Course Of High-dose Corticosteroids Research Articles

A CASE OF MYCOBACTERIUM AVIUM COMPLEX PULMONARY INFECTION WITH SEVERE EOSINOPHILIA TREATED WITH MEPOLIZUMAB

A CASE OF MYCOBACTERIUM AVIUM COMPLEX PULMONARY INFECTION WITH SEVERE EOSINOPHILIA TREATED WITH MEPOLIZUMAB

S1969 Treatment of Refractory ICI-Associated Colitis With Fecal Microbiota Transplant

Introduction: The clinical benefits of immune checkpoint inhibitors (ICIs) have been associated with immune-related adverse events (irAEs), with ICI-associated colitis among the most reported. ICI-associated colitis is routinely treated with immunosuppressive therapy, including corticosteroids and anti-TNF agents. Recent studies have suggested fecal microbiota transplant as a potential treatment for refractory ICI-associated colitis. Case Description/Methods: Middle aged female with multiple sclerosis in remission and stage IV melanoma with bone and pulmonary involvement who was first diagnosed about 3 years ago. She underwent palliative radiation followed by 4 cycles of ipilimumab and nivolumab initially. Despite this therapy she had cancer progression. She was then started on treatment with cisplatin, vinblastine and dacarbazine (CVD), however she failed to respond. She was switched to targeted therapy with encorafenib and binimitinib. Within 2 months, she was admitted to the hospital with anemia and hypotension, endoscopic evaluation revealed multiple intestinal and colonic ulcers. Based on these findings she was suspected to have ICI enterocolitis and received 2 cycles of infliximab plus high dose corticosteroids. She resumed encorafenib and binimitinib after clinical improvement and started single agent nivolumab. She was readmitted within 3 months and again at 4 months after for anemia and melena despite receiving additional treatment with vedolizumab and multiple courses of high dose corticosteroids. She was then treated with ustekinumab; however, she was again hospitalized a fourth time for similar symptoms. Decision was made to treat her refractory colitis with fecal microbiota transplant (FMT) as compassionate use. She had a remarkable response, with complete resolution of her GI symptoms with no additional immunosuppressive therapy or hospitalizations. However, patient’s cancer continued to progress. Her course was further complicated by oculomotor nerve dysfunction and ultimately was transitioned to hospice care and passed away 4 months later (Figure). Discussion: Fecal microbiota transplant has emerged as novel therapeutic option for treatment of refractory ICI-associated colitis. Combination treatment with ICI and targeted therapy may be a risk factor for more severe colitis with significant ulcers and refractory disease course. Further studies are needed to assess the risk factors related to combination therapy and guide more effective treatment.Figure 1.: A: Altered anatomy near cecum, B: Ulcer in terminal ileum, C: Ulcerated mass in ascending colon, D: Ascending colon narrowing.

Diagnostic d’une granulomatose éosinophilique avec polyangéite sous benralizumab

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare necrotizing vasculitis affecting small vessels and associated with severe asthma and eosinophilia. Monoclonal antibodies blocking the IL-5 signaling pathway, one example being benralizumab, decrease the proliferation of eosinophils and represent an effective treatment in severe eosinophilic asthma. They are a therapeutic option currently studied for EGPA. We report the paradoxical clinical case of EGPA appearing following the initiation of treatment with benralizumab (anti-IL-5R monoclonal antibody). We describe the case of a 66-year-old female patient with severe asthma. Following the initiation of benralizumab, she showed deterioration of her general condition, associated with severe peripheral neuropathy of the lower limbs. At the same time, she developed massive hypereosinophilia. After an extensive workup, the patient was eventually diagnosed with an EGPA with multisystem involvement. Benralizumab was stopped and a course of high dose corticosteroids and immunosuppressants was initiated, enabling slow clinical recovery. Anti-IL5 monoclonal antibodies, including benralizumab, are being investigated for new therapeutic indications, including EGPA. Paradoxically, a few rare cases of EGPA associated with these molecules have been reported in the literature. The causal link of this association remains hypothetical. Close monitoring of patients on benralizumab consequently seems indispensable.

MOG-related bilateral optic neuritis in a patient with cystic fibrosis

Optic neuropathy secondary to Cystic Fibrosis (CF) has been described as a manifestation of chloramphenicol toxicity. Inflammatory optic neuritis and Myelin Oligodendrocyte Glycoprotein (MOG)-related disorders have not been previously described in patients with CF. We report the case of a 19-year-old woman with cystic fibrosis who presented for sub-acute onset decreased visual acuity, dyschromatopsia, and optic disk swelling in both eyes, with near-complete resolution after a course of high-dose corticosteroids. MOG-IgG were positive in the serum. MOG-related optic neuritis can occur in CF and represent a diagnostic and long-term therapeutic challenge. Keywords: Optic neuritis; MOG; cystic fibrosis.

Prevalence and predictors of SARS-CoV-2 antibodies among solid organ transplant recipients with confirmed infection.

It remains uncertain whether immunocompromised patients including solid organ transplant (SOT) recipients will have a robust antibody response to SARS‐CoV‐2 infection. We enrolled all adult SOT recipients at our center with confirmed SARS‐CoV‐2 infection who underwent antibody testing with a single commercially available anti‐nucleocapsid antibody test at least 7 days after diagnosis in a retrospective cohort. Seventy SOT recipients were studied (56% kidney, 19% lung, 14% liver ± kidney, and 11% heart ± kidney recipients). Thirty‐six (51%) had positive anti‐nucleocapsid antibody testing, and 34 (49%) were negative. Recipients of a kidney allograft were less likely to have positive antibody testing compared to those who did not receive a kidney (p = .04). In the final multivariable model, the years from transplant to diagnosis (OR 1.26, p = .002) and baseline immunosuppression with more than two agents (OR 0.26, p = .03) were significantly associated with the antibody test result, controlling for kidney transplantation. In conclusion, among SOT recipients with confirmed infection, only 51% of patients had detectable anti‐nucleocapsid antibodies, and transplant‐related variables including the level and nature of immunosuppression were important predictors. These findings raise the concern that SOT recipients with COVID‐19 may be less likely to form SARS‐CoV‐2 antibodies.

Risk factors assessment and therapeutic drug management of sars covid-19 virus

Severe acute respiratory syndrome corona virus (COV)-2(SARS-COV-2) previously called 2019 novel cov emerged from china. This virus causes cov disease-19(COVID-19), favipiravir (1000mg) is an oral anti-viral that inhibits RNA polymerase that is a pproved in Russia during phase 2/3 clinical trials for the treatment of covid. Ivermectin an antiparasitic drug showed an in-vitro reduction of viral RNA in vero-hslam cells 2hr post-infection with SARS-COV-2.corticosteroids include dexamethasone (6mg), Methyl Prednisolone (80mg) can induce harm through immunosuppressant effects during treatment of infection and a study in the Netherlands showed a 5-day course of high dose corticosteroids accelerated respiratory recovery lowered hospital mortality rates and reduced the likelihood of mechanical ventilation in patients with severe COVID-19 associated cytokine storm syndrome. Use of convalescent PLASMA after a multicentre study conducted by Mayo clinic indicates transfusion of ABO-compatible human covid-19 is safe and effective in hospitalized adults. NAK and JAK inhibitors may mitigate systemic and alveolar inflammation in patience with covid-19 pneumonia by inhibiting essential cytokine signaling drugs include baricitinib (4mg), fedratinib (100mg), ruxolitinib (5mg). Statins decrease the inflammatory processes of atherosclerosis. Vitamins and mineral supplements have been promoted for the treatment of respiratory viral infections. Hydroxychloroquine(400mg) and chloroquine (600mg) are widely used anti-malarial drugs that elicit immunomodulatory effects based on PBPK models recommended loading dose of HCQ is 400mg (BID) followed by 200mg (BID) for four days. In a randomized controlled, open-label trial of hospitalized adults with conformed SARSCOV-2, recruited patients had 02 saturation of 94% less than ambient air or pao2 of less than 300mmhg were randomized to receive Lopinavir/Ritonavir 400mg/100mg for 14 days, Adjunctive nutritional therapies also recommended.

Acute interstitial nephritis following treatment with direct-acting antiviral agents in hepatitis C virus-infected patients: A case series.

Hepatitis C virus (HCV) infection has been associated with several extrahepatic adverse clinical outcomes, including an accelerated rate of loss of kidney function in patients with chronic kidney disease (CKD) and an increased mortality in patients with CKD and kidney failure on hemodialysis. Clinical trials using direct-acting antiviral (DAA) agents have uniformly achieved sustained viral response at 12weeks (SVR12) rates of >90% in the general population as well as in patients with CKD/kidney failure on hemodialysis. Sofosbuvir is a DAA prodrug that is phosphorylated into the active metabolite GS-461203, with subsequent dephosphorylation into the inactive metabolite GS-331007. The kidneys clear both sofosbuvir and GS-331007, and its use has been associated with worsening kidney function in some studies. In the HCV-TARGET study, patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min at the initiation of sofosbuvir-based therapy had higher rates of deterioration of kidney function compared to patients with higher eGFR [1]. However, based on recent data demonstrating safety in patients with advanced CKD, the US Food and Drug Administration (FDA) approved the use of sofosbuvir-containing regimens in patients with CKD 4/5 (eGFR of less than 30 mL/min/1.73m2) and end-stage renal disease (ESRD) in late 2019. The current report describes 8 HCV-infected patients who developed acute kidney injury (AKI) with biopsy-proven acute interstitial nephritis (AIN) temporally associated with the use of DAAs. The mean age of the group was 61.3 (±6 years). The most common HCV genotype (GT) was 1a (n=7). The DAA formulations were sofosbuvir/ledipasvir (n=5), elbasvir/grazoprevir (n=2), and sofosbuvir/simeprevir (n=1). All patients achieved an SVR12. The mean serum creatinine at the initiation of DAA treatment was 1.5 mg/dL (± 0.6) and increased to 2.03 mg/dL (± 0.7) by the last day of DAA administration. The kidney biopsies were performed at a mean of 320 days (± 247) after achieving an SVR12, at which point the mean creatinine had increased to 2.3 mg/dL (± 1.4). All patients received a course of high-dose corticosteroids after the diagnosis of AIN was confirmed by biopsy. Serum creatinine levels at 3 and 6months following the completion of steroid therapy were 2.8 (±1.2) and 3.1mg/dL (±1.5), respectively. Three patients had worsening CKD and progressed to kidney failure requiring hemodialysis. These results are consistent with earlier studies demonstrating the efficacy of the DAAs in HCV-infected CKD patients. Of note, the demonstration of AIN in these patients may explain some of the AKI events reported with the use of DAAs in patients with CKD.

Impact of Corticosteroids on Short- and Long-Term Mortality in Patients with Sepsis and Septic Shock: A Meta-Analysis with Trial Sequential Analysis

Background Findings on the benefits and harms of corticosteroids for sepsis and septic shock from published meta-analyses are conflicting. With new randomized evidence emerging, an updated analysis of best available evidence on the effects of corticosteroids in sepsis and septic shock is warranted. Methods We did a conventional and cumulative meta-analysis and trial sequential analysis. Ovid MEDLINE, Ovid Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and LILACS were searched until May 2, 2018. Two reviewers selected randomized controlled trials (RCTs) reporting benefits and harms of corticosteroids as compared to placebo, standard therapy or no steroids in patients with sepsis and septic shock and independently collected data of interest. Primary outcomes were short-term (14-day and 28-day) mortality and long-term (90-day, 180-day, 1-year) mortality. Secondary outcomes included intensive care unit (ICU)- and hospital mortality, shock reversal by day 7 and 28, length of ICU and hospital stay, sequential organ failure assessment (SOFA) score at day 7 and adverse events. Fixed-effect and random-effects models were used to provide pooled estimates on predefined outcomes. This study is registered with PROSPERO, number CRD 42018092849. Findings Thirty-four RCTs including 9,942 participants were included in this meta-analysis. Results showed that long course of low-dose corticosteroids could improve 28-day mortality (relative ratio (RR), 0.91; 95% confidence interval (CI), 0.86 to 0.97; I2=0%; high-quality evidence), ICU mortality (RR, 0.87; 95%CI, 0.79 to 0.95; I2=21%; moderate-quality evidence) and hospital mortality (RR, 0.89; 95%CI, 0.79 to 0.99; I2=40%; low-quality evidence). Meta-regression analyses confirmed the benefits of corticosteroids in14-day and 28-day mortality and indicated that the use of hydrocortisone at least 135mg per day for at least 87h was associated with significant benefits. However, this meta-analysis found no benefits for 90-day mortality from low-quality evidence (RR, 0.96; 95%CI, 0.85 to 1.09; I2=44%), 180-day mortality and 1-year mortality and about 38,340 participants were required for clarification of the effect of 90-day mortality. In terms of adverse events, long course of low-dose corticosteroids were associated with hyperglycaemia (RR, 1.20; 95%CI, 1. 09 to 1.32; I2=40%) and hypernatraemia (RR, 1.60; 95%CI, 1.26 to 2.02; I2=0%). Short course of high-dose corticosteroids showed no significant benefits in any of the predefined outcomes. Interpretation Long course (at least 87h) of low-dose (at least 135 mg per day) hydrocortisone could improve 28-day mortality of patients with sepsis and septic shock as well as ICU- and hospital mortality, with varied quality of evidence. However, it could not reduce long-term (90-day, 180-day and 1-year) mortality. Funding: None. Declaration of Interest: We declare no competing interests.

An Unexpected Case of Eosinophilic Cholangitis

When evaluating a patient with biliary stricture one needs to consider both benign and malignant causes. About 10% of biliary stricture are benign. Eosinophilic cholangitis (EC) is an extremely rare benign disorder of the biliary tract caused by a fibrosis and stricture from eosinophilic infiltration. Etiology of the disease remains unclear, and often times patients present with obstructive jaundice. A 23-year-old male presented with worsening abdominal pain, vomiting, 17-pound weight loss and jaundice. He reported having clay colored stools, dark colored urine, and pruritus. Physical exam showed mild epigastric tenderness with negative Murphy's sign. Lab work up revealed: WBC with 22.9% eosinophils, Total bilirubin 18.7 mg/dl, direct bilirubin >10.0 mg/dl, AST 247 U/L, ALT 606 U/L, and alkaline phosphatase 588 U/L. Autoimmune antibodies and viral hepatitis serology were negative. Ultrasound of the right upper quadrants showed mild intra-hepatic and extra-hepatic biliary dilation. MRCP depicted moderate to severe intrahepatic biliary ductal dilation at the level of the porta hepatis with consideration for acute obstruction versus post-inflammatory changes. Further evaluation with ECPR revealed a 25mm stricture in the common hepatic duct, a 10mm sphincterotomy was performed and a 10x80mm plastic stent was diploid. Histopathology showed benign ductal mucosa with subepithelial fibrosis and mixed eosinophils and lymphocytes inflammation. Patient was started on high-dose steroids for three months. Follow up CBC revealed a down trending eosinophil count to 4.1% of total WBC. Repeat ECRP revealed incomplete resolution of the stricture. Patient was referred to hepatobiliary surgery for a Roux-en-Y hepaticojejunostomy. Eosinophilic cholangitis is a rare cause of biliary strictures. Diagnoses of eosinophilic cholangitis is based on histopathological evidence of eosinophilic infiltration with or without peripheral eosinophilia. Treatment is a course of high dose corticosteroids, however there is no specific guidelines on duration and dosing of therapy. Resolution of biliary stenosis is usually seen 3-5 weeks after initiation of corticosteroids; in such cases surgical option should be explored.Figure: ERCP displaying intrahepatic and extra hepatic ductal dilation.

Coccidioidal meningitis complicated by central nervous system vasculitis in a patient with leukemia

Central Nervous System (CNS) vasculitis is the most common life-threatening complication of coccidioidal meningitis. It is manifested by cerebral ischemia, hemorrhage, and infarction. We report a case of CNS vasculitis in a patient receiving chemotherapy and review of the literature on coccidioidal meningitis. The patient was treated with combination antifungal therapy and a short course of high dose corticosteroids with a modest improvement in her neurological examination after initiation of steroids.

Methylprednisolone blocks interleukin 1 beta induced calcitonin gene related peptide release in trigeminal ganglia cells

BackgroundMethylprednisolone (MPD) is a rapid acting highly effective cluster headache preventive and also suppresses the recurrence of migraine attacks. Previously, we could demonstrate that elevated CGRP plasma levels in a cluster headache bout are normalized after a course of high dose corticosteroids. Here we assess whether MPD suppresses interleukin-1β (IL-1β)- and prostaglandin E2 (PGE2)-induced CGRP release in a cell culture model of trigeminal ganglia cells, which could account for the preventive effect in migraine and cluster headache. Metoprolol(MTP), a migraine preventive with a slow onset of action, was used for comparison.MethodsPrimary cultures of rat trigeminal ganglia were stimulated for 24 h with 10 ng/ml IL-1β or for 4 h with 10 μM PGE2 following the exposure to 10 or 100 μM MPD or 100 nM or 10 µM MTP for 45 min or 24 h. CGRP was determined by using a commercial enzyme immunoassay.ResultsMPD but not MTP blocked IL-1β-induced CGRP release from cultured trigeminal cells. PGE2-stimulated CGRP release from trigeminal ganglia cell culture was not affected by pre-stimulation whether with MPD or MTP.ConclusionMPD but not MTP suppresses cytokine (IL-1β)-induced CGRP release from trigeminal ganglia cells. We propose that blockade of cytokine mediated trigeminal activation may represent a potential mechanism of action that mediates the preventive effect of MTP on cluster headache and recurrent migraine attacks.

Multiple sclerosis and pregnancy

Multiple sclerosis (MS) is a chronic, neurodegenerative disease that has a high impact on patients׳ quality of life. The majority of diagnosed patients are women of childbearing age, making pregnancy-related issues (conception, contraception, childbirth, lactation) a key concern. MS typically stabilizes during pregnancy, particularly in the last trimester. Evidence suggests that the disease does not affect fertility, delivery, fetal health or pregnancy itself and does not cause birth defects. There is no increase in spontaneous abortions although a decreased birth weight has been reported. Epidural analgesia is safe in women with MS and hasn´t worsened disability in the postpartum period. Small differences in MS risk according to month of birth have been reported (higher in spring, lower in autumn). MS risk is lower among women born to mothers with high vitamin D intake during pregnancy, supplementing vitamin D-deficient mothers could be useful. No single gene produces MS . The risk for MS is about 2% for a child with one MS parent, and 6–12% for children where both parents have MS. Regarding the course of the disease, pregnancy had no effect on disability and no negative long-term impact. It seems that pregnancy could accelerate disease in RIS patients. High relapse rate or disability before pregnancy as well as relapse during pregnancy, have been associated with increased risk for postpartum attacks. An increase in new or enlarging MRI lesions post-partum was reported in several studies.MS itself does not pose any obstacles to breastfeeding and there is no risk of disease transmission through breast milk. Conflicting data indicate either no effect from breast-feeding or a positive benefit in reducing MS activity. The FDA has said that DMTs should not be used in MS patients who are pregnant, trying to become pregnant, or breast-feeding. Even though studies which have considered this aspect have found no effect of glatiramer acetate and only minor adverse effects of interferons. Glatiramer acetate has the most favorable pregnancy rating (class B). Natalizumab, fingolimod and BG12 have been given a pregnancy category C rating by the FDA based on results of animal studies and teriflunomide has been designated pregnancy category X. It is also recommended to discontinue symptomatic therapies prior to conception if they are not absolutely necessary. A short course of high-dose corticosteroids to hasten recovery from disabling relapses appears relatively safe during pregnancy, but there is a possible increased risk of fetal cleft palate associated with their use in the first trimester. There is little information regarding effects of MS disease modifying treatments on human male fertility or pregnancy outcomes in fathers receiving treatment

Short Course Infliximab and Extracorporeal Photopheresis As Therapy For Steroid-Refractory Acute Gvhd In Matched Related and Unrelated Allogeneic Hematopoietic Cell Transplant (HCT)

Background Steroid-refractory (SR) acute graft-versus host disease (aGVHD) is a serious complication of allogeneic HCT, for which there is no established standard treatment. Both ECP and cytokine inhibitors such as Infliximab have apparent single agent activity in the therapy of SR aGVHD, but there are no published data that address the efficacy of combination anticytokine therapy and ECP in this setting. We report here results in 18 adult patients (pts) with grade III or IV SR aGVHD who were treated with concurrent Infliximab and ECP. Patients All pts underwent allogeneic HCT (first transplant, n=15, second transplant, n=3) for a hematologic malignancy at Mayo Clinic Arizona between March 2012 and May 2013. The median age was 61 (range 22-70), and the median follow-up of 6 surviving pts is 263 days (range 79-433). Donors were related in 3, matched unrelated in 8, and mismatched unrelated in 7. GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil in 13 pts and tacrolimus/methotrexate in 5; in addition, 17 pts received in vivo T-cell depletion with Thymoglobulin 2.5 – 7.5 mg/kg. All pts developed grades III-IV aGVHD at a median day 27 post-transplant (range 10-107) and failed to respond to a course of high-dose corticosteroids (methylprednisolone or equivalent 2 mg/kg daily) for at least 5 days. Treatment Regimen At diagnosis of SR aGVHD, pts were scheduled to receive weekly Infliximab 10 mg/kg (maximum 4 doses), concurrent with ECP performed twice or thrice weekly for one month, followed by a pre-specified taper schedule (anticipated total treatment duration of 6-9 months). To minimize infectious risk and morbidity, corticosteroids were tapered rapidly after the start of Infliximab/ECP therapy. Results Thirteen pts (72%) responded to the Infliximab/ECP combination; complete response (CR; resolution of all GVHD symptoms for at least 30 days and able to discontinue corticosteroids) was observed in 6 pts (33%), and partial response (PR; improvement in GVHD symptoms, partial taper of corticosteroids, and no additional agent for at least 30 days) in 7 pts (39%). At the time of this report, 6 pts are alive, and the Kaplan-Meier estimate of one-year survival is 22.5 % (95% CI, 8.8%-47%). Only pts who achieved CR had good outcomes (5/6 surviving and clinically well); among 13 pts with PR (7) or no response/progression (6) to Infliximab/ECP, 12 have died and one is day 79 post transplant and remains on ECP and low-dose prednisone. Eleven of the 12 deaths were related to GVHD or complications of its treatment (infection, multi-organ failure). Conclusions In this retrospective study of adult pts with severe (grade III/IV) SR aGVHD, treatment with 4 doses of weekly Infliximab and concurrent ECP resulted in an overall response rate of 72%, with one-third of pts achieving CR; the regimen was well-tolerated and facilitated early taper and rapid discontinuance of corticosteroids. Unfortunately, the overall survival of 22.5% at one year does not appear superior to other single agent or combination therapies reported in the literature, or to historical data from our program. Although a small percentage of pts appear to be long-term survivors, the majority of pts succumb to complications of progressive GVHD or infection. Given poor results with available therapies, and the dismal prognosis of pts with SR aGVHD, future research should focus on better preventative strategies for this devastating complication of allogeneic HCT. Disclosures: No relevant conflicts of interest to declare.

Acquired factor V deficiency in a patient without evidence of a classical inhibitor

Acquired factor V deficiency in a patient without evidence of a classical inhibitor

Nitrofurantoin-induced Autoimmune Hepatitis: A Case Report

Introduction: Several commonly used medications are well-established in triggering drug-induced autoimmune hepatitis (DIAIH), with nitrofurantoin being a widely used antibiotic in the treatment of recurrent urinary tract infections (UTIs), which has been reported to elicit a wide spectrum of hepatic insults ranging from acute self-limited hepatitis to chronic hepatitis. Case Presentation: A 54-year-old woman with CAD and recurrent urinary tract infections on prophylactic nitrofurantoin for over 2 years was evaluated for sudden onset lower extremity edema, jaundice, and dark urine. She is not known to have liver disease, alcohol, or intravenous drug abuse. Examination was significant for jaundice and lower extremity edema in the absence of other stigmata of chronic liver disease. Labarotary evaluation showed abnormal liver function tests (ALT 535, AST 650, ALK-P 362, total bilirubin /direct bilirubin 4.7/3.6), along with normal blood count, coagulation screen, cardiac, and renal function. Serologic evaluation was negative for viral hepatitis. RUQ US with mild-to-moderate ascites with cirrhotic liver appearance. Abdominal CT showed a shrunken nodular liver with patent portal and hepatic veins. Immunologic evaluation was positive ANA and ASMA, but negative for AMA, anti ds-DNA, and anti LKM. Liver biopsy confirmed liver cirrhosis with no evidence of steatohepatitis or other superimposed liver disease. Expectant management with nitrofurantoin withdrawal alone only achieved partial recovery that was eventually hastened and maintained with additional limited course of high-dose corticosteroids. Discussion: Drug-induced autoimmune hepatitis represents a significant percentage of all AIH cases (9-17%). A definite association exists between commonly used medications (nitrofurantoin, minocycline) and DIAIH that we should be aware of as practicing clinicians. The time course between introduction of nitrofurantoin and DIAIH can be variable with tendency to present with acute symptomatology at various stages of treatment, with certain predilection for elderly females on prolonged prophylactic treatment for recurrent urinary tract infections. Nitrofurantoin, unlike minocycline, could present with significant fibrosis and cirrhosis, which is clearly reflected in our patient. Partial recovery upon drug withdrawal is to be expected in nitrofuratoin-induced AIH, with tendency for complete resolution on steroid challenge.

Rituximab Associated Pneumonitis in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Rituximab is gaining use in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis. We report the first case of rituximab-induced pneumonitis in a patient with antineutrophil cytoplasmic antibody-associated vasculitis. Our patient with granulomatosis with polyangiitis (Wegener granulomatosis) had a relapse complicated by diffuse alveolar hemorrhage and acute kidney injury. His treatment included rituximab, steroids, cyclophosphamide, and plasmapheresis. Two weeks after his second dose of rituximab, he developed an acute deterioration in respiratory function. Rituximab-induced pneumonitis was diagnosed on a combination of computed tomography imaging, bronchoalveolar lavage, and negative tests for active vasculitis and infection. He was treated with a course of high-dose corticosteroids with improvement in respiratory function, computed tomography imaging of his chest, and inflammatory markers. Acute drug-induced pneumonitis is a rare but serious complication of rituximab. Distinguishing this complication from alveolar hemorrhage or pulmonary infection may be difficult. This diagnosis needs to be considered early in the right clinical context.

Mycophenolate Mofetil and Thrombopoietin Receptor Agonists in the Treatment of Refractory Thrombocytopenia in Patients with Autoimmune Lymphoproliferative Syndrome

Abstract 2218Autoimmune lymphoproliferative syndrome (ALPS), often due to an inherited defect in the FAS gene, presents with chronic non-malignant lymphadenopathy, splenomegaly, and autoimmune cytopenias (Oliveira JB et al. “Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop”. Blood. 2010 Oct 7;116(14):e35-40). Thrombocytopenia has been noted in approximately 23% of ALPS patients. These patients, especially those with massive splenomegaly and hypersplenism, are often refractory to standard dose short-term corticosteroid regimens and intravenous immunoglobulins (IVIG). Mycophenolate mofetil (MMF) has been used for persistent thrombocytopenia as a steroid sparing long-term measure in 40 out of 245 ALPS patients in our cohort. The median age at initiation of MMF was 10.5 years (range 7 months to 43 years) with an average follow-up of 3.8 years on MMF (range 3 months to 11 years). Here we share our experience over the last 7 months related to the use of thrombopoietin receptor agonists in 3 ALPS patients who have persistent, severe, MMF-refractory thrombocytopenia (platelets <10,000/uL) (Figure).Patient 1 is a 21 year old man with ALPS-FAS and splenomegaly who has been on MMF for 2 years. He presented with monthly episodes of thrombocytopenia requiring high dose corticosteroids and IVIG followed by four weeks of rituximab and daily prednisone without any durable improvement in his thrombocytopenia. He was started on eltrombopag 50mg daily and was able to taper off prednisone in one month with sustained stable platelet count. Three months after starting eltrombopag, he was able to survive surgical intervention for a spontaneous pneumothorax while on eltrombopag and MMF.Patient 2 is an 18 year old woman with ALPS-FAS and surgical asplenia who has been on MMF for approximately 7 years. She began having significant, symptomatic thrombocytopenia refractory to high-dose corticosteroids with transient responses to IVIG. She was started on eltrombopag 50mg daily with MMF and initially responded. However, when MMF was discontinued her platelet count plummeted. Despite reinitiating MMF, her platelet counts never recovered on eltrombopag and she continued to require monthly IVIG. She was eventually switched to romiplostim, and was incrementally increased to the maximum dose of 10mcg/kg/week. Her platelet counts continue to fluctuate, but she has not required any IVIG in over one month.Patient 3 is a 19 year old man with ALPS-U and surgical asplenia who has been on MMF for the last 9 years. During the past year he has had episodes of symptomatic thrombocytopenia requiring monthly courses of high dose corticosteroids and IVIG. After initiation of eltrombopag, he had a significant rise in his platelet counts. However, upon discontinuation of MMF, his platelet counts plummeted. MMF was restarted and he was trialed on multiple, different eltrombopag dosing regimens leading to supratherapeutic responses with platelet counts over 1,000,000/uL. Eltrombopag was held during these periods to allow for the significant thrombocytosis to resolve, but withholding eltrombopag led to platelet counts to eventually fall precipitously. Furthermore, he also developed severe headaches due to MMF and MMF had to be discontinued. After multiple dosing regimens, he eventually maintained a stable platelet count on eltrombopag 50mg daily for 5 days alternating with eltrombopag 25mg for 2 days without the concomitant use of MMF.Recently, there has been increasing evidence supporting the use of thrombopoietin receptor agonists in the treatment of refractory immune thrombocytopenia. MMF continues to be well tolerated as a long-term corticosteroid sparing drug for patients with ALPS complicated by chronic, refractory thrombocytopenia. Our preliminary experience suggests that there may be a role for thrombopoietin receptor agonists, most likely in combination with an immunosuppressive agent such as MMF, in the treatment of refractory thrombocytopenia in patients with ALPS. However, schedule and duration of therapy with this class of drugs needs further long term evaluation. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Rhodococcus equiInfection After Lung Transplantation

Rhodococcus equi is an emerging opportunistic pathogen in immunocompromised patients. A lung-transplant recipient developed weight loss, nonproductive cough, dyspnea, and somnolence. Computed tomogram showed a pulmonary nodule and pleural changes in the right allograft that was due to R. equi infection. Alteration of cell-mediated immunity is a predisposing risk factor for R. equi infection in humans. Our patient developed R. equi infection soon after a course of high-dose corticosteroids for acute allograft infection and animal exposure. A course of intravenous vancomycin followed by single-agent long-term therapy with oral ciprofloxacin was successful.

Fibrodysplasia Ossificans Progressiva: Clinical and Genetic Aspects

Fibrodysplasia ossificans progressiva (FOP) is a severely disabling heritable disorder of connective tissue characterized by congenital malformations of the great toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites. The worldwide prevalence is approximately 1/2,000,000. There is no ethnic, racial, gender, or geographic predilection to FOP. Children who have FOP appear normal at birth except for congenital malformations of the great toes. During the first decade of life, sporadic episodes of painful soft tissue swellings (flare-ups) occur which are often precipitated by soft tissue injury, intramuscular injections, viral infection, muscular stretching, falls or fatigue. These flare-ups transform skeletal muscles, tendons, ligaments, fascia, and aponeuroses into heterotopic bone, rendering movement impossible. Patients with atypical forms of FOP have been described. They either present with the classic features of FOP plus one or more atypical features [FOP plus], or present with major variations in one or both of the two classic defining features of FOP [FOP variants]. Classic FOP is caused by a recurrent activating mutation (617G>A; R206H) in the gene ACVR1/ALK2 encoding Activin A receptor type I/Activin-like kinase 2, a bone morphogenetic protein (BMP) type I receptor. Atypical FOP patients also have heterozygous ACVR1 missense mutations in conserved amino acids. The diagnosis of FOP is made by clinical evaluation. Confirmatory genetic testing is available. Differential diagnosis includes progressive osseous heteroplasia, osteosarcoma, lymphedema, soft tissue sarcoma, desmoid tumors, aggressive juvenile fibromatosis, and non-hereditary (acquired) heterotopic ossification. Although most cases of FOP are sporadic (noninherited mutations), a small number of inherited FOP cases show germline transmission in an autosomal dominant pattern. At present, there is no definitive treatment, but a brief 4-day course of high-dose corticosteroids, started within the first 24 hours of a flare-up, may help reduce the intense inflammation and tissue edema seen in the early stages of the disease. Preventative management is based on prophylactic measures against falls, respiratory decline, and viral infections. The median lifespan is approximately 40 years of age. Most patients are wheelchair-bound by the end of the second decade of life and commonly die of complications of thoracic insufficiency syndrome.

Fluticasone, azithromycin and montelukast therapy in reducing corticosteroid exposure in bronchiolitis obliterans syndrome after allogeneic hematopoietic SCT: a case series of eight patients

BackroundBronchiolitis obliterans syndrome (BOS) is a devastating pulmonary complication affecting long term survivors of allogeneic hematopoietic cell transplantation. Treatment of BOS with prolonged courses of high dose corticosteroids is often associated with significant morbidity. Reducing the exposure to corticosteroids may reduce treatment related morbidity. Our institution has recently begun to treat patients with emerging therapies in an effort to diminish steroid exposure.MethodsWe retrospectively reviewed the 6-month corticosteroid exposure, lung function, and failure rates in 8 patients with newly diagnosed BOS who were treated with a combination of fluticasone, azithromycin and montelukast (FAM) and a rapid corticosteroid taper. These patients were compared to 14 matched historical patients who received high dose corticosteroids followed by a standard taper.ResultsThe median 6-month prednisone exposure in FAM-treated patients was 1819 mg [0 mg to 4036 mg] compared to 7163 mg [6551 mg to 7829 mg] in the control group (p = 0.002). The median FEV1 change in FAM-treated patients was 2% [−3% to 4%] compared to 1% [−4 to 5%] in the control group (p = 1.0).DiscussionPrednisone exposure in FAM patients was one quarter that of a retrospective matched group of patients, with minimal change in median FEV1, suggesting that BOS may be spared of the morbidities associated with long-term corticosteroid use by using alternative agents with less side effects.