Weeks Of Steroids Research Articles

A pediatric case of tubulointerstitial nephritis and uveitis syndrome

Tubulointerstitial Nephritis and Uveitis Syndrome (TINU Syndrome) is a rare entity of unknown origin. Most cases described affect adolescents and women. It often implies a renal biopsy and is established upon the presence of uveitis and tubulointerstitial nephritis in the same patient, after all possible causes are excluded. The authors report the case of a 12-year-old teenage boy with nausea, vomiting, and weight loss lasting two weeks, taken to his local hospital with acute kidney injury, oliguria, and high blood pressure. After transfer to a specialized centre and exclusion of infectious, toxic, and autoimmune causes, intravenous and oral corticosteroid therapy was started. Renal biopsy confirmed interstitial nephritis of undetermined aetiology and the patient was discharged after favourable restauration of renal function, with a course of 4 weeks of steroids and progressive decrements over 10 weeks. Four months after the onset of the condition, the teenager was taken to the hospital with eye redness and tenderness. Bilateral anterior uveitis was described, which established the diagnosis of TINU Syndrome. After two years of joint follow-up by Paediatric Nephrology and Ophthalmology, the patient remains stable, without relapses, or ocular or renal sequelae.

342: NSAIDS AND THROMBOTIC THROMBOCYTOPENIC PURPURA: CAN USE OF A PAIN MEDICATION BE FATAL?

Introduction: Thrombotic Thrombocytopenic Purpura (TTP) is a fatal condition that can be induced by medications. NSAIDs are one of the medications known for this complication. Nimesulide is a banned NSAID in the USA and as per our knowledge one case of TTP associated with Nimisulide has been reported which resolved with a week of steroids and Plasma Exchange (PEX). Description: 46-year-old hispanic male with a history of migraine came to ER after a fall and right facial droop. The patient took Nimisulide 100 mg every 4 hours over the past three days for knee pain. He had headache, dizziness, blurry vision, confusion and petechiae on presentation. His stroke workup was negative. He was sedated for severe agitation and intubated for airway protection. His labs revealed severe thrombocytopenia, microangiopathic hemolytic anemia, elevated INR and D-Dimer, low fibrinogen, and acute kidney injury. The PLASMIC score was 7, TTP was suspected, and treatment was started with PEX and high dose steroids. He was treated empirically for meningitis and tick-borne illness, but his workup for infection, including a lumbar puncture was unremarkable and flowcytometry did not reveal hematologic malignancy. With clinical improvement, we switched steroids to the standard dose and extubated the patient. Initial ADAMTS13 activity was < 3%. After a transient response, the patient’s platelet count plummeted, and he developed worsening agitation. He had refractory disease, for which we started him on twice daily PEX, weekly Rituximab, and daily Caplacizumab. After that, he continued to show neurological and platelet count improvement. ADAMTS13 activity improved to 8% with inhibitor level 1.3 U/ml, and we monitored it biweekly. Over the next few weeks, we tapered PEX to once weekly, switched steroids to the standard dose, and Caplacizumab to once weekly. The current plan is to taper steroids once ADAMTS13 exceeds 30%. Discussion: This is a case of Nimesulide induced TTP which was refractory to the initial management with PEX and steroids. We report this case to raise awareness amongst physicians towards NSAID induced TTP. Further study is needed to determine if these patients should avoid NSAIDs for life. We also need additional data to comment on the clinical course of similar patients.

ODP615 Emergence of Graves’ Ophthalmopathy in the Setting of Sudden Hypothyroidism: Possible Mechanisms Explored

Abstract Background Ninety percent of thyroid eye disease (TED) patients are hyperthyroid and at least 10% of TED occurs in the setting of euthyroidism or hypothyroidism. When Graves’ hyperthyroidism is diagnosed, 74% may not present with ophthalmopathy. Clinical Case A 58 year old woman diagnosed with Multinodular nontoxic goiter without nodule suspicious for malignancy was carefully monitored. No Levothyroxine treatment started. In 2017, patient had sudden onset of tremors, weight loss and palpitations. There were no signs of thyroid associated orbitopathy. Her TSH was &amp;lt;0. 009 uIU/ml (0.30-4) and FT4 29. 06pmol/L (10-22). Thyroid scan showed elevated 2- and 24-hours RAI uptake (as high as 80%) in both lobes. She was started on Methimazole but developed adverse reactions hence RAI (10 mci) was given. A month after RAI, she was rendered hypothyroid with of TSH 73.48uIU/ml (0.27-3.75), FT4 2.257pmol/L (8.8-44). She was maintained on Levothyroxine and remained euthyroid for four years. One year post RAI, ultrasound showed a small sized thyroid gland (right lobe: 3×0.6×1.5cm and left lobe: 2.2×0.3×1.3cm). May 2021, she followed up due to bulging eyes with scratchy sensation. She was noncompliant with Levothyroxine for several months. TSH was elevated to 46.19 uIU/ml (0.3-4. 00) and FT4 12.35 pmol/L (10.20-22.50). Levothyroxine dose was adjusted and repeat TSH was normal to 0.38 uIU/ml (0.30-4. 00) with FT4 of 22.40 pmol/L (10.20-22.50). Despite euthyroidism, there were progressive eye protrusion, conjunctival redness, pain and blurring of vision. TSHrAb was elevated to 21.62 U/L (N: &amp;lt;1 U/L). TSI was elevated to 6.59 IU/L (N: &amp;lt;0.10). . MRI of the orbit showed findings suggestive of Graves’ ophthalmopathy. She was started on Prednisone 60mg/day. Repeat TSHrAb was 9.85 U/L (&amp;lt;1U/L) after 3 weeks of steroids. Levothyroxine was stopped to check whether she had recurrence of Graves’ disease. When Levothyroxine was discontinued, there was worsening of eye disease and it was confirmed that patient was hypothyroid with TSH of 48.91 uIU/ml (0.55-4.78). Levothyroxine was resumed at 100mcg 1 tablet once daily and continued with Prednisone in tapering doses. Conclusion There were possible mechanisms that can lead to Graves’ ophthalmopathy in patients who had RAI and suddenly became hypothyroid. The rapid and protracted hypothyroidism caused increased secretion of TSH that stimulate antigen production by thyrocytes or induce proliferation in retro-orbital preadipocytes which express the TSH receptor. The protracted hypothyroidism can also be related to fluctuating TSHrAb post RAI. It was suggested that remission of TSH-receptor autoimmunity after RAI is less common. Clinicians should acquire baseline and monitoring of TSHrAb or ophthalmology consultation for all patients undergoing RAI regardless of whether they have eye signs or not. Maintenance of euthyroidism will help prevent emergence of Graves’ ophthalmopathy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

A CASE OF LOMUSTINE-INDUCED PNEUMONITIS

A CASE OF LOMUSTINE-INDUCED PNEUMONITIS

S3272 A Potential New Use for Tocilizumab: A Case of Refractory Checkpoint Inhibitor Hepatitis

Introduction: Immune checkpoint inhibitors (CPI) are becoming increasingly common treatment options for several types of cancers. While their use in cancer treatment is very promising, these medications are not without side effects. Specifically, these drugs are commonly associated with hepatic adverse events, including auto-immune hepatitis (AIH). In fact, in one study, AIH was found in approximately 5% of people treated with a CPI. While we know that CPI hepatitis is a potential outcome of treatment with CPIs, we have yet to establish the best treatment options for this adverse event. Based on expert opinion, the recommended course of treatment involves high dose steroids and immunomodulators if needed. There is not, however, much literature on management of CPI hepatitis that is refractory to the typical treatments, though use of tocilizumab has shown some success previously in treatment of immune-related adverse events secondary to CPIs . Case Description/Methods: A 35 y.o. female with recurrent right renal cell carcinoma, status-post resection with nephrectomy, on palliative treatment with nivolumab/ipilimumab, presented to the hospital for further evaluation of elevated liver function tests (LFT) and an abdominal MRI concerning for hepatitis. At time of admission, she was on her 3rd week of steroids, started with concern for drug-induced autoimmune hepatitis due to her checkpoint inhibitor (CPI) treatment. At admission, she was started on IV steroids and mycophenolic acid. LFTs and bilirubin continued to rise despite several days of this treatment and she was given a dose of rituximab. Liver biopsy was obtained which was consistent with CPI induced hepatitis. LFTs and bilirubin continued to rise and tocilizumab was given. 4 days after that treatment, AST and ALT were nearly half their pretreatment values and bilirubin began downtrending. At this point, the patient was stable enough for discharge with very close follow up (Figure). Discussion: Studies from 2019 reveal that 43.68% of all people with cancer in the United States are eligible for CPI therapy. This number translates to 7.9 million patients who are potentially eligible for CPI therapy. With the incidence of severe CPI hepatitis suspected to be up to 20% of all people taking CPIs, this equates to 1.58 million people of whom could be affected. More studies need to be done to address treatment for refractory auto-immune CPI hepatitis, and to better understand the underlying pathogenesis in this rapidly growing population.Figure 1.: Liver biopsy with significant lobular hepatitis, loss of zone 3 hepatocytes, acidophil bodies, and Kupffer cell hyperplasia consistant with checkpoint inhibitor auto-immune hepatitis.

Request for biliary drainage for IgG4-SC could be waived before steroid administration?

In IgG4-related sclerosing cholangitis (IgG4-SC), the necessity of biliary drainage (BD) is unclear. In this study, we aimed to retrospectively investigate the improvement of liver damage and jaundice in cases of IgG4-SC with and without BD, before starting steroids. A total of 52 patients with IgG4-SC were investigated in the study. The study endpoints were the normalization rate of alkaline phosphatase (ALP)/total bilirubin (T-Bil) after 8 weeks of steroids, with and without BD. Propensity score matching was performed based on ALP and T-Bil, and 28 patients were included. There were 14 patients each in the BD and non-BD groups. Before initiation of steroids, the mean ALP in the BD group and the non-BD group was 378/461 (P=.541); the mean T-Bil was 2.5/1.8 (P=.401). Eight weeks after initiation of steroids, ALP improvement rate in the BD group/non-BD group was 69.2%/61.5% (P=1.000), and T-Bil improvement rate was 100%/100% (P=Ns). Steroids for IgG4-SC could prove effective in improving liver damage and jaundice, regardless of the presence or absence of BD. BD for IgG4-SC aimed to improve jaundice may not be necessary.

High Incidence of COL4A Genetic Variants Among a Cohort of Children With Steroid-Resistant Nephrotic Syndrome From Eastern India

High Incidence of COL4A Genetic Variants Among a Cohort of Children With Steroid-Resistant Nephrotic Syndrome From Eastern India

Chronic immune checkpoint inhibitor (ICI) pneumonitis in patients (pts) with non-small cell lung cancer (NSCLC).

9103 Background: ICI pneumonitis is an immune-related adverse event (irAE) of the lung and often requires discontinuation of ICI. While some pneumonitis cases resolve within the recommended 4-6-week period of corticosteroid therapy, others either fail to improve or have multiple flares necessitating longer or repeated courses of steroids. We investigated the clinical features and courses of pts with chronic pneumonitis. Methods: We analyzed 869 pts with NSCLC initiated on ICIs at our institution between 2011 and 2019 for development of ICI pneumonitis. Chronic pneumonitis was defined as any pneumonitis requiring a total of ≥12 weeks of steroids, given either continuously or over multiple courses of treatment. Cases of chronic pneumonitis in which the initial course of steroids lasted ≥12 weeks without interruption were termed “primary refractory pneumonitis”. Subsequent episodes of pneumonitis were categorized as either “recurrent pneumonitis” from ICI rechallenge or “pneumonitis flare” after steroid taper without ICI rechallenge. Chest CT scans were analyzed to classify the imaging patterns. Results: Of the 869 pts analyzed, 44 developed ICI pneumonitis (5.1%) and 22 of the 44 (50%) experienced chronic pneumonitis (Grade 2 in 11, Grade 3 in 9, and Grade 4 in 2). A cryptogenic organizing pneumonia (COP) pattern was the most common CT pattern among all pneumonitis cases (30/44) and in chronic pneumonitis cases (14/22). Among chronic pneumonitis cases, the median number of total weeks on corticosteroid therapy was 25.9 (range: 12.4 – 114.4 weeks). Four pts required additional immunosuppressive agents including mycophenolate or infliximab. Fourteen of 22 pts with chronic pneumonitis had primary refractory pneumonitis, while the remaining 8 pts were weaned off of steroids within 12 weeks but later developed additional episode(s) of pneumonitis, ultimately resulting in a total steroid duration of ≥12 weeks. The 14 pts with primary refractory pneumonitis had significantly shorter time to pneumonitis onset compared to the other 8 pts (median time to onset: 1.8 vs. 5.5 months, Wilcoxon ranksum p = 0.04). Seventeen of 22 patients had their ICI permanently discontinued; of these, 9 pts subsequently experienced pneumonitis flare after steroid taper, necessitating additional course(s) of steroid therapy. 5 of the 22 patients were rechallenged with ICI, and 4 of them had recurrent pneumonitis with ICI rechallenge. Conclusions: Half of the pts diagnosed with pneumonitis developed chronic pneumonitis requiring at least 12 weeks in aggregate of glucocorticoid therapy. Some patients had an initial prolonged steroid course while others initially improved and then flared, even after ICI discontinuation. Recognition of chronic pneumonitis as a distinct and common clinical entity is important in management of pts with ICI pneumonitis.

RARE ACUTE FIBRINOUS PNEUMONIA ASSOCIATED WITH LEGIONNAIRE’S DISEASE

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Acute fibrinous organizing pneumonia (AFOP) is a newly proposed, rare histological variant of subacute interstitial pneumonia, which can be fatal. This case report describes an uncommon case of AFOP. CASE PRESENTATION: A 79-year-old female presented to the emergency department (ED) with worsening shortness of breath associated with hemoptysis, fever, and chills. Past medical history of remote Stage 1B adenocarcinoma of the lung status post-definitive chemo-radiotherapy, hypertension, coronary artery disease and permanent atrial fibrillation. In ED, the patient was afebrile, tachycardic and tachypneic. Her physical examination was significant for inspiratory crackles and wheezing throughout the lung fields. Laboratory data included a WBC of 9.1 k/µL, hyponatremia (122 mmol/L). A chest CT scan showed areas of airspace opacities in the right upper and left lung base. Legionella pneumophila serogroup 1 antigen was positive, compatible with acute Legionnaires disease. The patient was treated with 8 days of Levofloxacin and discharged home. After 3 weeks, the patient reported minimal improvement of symptoms, persistence of fatigue and shortness of breath with 10 lb weight loss. Repeat CXR displayed consolidative opacities in the upper lobes bilaterally, unchanged from previous imaging. Given the persistent infiltrates, and concern for progression of her known malignancy, a CT-guided biopsy was done. It contained core fragments of lung parenchyma with interstitial fibromyxoid tissue and organizing fibrin; without evidence of granulomas/neoplasm. These findings were consistent with a diagnosis of AFOP. After 1 week of steroids, her CXR highlighted interval resolution of patchy parenchymal opacities and resolution of symptoms. DISCUSSION: AFOP is a rare pathological disease with only a few cases reported in the literature. The exact etiopathogenesis remains unknown and clinical manifestations are usually non-specific. CT findings typically consist of bilateral opacities and areas of consolidation, but a definite diagnosis is made via lung biopsy. Currently, there is no standard therapeutic regimen for AFOP and is under investigation, making it controversial. The small number of case reports have highlighted that patients respond positively with a longer course of corticosteroids and/or immunosuppressive agents(1). Our patient showed marked symptomatic and radio-graphic improvement within 1 week of steroid therapy. As such, shorter courses of prednisone treatments may be considered in the appropriate clinical setting and if associated with side effects & morbidity from steroids. CONCLUSIONS: The diagnosis of AFOB can be very challenging as the clinical picture may mimic other potential etiologies such as inflammatory lung disorders, or malignancy. The mortality rate of untreated AFOB is high and therefore, consideration of this diagnosis in the appropriate clinic context can be potentially lifesaving. Reference #1: Gomes, R., Padrão, E., Dabó, H., Soares Pires, F., Mota, P., Melo, N., Jesus, J. M., Cunha, R., Guimarães, S., Souto Moura, C., & Morais, A. (2016). Acute fibrinous and organizing pneumonia: A report of 13 cases in a tertiary university hospital. Medicine, 95(27), e4073. https://doi.org/10.1097/MD.0000000000004073 DISCLOSURES: No relevant relationships by Sanchit Chawla, source=Web Response No relevant relationships by Anu Suri, source=Web Response

An Atypical Presentation of Giant Cell Arteritis with Bilateral Choroidal Ischaemia

Background: Giant cell arteritis is an immune-mediated, medium to large vessel vasculopathy affecting individuals over 50 years of age. It can cause sudden, severe and irreversible loss of vision, most commonly from an arteritic posterior ciliary artery occlusion causing anterior ischaemic optic neuropathy. The optic nerve appearance would typically be swollen and chalky white. Visual reduction secondary to choroidal ischaemia is a much less frequent presentation, the signs of which can be more subtle in appearance, making its early recognition potentially more challenging. Case Presentation: A 51-year-old male presented to eye casualty complaining of a one-week history of neck pain, intermittent headaches and jaw claudication, associated with reduced vision in his right eye. Presenting visual acuity was hand movements and 6/5 in the right and left eyes respectively. On examination, he was noted to have a right relative afferent pupillary defect, a pale macular area in the right eye with a possible cherry red spot. There was no optic disc swelling. ESR was 34 and CRP was 46 and he was wrongly diagnosed with a non-arteritic central retinal artery occlusion. He subsequently re-presented 5 weeks later with vision loss in his left eye. Best corrected visual acuity was now 6/60 and 6/12 in the right and left eyes respectively. Dilated fundoscopy showed multiple yellow-white lesions in the posterior pole of the left eye and a retinal cotton wool spot. The right optic nerve was pale, and left was normal. A fundus fluorescein angiogram showed delayed choroidal filling and the temporal artery biopsy was suggestive of GCA. He was started on 110mgs of oral prednisolone. After 4 weeks of steroids his BCVA was 6/36 and 6/6 in the right and left eyes respectively. His neck pain, headaches and jaw claudication had all resolved and his ESR and CRP had returned to normal levels. Conclusion: Our case highlights the need for increased awareness of this uncommon presentation of this potentially blinding disease, to allow prompt and appropriate treatment. Our case is unusual in that despite a delayed diagnosis of 5 weeks, visual acuity initially improved with treatment.

Reduction of Vertebral Bone Density in Patients with Hodgkin Lymphoma Above 30 Years of Age Correlates with the Cumulative Dose of Steroids They Receive As Part of Treatment Protocol

Introduction: In the last decades, Hodgkin lymphoma (HL) has become a curable disease with a long-term disease-free survival achieved in about 80% of patients. The two main chemotherapy protocols presently used in HL treatment are: ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP (EB) (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone). Patients treated with ABVD also receive glucocorticoids to minimize regimen toxicity and as antiemetic prophylaxis. Similarly, prednisolone given for 14 days is an integral part of the EB regimen. However, glucocorticoids are known to interfere with bone formation and remodeling, which results in increased fracture risk. To reduce the rate of complications, such as aseptic necrosis of the femur head, according to the H2 Israeli protocol, patients treated with EB receive prednisone for seven days only. The current study was designed to evaluate the vertebral density (VD) changes associated with HL therapy. Methods: In this retrospective study, data on all newly-diagnosed HL patients treated at the Rambam Health Care Campus between 2008-2016 were retrieved from the institutional computerized database. Patients were grouped based on their treatment protocol and further sub-grouped according to the number of treatment cycles: I ‒ ABVDx2-4, II ‒ ABVDx6, III ‒ EBx2+ABVDx4, IV ‒ EBx4-6+ABVDx2. VD findings of PET/CT scans performed at baseline and post-treatment were compared at L3 vertebral level. The Hounsfield unit (HU) scale was used to evaluate bone mineral density (BMD). The dose of hydrocortisone equivalents (HE) per meter square of the body surface area was calculated for each patient. Results: All the identified newly-diagnosed HL patients (n=213) were included in the analysis. Their median age was 29 (18-59) years. Both baseline and post-treatment scan results were available for all patients. Mean VD at baseline was 198 HU (30.5-320) and post-treatment ‒ 165.5 HU (27.5-277.3). At baseline, 7 patients had osteopenia (&lt;120 HU) and 1 patient had osteoporosis (&lt;90 HU). The corresponding post-treatment numbers were 21 and 9 patients, respectively. Data on mean VD at baseline and post-therapy categorized according to the treatment received are presented in Table 1. The mean VD change from the baseline level was 14.7% in the ABVD group as a whole, 9.3% HU in the ABVDx2-4 subgroup and 17.3% in the ABVDx6 subgroup. The mean VD change from the pre- to post-therapy level was 20.5% for the whole EB group, 24.3% for the EBx2 + ABVDx4 subgroup and 15.4% for the EBx4-6 + ABVDx2 subgroup. The relative VD decreased post-treatment in all the subgroups. Using the ABVDx2-4 group as reference (HR=1), the HR for ABVDx6 group was 6.51 (95% CI 2.8-15.3; P=0.000), with HR=16.11 (95% CI 5.6-46.8; P=0.000) for EBx2 + ABVDx4 group and HR=2.78 (95% CI 0.9-8.2; P=0.065) for EBx4-6 + ABVDx2 group. There was a significant decrease in VD of 116 patients with HE &gt;3.4gm/m2 compared to 24 patients with HE ≤2.1 gm/m2 (HR=6; 95% CI 2.1-17.2; P=0.001). The present study demonstrated a bone density loss of ≥16% in 48% of patients and of ≥26% in 20% of patients. Osteopenia and osteoporosis developed in 7% and 4% of treated patients. Individuals receiving EBx6 had a less significant bone loss compared to those receiving EBx2 +ABVDx4. This could be explained in part by the older age (19% were above 46 years) of the latter patients. A similar VD loss of ≥16% was observed in patients treated with ABVDx6 and those receiving EB containing regimen (one week of steroids only) (56.6 and 59%, respectively). A multivariate analysis for prediction of VD loss showed that age ≥30 (HR=2.19; 95% CI 1.13-4.24; P=0.02) and chemotherapy protocols other than ABVDx2-4 (ABVDx6: HR=6.65; 95% CI 2.80-15.78; P=0.000; BEACOPPx2-6: HR=7.87; 95% CI 3.14-19.71; P=0.000) were significant risk factors (Fig. 1). Conclusions: The current study demonstrates that VD reduction is a significant problem in HL patients above the age of 30 years, treated with 6 cycles of chemotherapy containing HE &gt;3.4gm/m2. As it may lead to osteopenia, a restrictive approach to the use of glucocorticoids should be applied in this patient population. These findings suggest that bone density should be followed in this group of HL survivors. Disclosures No relevant conflicts of interest to declare.

Niflumic Acid Reverses Airway Mucus Excess and Improves Survival in the Rat Model of Steroid-Induced Pneumocystis Pneumonia.

Although the role of adaptive immunity in fighting Pneumocystis infection is well known, the role of the innate, airway epithelium, responses remains largely unexplored. The concerted interaction of innate and adaptive responses is essential to successfully eradicate infection. Increased expression of goblet-cell-derived CLCA1 protein plus excess mucus in infant autopsy lungs and in murine models of primary Pneumocystis infection alert of innate immune system immunopathology associated to Pneumocystis infection. Nonetheless, whether blocking mucus-associated innate immune pathways decreases Pneumocystis-related immunopathology is unknown. Furthermore, current treatment of Pneumocystis pneumonia (PcP) relying on anti-Pneumocystis drugs plus steroids is not ideal because removes cellular immune responses against the fungal pathogen. In this study, we used the steroid-induced rat model of PcP to evaluate inflammation and mucus progression, and tested the effect of niflumic acid (NFA), a fenamate-type drug with potent CLCA1 blocker activity, in decreasing Pneumocystis-associated immunopathology. In this model, animals acquire Pneumocystis spontaneously and pneumonia develops owing to the steroids-induced immunodeficiency. Steroids led to decreased animal weight evidencing severe immunosuppression and to significant Pneumocystis-associated pulmonary edema as evidenced by wet-to-dry lung ratios that doubled those of uninfected animals. Inflammatory cuffing infiltrates were noticed first around lung blood vessels followed by bronchi, and both increased progressively. Similarly, airway epithelial and lumen mucus progressively increased. This occurred in parallel to increasing levels of MUC5AC and mCLCA3, the murine homolog of hCLCA1. Administration of NFA caused a significant decrease in total mucus, MUC5AC and mCLCA3 and also, in Pneumocystis-associated inflammation. Most relevant, NFA treatment improved survival at 8 weeks of steroids. Results suggest an important role of innate immune responses in immunopathology of steroid-induced PcP. They warrant evaluation of CLCA1 blockers as adjunctive therapy in this condition and describe a simple model to evaluate therapeutic interventions for steroid resistant mucus, a common condition in patients with chronic lung disease like asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis.

Outcomes after early initiation of nonsteroidal immunosuppressive therapy in patients with immune checkpoint inhibitor-induced colitis.

2571 Background: Current treatment guidelines for immune-mediated colitis (IMC) recommend 4 to 6 weeks of steroids as first-line therapy, followed by nonsteroidal immunosuppressive therapy (NSIST) (infliximab or vedolizumab) in patients who do not respond to steroids. We assessed the effect of early NSIST introduction and number of NSIST infusions on clinical outcomes. Methods: We performed a retrospective review of patients with IMC who received NSIST between January and December 2018. Logistic regression analyses were used to assess associations between clinical features and outcomes of IMC (Table). Results: Of the 1,459 patients who received immune checkpoint inhibitor, 179 developed IMC of any grade; 84 of them received NSIST. Of the 84 patients who received NSIST, 79% were males with mean age of 60. Compared with patients who received NSIST &gt;10 days after IMC onset, patients who received early NSIST (≤10 days) required fewer hospitalizations ( P=0.03), experienced steroid taper failure less frequently ( P=0.03), had fewer steroid tapering attempts ( P&lt;0.01), had a shorter course of steroid treatment ( P=0.09), and had a shorter duration of symptoms ( P&lt;0.01). Risk factors of IMC recurrence after weaning off steroids included: 1) needing multiple hospitalizations ( P&lt;0.01), 2) experiencing steroid taper failure after NSIST ( P=0.02), 3) receiving infliximab rather than vedolizumab ( P=0.02), 4) receiving fewer than three infusions of NSIST ( P=0.02), 5) having higher fecal calprotectin levels after NSIST ( P=0.01), and 6) receiving a longer course of steroids ( P=0.02), hospitalization ( P&lt;0.01) and IMC symptoms ( P&lt;0.01). Unsuccessful weaning from steroids after NSIST was associated with high IMC grades ( P&lt;0.01); multiple hospitalizations ( P&lt;0.01); steroid-resistant IMC ( P&lt;0.01); long interval from IMC to NSIST initiation ( P=0.01); and long duration of steroids ( P&lt;0.01), IMC symptoms ( P&lt;0.01), and hospitalization ( P&lt;0.01). Conclusions: NSIST should be introduced early in the disease course of IMC instead of waiting until failure of steroid therapy or steroid taper. Patients who received three or more infusions of NSIST had more favorable clinical outcomes.

Early introduction of selective immunosuppressive therapy associated with favorable clinical outcomes in patients with immune checkpoint inhibitor\u2013induced colitis

BackgroundCurrent treatment guidelines for immune-mediated colitis (IMC) recommend 4 to 6 weeks of steroids as first-line therapy, followed by selective immunosuppressive therapy (SIT) (infliximab or vedolizumab) in patients who do not respond to steroids. We assessed the effect of early SIT introduction and number of SIT infusions on clinical outcomes.MethodsWe performed a retrospective review of patients with IMC who received SIT at The University of Texas MD Anderson Cancer Center between January and December 2018. Logistic regression analyses were used to assess associations between clinical outcomes and features of IMC.ResultsOf the 1459 patients who received immune checkpoint inhibitors, 179 developed IMC of any grade; 84 of these 179 patients received SIT. Of the 84 patients who received SIT, 79% were males, and the mean age was 60 years (standard deviation, 14). Compared with patients who received SIT > 10 days after IMC onset, patients who received early SIT (≤10 days) required fewer hospitalizations (P = 0.03), experienced steroid taper failure less frequently (P = 0.03), had fewer steroid tapering attempts (P < 0.01), had a shorter course of steroid treatment (P = 0.09), and had a shorter duration of symptoms (P < 0.01). Patients who received one or two infusions of SIT achieved histologic remission less frequently (P = 0.09) and had higher fecal calprotectin levels after SIT (P = 0.01) compared with patients who received three or more infusions. Risk factors for IMC recurrence after weaning off steroids included: 1) needing multiple hospitalizations, 2) experiencing steroid taper failure after SIT, 3) receiving infliximab rather than vedolizumab, 4) receiving fewer than three infusions of SIT, 5) having higher fecal calprotectin levels after SIT, and 6) receiving a longer course of steroids, hospitalization and IMC symptoms. Unsuccessful weaning from steroids after SIT was associated with high IMC grades; multiple hospitalizations; steroid-resistant IMC; long interval from IMC to SIT initiation; and long duration of steroids, IMC symptoms, and hospitalization.ConclusionSIT should be introduced early in the disease course of IMC instead of waiting until failure of steroid therapy or steroid taper. Patients who received three or more infusions of SIT had more favorable clinical outcomes.

Necrotizing myopathy as paraneoplastic disorder in tonsillar squamous cell carcinoma

Introduction: Myositis including polymyositis and dermatomyositis has been reported in different types of cancer mainly lung, breast and ovarian cancer. Case Report: We report a case of necrotizing myopathy presenting in a 59-year-old patient after a recent diagnoses of squamous cell carcinoma of the tonsil. Three weeks later, the patient was admitted for worsening generalized weakness, dysphagia and constipation. Patient was bed bound requiring full assistance. Physical examination was significant for symmetrical weakness in his proximal muscle groups of upper and lower extremity. Creatinine kinase (CK) was 13,000 U/L with markedly elevated liver enzymes. EMG showed myotonia in all muscle groups with more prominence in axial and proximal muscles than distal. Following the biopsy of biceps muscle, IV steroid was initiated. IVIG was started later in addition to oral steroids due to suboptimal response. In the interim, biopsy showed severe necrotizing myopathy. Myositis Ab panel and paraneoplastic antibody panel including voltage gated potassium channel (VGPC) Ab, ANNA-1, ANNA-2 and PCA-1 Abs were negative. CK trended down to 1196 U/L after three weeks of steroids with moderate improvement in the muscle weakness. Conclusion: Necrotizing myopathy can be associated with squamous cell carcinoma of tonsil. Serology may be negative and the presence of diffuse myotonia suggests myopathy. However, biopsy shows myofibers undergoing myophagocytosis with minimal inflammatory cells thus confirming necrotizing myopathy.

Impact of salivary hypofunction on incidence of orofungal infections with use of topical steroids for management of oral lichen planus and xerostomia

The aim of this study was to determine if salivary hypofunction increases the incidence of oral fungal infections (OFIs) after topical steroid use for the management of oral lichen planus (OLP). Patients with a diagnosis of OLP, treated for at least 2 weeks with topical steroids, had baseline salivary flow evaluations completed, and had a follow-up visit within 5 weeks of steroids being prescribed were assessed. Patients were evaluated for clinical signs of fungal infection at follow-up visits. Forty-Seven patients (91% female) met the inclusion criteria, with 21.3% developing an OFI after topical steroid use. Demographic characteristics, type of OLP, steroid used, and antifungal used did not impact the development of an OFI. The mean stimulated salivary flow was significantly lower in the group that developed an OFI compared with the group that did not develop an OFI (8.31 mL/15 min vs 15.4 mL/15 min, respectively; P = 0.0006). A higher incidence of OFIs occurred in the low stimulated flow group versus the normal flow group (39% vs 4%, respectively). Most patients in the OFI group received a preventative antifungal (90%). OFIs increased after steroid treatment in patients with OLP who had low stimulated salivary flows. Antifungals (90%) were not effective in preventing OFIs in patients with OLP who had salivary hypofunction and were treated with topical steroids.

P036 EXPLORING EARLY-RESPONSIVE PHARMACODYNAMIC BIOMARKERS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE (IBD)

The generation of high-quality pilot data that leads to “go/no-go decisions” regarding new or repurposed drugs is often problematic, particularly with a high placebo response rate. In short duration trials, pharmacodynamic (PD) biomarkers can demonstrate proof-of-concept of drug action that may or may not be bridged to clinical outcomes. We sought to identify early-changing PD biomarkers in patients with IBD. Clinical scores and serum were obtained at baseline and after 1–2 weeks of corticosteroids in 5 IBD patients. Using the SOMAscan assay, 45 published chronic steroid and infliximab-responsive proteins were evaluated. All were log-transformed and normality verified using the Shapiro-Wilk test. Pre- to post- treatment comparisons were performed using a paired t-test (p<0.01). Label-free proteome profiling using mass spectrometry was performed. Thirteen proteins responded consistently to 1–2 weeks of corticosteroids. These included biomarkers previously shown to be responsive in pediatric IBD patients after 2 doses of infliximab (CCL23, carnosinase, p-cadherin, CCL25, testican-2, AGT, and FAM3B) and after longer courses of corticosteroid therapy (AGT, afamin, GHBP, CCL22, MMP12, PROT C, Ly9). Four were detected by label-free mass spectrometry (AGT, afamin, PROT C, and carnosinase). Most are involved in regulation of inflammation, immune homeostasis, and extracellular matrix binding. In this small sample, change in some biomarkers correlated with short-term clinical response (carnosinase, testican-2, FAM3B). We have identified treatment-responsive proteins in IBD patients after several weeks of steroids, after 2 doses of infliximab, and within 1–2 weeks of treatment with steroids; these biomarkers may be useful for screening trials of anti-inflammatory drugs. For selection of candidates to study in larger, controlled trials, short-duration biomarker-based trials would be beneficial for patients.

Association of Acute Myeloid Leukemia and Systemic Lupus Erythematosus: A Case Report

Systemic lupus erythematosus is an autoimmune Inflammatory disease that can affect multiple systems and organs of the body including skin, kidneys, lungs, joints and nervous system.Some previous studies up light thatSLE was associated with increased risk of Acute leukemia (SIR = 2.3). The incidence ofthe association of AMLand SLE is not known but there are few case reports in literature. The aim of this report was to up light the difficulties wich occurred in the diagnosis and the management of acute myeloid leukemia in patient with systemic lupus erythematosus. Patient, 43 years old, diabetic treat withinsulin, wichsister is followed for Behcet's disease, was admited for AML with trisomy of chromosome 4 and 8 and thrombophlebitis of the superior sagittal sinus, Chest CT-Scan showed minimal bilateral pleural effusion. She was treated according to Morocco National protocol AML-MA-2011. CT-Scan was done atday 12 ofchemotherapy and noticedthe persistance of the minimal bilateral pleural effusion.At day 19 the patient presentedmalar rash, and right axillary adenitis. The biopsy of the adenitis show the presence of LE cells. According to internal physician recommendations we add steroids to the treatement. The cough and fever deasapear. The CT-scan for control was normal after two weeks of steroids. Patient is in complete remission after induction I. After a following-up of five months, the patient still well,but present severy infections during chemotherapy cycles and a bad tolerance for the treatement. The association SLE-AML is rare. The diagnosis of the association SLE-AML is difficult. It is management is also difficult according to commorbidity, severy infectious because of dicline of immunity, and less tolerance to AML chemotherapy.

95 - Biomarkers Predict Graft-Vs-Host Disease Outcomes Better Than Clinical Response after One Week of Treatment

Graft-versus-host disease (GVHD), the primary cause of non-relapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation, does not always respond to treatment with high dose systemic corticosteroids. We have recently shown that a combination of three biomarkers (TNFR1, ST2, and REG3α) measured at onset of GVHD can predict day 28 response to treatment and 6-month NRM (Levine, Lancet Haem, 2015). Our goal in the current study was to determine if the same biomarker-based Ann Arbor GVHD algorithm can alsopredict treatment response andmortality whenapplied after one week of systemic corticosteroid treatment. The study population consisted of 378 patients (pts) with acute GVHD from 11 centers in the Mount Sinai Acute GVHD International Consortium. All pts were treated with systemic steroids and provided a plasma or serum sample obtained after one week of treatment (±3 days). The median starting dose of systemic steroids for Grade II-IV GVHD was 2.0 mg/kg/day and for Grade I was 1.0 mg/kg/day, after which treatment varied. Patients were divided into test (n=236) and validation (n=142) cohorts. We applied the Ann Arbor GVHD algorithm to concentrations of TNFR1, ST2, and REG3α measured after one week of treatment to generate a predicted probability of 6-month NRM, which we term the treatment score (TS). We employed unsupervised k-medoidclustering to partition TS values from the test cohort into two groups (high and low). This unbiased approach identified a high score group made up of 25% of pts (n=58) in the test cohort. We observed that the day 28 response rate (complete, CR + partial, PR) was significantly lower in pts with high scores compared to low scores in the test cohort (24% vs 65%, p Approximately half of the pts in each cohort (test: 48%; validation: 44%) responded (CR+PR) to the first week of steroids and these ptshad significantly lower 6-month NRM than non-responders (NR) (test: 17% vs 36%, p=0.0002; validation: 13% vs 36%, p=0.0014). Yet the TS continued to stratify mortality risk independently of clinical response. In the test cohort, pts with a high score comprised 16% of all early responders and experienced more than twice the NRM of early responders with a low score (33% vs 13%, p=0.022) (Fig 2A). Conversely, test cohort pts who did not respond by day 7, but had a low score, fared much better than non-responders with a high score (NRM 21% vs 68%, p In conclusion, a treatment score based on three GVHD biomarkers measured after one week of steroids stratifies pts into two groups with distinct risks for treatment failure and 6-month NRM. It is particularly noteworthy that the TS identifies two subsets of pts with steroid refractory (SR) GVHD who have highly different outcomes (Fig 2B/D). The much larger group, approximately two thirds of all SR pts, may not need the same degree of treatment escalation as is traditional for clinical non-response, and thus overtreatment might be avoided. Because the TSis measured at a common decision making time point, it may prove useful to guide risk-adapted therapy. Disclosures Mielke:Novartis: Consultancy; MSD: Consultancy, Other: Travel grants; Celgene: Other: Travel grants, Speakers Bureau; Gilead: Other: Travel grants; JAZZ Pharma: Speakers Bureau. Kroeger:Novartis: Honoraria, Research Funding. Chen:Incyte Corporation: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Novartis: Research Funding. Jagasia:Therakos: Consultancy. Kitko:Therakos: Honoraria, Speakers Bureau. Ferrara:Viracor: Patents & Royalties: GVHD biomarker patent. Levine:Viracor: Patents & Royalties: GVHD biomarker patent.

Biomarkers Predict Graft-Vs-Host Disease Outcomes Better Than Clinical Response after One Week of Treatment

Graft-versus-host disease (GVHD), the primary cause of non-relapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation, does not always respond to treatment with high dose systemic corticosteroids. We have recently shown that a combination of three biomarkers (TNFR1, ST2, and REG3α) measured at onset of GVHD can predict day 28 response to treatment and 6-month NRM (Levine, Lancet Haem, 2015). Our goal in the current study was to determine if the same biomarker-based Ann Arbor GVHD algorithm can alsopredict treatment response andmortality whenapplied after one week of systemic corticosteroid treatment.The study population consisted of 378 patients (pts) with acute GVHD from 11 centers in the Mount Sinai Acute GVHD International Consortium. All pts were treated with systemic steroids and provided a plasma or serum sample obtained after one week of treatment (±3 days). The median starting dose of systemic steroids for Grade II-IV GVHD was 2.0 mg/kg/day and for Grade I was 1.0 mg/kg/day, after which treatment varied. Patients were divided into test (n=236) and validation (n=142) cohorts. We applied the Ann Arbor GVHD algorithm to concentrations of TNFR1, ST2, and REG3α measured after one week of treatment to generate a predicted probability of 6-month NRM, which we term the treatment score (TS). We employed unsupervised k-medoidclustering to partition TS values from the test cohort into two groups (high and low). This unbiased approach identified a high score group made up of 25% of pts (n=58) in the test cohort.We observed that the day 28 response rate (complete, CR + partial, PR) was significantly lower in pts with high scores compared to low scores in the test cohort (24% vs 65%, p<0.0001) (Fig 1A). Analysis of the validation cohort using the same TS definitions showed similar differences in response rates (22% vs 61%, p<0.0001) (Fig 1B). Further, nearly four times as many pts with high scores in both cohorts died within 6 months from non-relapse causes compared to pts with low scores (test: 57% vs 17%, p<0.0001; validation: 57% vs 14%, p<0.0001) (Fig 1C/D). As expected, the majority of non-relapse deaths in pts treated for GVHD were directly attributable to GVHD (test: 95%; validation: 89%). Relapse rates for high and low score pts were similar (data not shown), and thus pts with a high TS experienced significantly worse overall survival in both cohorts (test: 37% vs 72%, p<0.0001; validation: 38% vs 79%, p<0.0001) (Fig 1E/F).Approximately half of the pts in each cohort (test: 48%; validation: 44%) responded (CR+PR) to the first week of steroids and these ptshad significantly lower 6-month NRM than non-responders (NR) (test: 17% vs 36%, p=0.0002; validation: 13% vs 36%, p=0.0014). Yet the TS continued to stratify mortality risk independently of clinical response. In the test cohort, pts with a high score comprised 16% of all early responders and experienced more than twice the NRM of early responders with a low score (33% vs 13%, p=0.022) (Fig 2A). Conversely, test cohort pts who did not respond by day 7, but had a low score, fared much better than non-responders with a high score (NRM 21% vs 68%, p<0.0001) (Fig 2B). Two thirds of early non-responders comprised this more favorable group. These highly significant results reproduced in the independent validation cohort in similar proportions (CR+PR: 45% vs 6%, p=0.0003; NR: 61% vs 22%, p=0.0001) (Fig 2C/D). Finally, a subset analysis revealed that pts classified as NR after one week of steroids due to isolated, yet persistent, grade I skin GVHD (24/378, 6%) overwhelmingly had low treatment scores (22/24, 92%) and experienced rates of NRM (9%) comparable to responders with low scores, thus forming a distinct, albeit small, subset of pts with non-responsive GVHD that fares particularly well (Fig 3).In conclusion, a treatment score based on three GVHD biomarkers measured after one week of steroids stratifies pts into two groups with distinct risks for treatment failure and 6-month NRM. It is particularly noteworthy that the TS identifies two subsets of pts with steroid refractory (SR) GVHD who have highly different outcomes (Fig 2B/D). The much larger group, approximately two thirds of all SR pts, may not need the same degree of treatment escalation as is traditional for clinical non-response, and thus overtreatment might be avoided. Because the TSis measured at a common decision making time point, it may prove useful to guide risk-adapted therapy. [Display omitted] [Display omitted] [Display omitted] DisclosuresMielke:Novartis: Consultancy; MSD: Consultancy, Other: Travel grants; Celgene: Other: Travel grants, Speakers Bureau; Gilead: Other: Travel grants; JAZZ Pharma: Speakers Bureau. Kroeger:Novartis: Honoraria, Research Funding. Chen:Incyte Corporation: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Novartis: Research Funding. Jagasia:Therakos: Consultancy. Kitko:Therakos: Honoraria, Speakers Bureau. Ferrara:Viracor: Patents & Royalties: GVHD biomarker patent. Levine:Viracor: Patents & Royalties: GVHD biomarker patent.