Course Of Prednisone Research Articles

Update on the treatment of steroid-sensitive nephrotic syndrome.

Steroid-sensitive nephrotic syndrome (SSNS) is a rare condition that develops primarily in preadolescent children after the age of 1 year. Since the 1950s, oral corticosteroids have been the mainstay of treatment of all children presenting with nephrotic syndrome, with most patients responding within 4 weeks to an oral course of prednisone (PDN). However, corticosteroids have important side effects and 60-80 % of patients relapse, developing frequently relapsing or steroid-dependent forms. For these reasons, many patients require second-line steroid-sparing immunosuppressive medications that have considerably improved relapse-free survival, while avoiding many PDN-related toxicities. Since most patients will eventually heal from their disease with a normal kidney function, the morbidity of SSNS is primarily related to side effects of drugs that are used to maintain prolonged remission. Therefore, treatment is essentially based on balancing the use of different drugs to achieve permanent remission with the lowest cumulative number of side effects. Treatment choice is based on the severity of SSNS, on patient age, and on drug tolerability. This review provides an update of currently available therapeutic strategies for SSNS.

P78.11 Immunotherapy-Induced Coeliac Disease in the Curative Lung Cancer Patient on Adjuvant Durvalumab

The PACIFIC study led to the approval of durvalumab in the adjuvant setting for patients with unresectable, stage III non-small cell lung cancer (NSCLC) after chemo-radiotherapy (CRT)1, and whose tumours express programmed death-ligand-1 (PDL-1) in >1% of cells. PDL-1 is an immune regulating molecule which has been hypothesized to aid neoplastic lesions to evade the host’s immune system. Durvalumab is a human monoclonal IgG1 antibody which blocks PDL-1 on cytotoxic T-cells, leading to increased cytotoxic T-cell proliferation and activity, and cytokine production1. The activation of T-cells can lead to immune-related adverse events (IrAEs). A 68-year-old female with stage III NSCLC received adjuvant durvalumab. Her PDL-1 was 90-100%. After four cycles of durvalumab, she presented with Grade 2 diarrhoea2. She was admitted to hospital and started on prednisone 50mg (1mg/kg). After three days, she had a sigmoidoscopy which appeared macroscopically normal. Biopsies showed a non-specific increase in intraepithelial lymphocytes. The diarrhoea resolved, and she was discharged on a weaning regime of prednisolone for presumed immune checkpoint inhibitor (ICPi)-induced colitis. Two months later, she represented with Grade 3 diarrhea2. Examination and imaging was normal. Positive findings were an elevated serum anti-transglutaminase (anti-tTG) IgA level at 10.2unit/mL, low folic acid and low vitamin D. An oesophagogastroduodenoscopy (OGD) showed scalloping of the duodenum and biopsies showed marked villous blunting, chronic inflammation of the lamina propria and increased intraepithelial lymphocytes; all findings consistent with the diagnosis of CD. She was started on a lifelong gluten-free (GF) diet and given a weaning course of oral prednisone with the intention of improving her symptoms rapidly. Her diarrhoea immediately improved and a decision was made to restart immunotherapy once the steroids were complete. She did not report recurrence of her symptoms following an additional seven cycles of durvalumab therapy whilst on a GF diet. The anti-tTG IgA normalised after 3 months. This case highlights a rare IrAE of CD presenting during ICPi treatment. Durvalumab may have unmasked previously undiagnosed CD. Alternatively, the patient may have developed CD de-novo, as a direct consequence of ICPi treatment. The detection of rare toxicities requires a large number of patients to be treated with ICPis, therefore rarer toxicities are often identified post licensing, when the number of patients receiving these drugs increases exponentially. There are three published cases of patients receiving immunotherapy developing CD after the commencement of the drug but the exact incidence of this IrAE and exact underlying mechanism for the development of CD secondary to immunotherapy is unknown. This is the first reported case of CD arising following ICPis in both the adjuvant lung cancer setting, and with the drug durvalumab. A new diagnosis of CD will have long-term consequences for this patient who may have been cured with CRT alone. However, the majority of patients with stage III NSCLC have disease progression despite CRT and therefore the addition of immunotherapy in improving survival is significant. Although diarrhoea due to CD is an exceptional IrAE, symptoms can resolve quickly once a diagnosis is made and a GF diet commenced.

A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL

AbstractFirst-line therapy for younger patients with peripheral T-cell non-Hodgkin lymphoma (T-NHL) consists of 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide (CHOEP), consolidated by high-dose therapy and autologous stem cell transplantation (auto-SCT). We hypothesized that allogeneic stem cell transplantation (allo-SCT) could improve outcomes. 104 patients with peripheral T-cell non-Hodgkin lymphoma, except ALK+ anaplastic large cell lymphoma, 18 to 60 years, all stages, and all age adjusted International Prognostic Index scores, except 0 and stage I, were randomized to 4 cycles of CHOEP and 1 cycle of dexamethasone, cytosine-arabinoside, and platinum (DHAP) followed by high-dose therapy and auto-SCT or myeloablative conditioning and allo-SCT. The primary end point was event-free survival (EFS) at 3 years. After a median follow-up of 42 months, the 3-year EFS after allo-SCT was 43%, as compared with 38% after auto-SCT. Overall survival at 3 years was 57% vs 70% after allo- or auto-SCT, without significant differences between treatment arms. None of the 21 responding patients proceeding to allo-SCT relapsed, as opposed to 13 of 36 patients (36%) proceeding to auto-SCT. Eight of 26 patients (31%) and none of 41 patients died of transplant-related toxicity after allo- and auto-SCT, respectively. The strong graft-versus-lymphoma effect after allo-SCT was counterbalanced by transplant-related mortality. This trial is registered at www.clinicaltrials.gov as #NCT00984412.

Using Dose-Effect Relationship for Optimising Systemic Corticosteroid Dosage in Treatment of Inflammatory Bowel Diseases

Aim.Estimation of an optimal corticosteroid (CS, prednisone) dosage for the remission induction in patients with ulcerative colitis (UC) and Crohn’s disease (CD) based on the construction of a dose-effect relationship during the first and second courses of therapy.Materials and methods.The study included 86 patients with moderate to severe active disease (61 with UC and 25 with CD) aged 18 to 65 years. To induce remission, all patients had the first course of prednisone at a starting dose of 30 to 60 mg/day, with a subsequent reduction. Prednisone was continued in a repeat course in 28 patients. The effect was evaluated past two weeks and at a time of complete withdrawal of prednisone using the generally accepted clinical response and remission criteria. The dose-effect relationship for prednisone was constructed using an original method. The method realises an adequate statistical transformation of primary clinical data in form of a quantitative expression of factual doses and registered alternative responses established with endpoint criteria into a visual efficacy function graph suitable for downstream analyses. The mean at each point was estimated with the regression kernel scoring method. The mean confidence intervals and significance values were estimated with the Student’st-test.Results.The dose-effect relationship constructed upon completion of the first prednisone course is a graph showing the plateau point of the efficacy function as a statistical measure of character saturation and a clinical measure of the highest expected drug effect. This graph is referred to as the optimal clinically effective dose (OCED). The first induction prednisone course had the OCED estimates of 50.70 ± 0.65 (49.41÷51.98) mg (p= 0.05). A highest expected effect for this dose was obtained in the interval of 82.21 ± 8.23 (66.08÷98.33)% (p= 0.05). The repeat prednisone course had OCED values of 51.43 ± 1.55 (48.24÷54.61) mg (p= 0.05), with the expected effect of 40.02 ± 12.86 (13.59÷66.45)% (p= 0.05).Conclusion.In medium to severe UC and CD patients, the first induction prednisone course had OCED estimates of 50.70 ± 0.65 mg/day prescribed at the onset of therapy. The highest effect at this dose was 82%, and 18% of the patients did not respond to the prednisone treatment, accordingly. The repeat CS treatment had the same OCED values of 51.43 ± 1.55 mg/day, but a 42% lower expected effect compared to the first course. The effect did not exceed 40% suggesting its inadequacy in repeat CS treatments in this category of patients.

Low Dose Daily Corticosteroid Tapering Regimen Allows Highly Effective and Practical Desensitization for Multiple Myeloma Patients with Skin Rash after Immunomodulatory Drugs

Introduction: Immunomodulatory drugs (IMiDs) are being frequently used as an integral part of induction regimen as well as maintenance after Bone Marrow Stem cell Transplant (BMSCT) therapy as backbone of therapy for patients with plasma cell neoplasm (PCN) including Multiple Myeloma (MM). Therapy is often complicated by dermatologic adverse effects which may herald a favorable prognosis suggesting a more robust immune stimulation by this class of drugs. The incidence of IMiD-associated rash is up to 27% in some reports and can range from mild to moderate to severe and life threatening skin toxicity including Steven-Johnsons syndrome and toxic epidermal necrolysis. IMiD-associated skin eruptions are thought to result from differential T cell immune modulation. The optimal management strategy for IMiD induced rash is unknown. The European Myeloma Network recommends topical corticosteroids and antihistamines for localized skin reactions. For severe reactions, a desensitization protocol with prolonged 6-week steroid taper is recommended based on a case series of five patients that developed delayed cutaneous adverse effects to IMiD [Lee MJ et al]. Dexamethasone used concomitantly with IMiD as part of the treatment regimen does not decrease the occurrence of skin rash as shown by Sviggum et al. The likely explanation is that concurrent dexamethasone is not effectively able to exert immunosuppressive activity to mitigate the occurrence of cutaneous reactions. Hence, a prolonged, daily steroid protocol is required for effective desensitization. Therefore, we designed a standardized 3-week steroid rash prophylaxis protocol with a low dose daily corticosteroid tapering regimen that allows desensitization and reinstitution of the same IMiD. We assessed the impact of this desensitization regimen on clinical outcomes, by comparing patients with versus without dermatologic manifestations. Methods: Dermatologic adverse effects associated with IMiDs in our study were managed by a single oncologist using a standardized approach. A total of 87 patients were evaluated, 24 patients in the rash group vs 63 controls. A cohort of age- and gender-matched without rash (n = 63) was randomly selected from the institutional database. The effects of rash on overall and progression free survival (OS and PFS) were further estimated using Cox regression controlling for the effects of age and gender. Results: Median time to development of rash after IMiD initiation was 28 days (range 2-232 days). The incidence of rash was 27.6% (95% CI: 19.3%-37.8%). All patients were managed by temporary treatment interruption and upon clearance of rash, re-institution of the same IMiD concomitantly with a standardized 3-week steroid rash prophylaxis protocol (prednisone at 10 mg daily for 10 days, followed by 5 mg daily for 10 days, followed by 5 mg on alternate days for 10 days). As a result, all patients were able to restart the same IMiD with none re-experiencing any dermatologic adverse effect afterward. Comparing to controls without rash, there was no significant difference in PFS (p=0.769) or OS (p=0.24) in the multivariable regression model. Conclusions: Proposed 3-week corticosteroid regimen showed 100% success rate in re-instituting IMiDs without recurrence of skin rashes in our cohort. The results of our study indicate that the 30-day prednisone course is practical, well tolerated, effectively desensitizes and allows re-institution of IMiD enabling patients to enjoy comparable outcomes to those without skin rash. Whether development of rash correlates with improved outcomes is unknown. Here, outcomes were similar in both cohorts. Disclosures Caimi: Celgene Corp: Other: Incyte Corporation - Ownership - Pharmacyclics, Inc. - Ownership - Celgene Corp. - Other, Speakers Bureau; ADC Therapeutics: Research Funding; Genentech: Research Funding. de Lima:BMS: Other: Personal Fees, advisory board; Celgene: Research Funding; Pfizer: Other: Personal fees, advisory board, Research Funding; Incyte: Other: Personal Fees, advisory board; Kadmon: Other: Personal Fees, Advisory board. Malek:Bluespark: Research Funding; Takeda: Other: Advisory board , Speakers Bureau; Medpacto: Research Funding; Cumberland: Research Funding; Amgen: Honoraria; Clegene: Other: Advisory board , Speakers Bureau; Sanofi: Other: Advisory board; Janssen: Other: Advisory board, Speakers Bureau.

Primary Epstein-Barr Virus Infection With Marked Cholestasis, Warm Autoimmune Hemolytic Anemia, and Pancytopenia

Abstract Primary Epstein-Barr virus (EBV) infection may rarely present with cholestatic hepatitis or hemolytic anemia. We share a case of EBV-associated infectious mononucleosis presenting with a unique triad of findings comprising cholestatic hepatitis with marked hyperbilirubinemia, warm autoimmune hemolytic anemia, and pancytopenia. Early diagnostic challenges included negative Monospot heterophile testing. Additional testing revealed EBV serologies consistent with acute primary infection, EBV viremia and bone marrow biopsy showing EBV-encoded RNA–positive cells. A tapered prednisone course was administered for warm autoimmune hemolytic anemia. Improvement in symptoms and laboratory findings occurred over 3 weeks.

EFFICACY AND SAFETY OF MEPOLIZUMAB IN SEVERE ASTHMA: REAL-LIFE EXPERIENCE IN A TERTIARY CENTER IN SAUDI ARABIA

SESSION TITLE: Obstructive Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Severe asthma is asthma that is uncontrolled despite adherence to maximal optimized controller therapy e.g medium or high dose inhaled steroids with a second controller or maintenance Oral Corticosteroids. Over the past few years, multiple biological therapies have been used to treat severe eosinophilic asthma. One of the first ones approved was Mepolizumab which is an anti-IL-5 antibody that has been utilized to treat severe asthma. Our study aims to evaluate the efficacy and safety of Mepolizumab for the treatment of severe asthma in a real-world severe asthma clinic in a tertiary hospital in Riyadh, Saudi Arabia. METHODS: We did a chart review on severe asthma patients who were started on Mepolizumab in the past two years. Multiple outcomes were observed which include the rate of annual asthma exacerbation, reduction in Oral Corticosteroids (OCS) dose, and improvement in Asthma Control. RESULTS: 53 severe asthma patients ( 75% females ) were on mepolizumab for the past two years. Mepolizumab was switched to Dupilumab in 4 patients. 3 of them were due to lack of effectiveness and one was due to significant headache post-injection. The average age was 45 +/- 13. 69% of patients were early-onset asthmatics (defined as asthma diagnosed < 13 years of age). 63.42% of patients were on Mepolizumab for one year or more. At baseline, patients had an average 18.46 Emergency Room (ER) visits due to asthma exacerbations and 12.8 short courses of Prednisone for asthma attacks. Their average Asthma Control Test (ACT) was 12 +/- 4.7 at baseline. 83% of patients were uncontrolled at baseline. 42% of patients were on daily OCS at baseline. After 12 months, the average ER visits dropped to 1.35 visits (reduction by 92.6%), and the need for short courses of prednisone was reduced to 2.4 courses ( reduction of 81%). At 12 months, 8 patients were off daily steroids (53% of total patients who were of daily steroids at baseline). There was a 36% improvement in ACT score after one year of Mepolizumab (ACT score 17.57) compared to baseline. 42% of patients became controlled after one year of Mepolizumab compared to baseline. CONCLUSIONS: In this retrospective real-life study, we have shown that Mepolizumab had a significant effect in reducing annual asthma exacerbations that require ER visits or short courses of Steroids. It also helped in reducing daily OCS dose. Overall, Mepolizumab was a safe medication as we only had one patient who had one significant side effect that led to its discontinuation. CLINICAL IMPLICATIONS: To the best of our knowledge, this is the first and largest real-life retrospective study in the country that examined the efficacy and safety of Mepolizumab on severe asthma patients. This will help in having better access to this medication and other biological therapies. DISCLOSURES: No relevant relationships by Riyad Al-Lehebi, source=Web Response No relevant relationships by Ali Alqahtani, source=Web Response No relevant relationships by Yahya Asiri, source=Web Response

REPEAT PRESENTATION OF A FEBRILE RESPIRATORY ILLNESS SECONDARY TO HYPERSENSITIVITY PNEUMONITIS

SESSION TITLE: Medical Student/Resident Occupational and Environmental Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Dyspnea is one of the most common reasons for presentation to the hospital. Antigen mediated lung diseases are an important cause of dyspnea however due to the wide variation in clinical presentation, the large number of possible antigens, and a lack of diagnostic tests identification can be difficult.1 Thus, a high index of suspicion must be maintained to prevent missed or delayed diagnosis. CASE PRESENTATION: A 44-year-old nonsmoker with an insignificant past medical history originally presented to an outpatient urgent care with an acute onset of fever, dyspnea, productive cough, and myalgias. He was empirically treated for bacterial pneumonia with an oral antibiotic. After initial improvement, his symptoms progressed and he ultimately presented to the emergency room with fever and worsening dyspnea. He was admitted with acute hypoxic respiratory failure and sepsis secondary to presumed post-influenza pneumonia (standard chest radiograph showed left lower lobe infiltrate). He was fluid resuscitated and received broad spectrum antibiotics. With antibiotics his fever dissipated although he continued to remain hypoxic and was discharged on hospital day seven on three liters of oxygen via nasal cannula. At hospital follow up one week later he continued to endorse dry cough and severe dyspnea (being only able to ambulate household distances with oxygen prior to having to rest). Exam was significant for crackles in the bilateral lung bases along with hypoxia (oxygen saturation dropped to 83% with removal of his nasal cannula during rest). Further history revealed the patient owned seven parakeets which were kept in the same room that the patient slept. He also endorsed unintentional 12-pound weight loss over the past 3 months. CT imaging was pursued which showed diffuse ill-defined centrilobular micronodularity and ground glass opacities throughout both lungs. Based upon this new information serum hypersensitivity pneumonitis screen was performed and ultimately returned negative for the presence of six antigens (only bird antigen on the screen was pigeon serum). Based upon the patient meeting five out of six clinical criteria for a validated clinical predication rule a diagnosis of hypersensitivity pneumonitis was established (92% Likelihood).2 He was advised to avoid further exposure to his birds and outpatient pulmonology consultation was arranged. After a short course of prednisone and avoiding further exposure the patient's symptoms resolved. DISCUSSION: Hypersensitivity pneumonitis is an important disease to keep on the differential for a patient presenting with dyspnea. CONCLUSIONS: Early diagnosis is of the upmost importance as with avoiding further exposure early lung disease can be potentially completely reversed. This case also illustrates the importance of taking a complete history and how routine use of validated clinical predication rules can help you make a diagnosis. Reference #1: 1. Riario Sforza, G.G., Marinou, A. Hypersensitivity pneumonitis: a complex lung disease. Clin Mol Allergy. 2017; 15, 6. Reference #2: 2. Lacasse Y, Selman M, Costabel U, Dalphin JC, Ando M, Morell F, Erkinjuntti-Pekkanen R, Muller N, Colby TV, Schuyler M, Cormier Y. Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med. 2003;168(8):952. DISCLOSURES: No relevant relationships by Catherine Cheney, source=Web Response No relevant relationships by Chris Morris, source=Web Response

S2277 Role of Oral Vancomycin in Inducing Remission for Biologic Experienced Ulcerative Colitis With Concomitant Primary Sclerosing Cholangitis and Liver Transplantation

INTRODUCTION: Ulcerative colitis associated with primary sclerosing cholangitis (UC-PSC) is distinct entity. One third of patients with UC may experience worsening colitis despite on immunosuppression after liver transplantation (LT) for PSC. We report a case of severe UC after LT for PSC refractory to Vedolizumab and Infliximab that responded to oral vancomycin (OV). CASE DESCRIPTION/METHODS: A 51-year-old man with mild ulcerative pancolitis and PSC presented with worsening bloody diarrhea. His UC was diagnosed at age 12, is mild and responding to oral mesalamine. He had LT for PSC 7 months ago, with normal post-transplant course on mycophenolate mofetil (MMF) and tacrolimus. Stool testing for Clostridium difficile, ova/parasites, and cultures were negative. Colonoscopy showed severe active (Mayo score 3) ulcerative pancolitis (Figure 1). Pathology showed severe inflammation, crypt abscesses, and negative CMV. Prednisone showed improvement. MMF switched to delayed release MMF. Vedolizumab started with tapering steroids, however patient had recurrence of bloody diarrhea, led to increasing frequency of Vedolizumab at week 14 of treatment. Repeat colonoscopy at 20 weeks of initiating Vedolizumab showed severe pancolitis (Mayo score 3) (Figure 2). Vedolizumab switched to Infliximab. Patient responded, hence prednisone was tapered off. However, had episodes of bloody diarrhea requiring 2 courses of prednisone, frequency of Infliximab was increased after 22 weeks of treatment initiation. After another flare requiring prednisone, infliximab levels checked were adequate at 19 mcg/ml without antibodies. At this point, OV was started. In the following 3 months, had significant clinical improvement and did not require prednisone. Repeat colonoscopy showed resolution of inflammation-Mayo endoscopic score of 1 (Figure 3). Patient still on OV and reduced dose of Infliximab without flares. DISCUSSION: UC-PSC has its unique pathophysiology and genetics, and therefore it responds differently than UC. They have gut microbiota less diverse compared to healthy controls, which could explain the refractory course and the utility of OV. OV has poor oral absorption, concentrates in the intestine. It acts as immunomodulator, by reducing cytokine release from T cells,and antimicrobial agent. In patients refractory to conventional therapies (5-ASA, steroids); azathioprine, anti-tumor necrosis factor antibodies, or Vedolizumab are recommended. In severe refractory colitis, surgery can be curative, which can be avoided by using OV.Figure 1.: Severe (mayo 3) inflammation in the descending colon.Figure 2.: Severe (Mayo 3) colonic inflammation.Figure 3.: Endoscopic remission seen after initiation of Oral Vancomycin.

S3054 Cocaine-Induced Vasculitis

INTRODUCTION: Once used as a chemotherapeutic with 5-fluorouracil in the treatment of advanced colon cancer, levamisole is now making news in the general population for its use in recreational drugs.The medication was banned by the FDA due to its adverse effects which include neutropenia, skin necrosis, and agranulocytosis. It now remains on the market as an antihelminth for livestock. Since 2008, the drug has made its way back into the limelight as an additive agent in cocaine with significant systemic manifestations complicating its prompt diagnosis. CASE DESCRIPTION/METHODS: 52 year-old female with bipolar disorder presented after a ground level fall. Per family, patient had ongoing weakness for several weeks. On the morning of the fall, patient reported that she was seated on the side of the chair when she suddenly lost her balance. She denied any symptoms leading up to her fall and any loss of consciousness, confusion, and loss of bowel or bladder control after. She was found to have extensive dry, gangrenous tissue or bilateral lower extremities and on the dorsal aspect of her left hand. Patient reported that her skin findings began as a generalized body rash about 9 months ago. She completed a 7-day course of prednisone. The rash appeared to subside at first but later became blister-like. She was referred to a dermatologist but was unable to follow up. In the months leading up to her fall, patient reported eruptions of these blisters with darkening of her skin along her extremities. On admission, she had extensive foul smelling necrosis of her extremities with intermittent, sharp pain at rest and with movement. She denied any travel, bites, gardening, and saltwater exposure, but admitted to daily oral cocaine use. She underwent extensive debridement. Biopsy was negative for neoplasia or granulomatous inflammation. Serology was positive for p-anca. She was discharged after counseling against cocaine use with high dose prednisone and mycophenolate mofetil for 2 months. She was followed up outpatient to monitor ESR and CRP levels and showed remarkable improvement in her overall strength and appearance with multidisciplinary support. DISCUSSION: Dry gangrene results from occlusion of arterial blood flow to the extremities and can be caused by thromboangitis obliterans, raynaud’s, trauma, and some aggressive forms of vasculitis. Levamisole-induced vasculitis has been associated with elevations in p-ANCA which may delay its diagnosis. Discontinuation of cocaine alone can result in near complete recovery.Figure 1.: After 1 month.Figure 2.: On day of presentation.Figure 3.: After 2 months.

S2268 A Unique Extra-Intestinal Manifestation of Ulcerative Colitis: Pulmonary Necrobiotic Nodules

INTRODUCTION: Ulcerative colitis (UC) can have a variety of extra-intestinal manifestations, some of which include pulmonary complications. They can range from interstitial lung disease, organizing pneumonia, to necrobiotic nodules. Necrobiotic nodules are sterile aggregates of inflammatory cells with necrosis. The appearance of these nodules can mimic other cavitating diseases, making them a diagnostic challenge. CASE DESCRIPTION/METHODS: A 25-year-old man with a PMH of UC (on mesalamine and non-compliant with steroid suppositories) presented from an outside hospital (OSH) with fevers, abdominal pain, and bloody diarrhea for 1 week. Imaging from OSH revealed diffuse colitis as well as several pulmonary nodules. Repeat imaging at our institution, showed multiple necrotic, cavitary pulmonary nodules, initially concerning for septic emboli and the patient was started on empiric antibiotics. The patient denied any history of drug abuse, cardiac history, or dental procedures. On physical exam, there was tenderness to palpation in bilateral lower quadrants of the abdomen with no rebound tenderness, and no murmurs. Laboratory markers were significant for elevated ESR, CRP, and fecal calprotectin. Infectious etiologies were negative for bacterial, viral and fungal pathogens, and stool studies were negative as well. Cardiac MRI and TTE did not show any vegetation, and blood cultures showed no growth. Further pertinent testing was negative for vasculitis and autoimmune etiologies such as granulomatosis with polyangiitis, and rheumatoid arthritis. A CT guided lung biopsy revealed fibrosis with mixed inflammatory infiltrate containing macrophages, lymphocytes, scatter neutrophils and plasma cells. After poor follow up and not initiating any immunosuppressants, symptoms returned one month later, and imaging showed persistent pulmonary nodules. The patient was then started on steroids and subsequently bridged to biologic agents and symptoms improved. DISCUSSION: This case illustrates a rare manifestation of necrobiotic pulmonary nodules in a patient with poorly controlled UC. Before making this diagnosis, a thorough, yet pertinent differential such as malignancy, septic emboli, vasculitis, and infectious etiologies must be excluded. There are only two case reports of this UC complication. One patient was treated with a course of prednisone and imaging showed resolution of the nodules.Figure 1.: CT Chest With IV Contrast Showing Multiple Lung Nodules, Several Necrotic and Demonstrating Cavitation.

IgM nephropathy complicated by cerebral venous sinus thrombosis: a case study

BackgroundIgM nephropathy is a rare disease with variable clinical presentations and is an unusual cause of nephrotic syndrome. Histopathological findings typically include mesangial hypercellularity with IgM and complement deposition, though the spectrum may range from normal glomeruli through to focal and segmental glomerulosclerosis. Thromboembolism is a well recognised complication of nephrotic syndrome, but cerebral venous sinus thrombosis is rarely described.Case presentationThis is the case of a 23-year-old male presenting with the nephrotic syndrome, whose initial renal biopsy was consistent with minimal change disease. Complete remission was achieved with prednisone, however multiple relapses and steroid dependence prompted re-biopsy, the results of which were more consistent with IgM nephropathy. His last relapse was complicated by cerebral venous sinus thrombosis. He then received rituximab and a weaning course of prednisone to again enter remission.ConclusionsThis case highlights the need to consider IgM nephropathy in the differential diagnosis of nephrotic syndrome. Additionally, it emphasises the risk of thrombosis in patients with severe nephrosis.

Fractional exhaled nitric oxide response to oral corticosteroids in children with mild-to-moderate asthma: Influence of race

BackgroundFractional exhaled nitric oxide (FeNO) is a noninvasive biomarker of type 2 asthma that can predict response to inhaled corticosteroid therapy. Little is known regarding the magnitude of FeNO reduction after an oral corticosteroid (OCS) course, and less is known whether there are differential responses based on race in children with mild-to-moderate asthma. ObjectiveTo assess the effect of a short course of OCS on FeNO in children with asthma and to determine whether the effect is influenced by race. MethodsChildren presenting with an acute asthma exacerbation, who had a FeNO measurement within the past 6 months when clinically stable, were enrolled. Spirometry and FeNO were obtained at the time of exacerbation and after a short course of prednisone. ResultsA total of 92 children were identified (aged 11 ± 3.3 years; white, n = 46 [50%], Hispanics, n = 30 [33%], African Americans [AAs], n = 16 [7%]). At baseline, AAs were more atopic and had higher mean FeNO values than both white (48.9 vs 25.6 ppb; P < .05) and Hispanic children (22.5 ppb; P < .05), despite being prescribed similar inhaled corticosteroid doses. During the exacerbation, AAs had the highest FeNO values, whereas there was no difference in lung function between AAs and non-AAs. After prednisone therapy, there was a 56.6% reduction in FeNO, and although AAs maintained the highest FeNO levels, the relative reduction was similar between AAs and non-AAs (53.9% vs 57.8%, respectively). ConclusionFeNO levels reduced by more than 50% after an OCS course. African American children had a greater degree of type 2–driven airway inflammation at baseline, during an exacerbation and after a short course of OCS, compared with non-AAs, although the relative reduction in FeNO was similar between the groups.

LB972 IL-17 inhibitor-induced remission of guttate psoriasis

Effective, targeted treatments for guttate psoriasis are lacking. Drugs that block the interleukin-17 (IL-17) pathway are highly effective in the treatment of plaque psoriasis. Given the overlap of immunopathogenic features between guttate and plaque psoriasis, including an over activation of Th17 cells, it is plausible that IL-17A inhibition would be an effective treatment for guttate psoriasis. Ixekizumab, a humanized IgG4 monoclonal antibody that targets interleukin-17A (IL-17A) is FDA-approved for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy, but to our knowledge has never been reported in the treatment of guttate psoriasis. Here we report three cases of guttate psoriasis successfully treated with ixekizumab. Three patients presented with guttate psoriasis involving 15-40% body surface area (BSA) and with psoriasis physician global assessment (PGA) scores ranging from 3-6. Two patients developed lesions idiopathically, and one developed lesions after a documented episode of streptococcal pharyngitis. Lesions had been present for 7-90 days at the time of presentation, and prior ineffective treatment attempts across patients by primary care providers included courses of keflex, triamcinolone cream, betamethasone ointment, oral prednisone, oral acyclovir, and expectant management. Patients were treated with standard ixekizumab dosing regimens for plaque psoriasis. Starting doses of 160mg subcutaneous injection and induction doses of 80mg every two weeks thereafter were given. Two patients achieved complete clearance after 2 doses of ixekizumab (clearance documented in clinic at 42 and 86 days after treatment initiation), and the third achieved 1% BSA involvement and PGA score of 1 after 3 doses (documented 61 days after treatment initiation). No adverse effects of treatment were noted. This report provides strong evidence for the potential efficacy of IL-17 inhibition in guttate psoriasis. Additional follow-up to assess for duration of clinical remission and progression to plaque psoriasis, as well as larger, randomized, controlled studies are needed.

Radioiodine Ablation of Remaining Thyroid Lobe in Patients with Differentiated Thyroid Cancer Treated by Lobectomy: A Systematic Review and Metaanalysis.

We aimed to conduct a systematic review and metaanalysis of studies reporting the performance of radioactive iodine (131I) therapy in differentiated thyroid cancer (DTC) patients requiring a completion treatment after lobectomy. We also evaluated the response to 131I therapy according to 2015 American Thyroid Association guidelines and the adverse events. Methods: A specific search strategy was designed to find articles evaluating the use of 131I in patients with evidence of DTC after lobectomy. PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science were searched. The search was updated until January 2020, without language restriction. Data were cross-checked and any discrepancy discussed. A proportion metaanalysis (with 95% confidence interval) was performed using the random-effects model. Metaregressions on 131I success were attempted. Results: The pooled success ablation rate was 69%, with better results in patients receiving a single administration of about 3.7 GBq; high heterogeneity was found (I2 test, 85%), and publication bias was absent (Egger test, P = 0.57). Incomplete structural responses were recorded in only 14 of 695 (2%) patients enrolled in our analysis. Incomplete biochemical responses were observed in 8%-24% of patients, with higher rates (24%) in patients receiving low radioiodine activities (∼1.1 GBq) and lower rates (8%-18%) in patients receiving higher activities of radioiodine (∼3.7 GBq). Neck pain due to thyroiditis was reported in up to 18% of patients, but in most cases, symptoms resolved after oral paracetamol or a short course of prednisone. Conclusion: Lobar ablation with 131I is effective, especially when high 131I activities are used. However, the rate of incomplete biochemical response to initial treatment appears to be slightly higher than in the classic scheme of initial treatment of DTC. Radioisotopic lobectomy should be considered for patients with low- to intermediate-risk DTC requiring completion treatment after lobectomy due to specific individual risk factors or patient preferences.

Dexamethasone Versus Prednisone for Pediatric Acute Asthma Exacerbations: Specialists' Practice Patterns.

Dexamethasone has emerged as a viable alternative to prednisone in the treatment of pediatric acute asthma exacerbations, with the potential for improved compliance secondary to decreased frequency of dosing, improved taste, and decreased cost. The objective of this study is to identify whether providers are prescribing dexamethasone for pediatric acute asthma exacerbations. Secondary objectives are to describe variation in practice between different specialties and to identify the commonly used dosing and frequency for dexamethasone. We conducted a cross-sectional, descriptive study with an anonymous, web-based survey (surveymonkey.com). The survey population included all fellowship program directors listed on FRIEDA Online for pediatric emergency medicine, pediatric pulmonology, and allergy and immunology, and emergency medicine residency directors through the Council of Emergency Medicine Residency Directors listserv. Program directors were contacted via e-mail up to 5 times for 3 months. Overall, 300 respondents (70% of the program directors) completed the survey. Response rates by specialty varied from 60% to 94%. One third of providers are using dexamethasone, whereas just more than half of providers (51%) are prescribing a 5-day prednisone course. The preferred maximum dose for dexamethasone is 10 mg (45%), with 82% using a dose of 0.6 mg/kg.Pediatric emergency medicine fellowship directors demonstrated a preference for dexamethasone (59%). Prednisone is favored by emergency medicine (56%), pediatric pulmonology (89%), and allergy and immunology (93%) program directors. Although most pediatric emergency medicine academic physicians have transitioned to using dexamethasone to treat acute pediatric asthma exacerbations, other specialties continue to favor prednisone.

Unexpected effects of systemic steroids on the CRSwNP proteome: is protein upregulation more important than inhibition?

Oral steroids, traditionally thought of as immunosuppressive agents that are broad in their immunomodulatory effects, are a mainstay of treatment to reduce disease burden in chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of this study was to determine how differentially expressed proteins in CRSwNP are affected by oral steroid therapy. Matched exosomal proteomic arrays were quantified using aptamer-based methods in systemic steroid-naive CRSwNP patients before and after a standardized oral prednisone course (n = 12). Previously identified differentially expressed proteins in CRSwNP patients were compared to determine the effect of steroids on expression. Fisher's exact test and t test were applied to normalized protein expression profiles to determine significance. Of 18 proteins previously identified to be highly underexpressed in CRSwNP, 16 (89%) had an average increase after systemic steroid treatment (p < 0.05). Lactoperoxidase, initially present at 9-fold lower concentrations in CRSwNP subjects, increased by 209% after steroid treatment. A similar trend was observed with other proteins of interest, including platelet factor 4 and C-C motif ligand 28. The converse of this steroid effect was not true; of the 53 proteins that are highly overexpressed in CRSwNP, only 22 (42%) decreased in quantity with steroid use. Proteomic analysis of differentially expressed proteins in CRSwNP demonstrates that systemic steroids cause almost uniform upregulation of transcriptionally decreased proteins, whereas the effects of steroids on transcriptionally increased proteins are more heterogeneous. Thus, proteomic analysis may be an effective tool to understand specific therapeutic benefits of steroid use in polyp disease and to create more targeted treatments.

Oral corticosteroids and asthma in children: Practical considerations.

Corticosteroids (CS) are among the most prescribed drugs in pediatrics. In allergy, CS are prescribed for several different conditions. If CS show clear benefits when adequately prescribed, CS are also associated with several side effects, well known by pediatricians. As for asthma exacerbations, the oral route is always the preferred one in pediatrics. Several authors debated if the use of a single dose of dexamethasone is better in terms of efficacy, compared with a 3- to 5-day course of prednisone or prednisolone. Another interesting issue that has not been fully clarified concerns whether oral corticosteroids should be prescribed in preschoolers presenting with acute wheezing. The present review aims to review the most recent publications on this topic and to try to clarify which may be the best option in children suffering from asthma exacerbations.

Patient preferences for maintenance therapy in Crohn's disease: A discrete-choice experiment.

ObjectiveTo quantify patient preferences for maintenance therapy of Crohn’s disease and understand the impact on treatment selection.MethodsWe conducted a discrete-choice experiment in patients with Crohn’s disease (n = 155) to measure the importance of attributes relevant to choosing between different medical therapies for maintenance of Crohn’s disease. The attributes included efficacy and withdrawals due to adverse events, as well as dosing and other rare risks of treatment. From the discrete-choice experiment we estimated the part-worth (importance) of each attribute level, and explored preference heterogeneity through latent class analysis. We then used the part-worths to apply weights across each outcome from a prior network meta-analysis to estimate patients’ preferred treatment in pairwise comparisons and for the overall group of treatments.ResultsThe discrete-choice experiment revealed that maintaining remission was the most important attribute. Patients would accept a rare risk of infection or cancer for a 14% absolute increased chance of remission. Latent class analysis demonstrated that 45% of the cohort was risk averse, either to adverse events or requiring a course of prednisone. When these preferences were used in modelling studies to compare pairs of treatments, there was a ≥ 78% probability that all biologic treatments were preferred to azathioprine and methotrexate, based on the balance of benefits and harms. When comparing all treatments, adalimumab was preferred by 53% of patients, who were motivated by efficacy, and vedolizumab was preferred by 30% who were driven by the preference to avoid risks. However, amongst biologic treatment options, there was considerable uncertainty regarding the preferred treatment at the individual patient level.ConclusionPatients with Crohn’s disease from our population were, on average, focused on the benefits of treatment, supporting intensive treatment approaches aimed at maintaining remission. Important preference heterogeneity was identified, however, highlighting the importance of shared decision making when selecting treatments.

Anti-TNF Rechallenge After Infliximab Induced Lupus in Crohn’s Disease

Question: A 54-year-old man with longstanding Crohn’s disease on maintenance azathioprine self-presented to hospital with a severe luminal flare and minimal improvement despite two short courses of oral prednisone. He reported abdominal pain and fever with ten loose and bloody bowel motions daily for 4 weeks. CME Exam 2: Anti-TNF Rechallenge After Infliximab Induced Lupus in Crohn’s DiseaseGastroenterologyVol. 158Issue 8Preview Full-Text PDF