High-dose Steroids Research Articles

Invasive fungal infection in ANCA-associated vasculitis: Between the Devil and Deep blue sea. Case series and review of the literature.

Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are susceptible to opportunistic infections, including invasive fungal infections (IFI). This is due to many factors, including prolonged immunosuppressive therapy. The treatment of AAV with such IFIs is challenging. A descriptive analysis of 5 patients with AAV complicated by concomitant invasive fungal infections was performed. We also have done a comprehensive literature review of IFIs in AAV using PubMed and Google Scholar databases. All 5 patients initially received immunosuppressive medication but subsequently acquired IFI. One patient had sphenoid sinus involvement, and four had lung parenchymal involvement. Aspergillus infection was diagnosed in three patients, Cryptococcus infection in one patient and mixed infection with Aspergillus and Mucor infection in one patient. All our patients were on low doses of corticosteroids for several months to years or had received high-dose pulse steroids with cyclophosphamide in the last few weeks before being diagnosed with IFI. It was difficult to distinguish disease activity from IFI in all the cases. Two of the five patients died despite antifungal therapy. The literature review revealed a prevalence of IFIs ranging from 1 to 9.6% (excluding pneumocystis pneumonia). Aspergillosis was the predominant type of IFI, affecting 46 of 86 patients. Most of these patients (40/46) had pulmonary involvement. The prognosis for patients with IFI was consistently poor, as evidenced by 19 deaths out of 29 reported outcomes. Overall, IFIs have a poor prognosis in patients with AAV. Differentiating disease activity from IFI is difficult because of similar organ distribution, imaging lesions, and histopathological characteristics. A high suspicion index and good-quality microbiology are needed for early treatment and prevention of mortality.

SAT155 Insulin Receptor Autoantibody Syndrome (Iras): A Rare Occurrence In Lymphoproliferative Disease

Abstract Disclosure: C. Villatoro Santos: None. E.A. Oral: None. Insulin receptor antibody syndrome (IRAS) may present as fasting hypoglycemia, high serum insulin, and serum autoantibodies to insulin receptor at low titers. We present a case of a patient with multiple myeloma (MM) who developed hypoglycemia suspected to be related to insulin receptor antibodies. The patient is a 60-year-old male with history of prediabetes, MM, anemia, and thrombocytopenia treated with carfilzomib, dexamethasone 20 mg weekly, and prior radiation to the right pelvis, who presented to the hospital for increased right hip pain and cough. Patient reported 4 days of markedly decreased appetite with poor intake. He noted increased chronic right hip and low back pain. On exam, he was cachectic, had hyperpigmentation under bilateral eyes, and muscle wasting. Hypoglycemia as low as 38 mg/dL (70-180 mg/dL) was noted. MM studies on hospital day 4 showed increased kappa-M protein and kappa-free light chains with worsening anemia and thrombocytopenia, concerning for progression of his disease. He later developed recurrent hypoglycemia; endocrinology was consulted on hospital day 6. He also had hyponatremia and borderline low blood pressure. Cortisol on hospital day 7 at 9:00 am was 15.4 μg/dL (5.3-22.5 μg/dL) in the setting of normoglycemia. On hospital day 9, hematology started dexamethasone 40 mg daily for 3 days for MM relapse, which resulted in marked improvement in his mental status, appetite, and resolution of hypoglycemia. On hospital day 11, he started weekly cyclophosphamide, bortezomib, plus dexamethasone for 3 weeks. Results for hypoglycemia workup returned on hospital day 12 from samples of Day 7: glucose 53 mg/dL (70-180 mg/dL), C-peptide 0.2 ng/mL (1-5.2 ng/mL), insulin 14.6 μU/mL (1-21 μU/mL), insulin antibodies undetectable, negative serum screen for oral hypoglycemic agents. His course was complicated by sepsis with gram-negative bacteremia treated with antibiotics and stress dose hydrocortisone. He was discharged to rehab on hospital day 34 on dexamethasone 4 mg daily. Glucose, c-peptide and insulin levels could be consistent with exogenous hyperinsulinemic hypoglycemia but may also represent delayed insulin clearance due to insulin receptor antibodies and autocrine suppression of pancreatic insulin production in a patient with no access to insulin. Therefore, the most likely diagnosis was IRAS. The insulin antibody radioactive essay was negative for native IgG and IgM antibodies; testing for insulin receptor antibodies is in progress as a clinical test is unavailable. Treatment is common with high doses of steroids. IRAs can be seen in patients with lymphoproliferative disorders and would respond to steroid treatment for hospital management. Definitive treatment should be tailored with oncology guidance. There is a need for an accessible clinical test for IRAS in the US. Presentation: Saturday, June 17, 2023

Novel therapies for graft versus host disease with a focus on cell therapies.

Graft versus host disease (GVHD) can occur at any period post allogeneic hematopoietic stem cell transplantation as a common clinical complication contributing to significant morbidity and mortality. Acute GVHD develops in approximately 30-50% of patients receiving transplants from matched related donors. High doses of steroids are used as first-line treatment, but are unsuccessful in around 40% of patients, resulting in the diagnosis of steroid-refractory acute GVHD. Consensus has yet to develop for the management of steroid-refractory acute GVHD, and prognosis at six months has been estimated at around 50%. Thus, it is critical to find effective treatments that increase survival of steroid-refractory acute GVHD. This article describes the currently known characteristics, pathophysiology, and treatments for GVHD, with a special focus on recent advances in cell therapies. In particular, a novel cell therapy using decidua stromal cells (DSCs) was recently shown to have promising results for acute GVHD, with improved effectiveness over previous treatments including mesenchymal stromal cells. At the Karolinska Institute, severe acute GVHD patients treated with placenta-derived DSCs supplemented with either 5% albumin or 10% AB plasma displayed a one-year survival rate of 76% and 47% respectively. Furthermore, patients with steroid-refractory acute GVHD, displayed survival rates of 73% with albumin and 31% with AB plasma-supplemented DSCs, compared to the 20% survival rate in the mesenchymal stromal cell control group. Adverse events and deaths were found to be attributed only to complications of hematopoietic stem cell transplant and GVHD, not to the study intervention. ASC Therapeutics, Inc, in collaboration with the Karolinska Institute, will soon initiate a phase 2 multicenter, open-label study to further assess the efficacy and safety of intravenous DSC treatment in sixty patients with Grade II-IV steroid-refractory acute GVHD. This novel cell therapy represents a promising treatment to combat the poor prognosis that steroid-refractory acute GVHD patients currently face.

THU246 What’s The Importance of GAD Antibodies In Patients With Stiff Person Syndrome

Abstract Disclosure: A. Barnett: None. G. Elshimy: None. Introduction: Stiff Person Syndrome (SPS) has a strong autoimmune component with positive serology for GAD-65 antibody as one of the diagnostic criteria. GAD is an enzyme selectively concentrated in neurons secreting the neurotransmitter gamma-aminobutyric acid (GABA) but is also present in pancreatic beta cells. Hence, insulin-dependent diabetes mellitus (LADA) can develop in patients with SPS. We present two cases that highlight the importance of this association and the difference in the time of onset to ensure appropriate screening. Case: Our first case was a 46-year-old female with systemic sclerosis and SPS that was diagnosed with steroid-induced diabetes in 2012 with HbA1c 8.7% (4.3-6.1%). Her GAD-65 antibody was significantly elevated at 1971 (less than 2nmol/L). For almost 8 years, the patient only required insulin therapy while on high dose steroids, but eventually developed persistent hyperglycemia requiring insulin therapy. Her C-peptide was 0.49 (0.78-5.19ng/mL) with plasma glucose of 201 (74-106mg/dL), consistent with beta-cell dysfunction. The second case was a 60-year-old female with a 20-year history of SPS who was diagnosed with type 2 diabetes in 2014 after receiving high doses of steroids while undergoing chemotherapy for breast cancer. She was initially well-controlled on oral medications until 2 years after her initial diabetes diagnosis where her HbA1c increased rapidly to 8.1% (4.8-5.9%). At that time, she was started on insulin therapy and antibody testing was pursued which showed positive GAD-65 antibody greater than 250 (less than 5IU/mL) consistent with LADA. She had a negative IA-2 antibody undetectable. Due to other autoimmune associations, she was also screened for thyroid disease revealing an elevated TPO-antibody with a normal TSH 4.02 that is being monitored. Discussion: SPS is associated with autoantibodies and other autoimmune disorders including but not limited to type 1 diabetes, anti-thyroglobulin antibodies and anti-parietal cell antibodies. In both cases, the diagnosis of SPS preceded the onset of diabetes then with a latent “honeymoon” phase not requiring long-term insulin therapy for years, most consistent with LADA. However, there are exacerbating factors including high-dose steroids which could be misleading and result in diagnosing these patients with type 2 diabetes initially. It should be taken into consideration that there is variability in the time of onset of beta-cell dysfunction, which varied from 2 to 8 years in our patients. Hence, the recognition of the correlation of autoimmune-mediated diabetes and the variable time course to insulin deficiency is critical for the continued monitoring in patients with SPS. Physicians should be aware of the importance of screening patients with SPS for type 1 diabetes mellitus and differentiate it from steroid-induced type 2 diabetes to avoid developing diabetic ketoacidosis in these patients. Presentation: Thursday, June 15, 2023

SAT140 A Rare Case Of Asymptomatic Severe Refractory Hypoglycemia Due To Hyper-Warburgism In A Young Patient With T-cell Acute Lymphoblastic Leukemia (ALL)

Abstract Disclosure: S. Choe: None. Background: Hyper-Warburgism, exaggerated Warburg effect, is a rare but serious paraneoplastic syndrome caused by excess glucose consumption by cancer cells through glycolytic pathway leading to lactic acidosis and treatment refractory hypoglycemia. Neuroglycopenic symptoms are absent in these patients hence patients do not meet Whipple triad. Clinical Case: A 33yo African American male with past medical history of recently diagnosed cardiomyopathy and atrial fibrillation was initially admitted to outside institution for cardiac ablation then subsequently transferred to our institution for escalation of care in the setting of post-procedural persistent hypoglycemia. He reported symptoms of fatigue and poor appetite. He noted an unintentional weight loss of 30lb over the past 2 weeks. However, he denied fever, night sweats, classic signs and symptoms of hypoglycemia. Vital signs and physical examination were unremarkable. Clinical manifestation of neuroglycopenia was absent despite serum glucose as low as 46 while serum lactate of 23.8 mmol/L (0.5-2 mmol/L). Initial laboratory test notable for lactic acid of 24.2 mmol/L, glucose of 57 mg/dL, bicarbonate of 12 mEq/L, anionic gap of 39 mEq/L, beta hydroxybutyrate of 5.3 mmol/L, IGF-1 of 192 ng/mL (75–212 ng/ml), IGF-II of 570 ng/mL (288–736 ng/ml), AM cortisol of 14.3 μg/dl, ACTH of 41.6 pg/ml, hemoglobin A1c of 4.8 %, fasting insulin of 1 IU/liter, C-peptide of 0.4 ng/ml, and pro-insulin of 2.9 pg/ml. Given suppression of insulin and proinsulin levels and IGF-II level >275 ng/ml, noninsulin-mediated hypoglycemia was suspected. A CT of chest/abdomen/pelvis revealed a subpleural soft tissue mass involving the posterior mediastinum measuring 4.4 x 3.6 x 3.7 cm, diffuse bilateral renal involvement suspicious for renal lymphoma, adenopathy in the bilateral inguinal, axillary, and external iliac chains. Bone marrow biopsy was performed and result was consistent with T-cell ALL. 20% dextrose infusion was titrated up to keep his BG above 70 mg/dl and high dose steroids was initiated to bridge to chemotherapy. Chemotherapy was initiated soon after confirmation of diagnosis by bone marrow biopsy. The lactic acidosis and hypoglycemia dramatically improved shortly after. PET/CT done 4 weeks after first cycle of chemotherapy failed to identify active disease proving the patient’s good response to chemotherapy. Conclusion: The patient presented with noninsulin-mediated hypoglycemia due to rapid glucose use by cancer cell leading to hyper-Warburgism, evident by severe lactic acidosis, spontaneous hypoglycemia, and large tumor burden on CT scan. Absence of neuroglycopenia presumable due to brain using lactate as fuel and, for this reason, Whipple triad cannot be applied to diagnose hypoglycemia in this case. Chemotherapy must be initiated timely manner as it would resolve metabolic abnormalities dramatically as it was seen in our patient. Presentation: Saturday, June 17, 2023

SAT621 Hemorrhage After Treatment: A Case Of Pituitary Apoplexy In Metastatic Prostate Cancer After Leuprolide

Abstract Disclosure: M. Dillon: None. S. Shteyman: None. W. Rashid: None. B.P. Ramchandani: None. A.G. Samat: None. Introduction: Hormone-sensitive cancers, including prostate and breast cancer, and some gynecological conditions can be treated with GnRH agonists, including leuprolide. However, pituitary apoplexy is a rare potential complication after administration. Case Description: 71-year-old gentleman with metastatic hormone-sensitive prostate cancer presented with an acute headache after receiving a dose of leuprolide. This was his first GnRH agonist dose after prior Degarelix treatment. After two hours, the patient developed a constant throbbing headache, palpitations, left eye tearing and non-bilious non-bloody vomiting. Vitals were within normal ranges, and initial lab work showed low serum cortisol of 4.6. CT scan of the head showed exophthalmos and a mildly enlarged sella. Subsequent MRI demonstrated pituitary hemorrhage and optic chiasm impingement from resulting swelling. Hormone levels remained normal. Since the patient did not develop visual field defects or other ocular complaints, the decision was to manage the patient medically rather than with surgery. The day after admission, he developed hypotension requiring high dose steroids. After discharge, outpatient repeat MRI showed interval resolution of hemorrhage into a predominantly cystic pituitary macroadenoma. Discussion: With continued stimulation, GnRH agonists desensitize the pituitary and cause a downregulation of hormonal induced cancer growth. However, there is an initial transient burst of stimulation that can induce pituitary apoplexy in patients who already have a large adenoma. The hemorrhage and subsequent swelling cause a sudden severe headache and possible visual loss or hypopituitarism. This is life-threatening due to hypotension from catecholamine insensitive blood vessels in the absence of cortisol. Treatment involves high dose steroids, frequent sodium checks and possible emergency neurosurgery for decompression. It is important with GnRH agonists to watch out for this rare complication, whether the hormonal axis is being suppressed for metastatic cancer treatment or for hormonally driven gynecological conditions. Sources: Briet C, Salenave S, Bonneville JF, Laws ER, Chanson P. Pituitary Apoplexy. Endocr Rev. 2015 Dec;36(6):622-45. doi: 10.1210/er.2015-1042. Epub 2015 Sep 28. PMID: 26414232. Tanios G, Mungo NA, Kapila A, Bajaj K. Pituitary apoplexy: a rare complication of leuprolide therapy in prostate cancer treatment. BMJ Case Rep. 2017 Jul 14; 2017:bcr2016218514. doi: 10.1136/bcr-2016-218514. PMID: 28710301; PMCID: PMC5534692. Presentation: Saturday, June 17, 2023

Rare case of refractory mixed autoimmune hemolytic anemia in a 6-year-old child: a case report

BackgroundMixed autoimmune hemolytic anemia (AIHA) shows combined clinical and laboratory characteristics of warm and cold AIHA. It is relatively uncommon in children. Consequently, knowledge about mixed AIHA prevalence, clinical presentation, treatment options, and prognosis in children is limited to very few case reports.Case presentationWe describe a six-year-old Asian girl presenting with profound anemia, blood group typing discrepancy and crossmatch incompatibility, post upper respiratory tract infection. Detection of red cell warm and cold reactive autoantibodies, led to the diagnosis of mixed AIHA. Autoantibodies with laboratory evidence of hemolysis persisted despite high dose steroid therapy. Due to the inability to wean further, the patient was subsequently commenced on mycophenolate mofetil to which she seems to be responding.ConclusionsMixed AIHA may be notoriously difficult to diagnose and treat. Detailed clinical and laboratory work-up is essential to establish the diagnosis. To the best of our knowledge, this is the first case report of mixed AIHA following upper respiratory tract infection. Awareness of this occurrence is important, as similar to warm AIHA, mixed AIHA should be treated immediately by early initiation of steroid therapy. In addition, prompt supportive care as well as long-term clinical follow-up are required to improve outcomes of these cases.

SAT174 Doege-Potter Syndrome In A Patient With Solitary Fibrous Tumor Of The Lung

Abstract Disclosure: N. Mon: None. S.S. Krishnasamy: None. Doege-Potter Syndrome is a non-islet cell tumor hypoglycemia (NICTH) due to a solitary fibrous tumor (SFT) with overexpression of Insulin-like growth factor 2 (IGF2). We report a case of refractory hypoglycemia in a patient with SFT of the lung. Case presentation: A 67-year-old homeless male with hypertension, chronic smoker presented with altered mental status after his blood glucose was found 34mg/dl by EMS. His confusion improved after D50W. He could not recall the event but he reported that he missed his dinner prior to the event. He denied taking any antidiabetic medications. He was diagnosed with left lung solitary fibrous tumor without metastases a week ago after he presented to ER with dyspnea, cough and wheezing. CT chest reported a 21x15.6x18.7 cm lesion with mass effect on the left hemidiaphragm, mediastinum shift to the right and occluded left lower lobe bronchi. Core needle biopsy of the mass revealed SFT with necrosis. He was discharged with Medrol dosepak 4mg daily for presumptive treatment of COPD exacerbation and a plan for elective surgery. While in the ER his BG improved to 136mg/dl after D50W. Few hours later BG dropped to 42mg/dl and D10W infusion was started. Physical exam was unremarkable except bilateral pedal edema. Work up showed BG 42mg/dl, Insulin 3.3 (2.6-24.9 uIU/mL), C peptide 0.39 (1.1-4.4ng/mL), Proinsulin 4.7 (<18.8pmol/L), beta-hydroxybutyrate <0.05 (0.02-0.27mmol/l), 8AM cortisol 10.7 (7.0-25.0 ug/dl), albumin 3.2mg/dl, HbA1c 5.8%, IGF1 53ng/mL (34-245ng/mL), IGF2 203ng/mL (267-616ng/mL) with a IGF2:IGF1 ratio of 3.8. In our patient, the IGF2:IGF1 ratio was not >10 since his IGF 2 was suppressed by the recent steroid use. The rest of the clinical and biochemical features strongly suggested NICTH. His preoperative evaluation showed new onset HFrEF with volume overload. He underwent staged percutaneous coronary interventions with stents placement. He was given hydrocortisone 50mg q6H then to q8H during hospitalization and discharged home with hydrocortisone 40mg TID. He underwent radical resection of lung tumor after optimization of his cardiac condition. He was on stress dose of steroid during surgery. Since he was on high dose steroid for > 3months, hydrocortisone dose was tapered slowly after the surgery. Final biopsy reported solitary fibrous tumor extending to parenchymal staple line. Tumor cells are positive for CD34 and STAT6, and negative for desmin, SMA, and SOX10. He recovered uneventfully and was discharged home with prednisone 5mg daily and follow up in endocrine clinic. Conclusion: NICTH is a rare paraneoplastic syndrome characterized by low levels of insulin, C-peptide, proinsulin, and beta-hydroxybutyrate. A ratio of IGF-2/IGF-1 more than 10 confirms NICTH; however, normal ratio cannot exclude the diagnosis and factors such as low IGFBP 3 or steroid therapy for other conditions need to be considered. Surgery is the mainstay of treatment. Presentation: Saturday, June 17, 2023

THU326 Subcutaneous Insulin Aspart Every 4 Hours In the Treatment Of COVID-19 Patients With Diabetic Ketoacidosis: A Retrospective Study

Abstract Disclosure: D. Chiewchalermsri: None. C. Wanittansirichok: None. C. Sriphrapradang: None. SUBCUTANEOUS INSULIN ASPART EVERY 4 HOURS IN THE TREATMENT OF COVID-19 PATIENTS WITH DIABETIC KETOACIDOSIS: A RETROSPECTIVE STUDY Introduction: COVID-19 infection increases the risk of diabetic ketoacidosis (DKA). To limit the healthcare workers’ exposure when taking care of the COVID-19 patients, treatment of DKA with subcutaneous (SC) rapid-acting insulin analogs every 4 hours was suggested in many professional recommendations. However, the evidence to support this strategy is lacking. We aimed to report the efficacy and safety of SC insulin aspart every 4 hours in the management of DKA in COVID-19 patients. Methods: We retrospectively reviewed all confirmed COVID-19 patients aged >15 years who developed mild-moderate DKA between July 2020 and October 2021 in our institution. Insulin aspart was delivered 0.4 units/kg SC every 4 hours. When blood glucose (BG) decreased to <250 mg/dL, the dose of insulin aspart was reduced to 0.2 units/kg every 4 hours until resolution of DKA. SC Basal insulin 0.15-0.2 units/kg was also initiated at the time of DKA diagnosis. Result: A total of 7 patients had mean age of 67.43±13.19 years with body mass index of 25.49±3.42 kg/m2. Most was 71.4% of female and all had pre-existing type 2 diabetes mellitus. All patients received high-dose steroid for COVID-19 treatment. Initial biochemical parameters were BG of 449±157.3 mg/dL, hemoglobin A1c of 10.58±2.81%, pH of 7.34±0.07, beta-hydroxybutyrate of 4.0±1.51 mmol/L, and HCO3 of 15.5±2.17 mmol/L. Time to resolution of DKA were 12.7±5.82 hours. Conclusion: From our cohort, SC rapid-acting insulin administered every 4 hours could be applied in the selected COVID-19 patients with mild-moderate DKA. Presentation: Thursday, June 15, 2023

Anti-Ma2 Antibody-Mediated Paraneoplastic Cerebellar Degeneration and Myeloneuropathy Secondary to Lymphoma.

A 61-year-old woman with a history of untreated low-grade B-cell lymphoma presented with blurry vision, unsteadiness, and worsening pain on touching skin of the upper trunk was enrolled. Blurry vision was attributed to oscillopsia from downbeat nystagmus, which later evolved into macrosaccadic oscillations. MRI brain and spine showed mild, longitudinally extensive T2 hyperintensity in the central gray matter of the spinal cord extending from the medulla to T11 level. Serum paraneoplastic panel was negative; however, she had very high titers of anti-Ma2 antibodies in cerebrospinal fluid. The diagnosis of paraneoplastic neurological syndrome was made. Empiric treatment with high dose of intravenous steroids followed by intravenous immunoglobulin infusions did not improve her symptoms. An extensive search for an underlying tumor commenced and was initially unrevealing. However, two-month follow-up positron emission tomography scan showed increased uptake in a right pulmonary nodule, which when biopsied confirmed diagnosis of extranodal marginal zone lymphoma. The final diagnosis was anti-Ma2 antibody-mediated paraneoplastic cerebellar degeneration and myeloneuropathy secondary to lymphoma.

Adult-onset Still's disease with Acute Kidney Injury Requiring Hemodialysis: A Case Report and Literature Review.

Adult-onset Still's disease (AOSD) is characterized by high spiking fever, evanescent rash, and arthritis. However, AOSD rarely presents with severe acute kidney injury (AKI). We herein present the case of a 56-year-old woman with new-onset AOSD who rapidly developed AKI. A physical examination and laboratory data revealed spiking fever, evanescent rash, thrombocytopenia, hyperferritinemia, and azotemia. The patient was diagnosed with AOSD complicated by AKI and macrophage activation syndrome. Treatment with high-dose steroids, hemodialysis, and plasma exchange successfully resolved her AKI. In this report, we review previously published reports on AOSD accompanied by AKI and discuss this rare complication in AOSD.

Suboptimal management of rheumatoid arthritis in France: a real-world study based on data from the French National Health Data System

ObjectivesThe emergence of targeted therapy is changing rheumatoid arthritis (RA) management, but real-world data remain limited. This study aimed to describe real-world RA treatment patterns using data from a French...

High- versus Low-dose Steroid Injection for Adhesive Capsulitis (Frozen Shoulder): A Systematic Review and Meta-analysis

BACKGROUND: Intraarticular steroid injections are a commonly used and proven treatment for frozen shoulder; however, there is no scientific basis for a certified dose. OBJECTIVES: This study aimed to identify the difference between high- and low-dose steroid injections treatments and suggest an appropriate dose. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The MEDLINE, EMBASE, and Cochrane electronic databases were searched through February 15, 2023 for eligible randomized controlled trials. The effects of high- and low-dose steroid injections were calculated as standardized mean differences (SMD) in pain, shoulder range of motion (ROM), and functional improvement. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate evidence quality. RESULTS: Four studies with 274 patients were included in the final analysis. The meta-analysis showed that improvement in pain (SMD, 0.10; 95% CI, -0.12 to 0.32), ROM (SMD, 0.07; 95% CI, -0.05 to 0.19), and functional improvement (SMD, 0.08; 95% CI, -0.10 to 0.26) did not differ significantly between the high- and low-dose steroid injections. Subgroup follow-up analyses also showed no clinically significant differences in SMD for pain, ROM, and functional scale measurement in any subgroups (after 3 weeks, 6 weeks, and one year). One article described that, although there was no significant difference in adverse events frequency between the high- and low-dose groups, flushing tended to occur more frequently in the high-dose group. LIMITATIONS: Limitations are the small number of studies included in the meta-analysis, no disease stage considered, and a short follow-up period. CONCLUSIONS: This meta-analysis suggests there are no significant differences between the high- and low-dose steroid groups in pain, ROM, or functional improvement. Therefore, considering the side effects of high-dose steroids, starting with low-dose steroids is recommended. However, further studies are needed to establish exact protocols according to disease severity. KEY WORDS: Frozen shoulder, adhesive capsulitis, steroids, triamcinolone acetonide, injections, intraarticular, optimal dose, meta-analysis, randomized controlled trial

Restoration of vision by combined experimental antithymocyte therapy, and orbital radiation with high-dose steroids for severe, acute, steroid-refractory, congestive thyroid orbitopathy

PurposeWe report diagnostic and therapeutic dilemmas in the difficult case of compressive optic neuropathy with severe visual acuity and visual field loss with subsequent visual recovery in both eyes, in a patient with Graves’ orbitopathy (GO) by a combination of experimental antithymocyte therapy, orbital radiotherapy with high-dose steroids.MethodsA 72-year-old man presented with severe vision loss in both eyes. The visual symptoms had appeared over a year before the GO diagnosis. He was initially misdiagnosed with neuroborreliosis and optic neuritis based on brain and orbital magnetic resonance imaging. There was no exophthalmos. The ophthalmological examination included visual acuity, visual field, tonometry in primary and upgaze eye position, optical coherence tomography (OCT), pattern electroretinogram (PERG), pattern, and flash visual evoked potentials (PVEP and FVEP). The patient received experimental therapy with ATG, followed by high-dose of intravenous steroids and orbital radiotherapy.ResultsDelayed VEP peaks became shorter after treatment. After systemic and local therapy lowering of intraocular pressure was achieved. Abnormal PERG has been found three months before ganglion cells atrophy was detected in OCT. Visual acuity and visual field improvement occurred in both eyes after therapy, despite partial left optic nerve atrophy. The patient regained full decimal visual acuity (1.0 right from as poor as 0.3 to 1.0 in the right eye and from hand movements to 0.9 in the left. Severe visual field loss with advanced absolute scotomata has improved to slight relative scotomata. The duration of follow-up time after the treatment was 4 months.ConclusionsIntensive treatment of steroid-resistant Graves’ orbitopathy (GO) may prevent total optic nerve atrophy. Despite severely advanced optic neuropathy, this report emphasizes the necessity of therapy even with nearly complete visual function loss hence there is always a possibility to regain full visual acuity and visual field. Patients with tense orbital septum may not present with significant exophthalmos, thus delaying the correct diagnosis of orbitopathy. A supporting sign of GO was the difference in intraocular pressure in the primary and upgaze eye positions. Electrophysiological examinations are helpful in the diagnosis and monitoring of GO therapy. To our knowledge, this is the first report of this kind presenting visual function restoration and structural recovery in a patient with advanced optic neuropathy in GO.

Management of donor-specific antibodies in lung transplantation.

The formation of antibodies against donor human leukocyte antigens poses a challenging problem both for donor selection as well as postoperative graft function in lung transplantation. These donor-specific antibodies limit the pool of potential donor organs and are associated with episodes of antibody-mediated rejection, chronic lung allograft dysfunction, and increased mortality. Optimal management strategies for clearance of DSAs are poorly defined and vary greatly by institution; most of the data supporting any particular strategy is limited to small-scale retrospective cohort studies. A typical approach to antibody depletion may involve the use of high-dose steroids, plasma exchange, intravenous immunoglobulin, and possibly other immunomodulators or small-molecule therapies. This review seeks to define the current understanding of the significance of DSAs in lung transplantation and outline the literature supporting strategies for their management.

Hydrocephalus in Neurosarcoidosis: Clinical Course, Radiographic Accompaniments, and Experience with Shunting

BackgroundHydrocephalus is an uncommon manifestation of neurosarcoidosis (7-14% of reported cohorts) that poses unique challenges to patient management. Despite being a recognized complication of neurosarcoidosis, very little is known about how hydrocephalus influences its clinical course, management, and prognosis. ObjectivesTo characterize hydrocephalus as a clinical manifestation of neurosarcoidosis, highlight which patients required cerebrospinal fluid (CSF) diversion, understand the mediating role of immunomodulatory treatments, and report outcomes in this cohort. MethodsPatients with a diagnosis of neurosarcoidosis seen at Emory Healthcare [01/2011-8/2021] were included if hydrocephalus was one manifestation of their disease. Means and proportions were compared between shunted and non-shunted groups using the Wilcoxon rank-sum test for continuous variables and the Fisher's exact test for categorical variables. ResultsTwenty-two patients with neurosarcoidosis and hydrocephalus as one disease manifestation were included (22/214, 10.3%). Hydrocephalus was communicating in 13 (13/20, 65.0%) and obstructive in 6 patients (6/20, 30.0%), with features of both seen in 1 patient (1/20, 5.0%). Chronic presentations were typical (12/22, 54.5%) with altered sensorium, gait dysfunction, headache, and weakness being present in the majority of patients. There was a rostral-to-caudal gradient in ventriculomegaly, with the lateral ventricles most affected (20/20, 100%) and the fourth ventricle the least (12/20, 60%). Meningoventricular inflammation was the most common neuroinflammatory accompaniment (18/20, 90.0%), especially infratentorial leptomeningitis (16/20, 80.0%) and fourth ventriculitis (9/20, 45.0%). Thirteen patients (13/22, 59.1%) required ventriculoperitoneal shunts (VPS). Factors associated with shunt placement were younger age at neurosarcoidosis onset (p = 0.019) and hydrocephalus onset (p = 0.015), obstructive hydrocephalus (p = 0.043), and lateral ventriculitis (p = 0.043). In the 6 patients (6/13, 46.2%) with preceding extraventricular drain (EVD) placement, all failed to wean, including 5/6 patients who received high-dose steroids while the EVD was in place. Almost all (19/20, 95.0%) were treated with steroid-sparing agents, including nine (9/20, 45.0%) with tumor necrosis factor (TNF) inhibitors. Modified Rankin Scale score at last outcome was 3.04 (range 0-6). ConclusionPatients with neurosarcoidosis and hydrocephalus experience unique challenges in the management of their disease, including the potential need for CSF diversion, in addition to traditional anti-inflammatory treatments. Younger patients, those with obstructive hydrocephalus, and those with lateral ventriculitis warrant particular consideration for VPS placement, but the decision to shunt likely remains a highly individualized one. The requirement for multiple lines of immunotherapy beyond steroids and moderate disability at last follow-up suggest hydrocephalus may reflect a more severe form of neurosarcoidosis.

OA04 Muscle weakness in chronic rheumatic diseases: the need for early diagnosis and tailored exercise programme

OA04 Muscle weakness in chronic rheumatic diseases: the need for early diagnosis and tailored exercise programme

OA14 The role of anifrolumab in treating life threatening systemic lupus erythematosus with severe mucocutaneous involvement

OA14 The role of anifrolumab in treating life threatening systemic lupus erythematosus with severe mucocutaneous involvement

P09 A catastrophic decline: a significant skin rash in a patient presenting with catastrophic antiphospholipid syndrome

P09 A catastrophic decline: a significant skin rash in a patient presenting with catastrophic antiphospholipid syndrome

OA18 Small vessel and large vessel vasculitis due to rheumatoid vasculitis: a case of mononeuritis multiplex with pulseless foot leading to amputation

Abstract Introduction Rheumatoid vasculitis occurs in patients with longstanding severe seropositive rheumatoid arthritis. The incidence has reduced drastically with availability of more effective medication. Rheumatoid vasculitis primarily affects small and medium vessels, and rarely large vessels as well. Case description This 77-year-old lady with deforming seropositive rheumatoid arthritis was stable on methotrexate under the care of multiple Trusts for the last 30 years. Methotrexate had been stopped a year ago due to pancytopenia and she was started on prednisolone and hydroxychloroquine. While on these medications she flared with arthralgia and had difficulty in walking attributed to ankle synovitis. She was started on adalimumab, after 3 doses of which she developed widespread skin psoriasis leading to discontinuation. Subsequently, she was admitted to our Trust with left foot gangrene and was referred to rheumatology. Further questioning revealed that numbness in both lower limbs, inability to walk and frequent falls had started following the cessation of methotrexate. On examination, there was bilateral foot drop, worse on the right side. The left foot was gangrenous with diminished pulses in dorsalis pedis and posterior tibial arteries with preserved all other pulses. There was no vasculitic rash or nail fold infarcts. Psoriatic rash had resolved and there was no active synovitis in the joints. Nerve conduction test revealed severe ongoing axonal degenerative type sensory and motor polyneuropathy in the lower limbs without any upper limb involvement. CT angiogram showed multifocal stenoses, more so in the left common iliac, external iliac and superficial femoral artery. There were no conventional vascular risk factors such as hypertension, diabetes, dyslipidaemia or smoking, and there was no past history of cardiovascular disease. PET-CT scan did not reveal any features of vasculitis or aortitis. The vasculitis screening was negative including cryoglobulins. Initially she was on IV antibiotics for left foot cellulitis, hence she was managed with steroids without any potent immunosuppressive agents. Subsequently, she underwent left sided below knee amputation. After the wound had healed, she was started on IV rituximab with low-dose methotrexate and steroid taper. Discussion Although rare, rheumatoid vasculitis can cause significant morbidity and complications. Rheumatoid vasculitis tends to occur in patients with so-called ‘burnt-out’ RA and strongly associated with seropositivity. While it can affect many organ systems, skin and the peripheral nervous system are most frequently affected. Cutaneous vasculitis occurs in around 90% of patients and is the most common clinical manifestation. This includes parable purpura, leg ulcers and nailfold infarcts. It may lead to digital ischaemia, necrosis and gangrene if large vessels are involved. Another common manifestation is a vasculitic neuropathy due to involvement of the vaso nervorum. Around 40% have a sensory neuropathy and 20% have a mixed sensory motor neuropathy like the index patient. Ocular manifestations such as scleritis have been described and may be the first indication of rheumatoid vasculitis. Aortitis in rheumatoid vasculitis may present with aortic insufficiency and aneurysm formation. Pericarditis has also been described as a possible disease manifestation in patients with rheumatoid vasculitis. Our patient did not have any of these clinical features and the PET-CT scan was unremarkable, which could have been due to the steroids she was on prior to the scan. Clinically, there was pulseless gangrene of the left foot with CT angiogram showing multiple stenosis suggesting large vessel involvement in the absence of conventional vascular risk factors. Renal involvement in rheumatoid vasculitis is very rare. PAN like renal involvement and glomerulonephritis has been described. Our patient did not have any haematuria or any significant proteinuria, and imaging did not reveal any renovascular aneurysms. Isolated nailfold infarcts do not require any systemic treatment. Systemic involvement with rheumatoid vasculitis requires aggressive treatment with high-dose steroids with cyclophosphamide or rituximab. Our patient had neuropathy and gangrene of the left foot, hence she was started on rituximab accordingly. Key learning points Rheumatoid vasculitis is a rare but serious complication which can present with a vasculitic neuropathy/mononeuritis multiplex. Rarely, it can cause ischemia and gangrene. If there is systemic involvement, aggressive therapy with steroids, cyclophosphamide or rituximab is needed.