Chronic Corticosteroid Treatment Research Articles

Spontaneous Abdominal Wall Hematoma: Early Recurrence without an Anticoagulant in an Elderly Woman Receiving Chronic Corticosteroid Treatment.

Spontaneous abdominal wall hematoma is a relatively uncommon condition triggered by various factors, including anticoagulation therapy and trauma. However, reports of unprovoked cases without anticoagulants that recur shortly after treatment are limited. We herein report an elderly woman who had been prescribed corticosteroids and experienced early recurrence of hematoma following treatment, with no discernible triggers. This case highlights the possibility that patients with underlying predisposing factors may experience early hematoma recurrence at the same site, even in the absence of apparent triggers. Clinicians should monitor these patients to promptly identify and address potential recurrences.

Chronic intranasal corticosteroid treatment induces degeneration of olfactory sensory neurons in normal and allergic rhinitis mice.

Nasal eosinophilic inflammation is the therapeutic target for olfactory dysfunction in allergic rhinitis (AR). Intranasal corticosteroids are commonly considered to offer targetable benefit given their immunosuppressive property. However, experimental evidence suggests that continuous corticosteroid exposure may directly cause olfactory damage by disrupting the turnover of olfactory sensory neurons (OSNs). This potentially deleterious effect of corticosteroids calls into question their long-term topical use for treating olfactory loss related to AR. The aim of this study was to assess the impacts of chronic intranasal corticosteroid treatment on olfactory function and OSN population in mice under normal and pathological conditions. BALB/c mice were intranasally treated with fluticasonepropionate (FP, 0.3mg/kg) for up to 8weeks. Additional mice were used to establish an ovalbumin-induced mouse model of AR, followed by nasal challenge with ovalbumin for 8weeks in the presence or absence of intranasal FP treatment. The authors examined olfactory function, OSN existence, neuronal turnover, and nasal inflammation using behavioral test, histological analyses, Western blotting, and enzyme-linked immunosorbent assay. Intranasal treatment with FP for 8weeks (FP-wk8) reduced odor sensitivity in normal mice. This reduction was concomitant with loss of OSNs and the axons projecting to the olfactory bulb, primarily resulting from increased neuronal apoptosis. In FP-wk8 AR mice, intranasal FP treatment attenuated olfactory impairment and eosinophilic inflammation but failed to reconstitute OSN population and axonal projections. These results suggest that chronic intranasal corticosteroid treatment contributes to OSN degeneration that may reduce the therapeutic effectiveness for AR-related olfactory loss.

Digital Pigmented Squamous Cell Carcinoma In-situ: A Case Report

Pigmented squamous cell carcinoma in-situ (SCCIS) is a rare variant of cutaneous SCC that can clinically mimic malignant melanoma. This variant is more commonly seen in patients with brown and black skin and often presents in sun-protected areas. We report a case of a 38-year-old man with a dark brown, expanding lesion on the lateral aspect of the left middle finger and history of immunosuppression secondary to chronic corticosteroid treatment for systemic sarcoidosis. Histologic examination of the lesion was consistent with a diagnosis of pigmented SCCIS. This report highlights a unique association between iatrogenic immunosuppression for inflammatory disease and development of pigmented SCCIS. Additionally, the case emphasizes the importance of surveillance for pigmented SCC in patients with skin of color, particularly those who may be at higher risk due to immunosuppression.

COVID-19-associated pulmonary aspergillosis (CAPA): Risk factors and development of a predictive score for critically ill COVID-19 patients.

BackgroundCOVID‐19‐associated pulmonary aspergillosis (CAPA) is a major complication of critically ill COVID‐19 patients, with a high mortality rate and potentially preventable. Thus, identifying patients at high risk of CAPA would be of great interest. We intended to develop a clinical prediction score capable of stratifying patients according to the risk for CAPA at ICU admission.MethodsSingle centre retrospective case–control study. A case was defined as a patient diagnosed with CAPA according to 2020 ECMM/ISHAM consensus criteria. 2 controls were selected for each case among critically ill COVID‐19 patients.Results28 CAPA patients and 56‐matched controls were included. Factors associated with CAPA included old age (68 years vs. 62, p = .033), active smoking (17.9% vs. 1.8%, p = .014), chronic respiratory diseases (48.1% vs. 26.3%, p = .043), chronic renal failure (25.0% vs. 3.6%, p = .005), chronic corticosteroid treatment (28.6% vs. 1.8%, p < .001), tocilizumab therapy (92.9% vs. 66.1%, p = .008) and high APACHE II at ICU admission (median 13 vs. 10 points, p = .026). A score was created including these variables, which showed an area under the receiver operator curve of 0.854 (95% CI 0.77‐0.92). A punctuation below 6 had a negative predictive value of 99.6%. A punctuation of 10 or higher had a positive predictive value of 27.9%.ConclusionWe present a clinical prediction score that allowed to stratify critically ill COVID‐19 patients according to the risk for developing CAPA. This CAPA score would allow to target preventive measures. Further evaluation of the score, as well as the utility of these targeted preventive measures, is needed.

Dupilumab Reduces Oral Corticosteroid Use in Patients With Corticosteroid-Dependent Severe Asthma: An Analysis of the Phase 3, Open-Label Extension TRAVERSE Trial

Many patients with severe asthma require chronic corticosteroid treatment to maintain asthma control. Are the reduction in oral corticosteroid (OCS) use and the clinical efficacy observed with dupilumab treatment maintained long-term in patients with severe OCS-dependent asthma? The LIBERTY ASTHMA TRAVERSE study (ClinicalTrials.gov identifier: NCT02134028) was a multinational, multicenter, single-arm, open-label extension study in patients≥ 12 years of age with asthma who participated in previous dupilumab studies. Treatment consisted of dupilumab 300mg every 2weeks for up to 96weeks. In this analysis, we present the data from patients who initially enrolled in the LIBERTY ASTHMA VENTURE study (ClinicalTrials.gov identifier: NCT02528214), a 24-week placebo-controlled study of dupilumab in patients with OCS-dependent severe asthma, and continued in the TRAVERSE study. The subgroups analyzed were: those who received dupilumab in both (dupilumab/dupilumab group) and those who received placebo in the VENTURE study and dupilumab in the TRAVERSE study (placebo/dupilumab group). Outcomes included OCS use, exacerbation rates, and measures of lung function and asthma control. Ninety patients treated with dupilumab/dupilumab and 97 patients treated with placebo/dupilumab in the VENTURE study were enrolled and treated in the TRAVERSE study, with a mean OCS dosage of 11.0mg/d (dupilumab) and 11.6mg/d (placebo) at VENTURE study baseline. At TRAVERSE week 0, the mean daily OCS dosage was 3.1mg/d and 6.4mg/d (percentage decrease from the VENTURE study baseline, 68.8%and 41.3%) for the dupilumab/dupilumab group and placebo/dupilumab group, respectively, and decreased to 2.2mg/d and 4.9mg/d (78.3%and 53.4%) at week 48 and to 1.2mg/d and 3.0mg/d (89.3%and 74.4%) at week 96, respectively. Exacerbation rates were low during the TRAVERSE study. Further improvements from the VENTURE to TRAVERSE studies also were seen in FEV1 and 5-item Asthma Control Questionnaire scores. Safety findings were consistent with the known dupilumab safety profile. In the open-label TRAVERSE study, dupilumab demonstrated the ability to sustain the OCS dosage reduction from the parent OCS-sparing study, while maintaining a low exacerbation rate and improved lung function. ClinicalTrials.gov; Nos.: NCT02134028 (TRAVERSE) and NCT02528214 (VENTURE); URL: www. gov.

Predictive factors for a severe course of COVID-19 infection in myasthenia gravis patients with an overall impact on myasthenic outcome status and survival.

Background and purposeMyasthenia gravis (MG) patients could be a vulnerable group in the pandemic era of coronavirus 2019 (COVID‐19) mainly due to respiratory muscle weakness, older age and long‐term immunosuppressive treatment. We aimed to define factors predicting the severity of COVID‐19 in MG patients and risk of MG exacerbation during COVID‐19.MethodsWe evaluated clinical features and outcomes after COVID‐19 in 93 MG patients.ResultsThirty‐five patients (38%) had severe pneumonia and we recorded 10 deaths (11%) due to COVID‐19. Higher forced vital capacity (FVC) values tested before COVID‐19 were shown to be protective against severe infection (95% CI 0.934–0.98) as well as good control of MG measured by the quantified myasthenia gravis score (95% CI 1.047–1.232). Long‐term chronic corticosteroid treatment worsened the course of COVID‐19 in MG patients (95% CI 1.784–111.43) and this impact was positively associated with dosage (p = 0.005). Treatment using azathioprine (95% CI 0.448–2.935), mycophenolate mofetil (95% CI 0.91–12.515) and ciclosporin (95% CI 0.029–2.212) did not influence the course of COVID‐19. MG patients treated with rituximab had a high risk of death caused by COVID‐19 (95% CI 3.216–383.971). Exacerbation of MG during infection was relatively rare (15%) and was not caused by remdesivir, convalescent plasma or favipiravir (95% CI 0.885–10.87).ConclusionsAs the most important predictors of severe COVID‐19 in MG patients we identified unsatisfied condition of MG with lower FVC, previous long‐term corticosteroid treatment especially in higher doses, older age, the presence of cancer, and recent rituximab treatment.

Efficacy and Safety of Nivolumab and AVD in Early-Stage Unfavorable Hodgkin Lymphoma: Extended Follow-up from the GHSG Phase II Nivahl Trial

Efficacy and Safety of Nivolumab and AVD in Early-Stage Unfavorable Hodgkin Lymphoma: Extended Follow-up from the GHSG Phase II Nivahl Trial

ACUTE GENERALIZED EXENTHEMATOUS PUSTULOSIS MIMICKING SEPTIC SHOCK: UNUSUAL PRESENTATION OF AN UNUSUAL DISEASE

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Acute generalized exanthematous pustulosis (AGEP) is a rare disorder, characterized by the development of acute sterile pustules. It is mostly caused by drugs, with antibiotics being the most likely culprits. AGEP is a self-limiting disease with favorable prognosis in the vast majority of patients. We present a case of a woman, admitted to the intensive care unit (ICU) with an unusually severe form of AGEP mimicking septic shock. CASE PRESENTATION: A 45-year-old female with systemic lupus erythematosus (SLE), underwent left hip replacement due to avascular necrosis. She received prophylactic cephazolin and discharged two days after surgery with an uncomplicated post-operative course. Two days later, she was admitted to the ICU with fever (103.6 F), tachycardia, and hypotension (54/36 mmHg). On physical exam, she had diffuse small pustules on an erythematous base (Fig 1). The incision site showed no signs of infection (Fig. 2). Labs were significant for leukocytosis (WBC 22,000), neutrophilia (18,500), left shift (Bands 13.9), eosinophilia (160), acute kidney injury (Cr 5.3, baseline 0.8), increased inflammatory markers (ESR 19, CRP 32.7), procalcitonin (2.49) and lactic acidosis. Random cortisol was normal and urine analysis was clear. Chest X-Ray showed no infiltrates and left hip CT scan showed no hematoma or abscess. She was initially managed as septic shock, started on broad spectrum antibiotics and required 2 vasopressors. Her hemodynamic status dramatically improved by the second day. Given her typical eruption and no source of infection identified, she was diagnosed with AGEP and antibiotics were discontinued on day 2. Patient continued to improve; vasopressors were weaned off by the third day. Cultures showed no growth. Kidney function and lactate levels normalized by the fifth day and she was discharged from the hospital on day 11. The skin pustules gradually coalesced into plaques (Fig. 3, 4) with subsequent sloughing. DISCUSSION: AGEP is a rare acute cutaneous reaction, with characteristic numerous, pinhead-sized pustules on an edematous erythematous background. It commonly presents with fever, neutrophilia, and skin eruption. Thus, often misinterpreted as an acute infectious process. AGEP is self-limiting, tends to resolve spontaneously with cessation of the offending agent, and no further measures are usually required. Multi-organ involvement is rare and highly atypical of AGEP. In contrast to most reported cases of AGEP, our case demonstrated an atypical presentation with severe systemic involvement and multi-organ failure mimicking septic shock. The patient had SLE and was on chronic corticosteroid treatment, which might explain her unusual life-threatening course. CONCLUSIONS: Prompt diagnosis of AGEP is crucial as the mainstay of treatment is the withdrawal of the offending drug. Every effort should be made to distinguish it from other causes of shock, mainly infection. Reference #1: idoroff A, Halevy S, Bavinck JN, Vaillant L, Roujeau JC. Acute generalized exanthematous pustulosis (AGEP)--a clinical reaction pattern. J Cutan Pathol. 2001;28(3):113-9 Reference #2: Roujeau JC, Bioulac-Sage P, Bourseau C, Guillaume JC, Bernard P, Lok C, et al. Acute generalized exanthematous pustulosis. Analysis of 63 cases. Arch Dermatol. 1991;127(9):1333-8 Reference #3: Krishna S, Ortega-Loayza A, Malakouti N, Brinster N. A rapidly progressive and fatal case of atypical acute generalized exanthematous pustulosis. J Am Acad Dermatol. 2014;71(3):e89-90 DISCLOSURES: No relevant relationships by Mohamed Elmassry, source=Web Response No relevant relationships by Amr Ismail, source=Web Response No relevant relationships by Haneen Mallah, source=Web Response No relevant relationships by Barbara Mantilla, source=Web Response No relevant relationships by Jasmine Sekhon, source=Web Response No relevant relationships by Victor Test, source=Web Response No relevant relationships by Myrian Vinan Vega, source=Web Response

Outcomes of Transcatheter Aortic Valve Implantation in Patients Receiving Chronic Systemic Corticosteroid Treatment

The aim of this study was to describe the effects of chronic systemic corticosteroid treatment (SCT) on early and late outcomes after transcatheter aortic valve implantation (TAVI). From October 2006 to November 2018, 1,299 patients underwent TAVI in our institution. Among them, 48 (3.7%) received chronic SCT at the time of procedure (SCT group). They were more frequently women (p = 0.08) and needed more often dialysis (p = 0.002). All other baseline characteristics were similar between both groups. At 30 days, there was no difference on mortality. However, after adjustment, the SCT group had more major vascular complications: 16.7% versus 7.4%, hazard ratio (HR) 2.52 (95% confidence interval [CI] 1.14 to 5.9, p = 0.023), major or life-threatening bleedings: 22.9% versus 12.4%, HR 2.02 (95% CI 1.00 to 4.08, p = 0.05), and tamponades: 8.3% versus 2.4%, HR 4.05 (95% CI 1.35 to 12.15, p <0.001) than the non-SCT group. One-year all-cause mortality was significantly higher in the SCT than in the non-SCT group (37.5% vs 12.5%, p <0.0001). Multivariate analysis confirmed that SCT use was an independent predictor of 1-year mortality (HR 2.29, 95% CI 1.16 to 4.50, p = 0.017). In conclusion, chronic use of SCT significantly increases the rates of early vascular complications, major or life-threatening bleedings and tamponade and is an independent predictor of 1-year all-cause mortality after TAVI.

Outcomes of transcatheter aortic-valve implantation in patients receiving chronic systemic corticosteroid treatment

The chronic use of systemic corticosteroid (CS) therapy is associated with greater tissue fragility. Data assessing the effects of this treatment on the results of transcatheter aortic-valve implantation (TAVI) are scarce. To describe the impact of chronic use of CS treatment on early and late outcomes after TAVI. All 1299 consecutive patients undergoing TAVI in our institution between October 2006 and November 2018 were included. Their mean age was 81 ± 10 years, 52.4% were male, their median EuroSCORE 2 was 4.7% (2.8–7.5). Among them, 48 (3.7%) received chronic systemic CS treatment at the time of the procedure and were compared to those without CS. Patients with chronic CS therapy tended to be women (60% vs. 47%, P = 0.078) and needed more frequently dialysis (12.5% vs. 2.6%, P = 0.002). All other baseline clinical and echocardiographic characteristics were similar between both groups. No differences were observed in 30-day mortality (6.2% vs. 4.3%, P = 0.46). However, after adjustment, patients in the CS group had more frequent major vascular complications (16.7% vs. 7.4%, hazard ratio (HR) 2.52, 95%Confidence Interval (CI) 1.14–5.9; P = 0.02), major or life-threatening bleedings (22.9% vs. 12.4%, HR 2.02, 95%CI 1.00–4.08; P = 0.05) and tamponades (8.3% vs. 2.4%, HR 4.05, 95%CI 1.35–12.15, P < 0.001) at 30 days than those in the non-CS group. At 1-year, all-cause mortality was significantly higher in CS group than in the non-CS group (37.5% vs. 12.6%, p-log rank < 0.0001). Multivariate analysis confirmed that chronic use of CS was an independent predictor of 1-year all-cause mortality (HR 2.29, 95%CI: 1.16–4.50, P = 0.017) ( Fig. 1 ). Chronic systemic CS treatment was associated with an increase in major or life-threatening bleedings, major vascular complications and tamponades at 30 days and was an independent predictor of 1-year all-cause mortality. This treatment should be taken into account in the risk stratification of TAVI candidates.

Corticosteroid treatment before TAVI and the risk of pacemaker implantation: A 2:1 matching study

Conductive disorders after TAVI remain frequent, leading to a 10-20% risk of permanent pacemaker implantation (PPI). Pre-existing conduction disorders or anatomical features can offer a good prediction of the risk of PPI, however, inflammatory and hemorrhagic process are responsible of transient abnormalities and 1/3 of the patients does not need the pacemaker at follow-up. In this setting, corticosteroid could be an interesting treatment to prevent or reduce the need of PPI. We aim to assess the influence of chronic or acute corticosteroid treatment in the occurrence of PPI after TAVI. All TAVI performed in our center 2013 and 2018 were prospectively included in the study. Patient treated either with chronic or acute corticosteroid before TAVI were gathered through medical database claim of the University Hospital of Dijon, France. They were matched 1:2 on sex, age, and the valve implanted. Preoperative parameters, corticosteroids dose and indication, and PPI rates after TAVI were collected. Among the 691 patients included, 18 (2.6%) patients had a corticosteroid prescription before TAVI procedure. 11(61%) had a chronic corticosteroid prescription, when the remaining patients were treated before and a few days after TAVI as prevention of contrast iodinated product allergy. When compared to the matched population ( n = 36), no significant difference was found on PPI rates during hospitalization (2 (11%) vs. 6 (17%), P = 0.70). Among others parameters collected, the only significant difference between the two groups was that corticosteroids patients less frequently had previous diabetes (3 (17%) 17 vs. 18(50%), P = 0.021). Corticosteroid treatment is uncommon before TAVI, reducing the statistical power of this analysis. Given the safety of this drug prescription on short duration prescription, a prospective randomized study could be performed to confirm our hypothesis.

Fatal pulmonary thromboembolism in a two-year-old dog receiving long-term corticosteroid therapy

A two-year-old female dog unexpectedly collapsed and was presented to Ross University Veterinary Clinic. On arrival, it appeared normal and was kept overnight for monitoring and further diagnostic assessment. In...

REBOUND PHENOMENON – IMPORTANT AND UBIQUITOUS IN PHARMACOTHERAPY

The rebound effect represents a common characteristic of the numerous classes of modern drugs and can result in serious and even fatal disorders. For example, prolonged administration of proton pump inhibitor (PPI) leads to moderate hypergastrinemia in 20-25%. This hypergastrinemia will result in rebound gastric acid hypersecretion in 30-40% of patients following the abrupt PPI discontinuation. PPIs are among the most widely used drugs worldwide. An abrupt cessation of chronic corticosteroid, beta blocker, or opioid treatment may also provoke rebound phenomenon. Even in heart failure patients, beta blocker withdrawal on admission resulted in a significant increase of the probability of in-hospital mortality. The incidence of a rebound phenomenon depends on numerous factors, including the intensity and duration of action of a particular drug and how long it has been applied; the susceptibility of an individual patient (regarding the comorbidities and the severity of the primary disease) and the related circumstances (e.g, co-therapy). The clinical importance of the rebound phenomenon varies from academic to lethal. Even rare rebounds found for some classes of drugs are becoming very important if the drug has been used often globally.

Strongyloides stercoralis infection in a Spanish regional hospital: Not just an imported disease

IntroductionStrongyloides stercoralis infection is more prevalent in tropical regions but autochthonous cases have been reported in Spain, mainly in La Safor (Valencia). The objective is to describe the strongyloidiasis cases registered in a regional hospital of Alicante province (Spain) and to determine if they were autochthonous cases. MethodsRetrospective study of all diagnosed cases of strongyloidiasis in Vega Baja Hospital (Orihuela, Alicante) between January 1999 and March 2016. ResultsA total of 10 cases were found, four of which were autochthonous cases. Two of them presented with a hyper-infection syndrome, with a fatal outcome. All autochthonous cases were in patients ≥69years old with gastrointestinal, cutaneous, and/or respiratory symptoms. Serology was positive in the 8 cases studied. Larvae were found in histopathological samples of the gastrointestinal tract of three patients. ConclusionsWe communicate the first autochthonous cases of strongyloidiasis in the region of Vega Baja. Screening programs should be implemented, especially in immunosuppressed patients or patients under chronic corticosteroid treatment.

Development of a New Self-Reporting Instrument Measuring Benefits and Side Effects of Corticosteroids in Duchenne Muscular Dystrophy: Report from a Pilot Study.

There is no cure for Duchenne Muscular Dystrophy (DMD); treatment is symptomatic and corticosteroids slow the progression. Side effects of corticosteroids - especially the physical effects - have been described, however patients' and caregivers perception on chronic corticosteroid treatment and their side effects is less well known, in particular with regards to cognition, behaviour, and emotional functioning. The primary aim of this pilot study was to (i) construct a self-report questionnaire to assess the perceived benefits and side effects of corticosteroids for patients with DMD and their parents. Furthermore we aimed to (ii) investigate the psychometric qualities of this questionnaire, (iii) whether there was a difference between parents' and patient's perceptions, and finally (iv) to what extent reported side effects may alter over time. A 23-item questionnaire (SIDECORT: side effect of corticosteroids) was constructed to assess the perception of these benefits and side effects in a systematic manner. In total, 86 patients (aged 5 - 28 years) and 125 of their parents completed the questionnaire. Internal consistency was good. Using factor analyses on the side effect items as reported by parents, two underlying factors were found, with the first factor describing cognitive, behavioural and emotional functioning, and the second factor describing physical functioning. The potential benefits of corticosteroids were highly rated among both parents and patients, although parents rated the importance of the benefits higher than their sons (p = 0.002). Similarly, parents rated the severity of the side effects generally higher than their sons (p = 0.011), especially with regards to the physical side effects (p = 0.014). Based on the parent's perception, the neurodevelopmental side effects generally appeared to decline the longer corticosteroids were used. To our knowledge, this is the first explicit study on perceived cognitive-, behavioural-, and emotional side effects and the allocation of benefits to corticosteroids in DMD. On the basis of our research we suggest a short form questionnaire, which proves to be reliable and valid for research- and clinical practice. This questionnaire could provide useful insights for the care of boys and men with DMD.

Time to steroid-free remission of uveitis in pediatric population

Chronic uveitis in children can lead to vision threatening complications due to the disease itself and chronic corticosteroid treatment. The purpose of the study was to evaluate the outcomes and time to achieve steroid-free remission with immunomodulatory therapy (IMT) in pediatric patients with uveitis.

Risk factors for hepatotoxicity in patients hospitalized for tuberculosis

Introduction:Combination therapy with four drugs (isoniazid, rifampicin, pyrazinamid and ethambutol) is the treatment of choice in tuberculosis but hepatotoxicity due to these drugs is an important medical concern. Therefore identification of patient groups with increased risk for antituberculosis therapy induced hepatotoxicity is crucial.Material and Methods:This retrospective cohort study included hospitalized patients with the diagnosis of tuberculosis during a ten year period. Only patients with microbiological (culture positive) or histopathological (presence of granulomatous reaction with caseification necrosis in the tissue) evidence of tuberculosis infection were included. Incidence of hepatotoxicity and the association of hepatotoxicity with known and unknown risk factors were investigated.Results:Sixty four patients (33 female-31 male; median age 48.0 years) were included into the study. Most of the patients had extrapulmonary tuberculosis (n=49). Antituberculosis therapy was started with four drugs in all patients and 7 patients developed hepatotoxicity. Age, gender, previous tuberculosis history, extent of tuberculosis, positive hepatitis B virus serology, diabetes mellitus and chronic renal insufficiency were not related with the development of hepatotoxicity. The presence of rheumatologic disease and chronic corticosteroid use was associated with increased risk of hepatotoxicity (p<0.01 and p=0.01, respectively).Conclusions:In this study we found that patients with rheumatologic diseases and patients on chronic corticosteroid treatment had increased risk for hepatotoxicity during antituberculosis therapy. These patients should be closely monitored for hepatotoxicity especially during the initial treatment phase.Objective:To assess the rate of hepototoxicity due to antituberculosis drugs and to determine factors associated with hepatotoxicity in hospitalized tuberculosis patients.

Successful Treatment of a Diamond-Blackfan Anemia (DBA) Patient with Eltrombopag

▪DBA is a rare bone marrow failure syndrome clinically defined by onset of hypoproliferative anemia in early childhood accompanied by a grossly normocellular bone marrow. With age, a significant fraction of patients progress to pancytopenia and a hypocellular bone marrow, with some increased risk of progression to leukemia. Autosomal dominant or sporadic heterozygous mutations in genes encoding for ribosomal subunit proteins have been etiologically linked to DBA. How loss of function mutations in ribosomal proteins results in selective loss of erythroid progenitors with variable severity is incompletely understood. Chronic transfusion therapy and corticosteroid treatment can alleviate anemia, but both cause severe long term toxicities. Hematopoietic stem cell transplantation, when available, is the only definitive treatment modality for the hematological manifestations, and the only known treatment for DBA patients once pancytopenia develops.Here we report on a 28 year old female patient diagnosed with DBA at age of one month based on clinical criteria. Recent mutational analysis identified a novel mutation in intron 4(c.356+3>C) of the RPS19 gene affecting a known splice donor site that has previously reported in DBA patients. She did not respond to corticosteroids and was maintained on transfusions. She failed various experimental therapies including danazol, hematopoietic growth factors including IL-3 and GM-CSF, and anti-thymocyte globulin/cyclosporine without sustained clinical response. After treatment with daclizumab in 2006 her transfusion requirements decreased for about 4 years. In 2012 she presented with progressive pancytopenia and hypocellular bone marrow without overt dysplasia, and normal cytogenetic analysis. She required red cell transfusions. The patient was enrolled in a clinical research protocol investigating the efficiency and safety of the thrombopoietin receptor agonist eltrombopag (EPAG) in patients with moderate aplastic anemia or those with bone marrow failure with unilineage cytopenia (ClinicalTrials.gov: NCT01328587). The study is designed as a non-randomized, phase II, dose modification study with the primary endpoint hematological response at 16 weeks. EPAG was administered at 50mg daily and escalated every 2 weeks by 25 mg to the maximal dose of 300mg daily. At response assessment the patient’s hemoglobin (Hgb) improved from 7.0g/dl to 8.9g/dl and platelets from 112K/ul to 171k/ul. She required no further transfusions, and was deemed a responder. EPAG was subsequently continued at the same dose level for an additional 6 months when the peripheral cells counts peaked at Hgb 11.9g/dl, platelets 251K/ul, ANC 3.19 K/ul, and EPAG was discontinued for protocol-defined robust response. After discontinuation of EPAG the patient’s hemoglobin steadily declined over a period of 8 months. EPAG was reinitiated at 300mg per protocol. Peripheral blood cell counts rapidly improved and the EPAG dose was slowly tapered. The patient is currently on EPAG 50mg daily with normal blood cell counts. We have not observed any EPAG related toxicities in our patient, and repeated cytogenetic studies on bone marrow documented a normal karyotype.To the best of our knowledge this is the first report documenting EPAG efficacy in a DBA patient. Trautman et al. (2012) previously reported a DBA patient that failed treatment with low dose EPAG after six months. Our observation warrants further systematic investigation of EPAG treatment for DBA patients within a clinical research study setting. [Display omitted] DisclosuresWinkler:GSK/Novartis: Research Funding. Townsley:Novartis: Research Funding. Desmond:Novartis: Honoraria. Dumitriu:GSK/Novartis: Research Funding. Grasmeder:GSK/Novartis: Research Funding. Young:GSK/Novartis: Research Funding. Dunbar:GSK/Novartis: Research Funding.

Strongyloides stercoralis en un hospital comarcal del Levante español: una enfermedad no solo importada

IntroductionStrongyloides stercoralis infection is more prevalent in tropical regions but autochthonous cases have been reported in Spain, mainly in La Safor (Valencia). The objective is to describe the strongyloidiasis cases registered in a regional hospital of Alicante province (Spain) and to determine if they were autochthonous cases. MethodsRetrospective study of all diagnosed cases of strongyloidiasis in Vega Baja Hospital (Orihuela, Alicante) between January 1999 and March 2016. ResultsA total of 10 cases were found, four of which were autochthonous cases. Two of them presented with a hyper-infection syndrome, with a fatal outcome. All autochthonous cases were in patients ≥69years old with gastrointestinal, cutaneous, and/or respiratory symptoms. Serology was positive in the 8 cases studied. Larvae were found in histopathological samples of the gastrointestinal tract of three patients. ConclusionsWe communicate the first autochthonous cases of strongyloidiasis in the region of Vega Baja. Screening programs should be implemented, especially in immunosuppressed patients or patients under chronic corticosteroid treatment.

The negative bone effects of the disease and of chronic corticosteroid treatment in premenopausal women affected by rheumatoid arthritis.

Osteoporosis is a well-known extra-articular complication in rheumatoid arthritis (RA). The chronic corticosteroid treatment, the functional impairment associated with RA and the disease itself appear to be the most relevant determinants. Most of the previous studies involved postmenopausal women, in whom the estrogenic deficiency might amplify the negative effect towards bone of both RA and corticosteroid therapy. We decided to evaluate bone health in a cohort of premenopausal RA patients. The study population includes 47 premenopausal women attending our outpatient clinic for RA and twice as many healthy age-matched control women selected from the hospital personnel. The bone density at the spine and femoral neck were significantly lower in patients with RA as compared with controls. When spine bone mineral density (BMD) values were adjusted for the cumulative glucocorticoid (GC) dose alone and for the cumulative GC dose plus body mass index (BMI) the mean differences between two groups decreased but they remained statistically significant. We found no difference when the spine BMD was adjusted for cumulative GC dose, BMI and health assessment questionnaire. The difference in femoral neck BMD remained statistically significant also after all the same adjustments. In conclusion, our study shows that a BMD deficiency is frequent also in premenopausal women affected by RA, especially at femoral site and that the main determinants of this bone loss are not only the disease-related weight loss, corticosteroid therapy and functional impairment, but also the systemic effects of the disease itself.