Periorbital Edema Research Articles

Real-World Data on the Use of Luspatercept in Greek Patients with Transfusion Dependent Thalassemia

Introduction: The EMA/FDA-approved, erythroid maturation agent, luspatercept, has been shown to decrease transfusion burden in patients (pts) with transfusion-dependent thalassemia (TDT). Data on efficacy and safety for non-selected pts, not involved in clinical trials, are lacking. Aim: In this multicenter, retrospective cross-sectional study, real-world data from the use of luspatercept in TDT pts, managed in 9 major Thalassemia Centers in Greece are presented. Methods: Inclusion criteria included: TDT pts, having received luspatercept as per approved indications, treatment duration for at least 12 weeks. Data cut-off date was 30/06/2022. We estimated the quantity of blood (in cc of Packed Red Blood Cells -PRBC) received over 12 weeks. The following intervals were assessed post starting therapy: 1-12 weeks; 5-16 weeks; 13-24; the last 12 weeks of the observation period and 12 weeks post dose increase. The 12 weeks before starting treatment was considered as baseline. Changes in mean pre-transfusion hemoglobin (Hb), and in biochemical and other hematological parameters, were analyzed. Adverse events (AE) were recorded. Statistical analysis performed with RStudio v.3.6.2. Results: One hundred two pts (median age: 47 years range:25-67, sex: M:F/57:45) received Luspatercept every 21 days. Sixty-nine (67%) pts had transfusion burden >20 PRBC units/24 weeks, which was an exclusion criterion for the registration trial 'Believe'. Pts had variable genotypes, which included: β0/β0 (12 pts), β+/β0 (28 pts), β+/β+ (26 pts), β+/β++(11 pts), β++/β0 (10 pts), β++/β++ (1 pt), not available (14 pts). Luspatercept was administered for a median of 24 weeks (range: 12-70 weeks). The initial dose of luspatercept was 1 mg/kg and increased selectively up to 1.25 mg/kg based on tolerability and efficacy and according to guidelines. Main results of the study are shown in Table 1. A statistically significant (p<0.005) decrease in transfused PRBCs compared to baseline was observed in all 12-weeks’ intervals. There were no significant differences of transfused PRBCs between the initial interval of 1-12 weeks and neither any subsequent 12 weeks’ intervals nor the interval post dose increase. As dose increase was reserved for poor responders, the latter comparison suggests that higher doses are required in this group of pts to reach satisfactory results. There were no significant changes in mean pre-transfusion Hb compared to baseline. The percentage of pts who had a reduction in the transfusion burden of at least 33% from baseline increased with time and at the interval of 13-24 weeks was 49%. Only one pt (42years old, HBB:c.92+1G>T /HBB:c.*6C>G) became transfusion independent. A statistically significant (p<0.005) increase in uric acid and LDH was observed for the interval 1-12 weeks in comparison with baseline (mean: 5.8±1.7mg/dl vs 5.1±1.6mg/dl, 343±170mg/dl vs 232±99mg/dl, respectively). Similar difference was observed between the 13-24 weeks interval and baseline for uric acid and LDH and for the 24-36 weeks interval only for uric acid and platelets. (mean: 6.1±1.6 mg/dl vs 5.3±1.6mg/dl, 485x10^9±226x10^9/L vs 404x10^9±234x10^9/L, respectively). Fifty pts (49%) reported at least one AE. The most common AEs included: bone pain 36 pts (35.2%), fatigue 17 pts (16.7%), headache 9 pts (8.8%) and periorbital edema 7 pts (6,9%). Frequent urination, dizziness, hypertension, hyperuricemia, swelling at injection site, blurry vision, tearing, libido decrease, tachycardia, abdominal flatulence, insomnia, dyspnea were also reported. Treatment was discontinued in 36 pts (35%) after 19.3±8.1 weeks (range 12-48 weeks). Reasons for discontinuation included: no response (15 pts), adverse events (8 pts), patient's decision (6 pts), no response and adverse events (4 pts), adverse events not related to treatment (3 pts; spondylodesis, osteonecrosis of the hip during COVID19 infection and death due to COVID19 infection, respectively). Compared to the registration trial 'Believe', there were higher percentages of pts decreasing transfusion burden ≥33% but also of therapy discontinuation. Conclusions: Real world data on the use of luspatercept in TDT parallel results from the registration trial, showing heterogeneous and lasting efficacy and acceptable toxicity, despite including pts with different characteristics. Longer follow up and increased number of pts are required to validate these observations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

An Updated Analysis on Safety and Efficacy of Avapritinib in Patients with Advanced Systemic Mastocytosis from the Explorer Clinical Study: Long-Term Efficacy and Safety

Introduction: Systemic mastocytosis (SM) is a rare myeloid neoplasm driven by KIT D816V mutations in ~95% of patients. Advanced SM (AdvSM) includes three subtypes: aggressive SM (ASM), mast cell leukemia (MCL), and SM with an associated hematologic neoplasm (SM-AHN; most common), all typically with poor prognoses. Avapritinib, an oral, highly selective inhibitor of KIT D816V, is approved in the USA for treatment of adult patients with AdvSM, and in Europe after ≥1 prior systemic therapy. Avapritinib is not recommended for the treatment of patients with AdvSM with platelet counts of <50×109/L. The aim of the multi-center, international, phase 1 EXPLORER (NCT02561988) clinical study was to determine maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety, and tolerability. Earlier data from this and the phase 2 PATHFINDER (NCT03580655) studies showed rapid, deep, and durable responses to avapritinib treatment regardless of prior therapy, AdvSM subtype, or presence of high-risk mutations. Here we present long-term analyses from EXPLORER showing sustained efficacy, deepening responses, mature progression-free survival (PFS), updated overall survival (OS), and consistent safety profile. Methods: Analyses included patients aged ≥18 years with centrally confirmed AdvSM who initiated 30-400 mg once daily avapritinib. Primary endpoints were MTD and RP2D, safety, and tolerability. Secondary endpoints included overall response rate (ORR) per modified International Working Group-Myeloproliferative Neoplasms Research and Treatment-European Competence Network on Mastocytosis (mIWG-MRT-ECNM) response criteria defined as complete remission with full (CR) or partial (CRh) recovery of peripheral blood counts, partial remission, or clinical improvement, as well as changes in objective disease burden measures (bone marrow mast cell [BM MC] burden, serum tryptase, KIT D816V variant allele fraction [VAF], and spleen volume), PFS, and OS. Results: As of April 5, 2022, 69 patients with AdvSM were enrolled; 12% (n=8) had ASM, 19% (n=13) MCL, and 70% (n=48) SM-AHN. Median age (range) was 67 years (34-83), 59% were male, 30% had Eastern Cooperative Oncology Group performance status 2-3, and 59% had prior systemic therapy. Median duration of treatment (range) was 23 months (2-67); after 24 weeks most patients (69%) were receiving 100 mg or 200 mg daily. ORR (95% confidence interval [CI]) per mIWG-MRT-ECNM criteria for evaluable patients (N=57) was 77% (64-87) (Table) with ORR of 100% (40-100), 85% (55-98), and 72% (56-85), for ASM, MCL, and SM-AHN subtypes, respectively. There were 4 additional CRs (n=57) since the previous analysis of 53 evaluable patients at median follow-up of 23 months and ORR of 75%. Median duration of response (DOR) for all responders was not reached (NR). In patients with no prior therapy, median DOR (95% CI) was 38 months (22-not evaluable [NE]) and NR for patients with at least one prior therapy. Most patients had observed reductions in objective measures of disease burden including ≥50% reduction in BM MC burden (94%, n=61/69), serum tryptase (99%, n=68/69), KIT D816V VAF (75%, n=50/69), and ≥35% reduction in spleen volume (83%, n=55/69). 52 (80%) patients had total clearance of neoplastic BM MC aggregates. Median PFS (95% CI) in response-evaluable patients was 49 months (31-NE). With a median follow-up of 45 months, only 17 (25%) patients had disease progression, including 7 who progressed to acute myeloid leukemia. Median OS was NR in all AdvSM, ASM, and MCL, and was 46.9 months (95% CI 29.6-NE) in SM-AHN (Table, Figure). The most frequent treatment-related adverse events (TRAEs; any grade) were periorbital edema (64%), anemia (42%), thrombocytopenia (36%), nausea (33%), and peripheral edema (33%). Grade ≥3 TRAEs were observed in 74% of patients. There were no additional intracranial bleeding events since previous reports. Cognitive effects were experienced by 44% of patients, mostly grade 1 and 2. There was no negative impact on clinical efficacy despite 73% of patients having dose reductions or 83% having dose interruptions due to TRAEs. TRAEs led to discontinuations in 27% of patients. Conclusions: At almost 4 years of follow-up, survival benefit was ongoing with median OS not reached. Among all patients treated with avapritinib, rapid, durable responses were observed. Avapritinib was generally well tolerated with a safety profile consistent with previous reports. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy and Safety of Bosutinib Versus Imatinib in US Patients with Newly Diagnosed Chronic Myeloid Leukemia after 5-Years Follow-up in the Bfore Trial

Introduction: Bosutinib is approved for the treatment of patients with Philadelphia chromosome positive, chronic phase (CP) chronic myeloid leukemia (CML). First-line bosutinib was approved based on the results from the phase 3 BFORE trial, which showed the superior efficacy of bosutinib versus imatinib after ≥12 months of follow-up (Cortes et al., J Clin Oncol 2018). The final efficacy and safety results from BFORE after 5-years of follow-up were recently published (Brümmendorf et al., Leukemia 2022). This analysis investigated the efficacy and safety of bosutinib versus imatinib after 5-years follow-up in a subpopulation of US patients enrolled in the BFORE trial. Methods: BFORE (NCT02130557) was a global, multicenter, open-label, randomized, phase 3 study of bosutinib versus imatinib. 536 patients with newly diagnosed BCR-ABL1-positive CP-CML were randomized 1:1 to a starting dose of bosutinib or imatinib 400 mg once daily. Study treatment was continued for 5-years or until treatment failure, unacceptable toxicity, death, or withdrawal of consent. Efficacy was assessed by major molecular response (MMR) rate in the intent-to-treat population (all randomized patients). Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs) and permanent treatment discontinuation in the safety population (patients who received ≥1 dose of study treatment). This analysis is based on the final database lock: June 12, 2020, after 5-years (240 weeks). Results: The US subpopulation in BFORE comprised 88 patients (16% of randomized patients); 39 received bosutinib and 49 received imatinib. Baseline disease characteristics were well balanced between treatment arms. The median (range) duration of treatment with bosutinib and imatinib was 54.8 (0.9-58.9) months and 54.8 (1.2-56.4) months, respectively. The median (range) dose intensity with bosutinib and imatinib was 383.5 (162-562) mg/day and 400.0 (189-754) mg/day, respectively. MMR rate at 12 months was 41.0% for bosutinib versus 32.7% for imatinib (Table 1). Cumulative MMR rate by 60 months was 74.4% for bosutinib versus 63.3% for imatinib (Table 1). All patients in both treatment arms experienced at least one TEAE. In the bosutinib arm, the most common TEAEs (≥30% of patients) were diarrhea (84.6%), nausea (61.5%), fatigue (53.8%), thrombocytopenia (41.0%), headache (35.9%), rash (33.3%), increased alanine aminotransferase (ALT; 30.8%), and constipation (30.8%). In the imatinib arm, the most common TEAEs were nausea (63.3%), diarrhea (55.1%), fatigue (36.7%), periorbital edema (34.7%), and muscle spasm (30.6%). 13 (33.3%) patients in the bosutinib arm permanently discontinued treatment due to AEs, versus 7 (14.3%) in the imatinib arm. The most common causes of permanent treatment discontinuation were increased ALT (7.7%) with bosutinib and increased lipase (4.1%) with imatinib. Additional analyses of the US subpopulation are ongoing and will be presented. Conclusions: The efficacy and safety outcomes in this US subpopulation from BFORE were generally consistent with the overall study population at 5 years (Brümmendorf et al., Leukemia 2022). These results confirm the use of bosutinib as a standard of care in patients with newly diagnosed CP-CML. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Avapritinib As First-Line Therapy in Patients with Advanced Systemic Mastocytosis: Efficacy and Safety from the Pathfinder Clinical Study

Introduction: Systemic mastocytosis (SM) is a rare myeloid neoplasm driven by the KIT D816V mutation in ~95% of patients. Patients with advanced SM (AdvSM) have a poor prognosis and treatment options are limited. Avapritinib, an oral, potent, highly selective inhibitor of KIT D816V, is approved in the USA for treatment of adults with AdvSM, and in Europe after ≥1 prior systemic therapy. Avapritinib is not recommended for the treatment of patients with AdvSM with platelet counts <50×109/L. Data from the multi-center, international, phase 1 EXPLORER (NCT02561988) and phase 2 PATHFINDER (NCT03580655) clinical studies demonstrated that responses to avapritinib treatment were rapid, deep, and durable regardless of prior therapy, AdvSM subtype, or presence of high-risk mutations. Here we present analyses from patients with AdvSM treated with avapritinib as first-line therapy in PATHFINDER. Methods: Analyses included adult patients with centrally confirmed AdvSM without prior antineoplastic treatment for AdvSM (treatment-naïve) who initiated 200 mg once-daily avapritinib in the PATHFINDER study. The primary endpoint was overall response rate (ORR), centrally evaluated according to the modified International Working Group-Myeloproliferative Neoplasms Research and Treatment-European Competence Network on Mastocytosis (mIWG-MRT-ECNM) response criteria defined as complete remission with full (CR) or partial (CRh) recovery of peripheral blood counts, partial remission (PR), or clinical improvement (CI). Secondary endpoints included, but were not limited to, mean change from baseline measures of disease burden (bone marrow mast cell [BM MC] burden, serum tryptase, blood KIT D816V variant allele fraction [VAF], and spleen volume), duration of response (DOR), time to response (TTR), overall survival (OS) and safety. Results: As of April 20, 2021, 107 patients with centrally confirmed AdvSM were enrolled, of whom 38 were treatment-naïve; 18% (n=7/38) had ASM, 74% (n=28/38) SM-AHN, and 8% (n=3/38) MCL. Median age (range) was 68 years (39-88), 53% were male, 16% had Eastern Cooperative Oncology Group performance status 2-3, and 95% exhibited KIT D816V. In 25 of 38 (66%) mIWG-MRT-ECNM response-evaluable patients, the ORR (95% CI) was 84% (n=21/25; 64-96) with 32% (n=8/25) achieving CR or CRh, 48% (n=12/25) achieving PR, and 4% (n=1/25) CI (Table). The median TTR (range) was 2.0 months (0.3-12.2). Median DOR across all subtypes was not reached at the time of analysis; however, the DOR rate (95% CI) was 100% (100-100) at 12 months and 86% (60-100) at 18 months. For patients with ASM, the DOR rate was 100% (100-100) at 12 and 18 months. In patients with SM-AHN, the DOR rate was 100% (100-100) at 12 months and 83.3% (53.5-100) at 18 months. After a median follow-up of 9.7 months, median OS in all patients was not reached. The OS rate was 96% (95% CI: 87-100) at 12 months and 88% (95% CI: 71-100) at 24 months. The OS rate at 12 months was 100% for patients with ASM or MCL and 94% (84-100) for patients with SM-AHN. At 24 months, OS rate was 86% (67-100) for patients with SM-AHN. In almost all patients, reductions of ≥50% in measures of disease burden including reduction in BM MC burden (84%, n=32/38), serum tryptase (95%, n=36/38), KIT D816V VAF (89%, n=34/38), and ≥35% reduction in spleen volume (66%, n=25/38) were observed. Total clearance of neoplastic MC aggregates in BM was achieved in 63% of patients (n=24/38). The most frequent (≥25% of N=38) treatment-related adverse events (TRAEs) were (any grade, grade ≥3) periorbital edema (53%, 5%), thrombocytopenia (45%, 21%), peripheral edema (37%, 3%), and anemia (26%, 13%). In total, 7 (18%) patients experienced cognitive effects, all grade 1 or 2; no intracranial bleeding events and no treatment-related deaths were reported. 28 (74%) patients had dose reductions and 25 (66%) had dose interruptions due to TRAEs. Thrombocytopenia was the most common TRAE leading to dose reduction (21%, n=8/38) and dose interruption (26%, n=10/38). 4 (10%) patients discontinued treatment due to TRAEs; 1 discontinuation each was due to neutropenia, thrombocytopenia, cognitive effects, and worsening weight loss. Conclusions: Avapritinib demonstrated a high level of efficacy as the first-line therapy for patients with AdvSM across all disease subtypes with an ORR of 84% and an OS rate of 88% at 2 years. Avapritinib treatment with a 200 mg once-daily starting dose was generally well-tolerated. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Minimal Change Disease Secondary to Either COVID-19 Infection or Pfizer-BioNTech COVID-19 Vaccination

Abstract Introduction/Objective Kidney injury has now become one of the known complications following COVID-19 infection and vaccination. Only few cases of minimal change disease following administration of COVID-19 vaccination and infection have been reported. This study was to highlight incidence of minimal change disease following COVID-19 infection or vaccination. Methods/Case Report Case 1:15 year-old female with past medical history of asthma and hypercholesterolemia presented for evaluation of periorbital edema, nephrotic-range proteinuria, hypoalbuminemia, elevated serum creatinine, elevated blood pressures, and hematuria after COVID-19 infection. Renal biopsy after 1 week of infection showed unremarkable glomeruli and negative immunofluorescent stains in glomeruli, and 20-30% fusion of foot processes. The biopsy was consistent with a minimal change disease with features of natural remission (her nephrotic-range proteinuria resolved soon after). Case 2: 18 year-old female with no significant past medical history presented with a chief complaint of generalized swelling, which started around the same time she received her 1st dose of Pfizer COVID vaccine (the 2nd dose 2 months later). She had a nephrotic range proteinuria and hypoalbuminemia, but normal level of serum creatinine. A renal biopsy after 4 months of vaccination showed unremarkable glomeruli by light microscopy, negative immunofluorescent study, but diffuse effacement of foot processes involving more than 80% of the examined loops by electron microscopy. This biopsy findings were consistent with a minimal change disease. Both patients did not receive any treatment before the renal biopsies. Results (if a Case Study enter NA) NA Conclusion Minimal change disease can be a rare complication following COVID-19 infection or Pfizer COVID-19 vaccination, raising a question if there are similar antigens induced by the infection or by the vaccination that trigger the minimal change disease. Further studies are needed to determine the incidence and pathophysiology of minimal change disease either post COVID-19 vaccines or following COVID-19 infections.

Streptococcus pneumoniae meningitis in a child with idiopathic nephrotic syndrome: a case report

BackgroundChildren with nephrotic syndrome are at increased risk of infections, including bacterial peritonitis, pneumonia, and cellulitis. However, bacterial meningitis, a potentially life-threatening complication, has not been highlighted as an infectious complication of nephrotic syndrome in recent reviews. We report a very subtle and unusual presentation of bacterial meningitis in a child with nephrotic syndrome, which without a high index of suspicion, would have been missed.Case presentationA 9-year-old African-American male with a history of steroid-dependent nephrotic syndrome presented to the nephrology clinic for routine follow-up. His medications included mycophenolate mofetil and alternate-day steroids. His only complaint was neck pain and stiffness that the mother attributed to muscle tightness relieved by massage. There was no history of fever, vomiting, headache, photophobia, or altered mental status. On physical examination, he was afebrile (99 °F), but had mild periorbital swelling and edema on lower extremities. He appeared ill and exhibited neck rigidity, and demonstrated reflex knee flexion when the neck was bent. Laboratory evaluation revealed leukocytosis, elevated C-reactive protein, hypoalbuminemia, and proteinuria. Cerebrospinal fluid suggested bacterial meningitis. The patient was treated with ceftriaxone and vancomycin. Both cerebrospinal and blood cultures grew Streptococcus pneumoniae; vancomycin was discontinued. The child completed a 2-week course of ceftriaxone and was discharged home.ConclusionsA high index of suspicion is necessary in children with nephrotic syndrome treated with corticosteroids, as symptoms may be masked, and thus, a life-threatening disease be missed. Bacterial meningitis should be highlighted as a serious infection complication in children with nephrotic syndrome.

RF35 | PSAT299 Thyroid Eye Disease Activation After mRNA SARS-CoV-2 Vaccination in Patients With Autoimmune Thyroid Disease

Abstract Background Occurrence of Graves’ disease (GD) has been reported following SARS-CoV-2 vaccine administration, but little is known about thyroid eye disease (TED) after SARS-CoV-2 vaccination. Case 1 A 50-year-old non-smoker male was diagnosed with GD in March 2019 and treated with methimazole. In April 2020, he developed TED with bilateral proptosis, pain, erythema and diplopia and clinical activity score (CAS) 6/7. Following poor response to 3-month oral steroids, he underwent total thyroidectomy in November 2020. In six weeks, his TED improved (CAS 4/7) and thyroid stimulated immunoglobulin (TSI) levels normalized from 4.13 IU/l (preoperatively) to 0.70 IU/l (reference&amp;lt; 1.75 IU/l). In January 2021, he received 2 doses of the mRNA BNT162b2-SARS-CoV-2 vaccine (Pfizer-BioNTech). Three weeks after the second dose, TED deteriorated significantly with severe eye pain, lid swelling, conjunctival erythema, and worsening proptosis and diplopia (CAS 6/7). TSI levels rose to 4.45 IU/l, while patient was euthyroid on levothyroxine (TSH 2.3 mIU/l). He received 12 weekly methylprednisolone infusions (cumulative dose of 4.5 g) with limited response. He was then treated with three monthly cycles of intravenous tocilizumab with partial response (CAS 5/7). Case 2 A 71-year-old non-smoker female had a 40-year history of hypothyroidism, controlled on levothyroxine. In March 2021, three days after her second dose of the mRNA-1273 SARS-CoV-2 vaccine (Moderna), she developed bilateral eye swelling and burning. She initially received anti-histamines and steroid eye drops without improvement. By August 2021, her eyes further deteriorated with eye pain, redness, lid edema and erythema, diplopia, and worsening proptosis (CAS 4/7). She also experienced 20 Ib weight loss, palpitations, tremors, and heat intolerance. TSI index was 5.5 (reference ≤1.3), TSH was undetectable, and FT4 1.4 ng/dl (reference 0.93-1.70 ng/dl). Levothyroxine was discontinued. Two weeks later she was admitted to the hospital with loss of color vision and decreased visual acuity in the right eye. She received 2 daily doses of 1 g intravenous methylprednisolone and intravenous teprotumumab on hospital day 3. She responded well to teprotumumab infusions every 3 weeks, with return of color vision and improvement of proptosis and periorbital edema (CAS 1/7). Discussion Activation of TED has so far only been described in four patients following SARS-CoV-2 vaccination. Here we report two more cases: one of TED deterioration in a GD patient with prior TED, and one of de novo TED progressing to dysthyroid optic neuropathy in a patient with a long history of Hashimoto's hypothyroidism. Possible etiologies include a maladaptive autoimmune/inflammatory syndrome from polyclonal B cell stimulation by adjuvants or activation of preexisting autoimmune disease. The possibility of new onset or deterioration of TED after SARS-CoV-2 vaccination in patients with underlying autoimmune thyroid disease and its mechanism should be further studied. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:18 p.m. - 1:23 p.m.

TO CHALLENGE OR AVOID? POSSIBLE ASPIRIN ALLERGY IN PATIENTS WITH CHRONIC IDIOPATHIC URTICARIA AND ANGIOEDEMA

<h3>Introduction</h3> Aspirin remains an important component of dual antiplatelet therapy following percutaneous coronary intervention (PCI). Despite studies showing safety in discontinuing aspirin post PCI through use of P2Y12 inhibitor therapy plus anticoagulation, no large, randomized trials evaluate an initial aspirin-free regimen post PCI without systemic anticoagulation. Aspirin intolerances occur in 20% of patients, with only 2% being true allergies. Most aspirin intolerances are linked to asthma, rhinitis, and chronic idiopathic urticaria (CIU). Differentiating this population is important for optimizing care. <h3>Case Description</h3> C.P. is a 54-year-old male with CIU referred for evaluation of aspirin allergy prior to coronary angiography with possible PCI. In 2001, C.P. developed right periorbital edema an hour after his third dose of daily aspirin therapy. Antihistamines reduced the swelling within hours, however due to reaction, his physician recommended discontinuing aspirin. He noted taking aspirin as a child and ibuprofen as an adult without incident. An in-clinic open oral drug challenge to aspirin was conducted. The patient was given 1/10^th of the full dose, followed by the remaining dose then monitored for 1 hour. The patient was diagnosed with NSAID exacerbated CIU and discharged with aspirin and antihistamines for control. <h3>Discussion</h3> Without clear guidelines for managing NSAID induced CIU, many physicians recommend avoidance, resulting in suboptimal care. 20-40% of CIU patients have flares triggered by NSAIDs, and many are misdiagnosed with an aspirin allergy. Our case demonstrates that through careful history and oral challenge, aspirin exacerbated CIU can be effectively managed without forgoing quality care.

BIPHASIC ALLERGY TO ACETAMINOPHEN: AN ADDITIONAL APPEARANCE IN THE POST-DELIVERY POPULATION

<h3>Introduction</h3> Acetaminophen is a widely used medicine with analgesic and antipyretic effects. Acetaminophen allergy is rare and biphasic reactions to it (within 72 hrs) are even less common. <h3>Case Description</h3> A 31 year-old female, with suspected allergy to acetaminophen presented with palmar pruritus, periorbital swelling and nasal congestion for allergy assessment. A drug provocation challenge (DPC) to acetaminophen was carried out for confirmation. An initial dose of 60 mg led to swelling of her lower lip and itching of her lips followed by right eyebrow swelling. Her blood pressure (BP) was stable at 119/82 mm[Hg]. She was confirmed as having an acetaminophen-induced allergic reaction and treated with rupatadine at 10 mg and recovered. That night, approximately 12 hours post-DPC, the patient awoke to feed her infant and experienced two consecutive syncopal episodes, followed by a rash and fever. There was no re-exposure to acetaminophen. Ambulance emergency services treated her with diphenhydramine and ER transport. There the patient was identified with a full-body rash and BP of 108/77 mm[Hg]. After a monitoring period of 4 hours, the patient was discharged home with a diagnosis of a biphasic allergic reaction to acetaminophen. <h3>Discussion</h3> This case illustrates a biphasic reaction to acetaminophen initially presenting post-delivery, a rare occurrence, in a patient previously tolerant to acetaminophen. In clinics choosing to test acetaminophen allergy, patients that fail oral challenge should be provided a care plan and education on how to treat any delayed reactions that may appear without allergen re-exposure.

TRAUMATIC “ANGIOEDEMA”: EXTENSIVE SUBCUTANEOUS EMPHYSEMA MASQUERADING AS ANGIOEDEMA

<h3>Introduction</h3> COVID 19 pandemic related precautions have resulted in suboptimal physical examination of the patients which may have affected the patient care and training of medical professionals. We present a case of a patient whose subcutaneous emphysema was misdiagnosed as angioedema. <h3>Case Description</h3> 25 years old female with cerebral palsy and developmental delay presented to hospital in June, 2020 with asymmetric left facial and periorbital swelling which developed an hour after her regular Depo-Provera injection. She had elevated blood pressure readings with tachycardia without hives, respiratory or gastrointestinal symptoms. Facial swelling did not improve after IM epinephrine, IV steroids and antihistamines. Flexible laryngoscopy noted mild edema of lingual surface of the epiglottis. Allergy service was consulted to evaluate for drug-induced anaphylaxis. Our physical examination revealed significant asymmetric periorbital edema, neck and chest swelling with distant breath sounds and distinct palpable crepitus. Serum Trytpase and C1-Estrase inhibitor levels were normal at 3.2ug/L and 28 mg/dl, respectively. Emergent imaging was recommended, which demonstrated multiple rib fractures, pneumomediastinum with extensive chest wall subcutaneous emphysema tracking to extra-cranial soft tissue. Patient was intubated and chest tube was placed due to concerns for airway compromise. She stayed in ICU for one week before being discharged to home. <h3>Discussion</h3> Facial edema, concerning for angioedema, is potentially life threatening condition and an allergic reaction should be higher on the differential diagnoses. Our case represents a learning opportunity regarding other potentially life threatening conditions that can mimic angioedema, requiring higher index of clinical suspicion and thorough physical examination.

ODP655 Apathetic Hyperthyroidism

Abstract Introduction Apathetic hyperthyroidism is a rare presentation of hyperthyroidism described in the elderly population. It is insidious in onset and symptoms are depression, lethargy, and weight loss. The adrenergic symptoms of hyperthyroidism are often absent. Furthermore, orbital disease associated apathetic hyperthyroidism has not been reported widely in literature. We present a clinical scenario of apathetic hyperthyroidism associated with orbitopathy. A 64-year-old lady presented with acute onset bilateral periorbital swelling that developed over 2 days. About 3 weeks prior, she began experiencing symptoms of brain fog, lethargy, intermittent nausea, anorexia, and headache. She experienced palpitations with exertion. Review of other systems was negative. Clinical exam: HR 70. Thyroid gland was enlarged, symmetric with no nodules and nontender, bilateral periorbital puffiness and mild conjunctival redness was noted. Lab data was significant for TSH at 0. 03 uIU/mL, elevated FT4 2.5ng/dL, total T3 of 222ng/dL, TSI 4.2 and sed rate of 10. Her thyroid ultrasound indicated hypervascular and heterogenous gland. Our patient was diagnosed with apathetic hyperthyroidism and thyroid eye disease. She was started on propranolol 60mg ER one tablet a day and methimazole 10mg a day. CT scan of the orbit indicated symmetric enlargement of extraocular muscles. Evaluation by the ophthalmologist confirmed the presence of thyroid eye disease with a clinical activity score of 6 out of 7 indicating severe thyroid eye disease and she was a candidate for treatment with teprotumumab. Discussion Apathetic hyperthyroidism was first described by Lahey in 1931, as a state of non-activated hyperthyroidism. It is manifested with gradual onset of apathy, depressed mood, lethargy, nausea, lack of appetite, weight loss, proximal muscle weakness, goiter, atrial fibrillation, and congestive heart failure. It lacks the typical presentation of a hyperadrenergic state of hyperthyroidism which include palpitations, anxiety, tremor, heat intolerance, and diaphoresis. Due to the lack of typical presentation of hyperthyroidism, timely diagnosis and treatment may be challenging. Concomitant occurrence of occult malignancy and hyperglycemia have been reported in case reports. Patients can also transition from apathetic state to hyperadrenergic state of hyperthyroidism and vice versa. Lahey emphasized the risk of unexpected death following surgery in apathetic hyperthyroidism. The absence of adrenergic symptoms could be supported by the theory that these patients are in a relative state of catecholamine deficiency or have a state of end organ catecholamine resistance. Significant orbital involvement in apathetic hyperthyroidism is not widely reported in the literature. Blepharoptosis has been mentioned in association with this form of hyperthyroidism. Our patient presented with acute onset eye symptoms which prompted testing of thyroid function. Further review of symptoms led to a diagnosis of apathetic hyperthyroidism with thyroid eye disease.

PSAT341 Hashimoto's Thyroiditis After Allogenic Bone Marrow Transplantation

Abstract Introduction Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is a common autoimmune-mediated thyroid disease triggered by an inappropriate T and B cells response. We present a case of a female without personal or family history of autoimmune disease, who developed Hashimoto's thyroiditis with severe hypothyroidism after undergoing bone marrow transplant (BMT). Clinical Case A 57-year-old woman with hypoplastic myelodysplastic syndrome (MDS) was initially started on immunosuppressive therapy, complicated by autoimmune hemolytic anemia and thrombocytopenia. Three years after diagnosis, she underwent allogenic BMT from a matched unrelated donor. A year later, she presented with weight gain, fatigue, cold intolerance, insomnia, eye puffiness and lower extremity weakness, developed over a month. Exam was notable for periorbital edema and delayed DTRs. Laboratory workup revealed an elevated TSH at 302 µIU/mL (0.27-4.2) with undetectable free T4 and total T4 levels and elevated anti-thyroglobulin antibodies of 2698 IU/mL (0-40) and antiTPO antibodies of 90 IU/mL (0-35). Cortisol was normal at 14 µg/dL. TSH was normal prior to the BMT. Thyroid ultrasound revealed a normal-sized thyroid with a slightly heterogeneous echotexture, suggestive of thyroiditis without distinct nodules. Myxedema coma was ruled out at the time of diagnosis. The patient was started on levothyroxine and noticed a significant improvement of her symptoms within few weeks. Our patient does not have a personal or family history of thyroid disease or other autoimmune disorders. She did not receive radiation treatment or steroid treatment prior to her hypothyroidism diagnosis. She had an RSV upper respiratory infection two months prior to the diagnosis of hypothyroidism without associated neck pain. The clinical and biochemical picture suggest that her hypothyroidism could be related to her allogenic BMT. The presumed mechanism for the autoimmune thyroid dysfunction noted in this patient is the transfer of autoantibodies and donor lymphocytes during BMT. Conclusion Adoptive autoimmune hypothyroidism can occur post-BMT, especially if the donor has genetic susceptibility. It is now accepted that autoimmune thyroiditis can be transferred from donors to recipients during BMT. Reference Buxbaum NP, Pavletic SZ. Autoimmunity Following Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol. 2020 Aug 25;11: 2017. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

LIMITED CUTANEOUS SYSTEMIC SCLEROSIS MIMICKING HEREDITARY ANGIOEDEMA WITH NORMAL C1 INHIBITOR

<h3>Introduction</h3> Hereditary angioedema with normal C1 inhibitor (HAE-nl-C1INH) is often diagnosed when patients with antihistamine-resistant angioedema respond to bradykinin-targeted therapies. We present a patient with limited cutaneous scleroderma initially diagnosed as HAE-nl-C1INH, with variable response to HAE therapy. <h3>Case Description</h3> 56-year-old woman with hypertension presented with recurrent periorbital swelling while on ACE inhibitor therapy. After discontinuation, she continued to have episodes of angioedema for two months, responsive to recombinant C1 inhibitor therapy. Initial workup included normal C1 esterase inhibitor antigen and function, C4, C1q, SPEP, tryptase, and thyroid studies. After a six-month symptom-free period, angioedema recurred in the setting of stressful life events, viral infection, and antihypertensive medication changes. When on-demand therapy with recombinant C1 esterase inhibitor was observed to provide insufficient control, she started lanadelumab prophylaxis which stabilized her symptoms. She then developed episodic fluid retention with daily joint and subcutaneous swelling involving the hands, abdomen, and lower extremities coincident with additional changes to her antihypertensive regimen. Discontinuation of suspected culprit medications did not resolve the progression of her symptoms. Evaluation by rheumatology for joint symptoms and persistent hand swelling led to the diagnosis of limited cutaneous systemic sclerosis (scleroderma). Angioedema symptoms resolved after starting mycophenolate mofetil and she no longer required HAE therapy. <h3>Discussion</h3> Our case highlights the complicated and nuanced nature of diagnosing HAE-nl-C1INH, particularly in patients with partial response to HAE therapy. Limited cutaneous scleroderma either mimicked or triggered angioedema in our patient. Her partial response to C1 inhibitor infusions and lanadelumab may have represented off-target effects of HAE therapy.

ODP533 Graves’ Ophthalmopathy in the Setting of Primary Hypothyroidism

Abstract Background Graves’ ophthalmopathy (GO) is commonly associated with hyperthyroidism secondary to Graves’ disease (GD). Although rare, there have been case reports of it occurring in patients who are hypothyroid with underlying Hashimoto's thyroiditis (HT), as well as in euthyroid patients. It is thought that the mechanism behind developing GO in these patients is due to the presence of stimulating thyrotropin receptor antibodies (TRAB). Below we describe a case of GO developing in a patient who has hypothyroidism secondary to HT. Clinical Case A 53 years-old female non-smoker, known to have primary hypothyroidism (Hashimoto's thyroiditis) diagnosed at the age of 39 years, on levothyroxine 75 mcg/day. Presented to our endocrine clinic complaining of diplopia and periorbital swelling for the past 5 months. The diplopia occurs on left gaze while both eyes are open, it resolves with closure of either eye. No history of ocular surgeries, injections, or trauma. No previous hyperthyroid state or radioactive iodine therapy. On physical examination there was no goiter, bruit, palpable lymphadenopathy, tremor, or pretibial myxedema. Ophthalmic examination showed left sided upper and lower eyelid swelling, limited abduction with diplopia and mild punctate keratopathy. Laboratory investigation revealed TSH 3.6 mIU/L (0.250 - 5), T4 14.6 pmol/L (11.5 - 22.7), positive thyroid peroxidase antibody 173.9 units (&amp;gt; 100 units positive) and positive thyroid stimulating immunoglobulin 500IU/ml (Normal &amp;lt; 140). On ultrasound the thyroid gland was small and heterogeneous. MRI orbits demonstrated bilateral ocular proptosis with intraocular muscles enlargement particularly the medial, inferior, superior rectus as well as the levator palpebrae superioris muscles. Our impression was active moderate-severe isolated GO with aBackground of HT, clinically and biochemically euthyroid on levothyroxine. The patient was referred to an ophthalmologist and was started on a course of high dose oral prednisone tapered over 3 months. She reported a 50% improvement in her symptoms after the first month of therapy. Patient was then started and maintained on selenium 100 mcg oral twice daily with lubricating eyedrops. During her last clinic visit she had stable thyroid eye disease and there was no need for further medical or surgical intervention. Conclusion GO can occur in patients with HT due to the development of stimulating TRAB targeting thyrotropin receptors expressed on orbital fibroblasts. The incidence varies between studies from 2-7.5%. Awareness of this clinical presentation is important, as early detection and treatment can prevent visual complications. To date there are no clear guidelines on how to treat GO with underlying HT. Treating our patient with high dose steroids extrapolated from treating GO secondary to GD showed significant improvement in her symptoms. Presentation: No date and time listed

Filler-based correction of tear trough depressions and eye bags in Japanese patients: A classification system and treatment algorithm.

Tear trough depressions are widely treated with fillers. However, it is questionable whether the same strategies can always be used for Caucasian and Japanese patients, owing to differences in bone and skin structures and epithelial thickness. To assess a novel classification system and treatment algorithm for correcting tear trough depressions and eye bags in Japanese patients. Tear trough depressions can be classified into three types according to the presence or absence of a "negative vector" based on retrusion of the maxilla relative to the anterior corneal surface, with or without eye-bag protrusion when smiling. Type 1 patients (without the negative vector) can be treated simply by filling the depression in the tear trough and the palpebromalar groove region. Type 2 patients (with a negative vector and no eye-bag protrusion on smiling) also require volume restoration in the mid-cheek (deep medial cheek fat, suborbicularis oculi fat, and pre-maxillary space); this not only enables volume recovery but also compensates for maxillary deficiency. Type 3 patients (with a negative vector and eye-bag protrusion on smiling) require an additional step, based on placing a filler in front of the eye bags and pushing orbital fat backward. Case presentations demonstrate the utility of the techniques involved. This system provides a simple and practical method for classifying and treating Japanese patients with tear trough depressions and eye bags. Further studies are warranted.

Sarcoidosis of the Extra-Ocular Muscles: Case Report

Sarcoidosis is one of the leading causes of inflammatory eye disease. Patients with ocular sarcoidosis can present with a wide range of clinical presentations and severity. This case demonstrates an unusual presentation of unilateral infiltration of the extra-ocular muscles, sparing the uveal tissues and lacrimal glands. This case highlights the importance of screening for ocular involvement in sarcoidosis, and to consider sarcoidosis in the differential for peri-orbital swelling and diplopia.

Limited eye movement caused by clumping of fibrin glue used in blowout fracture surgery: a care report

Fibrin glue is a topical agent widely used for hemostasis, wound healing, and surgical adhesion. Complications of fibrin glue itself are extremely rare because it is absorbed over time, but can occur as a result of inappropriate application. We report a case of a postoperative complication caused by inappropriate application of fibrin glue in blow-out fracture surgery. A 65-year-old male patient presented with periorbital swelling and an open wound on the right infraorbital area. Computed tomography showed a right orbital floor fracture. After reduction of the herniated tissue into the orbit, an implant was inserted and fibrin glue was applied to stabilize the implant. This procedure was performed without difficulty, but the patient complained of persistent diplopia and limited eyeball movement after surgery. An imaging study showed a mass-like lesion, which was not a hematoma, in the orbital cavity. In a second operation, the mass was identified as clotted fibrin glue that had not been applied properly. After removal, the patient's symptoms were relieved without further complications. Appropriate and careful application of fibrin glue is necessary to avoid unnecessary complications.

Subtle periorbital edema and hyperkeratotic papules in a woman of color

Case summary A 65-year-old African-American female presented to the dermatology clinic complaining of poorly controlled melasma over the past year. Physical examination incidentally revealed bilateral violaceous periorbital erythema and edema, accentuated on the left eye, patchy gray to violaceous pigmented patches on forehead and glabella, and flat-topped, hyperkeratotic papules overlying the metacarpophalangeal and proximal interphalangeal joints (Fig. 1). Upon further inspection with capillaroscopy, periungual, dilated, looped telangiectasias were evident (Fig. 2). The patient denied proximal muscle weakness, fatigue, weight loss, shortness of breath, chest pain, or dyspnea on exertion. A punch biopsy above the left metacarpophalangeal joint was taken revealing perivascular lymphocytic infiltrate with epidermal hyperplasia, acanthosis, slight increase of papillary dermal mucin, and mild vacuolar interface at the dermoepidermal junction. Direct immunofluorescence revealed C5b-9 and weak IgM and C3 deposition with cytoid bodies along the epidermal basement membrane.Fig. 1.: Flat-topped, hyperkeratotic papules overlying the metacarpophalangeal and proximal interphalangeal joints.Fig. 2.: Periungual, dilated, looped telangiectasias.Question 1 What is the correct diagnosis? A. Psoriasis B. Lichen planus pigmentosus C. Dermatomyositis D. Scleroderma E. Systemic lupus erythematosus Correct answer: C. Dermatomyositis Discussion Dermatomyositis is a rare idiopathic inflammatory myopathy with classic cutaneous characteristics. Dermatomyositis typically presents with a symmetric dusky erythematous to violaceous heliotrope rash with mild scaling and desquamation. The characteristic hand findings, termed Gottron’s papules, consist of erythematous to violaceous papules and plaques, distributed over the bony prominences. Several other non-pathognomonic cutaneous findings may be present, including malar rash, poikiloderma in a photosensitive distribution, periungual and cuticular changes, and alopecia.1 Most patients will also report proximal muscle weakness, but cutaneous findings without myopathy are possible - a process termed “amyopathic” dermatomyositis. In such a case, repeat testing for myopathy may be warranted in the future, as cutaneous symptoms may precede muscle inflammation by up to 2 years.1 When assessing a patient with suspected dermatomyositis, providers should test for proximal muscle weakness and draw labs for markers of muscle inflammation. The diagnosis can be confirmed with a muscle biopsy demonstrating perivascular lymphocytic inflammation in the perimysium and electromyography (EMG), which may show membrane irritability, fibrillary potentials, and decreased action potential amplitude.1 Skin biopsies are not routinely used in diagnosis, as findings resemble those seen in lupus erythematosus, but may be an important clue in the case of amyopathic dermatomyositis.1 In our case, creatine phosphokinase, troponins, and muscle strength testing were all negative. Muscle biopsy was not performed due to lack of indication from laboratory and clinical testing; however, the classic cutaneous findings and skin biopsy are consistent with a diagnosis of amyopathic dermatomyositis. The mainstay of treatment for dermatomyositis consists of immunosuppression, often with prednisone, either as monotherapy, or combined with another agent.1 Muscle inflammation is typically more responsive to treatment than skin manifestations, which may take longer to resolve. Treatment for amyopathic dermatomyositis includes topical corticosteroids, topical tacrolimus, hydroxychloroquine, low-dose methotrexate, and strict sun protection and avoidance of UV light, most notably UVA.1 Our patient was started on systemic corticosteroids and underwent extensive screening to evaluate for the possibility of solid organ malignancy, with no malignancies identified. She will continue to receive age-appropriate screening, as the risk of malignancy is highest in the first year of diagnosis, but remains elevated for up to 3 years after symptom onset.2 The patient is currently well-controlled on hydroxychloroquine 200 mg BID, prednisone 10 mg daily, and strict photoprotection. This case was selected to increase awareness among medical practitioners, highlighting how dermatomyositis can subtly present in patients with skin of color. With a female-predominant condition such as dermatomyositis, where coexisting malignancy is identified in 20–25% of cases,2 prompt identification, diagnosis, and referral for cancer screening is paramount, and practitioners should be confident in diagnosing this condition in patients of all skin types. Question 2 What autoantibodies are most frequently associated with dermatomyositis? A. Anti-Mi-2 B. Anti-SSA C. Anti-Jo-1 D. Anti-Ro E. ANA Correct answer: A. Anti-Mi-2 antibodies are most frequently associated with the classic cutaneous features of DM and correlate to a lower risk of interstitial lung disease and malignancy compared to other autoantibodies in DM.3 Anti-Jo-1 are most common in antisynthetase syndrome, now recognized as a distinct entity from other subgroups of myositis and are strongly associated with the development of interstitial lung disease.3 ANA antibodies are found in 60-90% of dermatomyositis patients but are nonspecific and present in numerous autoimmune conditions.1 Conflicts of interest None. Funding None. Author contributions Sara Asbeck contributed to the performance of the research and writing of the manuscript. Brittany Smirnov contributed to the performance of the research and review of the manuscript.

Angioedema mimicking nephrotic syndrome.: A case report

Abstract&#x0D; Nephrotic syndrome is characterized by diffuse edema, massive proteinuria and hypoalbuminemia. It usually occurs between the ages of 2-6. Due to periorbital edema these patients are mistakenly diagnosed with allergic disease. A 4-year-old 9-month-old male patient, who had no known disease under follow-up, was admitted to the pediatric surgery service due to bilateral hydrocele and inguinal hernia, was planned to be operated on, and bilateral swelling in his eyes was noticed in the preoperative evaluation, was consulted to the pediatric immunology-allergy department. His general condition was good, his skin turgor was normal, his eyelids were edematous. There was bilateral pretibial pitting edema and bilateral transluminated swelling in the scrotum. In laboratory examination: Albumin: 1.6g/dl, Sedimentation:76 mm/hr, C3:1.23 mg/dl, and C4: 0.24 mg/dl. In urine: density: 1051, protein: +++, protein/creatinine was 17.8 mg/mg. Both nephrotic syndrome and angioedema cause severe edema of the eyelids and genital area. Therefore, laboratory tests, clinical findings and careful examination are sufficient for differential diagnosis. In our study, we aimed to present a case of nephrotic syndrome with a prediagnosis of allergic angioedema.

BILATERAL PNEUMOTHORAX, PNEUMOMEDIASTINUM, AND SUBCUTANEOUS EMPHYSEMA: A CASE OF A RARE SYNCHRONOUS TRIAD IN ASTHMA EXACERBATION

BILATERAL PNEUMOTHORAX, PNEUMOMEDIASTINUM, AND SUBCUTANEOUS EMPHYSEMA: A CASE OF A RARE SYNCHRONOUS TRIAD IN ASTHMA EXACERBATION