTS: In the high-risk group (n = 150), 110 patients (73%) reached the target at 13 weeks, and 9 dropped out. Non-responders were randomized to intensification (n = 15) or continuation (n = 16), and after 26 weeks, 12 (80%) vs 7 (44%) of these, respectively, reached the target [difference: 36%, (95% CI 2%, 71%); P = 0.04]. In the low-risk group (n = 40), 17 (43%) reached the target. Non-responders were randomized to intensification (n = 8) or continuation (n = 7); 4 vs 3, respectively, reached the target.Adverse event rates were higher in the high-risk group, and higher in the intensification subgroup of that group. Serious adverse events were rare. Protocol violations were frequent and mostly led to mitigation of actual treatment intensification. CONCLUSION: Initial combination therapy was very successful in high-risk RA, and early intensification was beneficial in patients not reaching the strict target. The low-risk group was too small for drawing conclusions. In routine practice, adherence to early intensification based on strict targets is difficult. TRIAL REGISTRATION: Netherlands Trial Register (NTR), NL4393, https://www.trialregister.nl/.

Temporal trends in the cost and use of first-line treatments for infantile epileptic spasms syndrome.

OBJECTIVE: To describe the temporal trends in the cost and use of adrenocorticotropic hormone (ACTH), oral prednisolone, and vigabatrin, the first-line treatments for infantile epileptic spasms syndrome (IESS). METHODS: Retrospective observational study using the MarketScan Commercial database from 2006 to 2020. We identified patients with IESS diagnosed between birth and 18 months of age who received at least one of the first-line treatments within 60 days of diagnosis. Costs were adjusted for inflation using the Gross Domestic Product Implicit Price Deflator. RESULTS: A total of 1131 patients received at least one first-line treatment (median [p25 -p75 ] age: 6.3 [4.5-8.3] months, 55% male), of whom 592 patients received ACTH, 363 patients received oral prednisolone, and 355 patients received vigabatrin. After adjusting for inflation, the median average wholesale price of a 14-day course of treatment increased for ACTH from $3718 in 2006 to $100 457 in 2020, ~2700% (by a factor of 27), whereas it decreased for oral prednisolone from $169 in 2006 to $89 in 2020, ~50% (by a factor of 0.5), and increased for vigabatrin from $1206 in 2009 (first year with data on vigabatrin used for IESS) to $4102 in 2020, ~340% (by a factor of 3.4). During the first 60 days after diagnosis, inpatient admission days and costs where higher for ACTH than for oral prednisolone and vigabatrin-5.0 (3.0-8.3) days vs 2.0 (0.0-5.0) days vs 2.0 (0.0-6.0) days, p < .0001; and $32 828 ($14 711-$67 216) vs $16 227 ($0-$35 829) vs $17 844 ($0-$47 642), p < .0001. ACTH use decreased from representing 78% of first-line treatments in 2006 to 18% in 2020 (p < .0001). Sensitivity analyses confirmed the robustness of the results. SIGNIFICANCE: The gap between the cost of ACTH and the cost of oral prednisolone or vigabatrin has widened markedly from 2006 to 2020, whereas the relative proportion of ACTH use has decreased.

Post hoc analysis of clinical characteristics of patients with radiographic progression in a Japanese phase 3 trial of peficitinib and methotrexate treatment (RAJ4).

OBJECTIVE: To determine the efficacy of peficitinib in reducing joint damage and predictive factors affecting treatment response in Japanese patients with rheumatoid arthritis. METHODS: This post hoc analysis used data from a placebo-controlled, phase 3 trial (RAJ4) of peficitinib in patients with rheumatoid arthritis and inadequate response to methotrexate. Erosion and joint space narrowing (JSN) were assessed at baseline and at Week 28/early termination of treatment using the van der Heijde-modified Sharp method. A univariate logistic regression analysis of change from baseline in a modified total Sharp score identified predictive factors with significant treatment interaction; the effects of these factors on treatment response were further evaluated using a multivariate model. RESULTS: The analyses included 481 patients. For most joint groups, peficitinib demonstrated a reduced change from baseline at Week 28/early termination in erosion and JSN scores versus placebo; a numerically greater effect was observed with peficitinib 150 mg versus 100 mg. Baseline C-reactive protein (CRP) and prednisolone dose were identified as clinically significant negative predictive factors: the treatment effect decreased as CRP or prednisolone dose increased for both peficitinib doses. CONCLUSIONS: Peficitinib 100 mg and 150 mg reduced joint damage versus placebo, across almost all joint groups. Higher baseline CRP and/or prednisolone dose were associated with reduced peficitinib efficacy. CLINICALTRIALS.GOV IDENTIFIER: NCT02305849.

[Acquired hemophilia A that developed after BNT162b2 mRNA COVID-19 vaccination and worsened following re-vaccination].

An 86-year-old Japanese male patient visited a nearby hospital with painful swelling in his left upper and lower limbs 35 days after the second dose of the BNT162b2 mRNA coronavirus disease-2019 (COVID-19) vaccine. He was referred to our hematological department due to a prolonged activated partial thromboplastin time and was urgently admitted. He was diagnosed with acquired hemophilia A (AHA) based on factor VIII (FVIII) activity of 1.7%, FVIII inhibitor of 152.3 BU/ml, and FVIII-binding antibodies detected by enzyme-linked immunosorbent assay. Immunosuppressive therapy with prednisolone (PSL) at 0.5 mg/kg/day was started owing to the risk of infection due to old age and poor activities of daily living. Hemostasis treatment with bypass hemostatic preparations (rFVIIa preparation, FVIIa/FX) was administered for each bleeding event, such as intramuscular and knee joint bleeding, resulting in good hemostatic effects. Coagulative complete remission was achieved on day 69 with PSL treatment; however, FVIII activity decreased with PSL tapering. AHA relapse with rectus abdominis muscle hematoma was observed after the third vaccination. This is the first Japanese report of AHA after COVID-19 vaccination and the world's first case, in which the presence of anti-FVIII-binding antibodies were observed.

[Autoimmune hemolytic anemia following the third dose of the COVID-19 vaccine].

The development and exacerbation of autoimmune diseases following coronavirus disease 2019 (COVID-19) vaccination have been reported; however, there are few reports of autoimmune hemolytic anemia (AIHA). A 75-year-old woman was admitted to the emergency department 46 days after receiving her third dose of the mRNA-1273 COVID-19 vaccine because of fatigue and general weakness. Initial laboratory analyses revealed severe hemolytic anemia with positive direct and indirect Coombs test and elevation of serum indirect bilirubin and lactate dehydrogenase. The patient had no underlying disease after a close examination and was diagnosed with warm AIHA, which was thought to be associated with COVID-19 vaccination. The anemia improved daily after the administration of prednisolone. Clinicians should be aware of the possibility of AIHA being caused by COVID-19 vaccination, and monotherapy with prednisolone should be considered in cases of severe anemia.

Prednisolone does not improve olfactory function after COVID-19: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Prednisolone has been suggested as a treatment for olfactory disorders after COVID-19, but evidence is scarce. Hence, we aimed to determine the efficacy of a short oral prednisolone treatment on patients with persistent olfactory disorders after COVID-19. METHODS: We performed a randomized, double-blind, placebo-controlled, single-centered trial in the Netherlands. Patients were included if they were > 18 years old and if they had persistent (> 4 weeks) olfactory disorders within 12 weeks after a confirmed COVID-19 test. The treatment group received oral prednisolone 40 mg once daily for 10 days and the placebo group received matching placebo. In addition, all patients performed olfactory training. The primary outcome was the objective olfactory function on Sniffin' Sticks Test (SST) 12 weeks after the start of treatment, measured in Threshold-Discrimination-Identification (TDI) score. Secondary outcomes were objective gustatory function assessed by the Taste Strip Test (TST) and subjective self-reported outcomes on questionnaires about olfactory, gustatory and trigeminal function, quality of life, and nasal symptoms. The CONSORT 2010 guideline was performed. RESULTS: Between November 2021 and February 2022, we included 115 eligible patients, randomly assigned to the treatment (n = 58) or placebo group (n = 57). No difference in olfactory function between groups was obtained after 12 weeks. Median TDI score on SST was 26.8 (IQR 23.6-29.3) in the placebo group and 28.8 (IQR 24.0-30.9) in the prednisolone group, with a median difference of 2.0 (95% CI 0.75 to 1.5). There was similar improvement on olfactory function in both groups after 12 weeks. Furthermore, on secondary outcomes, we obtained no differences between groups. CONCLUSIONS: This trial shows that prednisolone does not improve olfactory function after COVID-19. Therefore, we recommend not prescribing prednisolone for patients with persistent olfactory disorders after COVID-19. TRIAL REGISTRATION: This trial is registered on the ISRCTN registry with trial ID ISRCTN70794078.

Response to treatment and outcomes of infantile spasms in Down syndrome.

AIM: To estimate the prevalence, and evaluate presentation, treatment response, treatment side effects, and long-term seizure outcomes in all known cases of children with Down syndrome and infantile spasms on the island of Ireland. METHOD: This was a 10-year retrospective multicentre review of clinical records and investigations, focusing on treatment response, side effects, and long-term outcomes. RESULTS: The prevalence of infantile spasms in Down syndrome was 3.0% during the study period. Fifty-four infants were identified with median age of spasm onset at 201 days (interquartile range [IQR] 156-242). Spasm cessation was achieved in 88% (n=46) at a median of 110 days (IQR 5-66). The most common first-line medications were prednisolone (n=20, 37%), vigabatrin (n=18, 33.3%), and sodium valproate (n=9, 16.7%). At follow-up (median age 23.7mo; IQR 13.4-40.6), 25% had ongoing seizures and 85% had developmental concerns. Treatment within 60 days did not correlate with spasm cessation. Seventeen children (31%) experienced medication side effects, with vigabatrin accounting for 52%. INTERPRETATION: Prednisolone is an effective and well-tolerated medication for treating infantile spasms in Down syndrome. Despite the high percentage of spasm cessation, developmental concerns and ongoing seizures were common.

Treatment with High-Dose Prednisolone in Vigabatrin-Refractory Infantile Spasms.

OBJECTIVES: This research aimed to study the short-term seizure outcomes following treatment with 8 mg/kg/day prednisolone in children with infantile spasms (IS) refractory to vigabatrin. We hypothesized that high-dose prednisolone may result in similar rates of electroclinical remission when compared to published ACTH rates. METHODS: All consecutive children with hypsarrhythmia or hypsarrhythmia variant on EEG with/without IS, who had been treated with vigabatrin as first-line anti-seizure medication (ASM) followed by high-dose oral prednisolone (8 mg/kg/day; maximum 60 mg/day) in cases who did not respond to vigabatrin, were included. Clinical and electroclinical response (ECR) at 2 weeks following initiation of treatment and adverse effects were assessed. RESULTS: Sixty-five children were included. A genetic etiology was seen in 38.5% cases. Complete ECR was seen in 30.8% (20/65) of the patients 2 weeks after vigabatrin. Complete ECR was noted in 77.8% (35/45) of the patients, 2 weeks after prednisolone initiation in children who failed vigabatrin, and this was sustained at 6 weeks in 66.7% (30/45) patients. Prednisolone was generally well tolerated. CONCLUSIONS: High-dose (8 mg/kg/day) oral prednisolone resulted in sustained complete ECR (at 6 weeks) in two-thirds of the children with hypsarrhythmia or hypsarrhythmia variant on EEG with/without parentally reported IS. It was generally well tolerated and found to be safe.

Acquired Hemophilia A following Pfizer-BioNTech SARS CoV-2 mRNA vaccine, successfully treated with prednisolone and rituximab.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare bleeding disorder, characterised by the presence of autoantibodies to clotting factor VIII (FVIII). AHA can be idiopathic or occur in the context of malignancy, autoimmune disease, drugs, or pregnancy. Recently, cases of AHA following both COVID-19 infection and vaccination have been reported. CASE REPORT: We report the case of a 95-year-old female who was immunised with the Pfizer-BioNTech SARS CoV-2 mRNA vaccine, with doses given three weeks apart. Spontaneous bruising over her extremities appeared one week after the initial dose, with hospital admission occurring three weeks after the second. Examination revealed a large haematoma on the dorsum of the right hand with resultant bleeding and widespread ecchymoses. Investigations confirmed a diagnosis of AHA. MANAGEMENT AND OUTCOME: Initial management included high dose prednisolone, recombinant Factor VIII and tranexamic acid. There was no significant clinical improvement after three days, so intravenous rituximab 100 mg weekly for four weeks was commenced. The activated partial thromboplastin time (aPTT) normalised after two doses and Factor VIII level reached 0.68U/ml on day + 22. The patient was successfully discharged from hospital after 37 days. DISCUSSION: Four cases of AHA following administration of COVID mRNA vaccines (Pfizer and Moderna) have been documented. AHA should be a differential in patients presenting with bleeding following COVID-19 vaccination, in the presence of a normal platelet count. Rapid recognition, prompt initiation of immunosuppressive treatment and rigorous supportive cares are required to minimise morbidity and mortality.

Oral immunosuppressants improve pregnancy outcomes in women with idiopathic recurrent miscarriage: A meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Reports said immunotherapy is effective for the treatment of idiopathic recurrent miscarriage (RM). Immunotherapy is invasive, and lymphocyte therapy carries some risk of infection. Oral immunosuppressants have the advantages of simple administration and convenience; however, there is no statistical analysis of whether they can improve pregnancy outcomes in patients with idiopathic RM. METHODS: Six databases were searched for studies on oral immunosuppressants and RM; 374 articles were identified. There were two oral immunosuppressants, cyclosporine A and prednisone; two studies were on cyclosporine A and three studies were on prednisone for RM. RESULTS AND DISCUSSION: In total, 554 RM patients were included in this analysis, including 357 patients who received oral immunosuppressive agents and 197 patients who received basic treatment, placebo, or no treatment. Oral administration of cyclosporine A or prednisolone increases live birth rate (OR = 3.6, 95% CI: 2.1-6.15, p < 0.00001) and ongoing pregnancy rate (OR = 8.82, 95% CI: 2.91-26.75, p = 0.0001) in patients with idiopathic RM. Drug use reduced miscarriage rate (OR = 0.21, 95% CI: 0.08-0.52, p = 0.0007); however, there was significant heterogeneity (I2  = 73%) and a moderate-to-severe risk of bias. There was no effect on premature birth rate (OR = 2.26, 95% CI: 0.96-5.31, p = 0.06). This meta-analysis cannot provide a reference for the duration of medication treatment because the selected studies had inconsistent durations. WHAT IS NEW AND CONCLUSION: We did a statistical analysis and found that oral immunosuppressants (including cyclosporine A or prednisolone) can improve pregnancy outcomes in patients with idiopathic RM, increase live birth rate and ongoing pregnancy rate, and reduce miscarriage rate.

Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in Adults.

BACKGROUND: Tacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study. METHODS: In this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg/kg twice-daily tacrolimus plus once-daily 0.5 mg/kg prednisolone, or once-daily 1 mg/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5-7.5 mg/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio <0.2 g/g). Secondary end points included time until remission and relapse rates (proteinuria and urine protein: creatinine ratio >3.0 g/g) after complete remission to within 24 weeks of study drug initiation. RESULTS: Complete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3-8 ng/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively; P=0.01). There were no clinically relevant safety differences. CONCLUSIONS: Combined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.

First-line Combination Strategy Provides Favorable 5-year Outcomes for Patients with Lupus Nephritis: A Single-center Observational Study.

This observational study aimed to clarify the long-term results of the combination of mizoribine (MZB), tacrolimus (TAC) and prednisolone as first-line therapy for lupus nephritis (LN). This was our institution's standard therapy between 2009 and 2015, when we saw 36 patients with LN. When a patient thus treated achieved SLEDAI remission (= 0) and/or the prednisolone dose could be tapered to 5 mg/day, either MZB or TAC was stopped, and the other was continued for maintenance therapy. If treatment failure or relapse occurred, second-line therapy was introduced. At years 1 and 5, overall complete renal response and SLEDAI remission were 94% and 88%, and 50% and 62%, respectively. Excluding 2 cases lost to follow-up, medications after 5 years were as follows: 20 (59%) were stable on 1 drug (MZB or TAC), 11 (32%) required continuation of both drugs (MZB + TAC), and 3 (9%) required second-line therapy. The 5-year retention rate was 91% (non-secondline), with 0% of relapse in this group. Our first-line combination strategy showed high remission rates in the induction phase, and subsequent maintenance therapy demonstrated good outcomes for up to 5 years. Research that fine-tunes the order of therapeutic agents and institutes appropriate treatment goals may further improve long-term outcomes for patients with LN.

Systemic corticosteroids in the treatment of warm autoimmune hemolytic anemia: A clinical setting perspective.

INTRODUCTION: There are unmet answers about the effect of the different forms of corticosteroids in the treatment of the warm autoimmune hemolytic anemia (WAIHA). We aimed to describe the initial response rate and the safety profile of different regimens and forms of parenteral corticosteroids versus the solo oral prednisolone as first-line strategies for newly diagnosed adult WAIHA. METHODS: We recruited 156 patients who treated with either oral prednisolone 1 mg/kg daily for 3 weeks or intravenous corticosteroids like dexamethasone 40 mg daily for 4 days, Methylprednisolone 1 g/day for 3 days, or Methylprednisolone 1 g/day for 5 days then followed by oral prednisolone 1 mg/kg/day for 3 weeks. Full clinical and laboratory evaluations were done every 3 days for 3 weeks. RESULTS: The primary outcome was the rate of response at the end of the third-week post treatment. The rate of response was more in the group started the treatment intravenously (81.6% versus 41.7% and p = 0.0001). Multivariate cox regression analysis proved the predictivity of intravenous corticosteroid therapy for initial response. CONCLUSION: The safety profile of the different forms and regimens of corticosteroids were comparable. Therefore, parenteral regimens can be used as a rescue treatment in severe cases of WAIHA.

A case of recurrence of adult-onset Still's disease in the third trimester: a case report and literature review.

BACKGROUND: Adult-onset Still's disease (AOSD) is a self-inflammatory disease showing macrophage and neutrophil activation by inflammatory cytokines such as TNF-α, IL-6, and IL-18. Although some cases with the flare of AOSD during pregnancy have been reported, most had flares in the first or second trimester and few had flares in the third trimester. In this report, we present the case of a patient with recurrent flare of AOSD in the third trimester and discuss the management of AOSD in the third trimester with the review of previous literatures. CASE PRESENTATION: A 38-year-old woman in complete AOSD remission without medication presented with impaired liver function, low platelet count, mild fever, abdominal pain, splenomegaly, and elevated ferritin and IL-18 levels at 30 gestational weeks. Although the laboratory data and physical examination finding suggested HELLP syndrome or acute fatty liver of pregnancy and we considered the termination of her pregnancy, her fetus was in a reactive status. Considering her fetal status, some specific findings of AOSD, and her AOSD history, we and rheumatologists diagnosed her with AOSD recurrence and started systemic steroid therapy. In her clinical course, three flares of AOSD occurred, twice in the third trimester and once in postpartum; twice systemic steroid pulse therapies were then needed. Ultimately, a healthy infant was delivered transvaginally at 36 gestational weeks spontaneously. CONCLUSIONS: Specific findings of the flare of AOSD such as fever, splenomegaly, elevated ferritin and IL-18 levels, and fetal status could be useful findings for differentiation from HELLP syndrome and AFLP in the third trimester. With the careful management supported by rheumatologists, patients complicated with the flare of AOSD may continue their pregnancy longer than we expected.

Aortic involvement in relapsing polychondritis: case-based review.

Relapsing polychondritis is a systemic inflammatory disease that mainly affects ears, nose, eyes, joints, and large airway. Relapsing polychondritis may also affect cardiac valves and large vessels with the aorta being most frequently involved. We conducted a systematic literature review to delineate the clinical characteristics, treatment, and outcome of relapsing polychondritis patients with aortic involvement including thoracic and abdominal aorta, aortic valve, and coronary arteries. 113 patients reported in 85 manuscripts were retrieved through the systematic literature search and references of the selected manuscripts. With the addition of a patient from our center, a total of 114 patients were included in the analyses. Aortic vessel involvement was the predominant type of involvement that was identified in 93 (82%) patients, while aortic valve involvement was identified in 41 patients (36%). The median age at aortic involvement was 37 years [IQR: 30-53] with a delay of 5 years [IQR: 1-8] between first relapsing polychondritis symptom and aortic involvement. Nineteen percent of the patients were asymptomatic at the time of aortic involvement diagnosis. The initial treatment was immunosuppressives in 41 patients (56%) and surgery in 28 patients (38%). The mortality ratio was 27% in a 24 month follow-up [IQR: 7.5-54 months]. Aortic dissection or rupture was the most frequent causes of mortality. Concomitant coronary artery involvement suggested a worse outcome. Aortic involvement in relapsing polychondritis is a mortal complication despite medical and surgical treatments. It may be asymptomatic in 19% of the patients which warrants the importance of screening.

Long-term outcome of a randomised controlled trial comparing tacrolimus with mycophenolate mofetil as induction therapy for active lupus nephritis.

OBJECTIVES: To report the 10-year outcome of lupus nephritis (LN) treated with mycophenolate mofetil (MMF) or tacrolimus (TAC) induction in a randomised controlled trial. METHODS: Patients with active LN were treated with MMF or TAC combined with high-dose prednisolone. Responders were switched to azathioprine (AZA) at month 6. Clinical outcomes at 10 years (renal flares, renal function decline and mortality) were assessed. Factors affecting prognosis were studied by Cox regression. Urine protein-to-creatinine ratio (uPCr) and estimated glomerular filtration rate (eGFR) at different time points were evaluated for their prediction of a poor prognosis by receiver operating characteristic (ROC) analysis. RESULTS: 150 patients were studied (age 35.5±12.8 years). Complete renal response rate was similar between MMF (59%) and TAC-treated patients (62%; p=0.71). AZA maintenance was given to 79% patients. After 118.2±42 months, proteinuric and nephritic renal flares occurred in 34% and 37% of the MMF, and 53% and 30% of the TAC groups of patients, respectively (p=0.49). The cumulative incidence of a composite outcome of ↓eGFR ≥30%, chronic kidney disease stage 4/5 or death at 10 years was 33% in both groups (p=0.90). Factors independently associated with a poor renal prognosis were first-time LN (HR 0.12 (0.031 to 0.39); p=0.01), eGFR (HR 0.98 (0.96 to 0.99); p=0.008) and no response at month 6 (HR 5.18 (1.40 to 19.1); p=0.01). ROC analysis revealed an uPCr >0.75 and eGFR of <80 mL/min at month 18 best predicted a poor renal prognosis. CONCLUSIONS: Long-term data confirmed non-inferiority of TAC to MMF as induction therapy of LN. An uPCr≤0.75 and eGFR of ≥80 mL/min at month 18 best predicted a favourable 10-year outcome and may be suitable targets for induction/consolidation therapy. TRIAL REGISTRATION NUMBER: NCT00371319.

Flare of Autoimmune Hepatitis Causing Acute on Chronic Liver Failure: Diagnosis and Response to Corticosteroid Therapy.

Autoimmune hepatitis (AIH) is considered less common in the Asia Pacific region. Due to this, AIH flare as a cause of acute on chronic liver failure (ACLF) is often overlooked and treatment delayed. We aimed at the defining clinical and histopathological spectrum and role of steroid therapy in AIH-ACLF. Patients with AIH-ACLF, prospectively recruited and followed between 2012 and 2017, were analyzed from the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group score or simplified AIH score with histopathological evidence. Of 2,825 ACLF patients, 82 (2.9%) fulfilled criteria of AIH (age 42.1 ± 18.1 years, 70% female). At baseline, mean bilirubin was 18.6 ± 8.2 mg/dL, Child-Turcotte-Pugh score was 11.7 ± 1.4, and Model for End-Stage Liver Disease (MELD) score was 27.6 ± 6.5. Mean immunoglobulin G was 21.61 ± 7.32 g/dL, and this was elevated ≥1.1 times in 97% of cases; 49% were seronegative. Liver histology was available in 90%, with median histological activity index of 10 (interquartile range, 7-12); 90% with moderate to severe interface activity; 56% showing significant parenchymal necrosis (bridging and confluent necrosis); and cirrhosis in 42%. Twenty-eight (34%) patients received steroid therapy and showed shorter intensive care unit (ICU) stay (median 1.5 versus 4 days, P < 0.001) and improved 90-day survival (75% versus 48.1%, P = 0.02) with comparable incidence of sepsis (P = 0.32) compared to those who did not. Patients of advanced age, more severe liver disease (MELD >27; 83.3% sensitivity, 78.9% specificity, area under the receiver operating characteristic curve 0.86), presence of hepatic encephalopathy, and fibrosis grade ≥F3 had an unfavorable response to corticosteroid therapy. Conclusion: AIH presenting as ACLF is not uncommon in Asian patients; a low threshold for liver biopsy is needed to confirm the diagnosis as nearly half the patients are seronegative; early stratification to steroid therapy or liver transplantation (MELD >27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.

Acne fulminans concomitant with vasculitis-like symptoms mimicking Henoch-Schoenlein purpura.

Acne fulminans is a severe form of acne vulgaris accompanied by systemic symptoms. A 17-year-old Chinese boy presented with an outbreak of necrotic lesions on his face eight days after the onset of palpable purpura, arthralgia, fever, abdominal pain, and proteinuria. He was successfully treated with oral prednisolone and isotretinoin. Vasculitis-like symptoms are rarely reported in acne fulminans; therefore, the physician needs to maintain awareness of this uncommon presentation.

Responses to Treatment According to the Cytokine Profiles of Pericardial Effusion in Two Children with Idiopathic Pericarditis.

Acute pericarditis is inflammation of the pericardium with or without pericardial effusion. In the pediatric population, most patients with acute pericarditis are diagnosed with idiopathic pericarditis. Herein, we present two children with idiopathic pericarditis who underwent immunological assessment of pericardial effusion for the first time. Both patients showed equally high levels of interleukin-6 in the pericardial effusion. However, they had different treatment responses, in accordance with the pericardial effusion and serum interleukin-10 concentrations. Our present cases suggest that interleukin-10 may be associated with the response to anti-inflammatory therapy in idiopathic acute pericarditis.