Oral Mycophenolate Mofetil Research Articles

7824 Orbital Lymphoma masquerading as Thyroid Eye Disease

Abstract Disclosure: S. Ganawa: None. S. Joseph: None. C. Anshuman: None. D. Luciane L: None. A. Sajid: None. C. Anne: None. S. Dhage: None. Thyroid eye disease (TED) is the most common extrathyroidal manifestation in Graves’ disease (GD). In this case report, we present a case of a 64 years old lady, who was initially diagnosed with thyroid eye disease about 9 years ago. However, she was clinically and biochemically euthyroid. She was offered an orbital decompression surgery by local ophthalmology team. Patient wasn’t keen on the surgery at this stage.Recently she experienced increased swelling of her eyes, with conjunctival redness, oedema, and diplopia bilaterally, more evident on the left side. She was initiated on intravenous methylprednisolone (IVMP) weekly, by local ophthalmology team and was referred to our specialist thyroid eye clinic for further management.On presentation to us, her clinical activity score (CAS) was 5/7, but she was euthyroid clinically and biochemically. She was continued on weekly IVMP and oral mycophenolate mofetil (MMF) was added on as per the latest EUGOGO guidelines published in 2021. Her treatment was reviewed after the anti thyroperoxidase (TPO) and anti-Thyroid Stimulating Hormone receptor (TSH) antibodies were reported as negative and her eyes worsened despite the treatment with IVMP and MMF.Her repeat MR orbit at this stage showed possible orbital lymphoma. Her immunosuppressive medications were discontinued at this stage. After further discussions at regional thyroid eye MDT and radiology MDT, an orbital biopsy was arranged for, which confirmed Extra nodal Marginal Zone lymphoma, with no high-grade component. She has been referred to the oncology unit for further assessment and management.This case highlights the importance of considering alternative differential diagnosis in certain patients with atypical features or those who are non-responders to the first line immunosuppressive therapies for thyroid eye disease. Details of this case and relevant literature will be reviewed in this report. Presentation: 6/3/2024

Morphea-like tattoo reaction in a patient with systemic sclerosis: Case report and review of the literature

Background: Morphea-like tattoo reactions are rare phenomena, with few cases reported in the literature. We present a case of a morphea-like tattoo reaction and a literature review of such reactions for comparison. Case Description: A 38-year-old woman with known history of systemic sclerosis presented with abnormal healing and skin thickening over a red tattoo. Histopathological examination revealed sclerosing dermatitis, consistent with morphea-like tattoo reaction. Treatment included topical clobetasol and oral mycophenolate mofetil. Methods: A literature search of PubMed and EMBASE was performed in August 2023 for known morphea-like tattoo reactions. No time or language filters were applied. Results: A total of six articles were included. Case reports of morphea-like tattoo reactions in patients with no significant past medical history comprise five articles. One review article notes that red tattoo ink with and without cinnabar is associated with adverse skin reactions. Conclusions: Morphea-like tattoo reactions can be triggered by ingredients of tattoo ink, possibly due to local hypersensitivity or the Koebner phenomenon. We encourage high clinical suspicion for morphea-like tattoo reactions when a patient with known history of connective tissue disease presents with skin changes around a tattoo.

Efficacy and safety of oral cyclophosphamide versus mycophenolate mofetil in childhood nephrotic syndrome: an open-label comparative study

IntroductionThere is a scarcity of research comparing the efficacy of cyclophosphamide and mycophenolate mofetil in childhood nephrotic syndrome. The aim was to evaluate the efficacy and safety of oral cyclophosphamide (CYC) and mycophenolate mofetil (MMF) in children with steroid-sensitive nephrotic syndrome in terms of the proportion of children who have been off steroids for at least 6 months without proteinuria (responders).MethodsThis open-label retrospective-prospective comparative study was conducted in a pediatric nephrology clinic of a referral center for children between 1 and 18 years of age with FR/SD nephrotic syndrome. Group A consisted of patients who received oral cyclophosphamide (100, 25% female) at a dose of 2–2.5 mg/kg once daily for a period of 8–12 weeks. Group B consisted of patients who received oral mycophenolate mofetil (n = 61, 18% female) (dose: 800–1200 mg/m2) for at least 12 months. Responders were defined as children who were off steroids for at least 6 months along with absence of proteinuria.ResultsIn the CYC group, 50% of the patients were responders, whereas 54% of the patients in the MMF group were responders (p = 0.614). The time to first relapse with CYC was 7 months (IQR 5.25–11) compared to 7 months (IQR 3.5–12) with MMF (p = 0.092). The relapse rate in the CYC group was 1.77 relapses per patient-year compared to 1.295 relapses per patient-year in the MMF group. The difference in relapse rate was significant (-0.474; 95% CI, 0.09 to 0.86 relapses/person-year) (p value = 0.009). Multivariate analysis revealed that an age of less than 5 years at the start of treatment was a significant factor for a better response to MMF (p value = 0.039, OR = 2.988, CI -1.055-8.468).ConclusionsThe efficacy of MMF was similar to that of CYC in terms of response (6 months without steroids) in children with FR/SD nephrotic syndrome. MMF showed a favorable response in terms of the frequency of relapse and treatment failure.Registration of the study with Clinical Trials Registry of India(http://ctri.nic.in;CTRI/2021/06/034421) (Dt: 28/06/2021).

Limited Sampling Strategies Fail to Accurately Predict Mycophenolic Acid Area Under the Curve in Kidney Transplant Recipients and the Impact of Enterohepatic Recirculation.

Therapeutic drug monitoring for mycophenolic acid (MPA) is challenging due to difficulties in measuring the area under the curve (AUC). Limited sampling strategies (LSSs) have been developed for MPA therapeutic drug monitoring but come with risk of unacceptable performance. The authors hypothesized that the poor predictive performance of LSSs were due to the variability in MPA enterohepatic recirculation (EHR). This study is the first to evaluate LSSs models performance in the context of EHR. Adult kidney transplant recipients (n = 84) receiving oral mycophenolate mofetil underwent intensive MPA pharmacokinetic sampling. MPA AUC0-12hr and EHR were determined. Published MPA LSSs in kidney transplant recipients receiving tacrolimus were evaluated for their predictive performance in estimating AUC0-12hr in our full cohort and separately in individuals with high and low EHR. None of the evaluated LSS models (n = 12) showed good precision or accuracy in predicting MPA AUC0-12hr in the full cohort. In the high EHR group, models with late timepoints had better accuracy but low precision, except for 1 model with late timepoints at 6 and 10 hours postdose, which had marginally acceptable precision. For all models, the good guess of predicted AUC0-12hr (±15% of observed AUC0-12hr) was highly variable (range, full cohort = 19%-61.9%; high EHR = 4.5%-65.9%; low EHR = 27.5%-62.5%). The predictive performance of the LSS models varied according to EHR status. Timepoints ≥5 hours postdose in LSS models are essential to capture EHR. Models and strategies that incorporate EHR during development are required to accurately ascertain MPA exposure.

Assessment of the Potential Impact of Mycophenolate Mofetil on Lowering Renal Biomarkers in Patients with Class III Lupus Nephritis: A Pilot Study to Predict Renal Function Progress

Abstract Background: Lupus nephritis (LN) is a potentially severe complication of systemic lupus erythematosus (SLE). Mycophenolate mofetil (MMF) is an oral immunosuppressive agent used in lupus patients who are intolerant of or refractory to other conventional therapies. The aim of this study was to assess the potential effect of MMF on lowering some biomarkers as a predictive of renal function in patients with Class III LN. Methods: This was a single-center, prospective cohort study that enrolled patients with Class III LN who received 2 g/day of oral MMF. The potential impact of MMF on renal biomarkers was evaluated at baseline and subsequently at 3-month intervals for 6 months according to changes in antinuclear antibodies (ANA), antidouble stranded deoxyribonucleic acid (anti-dsDNA), elastase α-1 proteinase inhibitor (α-1 PI), proteinuria, and the urine protein-to-creatinine ratio (P/C ratio). Results: A significant decrease over the course of MMF treatment compared to the baseline regarding ANA (1.37 ± 0.47 vs. 2.90 ± 1.05, P = 0.03); anti-dsDNA (23.39 ± 3.19 vs. 39.91 ± 8.1 IU/mL, P = 0.02); elastase α-1 PI (512.4 ± 74.12 vs. 696.35 ± 105.35 ng/mL, P = 0.03); proteinuria (0.25 ± 0.44 vs. 1.95 ± 0.76 g/24 h., P = 0.01); and P/C ratio (0.20 ± 0.22 vs. 1.37 ± 0.26, P = 0.04). Conclusion: MMF is effective in lowering renal biomarkers of Class III LN revealed by a significant reduction in ANA, anti-dsDNA, elastase α-1 PI, proteinuria, and P/C ratio over 6 months of MMF treatment.

Outcomes in Patients With Vogt–Koyanagi–Harada Disease From the First-Line Antimetabolites for Steroid-Sparing Treatment Uveitis Trial

PurposeTo compare the effectiveness of methotrexate (MTX) and mycophenolate mofetil (MMF) in achieving corticosteroid-sparing control of uveitis in patients with Vogt-Koyanagi-Harada (VKH) disease. MethodsA subanalysis of patients with VKH from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial, a randomized, observer-masked, comparative effectiveness trial, with comparisons by treatment (MTX versus MMF) and disease stage (acute versus chronic). Individuals with noninfectious uveitis were placed on a standardized corticosteroid taper and block randomized 1:1 to either 25mg weekly oral MTX or 1.5g twice daily oral MMF. The primary outcome was treatment success defined by corticosteroid-sparing control of uveitis at 6 months. Additional outcomes included change in best spectacle-corrected visual acuity (BSCVA), retinal central subfield thickness (CST), and resolution of serous retinal detachment (SRD). ResultsNinety-three out of 216 enrolled patients had VKH; 49 patients were randomized to MTX and 44 to MMF, of which 85 patients (46 on MTX, 39 on MMF) contributed to the primary outcome. There was no significant difference in treatment success by antimetabolite (80.4% for MTX compared to 64.1% for MMF; P=.12) or in BSCVA improvement (P=.78). Methotrexate was superior to MMF in reducing CST (P=.003) and resolving SRD (P=.02). There was no significant difference in treatment success by disease stage (P=.25), but patients with acute VKH had greater improvement in BSCVA (P<.001) and reduction of CST (P=.02) than chronic VKH patients. ConclusionsMTX and MMF have comparable outcomes as corticosteroid-sparing immunosuppressive therapies for VKH. Visual acuity improvement was greater in acute vs chronic VKH. Trial RegistrationClinicalTrials.gov Identifier: NCT 0182929

Bilateral Aggressive Mooren Ulcer in the Setting of Bilateral Pterygia and Pregnancy: A Unique Case.

To report an unusual case of bilateral aggressive Mooren ulcer that occurred in the setting of bilateral pterygia and showed a relentless course during pregnancy. A 39-year-old woman of Black African ethnicity, 36-week pregnant, presented to the eye casualty with bilateral nasal corneal ulcer and associated melt around preexisting pterygia. A detailed workup including microbial evaluation, culture and sensitivity, polymerase chain reaction for herpes simplex virus, varicella zoster virus, and cytomegalovirus, inflammatory blood profile, autoimmune markers, and human leucocyte antigen (HLA) screening was undertaken. Treatment was initiated in a stepwise approach. Infections and systemic autoimmune and rheumatologic conditions were ruled out. A diagnosis of bilateral Mooren ulcer was made by exclusion. The peripheral blood was positive for HLA DQ2. As the condition seemed refractory to medical management (topical steroids and intravenous pulse methylprednisolone followed by oral prednisolone and topical cyclosporine), urgent bilateral conjunctival resection with multilayered amniotic membrane transplantation was performed to reduce the inflammatory stimulus and keratolysis. Stabilization of the condition warranted the need for systemic immunosuppressive agents. Using a multidisciplinary approach, in liaison with Obstetricians and Rheumatologists, the patient was planned for an earlier elective Cesarean section and commencement of oral mycophenolate mofetil postpartum, which aided in successful control of the disease. Mooren ulcer could follow an aggressive course during pregnancy, especially in the setting of preexisting pterygium. The complex hormonal and immunological changes during pregnancy and the delivery of inflammatory mediators directly onto the cornea by pterygium could contribute to the severity. A well-planned, stepwise, and multidisciplinary management is pivotal for the treatment of this condition.

#1273 Rapidly progressive glomerulonephritis with anti-neutrophil cytoplasmic antibodies, in a patient on golimumab

Abstract Background 73-year-old Chinese lady presented with fever, gross hematuria, and dysuria of 1-week duration. She has seronegative arthritis and was treated with human anti-tumor necrosis factor alpha monoclonal antibody (TNF-alpha inhibitor), golimumab injection 50 mg monthly, as she had previous adverse reaction with sulfasalazine and methotrexate. She suffered from severe osteoporosis and was treated with oral alendronic acid. At presentation, her blood pressure was 172/76 mmHg and pulse rate 100 beats per minute. The highest recorded temperature was 38.1 degrees Celsius. Clinical examination was unremarkable. She was diagnosed with rapidly progressive glomerulonephritis (RPGN). Creatinine at presentation was 252 µmol/L, estimated glomerular filtration rate (eGFR) 16 mL/min/1.73 m2. Two months ago, her creatinine was 68 µmol/L, eGFR 66 mL/min/1.73 m2. Urinalysis showed dysmorphic red blood cells of more than 2250 per high power field, few white blood cells, and no epithelial cells. Urine protein/creatine ratio (UPCR) was 2.3 g/g and serum albumin level was 30 g/L. ANA was borderline raised at 1:160 titer with homogeneous pattern. Anti-double stranded DNA (anti-dsDNA) was indeterminate at 29.34 IU. Anti-myeloperoxidase (MPO) antibody was positive at 162 RU/mL (Normal &amp;lt; 20 RU/mL). Anti-proteinase-3 (PR3) antibody was negative. Serum complement levels (C3 and C4) were normal. Screening for hepatitis B, hepatitis C, and HIV was negative. Ultrasound imaging of the kidneys showed raised renal echoes and resistive index. Percutaneous kidney biopsy was performed. On light microscopy, 19 glomeruli were seen. Some displayed segmental increase in mesangial cells and expansion of mesangial matrix. 4 glomeruli showed cellular crescents (Fig. 1). Immunofluorescence showed dominant 2+ staining for Immunoglobulin A (IgA) in the mesangium and electron microscopy revealed electron dense deposits in the mesangial and para-mesangial region. An occasional tubuloreticular structure was found. Diagnosis of IgA nephropathy was made and Oxford classification was M0 E1 S0 T0 C1. Results Our patient presented with rapidly progressive glomerulonephritis (RPGN) with positive MPO antibody, as well as ANA and anti-dsDNA at indeterminate levels. TNF-alpha inhibitors may lead to autoantibody formation and kidney biopsy was the key in clinching the diagnosis for our patient. Diagnosis of IgA nephropathy was made on the basis of dominant mesangial IgA on immunofluorescence and ultrastructural electron dense deposits within the mesangial and para-mesangial area. To our best knowledge, there has been only one case of IgA nephropathy reported with golimumab that occurred after 3 years and with mild albuminuria and no decline in renal function. Golimumab was promptly discontinued for our patient and she was inducted with pulsed methylprednisolone and high dose oral prednisolone 1 mg/kg/day. As she had history of severe osteoporosis, oral mycophenolate mofetil at 750 mg twice a day was commenced as steroid sparing agent. Prednisolone dose was then tapered to 0.5 mg/kg/day. She achieved full clinical remission after 3 months of immunosuppressive therapy. MPO antibody level decreased to normal after 5 months. Arthritis activity remained quiescent and she was maintained on low dose prednisolone. Conclusion We report a case of IgA nephropathy with crescents associated with golimumab. Treatment was successful with withdrawal of drug, oral prednisolone and mycophenolate mofetil.

Exogenous Insulin Antibody Syndrome (EIAS) Presenting in an Elderly, Long-Term Patient with Type1DiabetesMellitus that Resolved with Low-Cost Outpatient Therapy with Mycophenolate Mofetil and Regular Insulin by Pump.

Exogenous insulin antibody syndrome (EIAS) has until recently been a rarely described complication of exogenous insulin therapy. EIAS results not only in hyperglycemia, but also in hypoglycemia and occasionally in ketoacidosis (DKA). The incidence of EIAS is increasing probably due to an overall increase in autoimmunity associated with the coronavirus disease 2019 (Covid-19) epidemic resulting in increasing binding of insulin by antibodies. Herein, we describe a case of EIAS occurring in an elderly patient with longstanding type 1 diabetes mellitus (T1DM) who had progressive loss of glycemic control. It responded positively, as we have previously described, to oral mycophenolate mofetil and the use of soluble regular insulin delivered by continuous subcutaneous insulin infusion (CSII). Therefore, EIAS is an increasingly frequent cause of hyperglycemia with and without DKA, and hypoglycemia in subjects with T1DM. Once diagnosed, they can be treated with mycophenolate mofetil and soluble insulin in an outpatient setting, which will decrease the rate of hospitalization and lower the expense of therapy.

Myasthenic Crisis in a Child: Successful Recovery after Early Identification and Intervention

Background: Juvenile myasthenia gravis (MG) is a rare autoimmune neuromuscular disorder and has a varied presentation in childhood making it a diagnostic challenge. Clinical Description: An 8-year-old girl presented to the pediatric emergency with multiple episodes of falling, drooling of saliva, dysphagia, and bilateral ptosis. Within a few hours of admission, she had acute deterioration, developed respiratory failure, and was put on ventilatory support. Management and Outcome: A myasthenic crisis was suspected and a neostigmine challenge test was done. She was managed in the emergency with atropine, neostigmine, intravenous immunoglobulin, and supportive care. Subsequently, she achieved complete remission with steroids, physostigmine, and oral mycophenolate mofetil over the next 6 weeks. Conclusion: Juvenile MG may rarely be the cause of generalized muscular weakness. A strong suspicion of myasthenic crisis must be kept in case of sudden deterioration involving bulbar and respiratory muscles, in a patient with neurologic weakness. Early intervention in this rare condition can be lifesaving.

A retrospective study describing the effective exchange of total blood plasma for disease control in the exacerbation of serpiginous choroiditis.

Serpiginous choroiditis presents with large yellow-white exudative lesions that occur near the optic nerve papillae, that progresses slowly with repeated relapses and cures. Although infection and autoimmunity have been implicated, the cause is unknown. A man was diagnosed with serpiginous choroiditis on clinical and other examinations. He started treatment with oral corticosteroids, cyclophosphamide, adalimumab, azathioprine, rituximab, and mycophenolate mofetil. Only the steroids and cyclophosphamide had a therapeutic effect. Plasma exchange was initiated, and the lesions quickly resolved. Disease control has been maintained by plasma exchange and cyclophosphamide during flare-ups in the fall and winter, suggesting that plasma exchange is effective in the treatment of serpiginous choroiditis. The reproducible response with each recurrence suggests a strong association between the disease and autoimmunity. Furthermore, that some, as yet unknown, autoantibodies are involved in the pathogenesis of serpiginous choroiditis.

Rare manifestations of sarcoidosis in a young boy

Sarcoidosis is a chronic multisystem granulomatous disease of unknown etiology. It is rare in young children. A 9-year-old boy presented with failure to thrive, skin rashes, persistent fever and respiratory symptoms since 5 years of age. Blood investigations done showed elevated serum calcium and angiotensin converting enzyme (ACE) levels and biopsy of the rashes on the left shin revealed non-caseating granulomatous lesion. Computed tomography (CT) of chest revealed interstitial lung disease (ILD) and examination of eyes showed bilateral uveitis. He also had sensorineural hearing impairment, nephrocalcinosis and short stature. The patient was treated with oral steroids and mycophenolate mofetil. At follow up there was improvement in his systemic features including rashes and arthritis. Early detection, diagnosis and appropriate treatment of sarcoidosis are vital for disease control and to avoid morbidity.

Influence of interruption of oral mycophenolate mofetil for graft-versus-host disease prophylaxis on outcomes after single cord blood transplantation

Influence of interruption of oral mycophenolate mofetil for graft-versus-host disease prophylaxis on outcomes after single cord blood transplantation

Immunoglobulin-G4 Related Disease with Multiple Organ Involvement

Dear Editor, Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disease affecting multiple organ systems. The clinical findings may range due to the affected organ. The main distinguishing histopathological features of IgG4-RD are lymphoplasmacytic infiltration, storiform fibrosis, obliterative phlebitis, and mild or moderate tissue eosinophilia. Rarely, it may affect the lungs, hearts, pituitary, meninges, skin, prostate, breast, and thyroid gland [1–3]. In this article, we present a case diagnosed with IgG4-related disease involving multiple organs, including the pituitary, lymphatic system, kidney, and heart, and the patient responded well to immunosuppressive treatment. A fifty-five-year-old female patient applied with complaints of fatigue, polydipsia, polyuria, widespread body pain, and 20 kg weight loss in the last year. After excluding other possibilities, with a prediagnosis of diabetes insipidus (DI) pituitary MRI was performed which showed an increase in size and heterogeneous patchy contrast enhancement in the adenohypophysis (Fig. 1a). Based on the current clinical and imaging findings, the patient's laboratory results were evaluated, and central DI was diagnosed. In computerized thorax tomography, multiple lymph nodes in the mediastinum were detected, the largest of which was 21x17 mm. Tissue sampling was performed with the guidance of EBUS, pathological examination showed no diagnostic findings. Transesophageal Echocardiography (TEE) revealed an appearance consistent with a 10-15 mm thick thrombus surrounding the left atrium wall and narrowing the cavity. Increased thickness narrowing the left atrial lumen was reported in thorax computed tomography (CT) (Fig. 2). Further, a cardiac MRI was performed and reported to be consistent with lymphoproliferative-inflammatory involvement rather than thrombus. Abdominopelvic CT was performed and a lesion of 54x28 mm in size, less contrast enhancing than the surrounding parenchyma, in the middle part posterior of the left kidney was detected (Fig. 3). Histopathological findings were consistent with inflammatory processes, and no findings in favor of a neoplastic lymphoproliferative process were detected in the samples. Since the patient was presented with pituitary involvement, mediastinal lymphadenopathy, renal and cardiac mass, the IgG4 level was ordered and resulted as 299 mg/dl (3-201). IgG4 staining could not be performed in the current biopsy specimen; for confirming the diagnosis of IgG4-related disease, a re-biopsy was performed on the kidney mass. Histopathological findings were consistent with IGG4-RD (Fig. 4). Due to multisystemic involvement, the patient received 0.6 mg/kg/day oral corticosteroid and mycophenolate mofetil 3x1000 mg/day. The pituitary MRI that was performed in the first month of treatment was normal (Fig. 1b). Desmopressin treatment was stopped. Also, control TEE in the first-month follow-up visit showed a significant reduction in the mass image in the left atrium. After three months of follow-up, there was a significant improvement in the patient's symptoms and acute phase response. The corticosteroid was tapered and maintenance treatment with mycophenolate mofetil was continued. IgG4-related disease is rare and difficult to diagnose, though its presentation may be in a wide variety of clinical features. It is crucial to make an early diagnosis and start treatment early in these patients to prevent morbidity and mortality. In cases with mass lesions and especially with multiple organ involvement, as in our case, IgG4-related disease should be kept in mind, and IgG4 staining should always be kept in mind. Kind Regards

Idiopathic Membranoproliferative Glomerulonephritis Type 1 Refractory to Immunosuppressive Therapy: An Educational Article and Expert Opinion

Background: Membranoproliferative glomerulonephritis which is also known as mesangio-capillary and mesangioproliferative glomerulonephritis has been established as a clinical-histopathological entity as early as the 1960s. As early as 2004, Gareth Jones from the United Kingdom and his research group reported a study which showed that treatment of patients with membranoproliferative glomerulonephritis with oral prednisolone and mycophenolate mofetil may help in preserving renal function in patients.

Body Surface Area-Based Dosing of Mycophenolate Mofetil in Pediatric Hematopoietic Stem Cell Transplant Recipients: A Prospective Population Pharmacokinetic Study.

Mycophenolate mofetil (MMF) is commonly used for acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). However, limited population pharmacokinetic (PPK) data are available for pediatric HSCT patients. This study aimed to develop a PPK model and recommend optimal oral MMF dosage in pediatric HSCT patients. This prospective study involved pediatric HSCT patients at a tertiary academic institution. Patients received oral MMF 15-20 mg/kg twice daily for aGVHD prophylaxis and treatment. The PPK analysis was conducted using a nonlinear mixed-effects modeling method. Simulation was performed considering different body surface areas (BSAs) (0.5 m2, 1.0 m2, 1.5 m2) and dosing (400 mg/m2, 600 mg/m2, 900 mg/m2 twice daily). Based on the simulation, an optimal dosage of oral MMF was suggested. A total of 20 patients and 80 samples were included in the PPK model development. A one-compartment model with first-order absorption adequately described the pharmacokinetics of mycophenolic acid (MPA). BSA was a statistically significant covariate on Vd/F. Simulation suggested the optimal dosage of oral MMF as 900 mg/m2 twice daily, respectively. A reliable PPK model was developed with good predictive performance. This model-informed optimal MMF dosage in pediatric HSCT patients can provide valuable dosing guidance in real-world clinical practice.

Evaluating Effective Therapeutic Options for Inhibitor Eradication in Patients with Acquired Hemophilia a: A 10-Year Single Center Experience

Background Acquired hemophilia A (AHA) is a rare disorder characterized by emergence of neutralizing antibodies or inhibitors to factor VIII. The main treatment strategy for AHA involves control of bleeding with factor VIII bypassing agents and eradicating the autoantibodies using immunosuppressive therapy (IST) for restoration of normal hemostasis. Previous studies have demonstrated the effectiveness of both cyclophosphamide and rituximab in combination with steroids for treating AHA, however, clear guidelines for choosing between these agents for rapid inhibitor eradication are lacking. This retrospective study aimed to compare the effectiveness of cyclophosphamide and rituximab as first-line therapies for rapid antibody elimination and relapse prevention. Methods We queried our hospital electronic health record system using ICD 9/10 code to identify patients &amp;gt;18 years that had at least 2 inpatient or outpatient encounters for the diagnosis of AHA between 1 st July 2013 and 30 th June 2023. Variables collected included initial aPTT value, serial factor VIII activity &amp; Bethesda inhibitor titer and immunosuppressive therapies used. Time to remission was defined when inhibitor titer was &amp;lt;1% along with improving factor VIII activity. At our institute, all patients received 1mg/kg of steroids initially, then either six cycles of 400mg/kg IV Cyclophosphamide every 28 days on day 1 along with 100mg of oral Prednisone days 1-5 or four cycles of IV Rituximab at a weekly dose of 375mg/m2 was used as 1 stline IST for patients with inhibitor titer &amp;gt;10%. Patients that did not achieve remission or those with persistently high inhibitor titers after 3 cycles of Cyclophosphamide were switched to 2 nd line therapy. In few patients oral Cyclophosphamide or Mycophenolate mofetil was used as maintenance therapy after 1 st or 2 nd line therapy. Bleeding control was achieved with use of rpFVIII or rFVII, FEIBA or emicizumab depending on product availability. Descriptive statistics (mean, SD) &amp; openAI.ChatGPT-4 generated correlation coefficient was used for data analysis. Results A total of 11 male and 5 female patients were identified. The mean age at diagnosis was 69 years and the average length of follow up was 672 days. The mean aPTT value at diagnosis was 84.3 seconds. Inhibitor titer ranged from 1.5 to 329% with an average of 63.62%. Patients with low inhibitor titer of &amp;lt;10% received only steroids and all of them achieved remission without relapse. Rituximab as first-line therapy led to remission in 100% of cases, while only 28.5% of patients treated with cyclophosphamide achieved remission without needing second-line therapy. The time to remission was significantly shorter in patients treated with rituximab compared to cyclophosphamide (43.4vs148.7days). Additionally, none of the patients treated with rituximab experienced a relapse after 1 st remission, while 57% of patients treated with cyclophosphamide did and majority needed 2 nd line &amp; maintenance therapy (Figure-1). Initial inhibitor titer had a moderate to strong positive correlation with the time to remission, the incidence of relapse, and the need for second line and maintenance therapy (Figure- 2). Conclusions Rituximab as first line IST appeared to be more effective than cyclophosphamide in achieving rapid remission and reducing incidence of relapse. Our analysis also revealed that initial inhibitor titer may serve as a useful predictor of disease course, potentially guiding therapeutic decision-making and eliminating need for cytotoxic medication or maintenance therapy. Future large prospective studies are needed to confirm these findings and further investigate other factors influencing therapeutic outcomes in patients with AHA.

Gaucher disease in a patient with membranoproliferative glomerulonephritis: case report

BackgroundGaucher disease (GD) is a rare autosomal recessive inherited, lysosomal storage disoder that involves liver, spleen, lung, bone, bone marrow even central nervous. However, GD associated membranoproliferative glomerulonephritis (MPGN) is seldom reported.Case presentationHere we described a case of 35-year-old man suffering from GD with hepatosplenomegaly, ascites, bone destruction, myelofibrosis and MPGN. Renal biopsy revealed MPGN and Gaucher cells presented in the glomeruli capillaries. β-glucosidase activity was 1.95nmol/1 h/mg and gene detection demonstrated that one homozygous pathogenic variant Leu483Pro in GBA. He received the treatment of oral prednisone and mycophenolate mofetil and his ascites and renal outcomes had been significantly improved.ConclusionsTherapy of prednisone and mycophenolate mofetil may be an optional choice for patients with Gaucher disease who have no opportunity to use enzyme treatment.

Growth Transformation of B Cells by Epstein-Barr Virus Requires IMPDH2 Induction and Nucleolar Hypertrophy.

The in vitro growth transformation of primary B cells by Epstein-Barr virus (EBV) is the initial step in the development of posttransplant lymphoproliferative disorder (PTLD). We performed electron microscopic analysis and immunostaining of primary B cells infected with wild-type EBV. Interestingly, the nucleolar size was increased by two days after infection. A recent study found that nucleolar hypertrophy, which is caused by the induction of the IMPDH2 gene, is required for the efficient promotion of growth in cancers. In the present study, RNA-seq revealed that the IMPDH2 gene was significantly induced by EBV and that its level peaked at day 2. Even without EBV infection, the activation of primary B cells by the CD40 ligand and interleukin-4 increased IMPDH2 expression and nucleolar hypertrophy. Using EBNA2 or LMP1 knockout viruses, we found that EBNA2 and MYC, but not LMP1, induced the IMPDH2 gene during primary infections. IMPDH2 inhibition by mycophenolic acid (MPA) blocked the growth transformation of primary B cells by EBV, leading to smaller nucleoli, nuclei, and cells. Mycophenolate mofetil (MMF), which is a prodrug of MPA that is approved for use as an immunosuppressant, was tested in a mouse xenograft model. Oral MMF significantly improved the survival of mice and reduced splenomegaly. Taken together, these results indicate that EBV induces IMPDH2 expression through EBNA2-dependent and MYC-dependent mechanisms, leading to the hypertrophy of the nucleoli, nuclei, and cells as well as efficient cell proliferation. Our results provide basic evidence that IMPDH2 induction and nucleolar enlargement are crucial for B cell transformation by EBV. In addition, the use of MMF suppresses PTLD. IMPORTANCE EBV infections cause nucleolar enlargement via the induction of IMPDH2, which are essential for B cell growth transformation by EBV. Although the significance of IMPDH2 induction and nuclear hypertrophy in the tumorigenesis of glioblastoma has been reported, EBV infection brings about the change quickly by using its transcriptional cofactor, EBNA2, and MYC. Moreover, we present here, for the novel, basic evidence that an IMPDH2 inhibitor, namely, MPA or MMF, can be used for EBV-positive posttransplant lymphoproliferative disorder (PTLD).

OA01 A case report of a patient with Type 1 diabetes mellitus and systemic lupus erythematosus: a management dilemma

Abstract Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs. Up to 30% of patients with SLE will develop other autoimmune conditions. A few cases of SLE and Type 1 Diabetes Mellitus (T1DM) have been reported in literature. Corticosteroids which is key in induction therapy increases the risk of hyperglycemia and hypertension. Other immunosuppressive agents such as mycophenolate mofetil used in management of lupus nephritis increase the risk of hyperglycemia. This poses a challenge in the management of SLE in a patient with T1DM. Aim To describe a management dilemma in caring for a child with T1DM and SLE at a tertiary referral teaching hospital in Nairobi, Kenya. Method Retrospective chart review of a child with T1DM and SLE at Aga Khan University Medical College East Africa, Nairobi, Kenya. Results We discuss a 16-year-old male patient with T1DM since nine years of age on insulin and on follow up in the endocrine clinic. He presented with complaints of facial and lower limb swelling of three days and severe frontal headache associated with nausea for one day. He was also noted to have a strong family history of Sjogren’s disease and diabetes. His initial examination revealed hypertension with a blood pressure of 184/118 mmHg, facial and lower limb oedema. He was commenced on labetalol infusion and amlodipine for blood pressure control, and was to continue with his insulin regimen. Initial urinalysis showed proteinuria and hematuria. An impression of hypertensive emergency with nephropathy was made. Rheumatology review was requested. Investigations revealed an ANA titer of &amp;gt; 1:1280; anti-smith and anti dsDNA antibodies were positive; low C3 and low C4. Echo showed pleural effusion. The kidney biopsy showed features of proliferative lupus nephritis class IV with no features of diabetic nephropathy. A diagnosis of SLE was made and management initiated with hydroxychloroquine, methylprednisolone for three days then oral prednisolone and mycophenolate mofetil. During methylprednisolone therapy, the patient was noted to have unrecordably high blood glucose necessitating an insulin infusion for six days and close adjustment of insulin doses by the endocrinologist. Initially, after the 1st dose of methylprednisolone, his blood pressure seemed to improve. During the course of treatment, his blood pressure was elevated and difficult to control despite being on labetalol infusion, amlodipine, enalapril and carvedilol. Adjustment of antihypertensive drug doses and addition of hydralazine were made by the nephrologist, cardiologist and critical care specialist. He was eventually discharged with controlled blood glucose and blood pressure. He is currently doing well and is on follow up in the nephrology, rheumatology and endocrinology clinics. Conclusion Our case report highlights the challenges that arise while managing patients with SLE and other illnesses such as T1DM. It also points out the necessity of multi-disciplinary care. This may be a challenge in many African health facilities due to a low number of specialized doctors.