High-dose Steroid Treatment Research Articles

Acute cardiac effects of high dose steroid treatment: A speckle tracking echocardiography study.

High-dose steroid therapy (HDST) has frequent side-effects that appear at its cessation and depend on its dose. However, there is a lack of studies about the acute effects of HDST on cardiac function in adult patients. We included in this study 30 patients who underwent HDST (intravenously at doses ranging from 250 to 1000 mg) and 30 healthy control subjects with similar demographic and clinical characteristics, between September and December 2016. Echocardiographic measurements were made before and during the first 3 hours after the end of treatment, and results were compared between patients and controls. There was no difference in baseline biochemical and echocardiographic characteristics between the patient and control groups. While left ventricular global longitudinal strain (LVGLS) and strain rate E were higher after treatment, no significant change was observed in conventional echocardiographic variables. LVGLS, but not conventional echocardiographic variables, showed an increase in cardiac systolic function at the acute phase of HDST.

Atypical depression associated with high-dose steroid treatment in an adolescent patient receiving liver transplantation

Atypical depression associated with high-dose steroid treatment in an adolescent patient receiving liver transplantation

Development of Focal Segmental Glomerulosclerosis and Thrombotic Microangiopathy in a Liver Transplant Patient on Sorafenib for Hepatocellular Carcinoma: A Case Report

Transplant patients are at risk for hemodynamic injury and glomerular diseases such as focal segmental glomerulosclerosis (FSGS) and thrombotic microangiopathy (TMA). Calcineurin inhibitors (CNI) can cause various patterns of acute kidney injury (AKI) in transplant patients and their effects must be differentiated from kidney injury due to other agents. Transplant populations are also at risk for atypical infections and malignancies. These conditions and the agents that are used to treat them can then induce their own set of glomerular diseases. We report a patient with hepatitis C who had received an orthotopic liver transplant and then developed recurrent hepatocellular carcinoma, which was treated with the oral tyrosine kinase inhibitor (TKI) sorafenib. In a manner temporally related to the initiation of the TKI, progressive AKI and high-grade rising proteinuria were noted. A biopsy disclosed FSGS and concomitant TMA. Despite the discontinuation of the TKI and high-dose steroid treatment, the patient developed end-stage renal disease and was initiated on hemodialysis. After determining the TKI as the probable culprit, as opposed to CNIs, the patient successfully received a living related renal transplant. CNIs are used to maintain renal and hepatic allografts without the development of hematuria, significant proteinuria, or significant impairment of renal function. It is noted that the pathologic phenotype observed in this case is only the second reported case of concomitant TMA and FSGS in a sorafenib-treated patient.

High-Dose Steroid Treatment of Bacterial Keratitis.

To describe the usage patterns of steroids in bacterial keratitis and to analyze the effect of steroids on patients' visual outcomes. This was a single-center retrospective review of patients with culture-positive bacterial keratitis treated between 1999 and 2015 at Princess Alexandra Hospital (Brisbane, Australia). Patients with culture-positive bacterial keratitis were identified through the Queensland Pathology Database, and clinical information was gathered through a subsequent medical record review. High-dose steroid treatment was classified as 6 or more drops of a steroid a day started within 7 days of corneal scraping. The outcome of a patient's episode of keratitis was classified as good if their final visual acuity was 6/12 or better; poor if it was 6/60 or worse or required a corneal transplant, otherwise it was classified as average. Microbiological and clinical variables' association with outcomes was evaluated in univariate analyses. Variables significant at P < 0.1 were examined in a multivariate ordinal logistic regression analysis created with forward variable selection with forced inclusion of steroid treatment (high, regular, low dose, and none). A total of 328 patients were included from the 1002 reviewed charts. Of these patients, 164 (50.0%) were treated with steroids. Factors significantly associated with outcomes in the multivariate model were high-dose steroid treatment, visual acuity on presentation, age group, cause of keratitis, infiltrate size, and location. The odds ratio of better outcomes with high-dose steroids was 5.49 (confidence interval, 1.6-19.0, P = 0.007). High-dose steroid treatment is significantly associated with better visual outcomes in patients with culture-positive bacterial keratitis in this case series.

Optic Neuropathy and Macular Ischemia Associated with Neurosarcoidosis: A Case Report.

In this study, we present a case of bilateral optic neuropathy and macular ischemia in the right eye associated with neurosarcoidosis. A 26-year-old woman presented to our clinic with complaints of bilateral blurred vision. Bilateral granulomatous anterior uveitis, vitritis, optic neuropathy, and macular ischemia were detected in the right eye in slit-lamp examination. She also reported complaints of fever, weakness, sweating, arthralgia, and headache for 2 months. She was referred to the pulmonary diseases unit of our hospital due to hilar lymphadenopathy seen in her chest x-ray, and biopsies were taken for diagnostic purposes. Histological analysis of the mediastinal lymph node biopsies revealed chronic, non-caseating, granulomatous inflammation. Furthermore, the patient was referred to a neurologist due to concomitant complaint of intense headaches. She was diagnosed with neurosarcoidosis supported by findings on cranial magnetic resonance imaging and lumbar puncture. She received a 3-day course of high-dose (1 g/day) intravenous steroid treatment (methylprednisolone) followed by a tapering dose of oral prednisone. The patient began receiving oral methotrexate 15 mg/week as a steroid-sparing agent. Significant improvement in neurological and ophthalmological symptoms occurred in the first week of treatment. In this case report, we emphasized that neurosarcoidosis should be included in the differential diagnosis of patients with both bilateral optic neuropathy and macular ischemia. Furthermore, early diagnosis and timely treatment of neurosarcoidosis are important for favorable visual outcomes.

Rhinogenic Optic Neuritis Caused by Sphenoid Mucocele with Sinusitis

A 59-year-old male who presented with a nonspecific headache at the vertex, resembling retrobulbar optic neuritis, was treated as such but did not show any improvement. Although optic nerve compression from sphenoid mucocele was finally discovered, the delayed diagnosis and improper treatment led to a permanent visual loss. Optic neuritis could be caused by a common problem, “mucocele/sinusitis,” but might be easily overlooked in general practice. Rhinogenic optic neuropathy should, therefore, be considered in every case of optic neuritis whenever atypical presentation occurs or is unresponsive to high-dose steroid treatment.

Upregulation of microRNA-320 decreases the risk of developing steroid-induced avascular necrosis of femoral head by inhibiting CYP1A2 both in vivo and in vitro

Steroid-induced avascular necrosis of femoral head (SANFH) occurs frequently in patients receiving high-dose steroid treatment for these underlying diseases. The target of this study is to investigate the effect of microRNA-320 (miR-320) on SANFH by targeting CYP1A2. CYP1A2 expression was detected using immunohistochemistry. Specimens were collected from patients with SANFH and femoral neck fracture. Seventy rats were assigned into seven groups. The targeting relationship between miR-320 and CYP1A2 was verified by bioinformatics website and dual luciferase reporter gene assay. RT-qPCR and Western blot analysis were used to detect miR-320 and CYP1A2 expressions. The enzymatic activity of CYP1A2 was detected by fluorescence spectrophotometry. Hemorheology and microcirculation were measured in rats. MiR-320 expression decreased and CYP1A2 expression and enzymatic activity increased in SANFH patients compared to those with femoral neck fracture. CYP1A2 was the target gene of miR-320. Hemorheology and microcirculation results showed that up-regulated expression of CYP1A2 promoted the development of SANFH while increased expression of miR-320 inhibited the development of SANFH. Compared with the SANFH group, the SANFH + miR-320 mimic group showed increased miRNA-320 expression, and decreased CYP1A2 expression and enzymatic activity. Opposite results were found in the SANFH + miR-320 inhibitor group. The SANFH + miR-320 inhibitor + pCR-CYP1A2_KO group showed decreased miRNA-320 expression and the SANFH + pCR-CYP1A2_KO group showed decreased CYP1A2 expression and enzymatic activity. Our findings provide evidences that miR-320 might inhibit the development of SANFH by targeting CYP1A2.

Psychiatric sequelae of corticosteroid use in hematology in Australia: A qualitative study.

Despite widespread steroid usage for treating hematological conditions, minimal attention focuses on associated psychiatric side-effects. In the present study, we examined hematology patients' experiences of high-dose steroid treatment. This was undertaken by the use of a qualitative, descriptive design, which included convenience sampling and the inductive, cyclic, and constant comparative thematic analysis of interview transcripts. Eighteen patients participated, who were diagnosed with lymphoma, myeloma, leukemia, or idiopathic thrombocytopenia purpura. Four themes emerged: side-effects, misattribution of cause, self-management, and fragmented information. The study results revealed that hematology patients administered steroids can experience negligible to extensive erratic side-effects, with severe adverse repercussions. Psychological reactions to steroids are often misattributed. Patients mostly self-manage adverse effects experienced and receive only fragmented preparatory information, often not understanding steroid side-effects. Nurses could provide helpful "in the moment" education for inpatients who misunderstood steroid-related adverse effects, such as aggressive urges. Adverse repercussions for family were occasionally evident. Education, support, and ongoing care for patients experiencing adverse steroid side-effects are inadequate. Health professionals need to develop patient- and family-centered educational resources for potential, unpredictable, and usually adverse steroid side-effects.

Renal lithiasis and inflammatory bowel diseases, an update on pediatric population.

Background and aim of the work: Historical studies have demonstrated that the prevalence of symptomatic nephrolithiasis is higher in patients with inflammatory bowel disease (IBD), compared to general population. The aim of the review was to analyze literature data in order to identify the main risk conditions described in literature and the proposed treatment. Methods: A research on the databases PubMed, Medline, Embase and Google Scholar was performed by using the keywords “renal calculi/lithiasis/stones” and “inflammatory bowel diseases”. A research on textbooks of reference for Pediatric Nephrology was also performed, with focus on secondary forms of nephrolithiasis. Results: Historical studies have demonstrated that the prevalence of symptomatic nephrolithiasis is higher in patients with inflammatory bowel disease (IBD), compared to general population, typically in patients who underwent extensive small bowel resection or in those with persistent severe small bowel inflammation. In IBD, kidney stones may arise from chronic inflammation, changes in intestinal absorption due to inflammation, surgery or intestinal malabsorption. Kidney stones are more closely associated with Crohn’s Disease (CD) than Ulcerative Colitis (UC) in adult patients for multiple reasons: mainly for malabsorption, but in UC intestinal resection may be an additional risk. Nephrolithiasis is often under-diagnosed and might be a rare but noticeable extra-intestinal presentation of pediatric IBD. Secondary enteric hyperoxaluria the main risk factor of UL in IBD, this has been mainly studied in CD, whether in UC has not been completely explained. In the long course of CD recurrent urolithiasis and calcium-oxalate deposition may cause severe chronic interstitial nephritis and, as a consequence, chronic kidney disease. ESRD and systemic oxalosis often develop early, especially in those patients with multiple bowel resections. Even if we consider that many additional factors are present in IBD as hypomagnesuria, acidosis, hypocitraturia, and others, the secondary hyperoxaluria seems to finally have a central role. Some medications as parenteral vitamin D, long-term and high dose steroid treatment, sulfasalazine are reported as additional risk factors. Hydration status may also play an important role in this process. Intestinal surgery is a widely described independent risk factor. Patients with ileostomy post bowel resection may have relative dehydration from liquid stool, which, added to the acidic pH from bicarbonate loss, is responsible for this process. In this acidic pH, the urinary citrate level excretion reduces. The stones most commonly seen in these patients contain uric acid or are mixed. In addition, the risk of calcium containing stones also increases with ileostomy. The treatment of UL in IBD involves correction of the basic gastrointestinal tract inflammation, restricted dietary oxalate intake, and, at times, increased calcium intake. Citrate therapy that increases both urine pH and urinary citrate could also provide an additional therapeutic benefit. Finally, patients with IBD in a pediatric study had less urologic intervention for their calculosis compared with pediatric patients without IBD. (www.actabiomedica.it)

Clinical value of PCR for viral detection of bronchoalveolar lavage fluid in the diagnosis and treatment of pneumonia after allogeneic hematopoietic stem cell transplantation

目的探讨肺泡灌洗液（BALF）病毒检测在异基因造血干细胞移植（allo-HSCT）后常规病原学检查阴性肺炎患者诊治中的意义。方法回顾性分析2015年5月至2017年3月行allo-HSCT后出现肺部病变，并行支气管镜检查有完整BALF病原学检查结果的患者临床资料，比较单纯病毒检测阳性患者与所有病原学检查阴性患者的临床特点及转归。结果71例患者因发生肺部病变行BALF病原学检查。临床诊断单纯病毒相关性肺部病变15例（检出率为21.13%），未发现任何病原学证据患者19例，两组肺部病变中位发生时间分别为移植后176（49~1 376）d和移植后196（57~457）d（z=−0.191，P=0.864），两组患者在一般临床情况及表现上差异均无统计学意义。肺炎发病后100 d肺炎的归因死亡率分别为13.3%（2/15）和26.3%（5/19）（χ2=0.864，P=0.426），应用大剂量糖皮质激素（等效剂量≥ 250 mg/d甲泼尼龙）治疗的患者与未用激素或应用常规剂量激素组患者的死亡率分别为60.0%（6/10）和4.2%（1/24）。病毒检出组2例死亡患者均为早期应用大剂量糖皮质激素，而11例未用激素或晚期应用患者均存活。结论对于allo-HSCT后常规病原学检查均阴性的肺炎患者，应重视病毒感染的可能，BALF病毒检查可提高诊断率，并对治疗有指导意义。

Ventricular repolarization disturbances after high dose intravenous methylprednisolone Theraphy

ObjectiveThere are no randomized trials evaluating the effects of pulse steroid treatment on cardiac electrophysiologic functions. The data are limited only to case series. In this study, we sought to evaluate the effects of high dose intravenous methylprednisolone therapy on indices of ventricular repolarization. MethodsFifty patients with various autoimmune and inflammatory disorders were enrolled to the study. Electrocardiography (ECG) was obtained 4h before and 12h after the pulse steroid treatment. All ECGs were thoroughly evaluated by an experienced electrophysiologist. Indices of ventricular repolarization including QTc, JT, Tp-Te, Tp-Te/QTc were measured and compared with before and after-treatment ECGs. ResultsThere were 36 female and 14 male patients. Mean age was 36±13years. Heart rate was significantly reduced after the therapy (87,16±17,45bpm vs 73,86±17,45 p:0,001). QT interval (361,0±29,91 vs 388,20±42,84 p:0,001) and corrected QT interval (QTc) was significantly prolonged (401,60±19,79 vs 413,72±26,38 p:0,01) after pulse steroid therapy. Also, JT interval (273,0±28,73 vs. 299,60±45,66 p:0,001) and JT interval index (JTI%) was significantly prolonged (118,18±17,54 vs. 110,56±13,92 p:0,01). Tp-e interval was significantly prolonged after high-dose steroid treatment (74,60±13,12 vs. 83,80±13,68 p:0.001). The ratio of Tp-Te to QTc was also significantly increased after pulse steroid therapy (0,18±0,03 vs 0,20±0,03 p:0,009). ConclusionOur study shows that indices of ventricular repolarization are significantly prolonged after pulse steroid treatment. These findings indicate an increased risk of arrhythmias related to high dose intravenous methylprednisolone therapy.

391 DRESS syndrome: A retrospective chart review and evaluation of a high-dose steroid treatment protocol

391 DRESS syndrome: A retrospective chart review and evaluation of a high-dose steroid treatment protocol

The effect of high-dose steroid treatment used for the treatment of acute demyelinating diseases on endothelial and cardiac functions.

Objective:The cardiovascular effects of short-term high-dose steroid treatment (pulse steroid treatment) have not yet been clarified. We exa- mined the short- and long-term effects of pulse steroid treatment in demyelinating diseases on endothelial and cardiac functions.Methods:In this prospective study, we included 35 patients (20 females and 15 males; mean age, 32.8±9.3 years) who were not treated with steroids and who were previously diagnosed with multiple sclerosis or neuromyelitis optica. Patients were evaluated before, 1 week after, and 3 months after the steroid treatment. Brachial artery flow-mediated relaxation and cardiac systolic/diastolic function were evaluated using echocardiography to assess physical examination results, carotid intima–media thickness, and endothelial function.Results:There was no difference between biochemical values, systolic function, left ventricular dimensions, and carotid intima–media thicknesses in the three evaluation periods. There were significant increases in the body mass index, body weight, and systolic/diastolic blood pressure measurements at 1 week and 3 months after treatment (p<0.001). There was a significant decrease in brachial artery flow-mediated relaxation at 1 week and 3 months (1 versus 2, p=0.042; 1 versus 3, p=0.003). In Doppler measurements at 1 week and 3 months, there was an increase in mitral A velocity, IVRT, and EDT values and a decrease in the E/A ratio in line with diastolic dysfunction.Conclusion:Pulse steroid therapy used for demyelinating diseases deteriorated endothelial and left ventricular diastolic functions in the early and late periods. Future studies are needed to evaluate the development of cardiovascular mortality and morbidity in patients receiving this type of treatment.

Efficacy of high dose steroid treatment in pulmonary hemosiderosis

Efficacy of high dose steroid treatment in pulmonary hemosiderosis

Cerebral amyloid angiopathy related inflammation: is susceptibility weighted imaging the clue for diagnosis?

Background - Cerebral amyloid angiopathy-related inflammation (CAA-ri) is characterized by various neurological symptoms such as gradually developing confusion, progressive cognitive decline, seizure or headaches; T2 hyperintensities on magnetic resonance imaging (MRI); and neuropathological evidence of cerebral amyloid angiopathy (CAA) and associated vascular or perivascular inflammation. Although histological confirmation is necessary for accurate diagnosis, in case of typical clinical features and neuroimaging, the diagnosis can be established without biopsy. Case summary - We present the case of a 57-year-old man with a history of hypertension who presented to the emer¬gency department 3-week history of progressive headache and a gradually developing altered mental status. On examination, he was found to have left sided weakness and decreased pscyhomotility. Routine clinical work-up (lab investigations, CT, cerebrospinal fluid analysis) did not show obvious diagnosis, so we performed an MRI. It raised the suspicion of CAA-ri which diagnosis was verified by neuroradiological evaluation. High dose steroid treatment was initiated. The patient rapidly responded to treatment, his focal neurological signs resolved. Control MRI after 1.5 months showed multiple haemorrhagic laesions in the field of previous inflammation which posteriorly supported the previous supposed work-diagnosis. Conclusions - Although histopathology is the gold standard for the diagnosis of cerebral amyloid angiopathy, the typical clinical presentation, good response to steroids and accurate neuroradiological criteria make biopsy unnecessary to diagnose CAA-ri.

Systemic Lupus Erythematosus Presenting as Monocular Elevation Deficiency

Purpose: To report a case of monocular elevation deficiency as the presenting manifestation of systemic lupus erythematosus (SLE). Case summary: A 23-year-old, otherwise healthy female presented with a 3-day history of vertical diplopia and headache. She had a left hypotropia, which worsened in adduction and supra-duction and a profound inferior oblique underaction (-3). Magnetic resonance imaging showed an enhancement around the left superior oblique muscle and multiple infarctions in the left midbrain. On repetitive serological tests, anemia, lymphopenia, and anti-phospholipid antibody were positive. A presumptive diagnosis was a myositis of left superior oblique muscle and hyper-coagulation related with anti-phospholipid antibody. Two months after high-dose steroid treatment, the vertical diplopia was resolved. Five months later, the left hypotropia recurred as a more severe form with the inability to elevate the left eye in all directions. In addition, the infarction associated with vasculitis recurred in the left midbrain. As the treatment with high-dose steroid failed to relieve her ocular symptoms, recession of the left inferior rectus was performed 8 months later. One month after the surgery, she developed multiple lesions of erythematous nodosa with tenderness. Skin biopsy of the lesion in the fingers showed the histological findings consistent with lupus. Conclusions: Eye movement abnormality can be an initial manifestation of SLE, which should be considered as a differential diagnosis especially in young female patients. J Korean Ophthalmol Soc 2016;57(1):161-166

Acute Paraplegia due to Thoracic Hematomyelia.

Spontaneous intraspinal intramedullary hemorrhage is a rare entity with the acute onset of neurologic symptoms. The etiology of idiopathic spontaneous hematomyelia (ISH) is unknown, and there are few published case reports. Hematomyelia is mostly associated with trauma, but the other nontraumatic etiologies are vascular malformations, tumors, bleeding disorders, syphilis, syrinx, and myelitis. MRI is a good choice for early diagnosis. Hematomyelia usually causes acute spinal cord syndrome due to the compression and destruction of the spinal cord. A high-dose steroid treatment and surgical decompression and evacuation of hematoma are the urgent solution methods. We present idiopathic spontaneous hematomyelia of a previously healthy 80-year-old male with a sudden onset of back pain and paraplegia.

A Case of Acute Disseminated Encephalomyelitis in a MIddle-Aged Adult

Objectives. Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder that is often preceded by infection or recent vaccination. Encephalopathy and focal neurological deficits are usually manifest several weeks after a prodromal illness with rapidly progressive neurologic decline. ADEM is most commonly seen in children and young adults, in which prognosis is favorable, but very few cases have been reported of older adults with ADEM and thus their clinical course is unknown.Methods. Here we present a case of ADEM in amiddle-aged adult that recovered well after treatment. Results. A 62-yearold man presented with encephalopathy and rapid neurological decline following a gastrointestinal illness. A brain MRI revealed extensive supratentorial white matter hyperintensities consistent with ADEM and thus he was started on high dose intravenous methylprednisolone. He underwent a brain biopsy showing widespread white matter inflammation secondary to demyelination. At discharge, his neurological exam had significantly improved with continued steroid treatment and four months later, he was able to perform his ADLs. Conclusions. This case of ADEM in a middle-aged adult represents an excellent response to high dose steroid treatment with a remarkable neurological recovery. Thus it behooves one to treat suspected cases of ADEM in an adult patient aggressively, as outcome can be favorable.

Pure Red Cell Aplasia - a New Manifestation of CTLA4 Mutation

The cytotoxic T lymphocyte antigen-4 (CTLA4) is an essential negative regulator of immune responses. Its loss causes fatal autoimmunity in mice. Patients with heterozygous mutations in CTLA4 were recently reported to present with an autosomal dominant immune dysregulation syndrome characterized by hypogammaglobulinemia, recurrent infections and multiple autoimmune clinical features (Schubert, D. et al., Nat. Med. 20: 1410-1416, 2014; Kuehn, H.S. et al., Science 345, 1623-1627, 2014). Here we report a family with a CTLA4 mutation that presents with hematological manifestations not previously associated with CTLA4 loss.The index case was a girl referred to our hospital with a very severe thrombocytopenia and anemia at the age of 17. Bone marrow examination revealed no megakaryocytes and just a few erythroblasts. In contrast, granulopoiesis was normal and clonal lymphocytes were not detected. No etiology of the lack of thrombopoiesis and erythropoiesis was discovered. Lack of response to high-dose steroid treatment, platelet counts below 10x109/l, short-lasting effect of transfused platelets and a bleeding tendency urged us to start treatment with horse anti-thymocyte globulin (ATG) and cyclosporine after 2 months. A positive clinical response was observed in 2 weeks. Hb and platelet counts were normalized by 4 weeks, and all medication discontinued by 5 months. Two months later, the patient suffered from generalized tonic-clonic seizures. MRI revealed multiple cerebral lesions, lymphadenopathy and multiple infiltrates in lungs and kidneys. A core kidney biopsy revealed no clonal lymphoid infiltrates. A cerebral biopsy suggested crystal-storing histiocytosis. Steroids were administered, and the infiltrates disappeared gradually during the following months. More than two years later the patient suffered from a Salmonella-induced gastroenteritis, and again she became severely anemic. Her bone marrow revealed now lack of erythropoiesis whereas thrombopoiesis and granulopoiesis were normal. She was then diagnosed with pure red cell aplasia (PRCA).An uncle of the index case had been referred to us with the diagnosis MDS at the age of 47, one year prior to the index patient's last referral and PRCA diagnosis. Dysplasia was not verified, and since the patient completely lacked red cell precursors, the diagnosis was changed to PRCA. In addition, both he, his mother and the index case had been suffering from diarrhea for years without any diagnosis. His mother also had pernicious anemia.The two familial cases of PRCA, a rare hematological manifestation, prompted us to conduct whole exome sequencing which revealed that the two patients with PRCA were both heterozygous for a 5 base pair-insertion in exon 1 of the CTLA4 gene, leading to a frameshift and premature stop codon causing haploinsufficiency. Familial segregation was tested by Sanger sequencing and showed that also the grandmother and the mother of the index case were carriers of the same mutation.Functional assays of our index patient, the two family members with autoimmunity (her uncle and grandmother) and her unaffected mother revealed fewer CD19+ B- and naïve T cells than normal. Furthermore, we found dysregulation of regulatory T (Treg) cells, reduced levels of T cell CTLA4, particularly FoxP3+ Treg CTLA4 (mean fluorescence intensity as well as frequency of CTLA4+ T cells and Tregs) and signs of hyperactivity of effector T cells. Our findings were as reported in the above cited publications.The discovery of a CTLA4 mutation in this family with 3 affected members and one unaffected carrier might have immediate implications for our index patient. As she did not respond to high-dose steroids as her uncle did, her genetic diagnosis opens up to additional treatment opportunities. Actual medication for patients with mutations in CTLA4 and autoimmunity could be mTOR inhibitors like sirolimus and possibly CTLA4 fusion proteins (abatacept and belatacept). These fusion proteins bind to CD80 and CD86 and inhibit CD28-mediated immune activation.In conclusion, we have detected a mutation in the CTLA4 gene with corresponding T cell aberrations in this family through the new manifestation PRCA. These findings may be of clinical importance for the family we have characterized as well as for other patients with similar manifestations. DisclosuresOff Label Use: Abatacept and belatacept are fusion protein consisting of a part of CTLA4. It can modulate a signal necessary for activating specific T lymphocytes and can be effective in patients with CTLA4 mutations..

Survival in Idiopathic pulmonary fibrosis acute exacerbations: the non-steroid approach.

BackgroundIdiopathic pulmonary fibrosis acute exacerbation (IPF-AE) constitutes IPF’s most devastating event, representing the unexpected superimposition of diffuse alveolar damage of unknown etiology. Guidelines recommend high-dose steroids treatment despite unproven benefit. We hypothesized that previous immunosuppression and the administration of high-dose steroids adversely affect IPF-AE outcome.MethodsWe studied all consecutive patients hospitalized in our department for IPF deterioration from 2007 to June 2013. Our protocol consisted of immediate cessation of immunosuppression (if any), best supportive care, broad-spectrum antimicrobials and thorough evaluation to detect reversible causes of deterioration. Patients were followed-up for survival; post-discharge none received immunosuppression.ResultsTwenty-four out of 85 admissions (28 %) fulfilled IPF-AE criteria. IPF-AE were analyzed both as unique events and as unique patients. As unique events 50 % survived; 3 out of 12 (25 %) in the group previously treated with immunosuppression whereas nine out of 12 (75 %) in the group not receiving immunosuppression (p = 0.041). As unique patients 35.3 % survived; 3 out of 6 (50 %) in the never treated group whereas three out of 11 (27.3 %) in the group receiving immunosuppression (p = 0.685). The history of immunosuppression significantly and adversely influenced survival (p = 0.035). Survival was greater in the never treated group compared to the immunosuppressed patients (p = 0.022). Post-discharge, our IPF-AE survivors had an 83 % 1-year survival.ConclusionsBy applying the above mentioned protocol half of our patients survived. The history of immunosuppression before IPF-AE adversely influences survival. Avoiding steroids in IPF patients may favor the natural history of the disease even at the moment of its most devastating event.