High-dose Prednisone Research Articles

P1197 Progression to colorectal cancer or high-grade dysplasia in individuals with inflammatory bowel disease and low-grade dysplasia: A cohort study of risk factors and incidence

Abstract Background Individuals with inflammatory bowel disease (IBD) face an increased risk for colorectal cancer (CRC) and high grade dysplasia (HGD) compared with individuals without IBD.1,2 Low-grade dysplasia (LGD) is recognized as a key risk factor for HGD and CRC development in IBD.3 However, the risk for progression from LGD to HGD or CRC is still debated. Studies report diverging results and are often limited by small sample sizes and selection bias.4 The influence of diagnosis-year and medications is particularly underexplored. Therefore, we sought to utilize the Danish healthcare registers to examine the impact of candidate risk factors for progression from LGD to either HGD or CRC among Danish individuals with IBD. Methods We conducted a cohort study, including all Danish individuals diagnosed with IBD and LGD between 1977 and 2022. IBD with LGD was defined as individuals with a LGD diagnosis up to 180 days before or any time after their first IBD diagnosis, using the latest date as index date. Individuals with a colectomy, HGD, or CRC before the index date were excluded. We investigated the cumulative incidence of progression to HGD or CRC, treating death as a competing risk. A univariate Cox regression model was used to assess hazard ratios (HRs) for potential risk factors. Variables with a P-value of ≤ 0.1 were included in the final multivariable cox regression model. Results We included 7,082 individuals with IBD and LGD for further analysis. As illustrated in figure 1 the cumulative incidence of progression from LGD to HGD or CRC at 15 years post-index was 6.70% (95% CI: 5.93–7.54). Several risk factors were identified (table 1). Of particular interest was the influence of index-year and treatment with prednisone and anti-TNF-α. In the final model, we observed a reduction in progression risk over time, with a decreased risk for progression in the period 2018-2021 (HR: 0.32 [95% CI: 0.21-0.50]) and 2015-2018 (HR: 0.53 [95% CI: 0.34-0.69]) relative to 1977-2010. High-dose prednisone treatment was associated with progression to HDG or CRC (HR: 1.77 [95% CI: 1.23-2.57]), whereas anti-TNF-α treatment was not (HR: 0.81 [95% CI:0.38–1.74]). Conclusion Among Danish individuals with IBD the risk of progression from LGD to HGD or CRC declined over time. Treatment with High-dose prednisone was associated with an increased risk of progression, whereas anti-TNF-α treatment was not. We speculate that recent advancements in biological treatments of IBD, the implementation of 'treat-to-target' strategies, and improved detection and resection of LGD lesions, may partly explain declining progression risk.

P43 Unmasking posterior reversible encephalopathy syndrome: a hidden threat in juvenile lupus

Abstract Introduction Posterior reversible encephalopathy syndrome (PRES) is a neurological condition identifiable through clinical presentation and magnetic resonance imaging (MRI). While PRES has been rarely documented in children as a complication of juvenile lupus, it remains a potentially reversible condition. However, it can be complicated by vasculopathy, infarction, or haemorrhage. The pathogenesis of PRES is still unclear. In juvenile lupus, the risk factors for PRES are multifaceted and interact with each other, including vasculitis, lupus nephritis, chronic kidney disease (CKD) leading to renal-origin hypertension, and iatrogenic hypertension caused by several hypertension-inducing drugs commonly used as first-line treatments for lupus. Case description A 14-year-old girl diagnosed with lupus presented with persistent fatigue, lower limb oedema, and abdominal symptoms (vomiting and diarrhoea). She experienced two episodes of PRES, three months apart. Active SLE was confirmed through clinical and laboratory findings, including positive autoimmune and serologic results for ENA antibody screen, high levels of anti-double-stranded DNA (>400), and low complements C3 (0.15 g/L) and C4 (<0.03 g/L). Urine analysis revealed 2+ RBCs, 3+ proteins, and an estimated glomerular filtration rate (eGFR) of ∼21 ml/min/1.73 m² with a plasma creatinine of 226 micromol/L. Renal biopsy identified lupus nephritis class IV and chronic kidney disease (CKD) changes, leading to a diagnosis of CKD stage 4. Initial treatment included a course of pulse methylprednisolone (1 g daily for 3 days) alongside rituximab and MMF for remission induction followed by high-dose oral prednisone (2 mg/kg/d). Her blood pressure started to increase following the first methylprednisolone pulse. In addition, two weeks later, severe fluid overload necessitated dialysis. Despite dialysis and the use of four antihypertensive agents (lisinopril, amlodipine, atenolol, doxazosin), her blood pressure fluctuated and remained uncontrolled. A week later, she experienced focal seizures. While a CT brain scan showed no abnormalities, an MRI revealed multifocal areas of bilateral cerebral hemispheric cortico-subcortical signal and diffusion alteration, indicating evolving PRES. A steroid weaning plan was implemented, and IV cyclophosphamide was initiated according to the National Institutes of Health protocol. Eight weeks later, she had another PRES episode, presenting with seizures confirmed by MRI findings. On both occasions, hypertensive encephalopathy was promptly recognized, and she was transferred to the PICU. Fortunately, her symptoms completely resolved within 12 hours of anticonvulsant and antihypertensive therapies. Discussion Common triggers of PRES include autoimmune conditions such as systemic lupus erythematosus (SLE), hypertensive encephalopathy, and drug toxicities (mainly cytotoxic and immunosuppressive drugs), all of which interact in lupus patients. However, it remains unclear how each factor contributes to the development of PRES. Additionally, the exact pathophysiological mechanism behind PRES is still debated. The two most widely accepted hypotheses involve: firstly, increased arterial blood pressure overwhelming cerebral autoregulatory mechanisms, leading to vascular leakage and vasogenic oedema. Secondly, endothelial dysfunction, where endothelial damage caused by circulating toxins enhances the release of vasoactive and immunogenic agents, altering vascular permeability. Our patient’s development of PRES is multifactorial, with lupus nephritis being a primary cause, aggravated by chronic kidney disease, leading to salt and water retention, which was further exacerbated by prednisolone. Other drugs, such as rituximab and cyclophosphamide, might have also been implicated in causing hypertension. PRES following rituximab infusion has been documented, with onset ranging from immediately after infusion to up to four weeks later. Proposed mechanisms include compromised blood-brain barrier integrity and immune dysregulation. Intravenous cyclophosphamide has also been identified as a potential trigger for PRES in patients with and without SLE, though the exact reason for this remains unclear. The dual role of these drugs in potentially precipitating life-threatening risks like PRES while being therapeutic agents presents a confusing dilemma. Much remains to be learned to enable the prevention and prompt response to PRES. Key learning points • Juvenile lupus with PRES is an uncommon neurological manifestation influenced by multiple factors. • Risk factors for PRES in juvenile lupus include lupus nephritis, CKD secondary to lupus, and iatrogenic hypertension including steroids, rituximab, and cyclophosphamide. These factors commonly exist and interplay together. • The pathogenesis of PRES in lupus, including the role of drugs, remains unclear. • Patients with lupus should be closely monitored, particularly their blood pressure. • Early diagnosis and prompt treatment of PRES can reverse radiologic and neurologic findings, leading to a favourable prognosis.

12490 Management Of Autoimmune Hepatitis Under Mitotane Therapy: Reintroduction Of Mitotane Under High Dose Corticosteroids For Targeted Mitotane Therapeutic Levels In A Patient With Recurrent Myxoid Adrenocortical Carcinoma

Abstract Disclosure: T. Hristova: None. D. Fenyves: None. C. Cloutier: None. M. Latour: None. Z. El-haffaf: None. P. Karakiewicz: None. H.J. Olney: None. I. Bourdeau: None. Histologically rare variants of adrenocortical carcinoma (ACC) include myxoid, oncocytic and sarcomatoid subtypes. There are about 50 reported cases of myxoid variants up to now that are described as more aggressive than classical ACC with poorer overall survival. Surgical resection offers the best chance of survival, with mitotane being the first line of treatment after surgery. Mitotane is currently the only approved adrenolytic drug for ACC. Among mitotane adverse effects, auto-immune hepatitis (AIH) is reported in monography, yet barely anything is reported in the literature about it. The precise mechanism of AIH has not been reported yet, but the mainstem therapy of AIH is corticosteroids alone or in combination with azathioprine. We report the case of a 43-year-old male who was diagnosed with non-secreting myxoid ACC subtype stage 2 (7x6x5,5 cm, ki67 18%, Weiss score 6/9). Multigene panel testing revealed a germline pathogenic variant in the ATM gene. Post adrenalectomy, mitotane was initiated within 2 months and increased to 2,5g daily within 6 weeks. 11 weeks after starting mitotane, liver enzymes were as follows: ALT 127 U/L (N: 10-39), AST 54 U/L (N: 13-39), ALP 165 U/L (N: 36-110), GGT 489 U/L (N: 9-47), while pre-mitotane levels were normal. Although mitotane was stopped, ALT increased to 255 U/L and remained high for 10 weeks after its cessation. Liver biopsy showed chronic hepatitis with moderate inflammation which was compatible with toxic hepatitis vs AIH. As kinetic liver enzyme tests increased after mitotane cessation, AIH was the retained diagnosis. Treatment with 40mg prednisone daily was then initiated. Pre-prednisone liver enzymes were ALT 202 U/L, AST 64 U/L, ALP 154 U/L, GGT 216 U/L, whereas 8 weeks later values had decreased to ALT 74 U/L, AST 20 U/L, ALP 108 U/L, GGT 84 U/L, and prednisone was lowered to 15mg daily. ACC recurred 3 months later, about one year after the initial adrenalectomy. After surgical resection, mitotane was restarted at 500mg daily with prednisone 40mg daily. As liver enzymes were within normal ranges, mitotane was slowly increased to 2.5g daily, with mitotane plasma levels of 11.3mg/L, whereas prednisone was decreased gradually to 12.5mg daily. Second ACC recurrence occurred one year later and mitotane was further increased to 3g daily under prednisone 12.5mg reaching mitotane levels up to 21.2 mg/L with surgical debulking. Further therapeutic avenues are being considered for a rapid recent ACC recurrence, such as PARP inhibitors for targeted therapy in the context of ATM gene mutation, but further considerations are required due to previous AIH. To the best of our knowledge this is the first reported case of AIH due to mitotane in a rare ACC subtype in a patient carrying a germline ATM gene mutation. We also report restart of mitotane therapy with concomitant high dose prednisone in the context of ACC recurrence that allowed to reach targeted therapeutic levels. Presentation: 6/1/2024

7203 A case of undifferentiated shock found to be due to voriconazole-related primary adrenal insufficiency

Abstract Disclosure: K.X. Zhang: None. C. Bergwitz: None. Primary adrenal insufficiency can be a rare effect observed with azole antifungal therapy, classically ketoconazole, via inhibition of cortisol and aldosterone synthesis. Whether primary AI can be observed with newer triazole drugs used for neutropenic prophylaxis and treating invasive fungal infections is far less understood. We describe a case of a 65-year-old man with medical history notable for COPD and gout, who was on voriconazole for Aspergillus pneumonia, and admitted to the medical ICU with confusion and undifferentiated shock. His potassium was 6.5 mmol/L, sodium 133 mmol/L, bicarbonate 18 mmol/L, and blood pressure 72/63 requiring pressor support. Voriconazole was withdrawn. He also had a fever to 101.7F that was attributed to a gout flare, and he received a course of high dose prednisone. His shock and electrolyte abnormalities quickly resolved, and he was discharged on isavuconazole. At the 1 week mark, he was found to have a morning cortisol 2.3 ug/dL, potassium 5.4 mmol/L, and sodium 134 mmol/L, along with fatigue, nausea, and hypotension, which prompted resumption of steroid and mineralocorticoid replacement. One month after completing his course of isavuconazole, morning cortisol normalized to 11.0 ug/dL and ACTH 22.3 pg/mL. We present a convincing clinical story supporting the etiology of this patient’s initial shock as primary adrenal insufficiency related to a voriconazole effect. This case illustrates how iatrogenic AI can be a missed diagnosis in the emergency room setting. Primary AI has classically been reported following ketoconazole therapy, but there are only 4 reports of primary AI involving the newer triazole posaconazole, and none for voriconazole or isavuconazole. Due to the rarity of this effect, AI due to voriconazole was not on the initial shock differential and timely endocrine labs to seal the diagnosis (morning cortisol, ACTH, and renin/aldosterone levels) were not obtained. If our patient had not received steroids serendipitously for gout, he may have been at risk for adrenal crisis. Whereas central AI is more common and induced by chronic use of systemic steroids, it is important to also think about AI caused by antifungal therapy with newer azoles. Presentation: 6/3/2024

Rare CCND2 (p.Thr280Ile) Variant Associated With Infantile Spasms in a Patient With Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome

BackgroundThis report describes a pediatric case of megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome, a rare neurodevelopmental disorder caused by pathogenic variants in the AKT3, CCND2, or PIK3R2 genes. We present a patient with a rare CCND2 variant (c.839C>T, p.Thr280Ile), associated with infantile spasms, ventriculomegaly, polymicrogyria, and intraventricular hemorrhage (IVH). MethodsA retrospective chart review and literature search were performed using PubMed. ResultsOur patient was found to have ventriculomegaly, grade 3 IVH, bilateral polymicrogyria, and restricted diffusion in the caudate nuclei prenatally. No polydactyly was observed. The patient developed infantile spasms at age 5 months. While high-dose prednisone treatment failed to control the spasms, they resolved with topiramate. By age 2 years, the patient continued to have significant developmental delays, including having poor tone and being nonverbal. ConclusionMPPH syndrome remains a rare and challenging diagnosis, with fewer than 100 cases reported. This case highlights the importance of early genetic testing and neuroimaging in the diagnosis and management of MPPH. The unique presentation of IVH and restricted diffusion warrants further investigation into the syndrome’s variable phenotypic spectrum. Early intervention and targeted therapy may help manage seizure activity and improve outcomes.

The impact of genotype on age at loss of ambulation in individuals with Duchenne muscular dystrophy treated with corticosteroids: A single-center study of 555 patients.

Studies have demonstrated that certain genotypes in Duchenne muscular dystrophy (DMD) have milder or more severe phenotypes. These studies included individuals treated and not treated with corticosteroids and multiple sites with potentially varying standards of care. We aimed to assess genotype-phenotype correlations for age at loss of ambulation (LoA) in a large cohort of individuals with DMD treated with corticosteroids at one center. In this retrospective review of medical records, encounters were included for individuals diagnosed with DMD if prescribed corticosteroids, defined as daily deflazacort or prednisone or high-dose weekend prednisone, for 12 consecutive months. Encounters were excluded if the participants were taking disease-modifying therapy. Data were analyzed using survival analysis for LoA and Fisher's exact tests to assess the percentage of late ambulatory (>14 years old) individuals for selected genotypes. Overall, 3948 encounters from 555 individuals were included. Survival analysis showed later age at LoA for exon 44 skip amenable (p = .004), deletion exons 3-7 (p < .001) and duplication exon 2 (p = .043) cohorts and earlier age at LoA for the exon 51 skip amenable cohort (p < .001) when compared with the rest of the cohort. Individuals with deletions of exons 3-7 had significantly more late ambulatory individuals than other cohorts (75%), while those with exon 51 skip amenable deletions had significantly fewer (11.9%) compared with other cohorts. This confirms previous observations of genotype-phenotype correlations in DMD and enhances information for trial design and clinical management.

Relapsing-Remitting Immunotherapy Responsive Small-Fiber Neuropathy: Longitudinal Tracking Through 10 Years Including Pregnancies.

To expand understanding of the pathogenesis, presentations, and treatment of initially idiopathic small fiber polyneuropathy (SFN). We longitudinally readministered validated metrics to track disease course and treatment responses in a previously healthy woman with acute, postinfectious, skin biopsy-confirmed, idiopathic SFN. During 5 years, viral respiratory infections triggered 3 separated episodes of acute, disabling burning hand, foot, and face pain (erythromelalgia). The initial 2 resolved with high-dose prednisone, and the third responded to repeated immunoglobulin treatments. Pregnancy with miscarriage triggered a fourth exacerbation refractory to corticosteroids and cyclosporin. Immunoglobulins restored total remission for 2 months; then, 2 rituximab doses slightly improved later flaring. Subsequently, daratumumab initiated 100-day remission later maintained by belimumab, initiated to permit another pregnancy. Remission continued after gestational week 13 all-treatment withdrawal. A week 30 fifth flare responded to plasmapheresis, with healthy birth at week 40. At 11-week postpartum, as symptoms returned, restarting belimumab restored remission maintained during ≥19 months of breastfeeding. This decade of tracking characterizes a relapsing-remitting course of SFN with initially separated monophasic episodes becoming more confluent, as with multiple sclerosis. This tempo and responsiveness to 5 immunotherapies suggest dysimmune causality. Validated metrics helped define the course and track treatment efficacy, particularly during pregnancy and breastfeeding. This is a single observational study without controls. This provides Class IV evidence.

Cutaneous ulcers following high-dose prednisone.

A 60-year-old man presented to the dermatology clinic with longstanding nonhealing ulcers to the lower legs.

Association of peripheral edema with immune checkpoint inhibitors: A systematic review.

187 Background: Immune checkpoint inhibitors (ICIs) are widely used to treat patients with cancer but immune-related adverse events occasionally disrupt treatments and affect their quality of life. Peripheral edema from ICI therapy appears rare but can occur due to increased peripheral vascular permeability. Thus, we aimed to report the incidence and outcomes of peripheral edema from ICIs. Methods: Medline, Embase, and Web of Science were searched to identify phase 3 randomized controlled trials (RCTs) reporting the incidence of peripheral edema in patients treated with ICIs. We calculated the incident rate of peripheral edema based on treatment patterns (monotherapy and combination therapy) and ICI subtypes (PD-1, PD-L1, and CTLA-4 inhibitors). We also performed a systematic review to identify articles reporting treatment outcomes of peripheral edema from ICIs. Results: Overall, 60 RCTs comprising 22,590 patients were identified for the incidence analysis. Treatment-related peripheral edema (Grade 1-5) occurred in 2.8% from ICI monotherapy (n = 195/6969; PD-1 inhibitors: 2.2% [n = 104/4694], PD-L1: 3.7% [n = 58/1557], CTLA-4: 4.6% [n = 33/718]), 5.0% (n = 112/2257) from ICI with chemotherapy, and 8.7% (n = 205/2349) from ICI with molecular-targeted therapy. Grade 3-5 treatment-related peripheral edema occurred in 0.3% of patients treated with ICI monotherapy (Table). For treatment outcomes of peripheral edema, a systematic review identified 19 studies (17 case reports/series,1 phase 1/2 clinical trial, 1 pharmacovigilance study) comprising 40 patients with immune-related peripheral edema. In total, 82.5% (n = 33/40) of cases received glucocorticoid treatment, and 55.0% (n = 22/40) required a high dose (≥ 1 mg/kg/day) of prednisone. ICI was discontinued in 77.5% (n = 31/40) due to peripheral edema (permanent discontinuation in 35% [n = 14/40]). Conclusions: Peripheral edema occasionally occurs in patients treated with ICIs but its occurrence often requires glucocorticoid administration, which may impact cancer treatment outcomes. [Table: see text]

Multiple-target Therapy for Posttransplant Focal Segmental Glomerulosclerosis.

There is no consensus on the ideal strategy to treat posttransplant focal segmental glomerulosclerosis. The multiple-target therapy, which consisted of high-dose intravenous cyclosporine, prednisone, and plasmapheresis, showed favorable results. This single-center, prospective study sought to evaluate the multiple-target therapy in an independent cohort of patients. Thirteen patients with posttransplant focal segmental glomerulosclerosis received multiple-target therapy. Complete remission was achieved in 2 patients (15.4%), and partial remission in another 2 patients (15.4%). Four patients (30.7%) did not show remission, and 5 patients (38%) lost the graft because of posttransplant focal segmental glomerulosclerosis during the 12-mo follow-up. Premature discontinuation of treatment occurred in 10 patients (77%), all associated with infectious adverse events. Cytomegalovirus was the most common complication, and preemptive therapy was used instead of prophylaxis. In this cohort of patients, the efficacy of the multiple-target therapy was poor and limited by the high incidence of infectious adverse events.

Allergic bronchopulmonary aspergillosis in a lung transplant recipient treated with mepolizumab

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to Aspergillus spp. ABPA diagnosis may be challenging due to its non-specific presentation. Standard ABPA treatment consists of systemic corticosteroids and antifungal agents. Mepolizumab, a monoclonal antibody against interleukin-5 seems to be a promising treatment for ABPA. Data about ABPA following lung transplantation (LuTx) are scarce. LuTx recipients are at higher risk for adverse effects of ABPA treatment compared to the general population.Here we present a case of a LuTx recipient who was successfully treated with mepolizumab for ABPA following LuTx. Prolonged administration of high dose prednisone was thus avoided. To our knowledge, this is the first case describing mepolizumab administration following LuTx. Mepolizumab seems particularly attractive as a corticosteroid-sparing agent or as an alternative option to antifungal treatments, because of its excellent safety profile and low risk of drug interactions.

Multisystem Inflammatory Syndrome in Children (MIS-C) in a Low-income Country: What Treatment Should be Adopted in Case of a Lack of Immunoglobulin?

In multisystem inflammatory syndrome (MIS-C), children typically present high-grade fever, gastrointestinal symptoms, Kawasaki-like symptoms, and even a toxic shock-like syndrome days to weeks after recovering from SARS-CoV-2 infection. It is important to raise awareness of this condition in order to have early diagnosis and immediate treatment of patients. We have, herein, reported 44 cases of MIS-C with various risk factors and symptoms. Furthermore, we have emphasized the efficacy of experience in treating children with MIS-C with high-dose corticosteroids as an alternative to immunoglobulin in low-income countries. We conducted a targeted survey of MIS-C from early May 2020 to October 2022 on 44 children and adolescents with characteristics of multisystem inflammatory syndrome admitted to the pediatric department of the university hospital center in Oujda, Morocco, to which patients diagnosed with MIS-C were referred. The case definition included six criteria: serious illness leading to hospitalization, age under 18 years, fever of at least 24 hours, laboratory evidence of inflammation, multi-organ involvement, biological inflammatory syndrome, and evidence of coronavirus infection based on polymerase chain reaction, antibody testing or exposure to people with COVID-19 in the past month. The criteria used to diagnose myocarditis were impaired left ventricular function, central mitral leak, and elevation of BNP or pro-BNP. Coronary involvement was assessed by the z-score and the criteria for its presence was a z-score equal to or greater than 2.5. Our study included 44 children and adolescents with MIS-C in our hospital, with male predominance (79%) and a median age of six years. Cardiovascular involvement was present in 91%, mucocutaneous in 78%, gastrointestinal in 70%, hematologic in 84%, and respiratory in 2% of patients. Coronary abnormalities (z-score ≥ 2.5) were documented in 21 cases (48%). Glucocorticoids were frequently used in comparison to immunoglobulin, which were uncommonly available and expensive. The therapeutic protocol that was adopted was high doses of short-term prednisone (Cortancyl) at 4mg/kg/day for 4 days. Favorable outcome was noted in all patients over a 2-year period.

P186 Impact of glucocorticoids on appearance and sense of self in rheumatic diseases

Abstract Background/Aims To explore patients’ perspectives on the impact of appearance changes attributed to glucocorticoid treatment. Methods We conducted a secondary analysis of semi-structured interviews with patients with rheumatic conditions receiving glucocorticoids in the UK, USA, and Australia. Interview data were analysed inductively to develop preliminary individual and overarching themes. Results 60 patient interviews were analysed. Patients ranged from 26-84 years, and 39 (65%) were female. Patients had diagnoses of systemic vasculitis (n = 19), inflammatory arthritis (n = 14), crystal arthropathy (n = 2), connective tissue disorders (n = 16), or other/multiple (n = 9). Interviews contained rich data on how appearance changes impacted health-related quality of life. Three preliminary overarching themes were identified. i) Societal influences: participants reported pressure to conform to cultural and societal ideals: “I think with the weight gain it was more of an emotional response. [⋯] There's a part of you that's thin is better. So, I think that impacted me the most, just because of that aspect of what others thought of me…” (Female [Mixed/Multiple ethnicity] aged 27, granulomatosis with polyangiitis [Australia]) and “…within a week my dad had seen me and said, “Gosh you’ve put on a lot of weight”. Obviously, that’s not what I want to hear [⋯] but I think it was just pure shock." (White female aged 40, eosinophilic granulomatosis with polyangiitis [UK])”.ii)?Impact on mental health and sense of self: glucocorticoids were often described as making participants ‘not look like’ themselves, associated with changes in mood, self-confidence, and reluctance to socialise: “It makes you feel down. It makes you feel depressed. You don't want to socialise because you're not you.” (White male aged 65, inflammatory myositis [Australia]) and “Yeah, that’s it and it will hopefully look nice, which is a really vain thing to think about isn’t it, but it does really affect [⋯] how you feel and kind of your state of mind and things…” (White female aged 39, Takayasu arteritis [UK]). iii) Burden of adjustments included dieting, purchasing additional clothing sizes, working from home, discontinuing hobbies, and postponing key life events: "I have a wardrobe right now that goes four different sizes as my weight goes up and down and up and down." (White female aged 55, systemic lupus erythematosus [USA]) and "Well, with the high dose of prednisone since I gained weight, I get really tired if I try to do like exercise or something. And I used to be very sporty, so that just completely changed." (Hispanic female aged 29, systemic lupus erythematosus [USA]). Conclusion Patients attribute a variety of impacts on their health-related quality of life to glucocorticoid-related appearance changes and report a burden of adjustments above management of their chronic rheumatic condition. Further work is required to establish ways to mitigate these through improved information provision and support. Disclosure S.J. Lax: Grants/research support; post funded by National Institute for Health and Care Research Advanced Fellowship [grant number NIHR300863]. E. Dures: Grants/research support; recipient of grants from Above &amp; Beyond Bristol Hospitals Charity, UWE Bristol, Vifor Pharma, National Institute for Health and Care Research (Research for Patient Benefit) and Sanofi. S. Bridgewater: None. C. Silverthorne: None. V. Lowndes: None. P. Richards: None. J. Dawson: None. C. Hill: Grants/research support; recipient of an Australian Rheumatology Association Project Grant, administered by Arthritis Australia. S. Goodman: None. S.L. Mackie: None. M.E. Ndosi: None. F.A. Pearce: Grants/research support; recipient of a National Institute for Health and Care Research Advanced Fellowship [grant number NIHR300863] and a grant from Vifor pharma. J. Robson: Consultancies; consultancy and speaking fees from Vifor Pharma. Grants/research support; recipient of grants from Above &amp; Beyond Bristol Hospitals Charity, UWE Bristol, Vifor Pharma, National Institute for Health and Care Research (Research for Patient Benefit) and Sanofi.

Purulent pericarditis caused by methicillin-sensitive Staphylococcus aureus bacteriuria

BackgroundPurulent pericarditis (PP)— a purulent infection involving the pericardial space—requires a high index of suspicion for diagnosis as it often lacks characteristic signs of pericarditis and carries a mortality rate as high as 40% even with treatment. Common risk factors include immunosuppression, diabetes mellitus, thoracic surgery, malignancy, and uremia. Most reported cases of PP occur in individuals with predisposing risk factors, such as immunosuppression, and result from more commonly observed preceding infections, such as pneumonia, osteomyelitis, and meningitis. We report a case of PP due to asymptomatic bacteriuria in a previously immunocompetent individual on a short course of high-dose steroids.Case presentationAn 81-year-old male presented for severe epigastric pain that worsened with inspiration. He had been on high-dose prednisone for presumed inflammatory hip pain. History was notable for urinary retention requiring intermittent self-catheterization and asymptomatic bacteriuria and urinary tract infections due to methicillin-sensitive Staphylococcus aureus (MSSA). During the index admission he was found to have a moderate pericardial effusion. Pericardial fluid cultures grew MSSA that had an identical antibiogram to that of the urine cultures. A diagnosis of purulent pericarditis was made.ConclusionPP requires a high index of suspicion, especially in hosts with atypical risk factors. This is the second case of PP occurring as a result of asymptomatic MSSA bacteriuria. Through reporting this case we hope to highlight the importance of early recognition of PP and the clinical implications of asymptomatic MSSA bacteriuria in the setting of urinary instrumentation and steroid use.

Vogt-Koyanagi-Harada disease developed during chemotherapy for Hodgkin lymphoma: a case report

BackgroundOcular manifestations are known for non-Hodgkin lymphoma, but are rare for Hodgkin lymphoma. We report a case of Vogt-Koyanagi-Harada (VKH) disease presenting as serous retinal detachment and uveitis in both eyes in a child undergoing chemotherapy for Hodgkin lymphoma.Case presentationThe patient was a 7-year-old boy with stage IIB Hodgkin lymphoma (nodular lymphocyte predominant type) who was undergoing chemotherapy, including 2 cycles of the OEPA regimen and 1 cycle of the COPDAC regimen. Two days after the end of the COPDAC regimen, the patient complained of headache and of blurred and decreased vision in both eyes. On the basis of optic symptoms, such as uveitis and serous retinal detachment in both eyes, increased cell counts in cerebrospinal fluid, and positivity for human leukocyte antigen (HLA)-DR4 in peripheral blood cells, incomplete VKH disease was diagnosed. Intravenous treatment with high-dose prednisolone (60mg/m2/day) for 7 days improved both visual acuity and serous retinal detachment and enabled the remains of the COPDAC chemotherapy cycle to be administered. With prednisolone treatment, visual acuity improved from 20/500 to 20/20 in the right eye and from 20/63 to 20/25 in the left eye. Because multiple vitiligo lesions later appeared in the abdomen, complete VKH disease was finally diagnosed.ConclusionThe onset of VKH disease occurred during chemotherapy for Hodgkin lymphoma. The patient was HLA-DR4-positive and might have had a predisposition to develop autoimmune diseases, including VKH disease. However, the anticancer drugs administered to this patient have not been reported to cause uveitis. Whether Hodgkin lymphoma triggered the development of VKH remains unclear. Early diagnosis of VKH disease and prompt treatment with high-dose prednisone enabled the patient to maintain good visual function despite chemotherapy for Hodgkin lymphoma.

Granulomatous Mastitis in a Systemic Lupus Erythematosus Patient: Case Report

Granulomatous Mastitis (GM) is an uncommon form of mastitis frequently associated with autoimmune diseases. This entity requires a differential diagnosis with breast tumor and infections and may be treated with glucocorticoids and methotrexate. We report a case of GM in a patient with systemic lupus erythematosus already using high doses of prednisone and immunosuppressants that responded to the use of doxycycline. Some pathophysiological, histological and treatment aspects are discussed.

Preexisting renal graft dysfunction as a major risk factor for SARS-CoV-2 Omicron variant pneumonia: A postinfection cross-sectional study of 312 immunosuppressed renal transplant recipients

ObjectivesSARS-CoV-2 pneumonia poses significant challenges to health systems worldwide, particularly, in severe and critical cases. Immunosuppressed renal transplant recipients appear to be at a particularly high risk for severe or critical COVID-19 illness. However, few studies elucidated the risk factors of SARS-CoV-2 pneumonia in renal transplant recipients with COVID-19. MethodsA postinfection cross-sectional survey was conducted in 312 renal transplant recipients and 503 age- and sex-matched controls to explore risk factors for SARS-CoV-2 pneumonia in immunosuppressed renal transplant recipients. ResultsThe results showed that renal transplant recipients had a much higher incidence of SARS-CoV-2 pneumonia (48.1%) after infection with the SARS-CoV-2 Omicron variant than controls (5.6%). The multivariate binary logistic regression analysis identified older age, lower creatinine clearance before infection, and higher dose of prednisone before infection as risk factors for SARS-CoV-2 pneumonia in renal transplant recipients. Preexisting renal dysfunction was a major risk factor for SARS-CoV-2 pneumonia, with an odds ratio of 3.27 (1.01-10.61). ConclusionsPreexisting renal graft dysfunction was a major risk factor for SARS-CoV-2 Omicron variant pneumonia. It is suggested that high-risk renal transplant recipients should undergo computed tomography scanning within 14 days after infection with SARS-CoV-2.

Simultaneous Determination of Prednisone and Prednisolone in Serum by Turbulent Flow Liquid Chromatography-Tandem Mass Spectrometry.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapeutic treatment for patients with high-risk hematologic malignancies and bone marrow failure syndromes. While allo-HCT can be highly effective, it is met with significant regimen-related toxicities and complications such as graft-versus-host disease (GVHD), poor immune reconstitution, and infections. Prednisone is the preferred treatment for patients with both acute and chronic GVHD. While effective, high-dose prednisone can cause many complications, including weight gain, skin fragility, muscle weakness, bone demineralization, hyperglycemia, insomnia, and psychosis. Optimizing prednisone (and prednisolone) dosing by measuring their concentrations and calculating their pharmacokinetic parameters will allow for personalized treatments for patients, producing more effective and safer treatments for GVHD. This chapter describes a method to measure both compounds simultaneously. Prednisone and prednisolone are extracted from serum by the addition of methanol containing deuterated internal standards. Chromatographic separation is achieved using a reversed-phase HPLC column followed by tandem mass spectrometry performed in the positive ion mode. This assay is fast, accurate, sensitive and allows for rapid drug measurements and timely dose modifications.

The impact of CHOP versus bendamustine on bone mineral density in patients with indolent lymphoma enrolled in the GALLIUM study.

Standard CHOP treatment includes a high cumulative dose of prednisone, and studies have shown increased fracture risk following CHOP. It is unclear whether reductions in bone mineral density (BMD) are caused by glucocorticoids or by the combination with chemotherapy. Our objective was to determine the effect of obinutuzumab (G)/rituximab (R)-bendamustine versus G/R-CHOP on BMD in follicular lymphoma patients. Patients in this GALLIUM post hoc study were ≥60 years old and in complete remission at induction treatment completion (ITC), following treatment with G or R in combination with bendamustine or CHOP. To assess BMD, Hounsfield units (HU) were measured in lumbar vertebra L1 on annual computed tomography. Furthermore, vertebral compression fractures were recorded. Of 173 patients included, 59 (34%) received CHOP and 114 (66%) received bendamustine. At baseline, there was no difference in HU between groups. The mean HU decrease from baseline to ITC was 27.8 after CHOP and 17.3 after bendamustine, corresponding to a difference of 10.4 (95% CI: 3.2-17.6). Vertebral fractures were recorded in 5/59 patients receiving CHOP and in 2/114 receiving bendamustine. CHOP was associated with a significant greater decrease in BMD and more frequent fractures. These results suggest that prophylaxis against BMD loss should be considered.

Abstract 18486: Recurrent Pericarditis Following Atrial Fibrillation Ablation: Unmasking Latent Tuberculosis Infection

Background: Tuberculous pericarditis is rare in the United States but can lead to serious sequelae in the absence of diagnosis and treatment. We report a case of recurrent pericarditis following catheter ablation of atrial fibrillation (AF) due to reactivation of latent TB infection. Case Summary: A 52-year-old male with no past medical history underwent a difficult trans-septal puncture &amp; cryo-balloon PV isolation, complicated by acute pericarditis and pericardial effusion with cardiac tamponade. He underwent pericardiocentesis with removal of 260cc bloody fluid. He had resolution of chest pain with ibuprofen, but experienced recurrence after 3 months and was given a longer NSAID course. Two months later, he presented with chest pain along with night sweats &amp; low-grade fever. He had an elevated C-reactive protein, and echocardiography revealed thickened pericardium &amp; constrictive physiology. He received high-dose aspirin, prednisone, and colchicine for recurrent pericarditis. Extensive Infectious Disease &amp; Rheumatology work-up ruled out autoimmune &amp; viral etiologies but his T-Spot TB test was positive. He denied personal or contact history of TB except travel to Asia 20 years ago. CT scan ruled out pulmonary TB infection. A 6-month course of Rifampin was prescribed. He experienced a 4th episode of pericarditis while tapering off prednisone, and restarted prednisone, Ibuprofen, and colchicine. Additionally, Rilonacept was prescribed. After completing 6-months of Rifampin and Rilonacept, he had significant improvement and no further recurrences on 1 year follow up. Discussion: Pericarditis is a common complication of catheter ablation, often resulting from direct injury. We report a case of recurrent pericarditis, initially believed to be a traumatic complication of AF ablation. However, investigation revealed underlying latent pericardial TB infection. Appropriate treatment led to complete resolution without sequelae.