Aggressive Immunosuppressive Therapy Research Articles

P029 Successful treatment of Rapidly progressive MDA-5 with dual combination therapy as a bridge to lung transplantation

Abstract Background/Aims Anti-melanoma differentiation-associated gene 5 (MDA5) is known to be associated with rapidly progressive interstitial lung disease (RP-ILD) and is fatal in most cases. The aim of this case report is to highlight the importance of early detection and aggressive treatment in improving the survival of these patients. Methods A 48-year-old Caucasian man, ex-smoker with 20 pack year history with well-controlled asthma, GORD, hiatus hernia and chondrocalcinosis in right knee on hydroxychloroquine was noted to have finger clubbing and decreased air entry at the right lung base on routine follow up. He worked in print finishing for 18 years. Results Investigations: CXR-increased interstitial shadowing. CT chest-extensive fibrosis NSIP pattern with honey combing, traction bronchiectasis throughout both lung fields and ground glass changes at the lower lobes. FVC 2.99 (63% predicted), FEV1 2.82 (73% predicted), FEV1/FVC ratio 0.95%, TLCO 2.75 (25% predicted), KCO 0.70 (46% predicted). CK- 76, Myositis blot- MDA 5 +ve, c ANCA +ve, PR3&MPO -ve and ANA -ve. CRP 70. Bronchoscopy-normal. He received IV methyl prednisolone 1 gm x 3 followed by prednisolone 60 mg daily and tapering dose along with Cyclophosphamide IVI 1 gm x 6 cycles. Long term home oxygen was prescribed. As he did not improve on initial immunosuppressive treatment, Rituximab IVI 1 gm x 2 was administered within two months of initial therapy. He was referred for lung transplant. As maintenance, he was on mycophenolate 1.5 gm BD, prednisolone 10 mg OD, Co-trimoxazole 960 mg x 3 days per week and rituximab 1 gm at six months and 12 months. He had bilateral lung transplant in Cambridge after two years from the diagnosis. Unfortunately, he developed organizing pneumonia, primary graft dysfunction requiring a brief ITU admission and tracheostomy soon after the transplant. His current medications include Prednisolone 5mg, Mycophenolate 2g Tacrolimus 3mg mane, 2mg nocte, Azithromycin 250mg three times weekly and Septrin 480mg od. He is now managing well, cycling 10-15 miles daily. He no longer requires ambulatory oxygen. His most recent FEV1 4.1L, FVC4.9L and resting saturation 97%. Dual combination aggressive immunosuppressive therapy led to significant disease control in this patient, enabling him to be enlisted for and finally to receive a double lung transplant within a reasonable time limit. It has been reported that patients with MDA 5 ILD have a 1-year survival of 67.5% and a 3-year survival of 46.7%. Conclusion Key Learning Points: Patients with MDA5-ILD have significantly high mortality rate but early diagnosis and optimal treatment combination can lead to favourable outcomes. These patients should be monitored for opportunistic infections. Patient commitment is important. Our patient stopped smoking, reduced weight to improve fitness to optimise the transplant success. Disclosure K. Yein: None. S. Sadiq: None. S. Zeb: None. A. Ahmed: None. E. Price: None.

209 Aggressive immunosuppressive therapy is beneficial early on in reducing autoreactive T cell proliferation in Omenn syndrome/Severe combined immunodeficiency

209 Aggressive immunosuppressive therapy is beneficial early on in reducing autoreactive T cell proliferation in Omenn syndrome/Severe combined immunodeficiency

Systemic lupus erythematosus with juvenile onset: current status of the problem (literature review)

Patients with juvenile-onset systemic lupus erythematosus (jSLE) account for up to 25% of all SLE patients. The main difference between jSLE and SLE in adults is the greater role of genetic factors in the pathogenesis, higher activity, earlier development of complications and the need for more aggressive immunosuppressive therapy, which allows us to consider the onset of the disease in childhood as a special phenotype of SLE. The relevance of the study of jSLE arises from the variability of clinical manifestations and the unpredictability of the course, the difficulty of early diagnosis, the rapid development of organ damage and the unfavorable life prognosis.The article presents the most important modern data on the diagnosis, classification, features of the clinical picture and treatment approaches of jSLE from a practical point of view.

Myositis-associated interstitial lung disease

Introduction/ObjectiveTo review the epidemiology, general clinical aspects and diagnosis, impact on morbidity and mortality, and general treatment approaches for myositis-associated ILD. Materials and methodsThe relevant literature was reviewed. ResultsThe clinical, radiographic, and histopathological features of interstitial lung disease (ILD) in idiopathic inflammatory myopathies (IIM) are similar to idiopathic ILD. Patients with a known diagnosis of myositis require prompt clinical evaluation including the determination of myositis-associated autoantibodies. Patients possessing autoantibodies associated with ILD or those with any pulmonary symptoms should undergo a pulmonary function test and high-resolution CT (HRCT) scanning of their lungs. ConclusionDespite the lack of placebo-controlled trials, systemic glucocorticoids are considered the mainstay of initial treatment of myositis-associated ILD. Glucocorticoid-sparing agents are often concomitantly administered, particularly in patients with severe disease. The first-line conventional immunosuppressive drugs include either mycophenolate mofetil or azathioprine. If these agents fail or if the pulmonary features are severe or rapidly progressive, then more aggressive immunosuppressive or immunomodulatory therapy including cyclophosphamide, tacrolimus or cyclosporine, rituximab, IVIg, or tofacitinib can be considered. Further investigations are required to assess the role of novel therapies in the treatment of myositis-associated ILD.

Ruptured popliteal artery aneurysm: An initial presentation of Behçet’s disease

Behçet’s Disease (BD) is an uncommon systemic vasculitic disorder, that can affect multiple organ systems. Arterial and venous aneurysmal and occlusive manifestations can occur. We report a case of a 25-year-old male presenting with a 4-week history of left leg pain and swelling, with acute deterioration due to ruptured popliteal aneurysm, confirmed on imaging. He underwent emergency popliteal bypass with ipsilateral reversed great saphenous vein. Subsequent workup revealed pulmonary aneurysms and features suggestive of BD. He received aggressive immunosuppressive therapy to good effect. The management of the patient’s popliteal aneurysm, diagnostic procedure and subsequent management are discussed.

Levamisole-Adulterated Cocaine-Induced Mucous Membrane Pemphigoid: Case Reports and Literature Review.

The aim of this study was to report 2 cases of levamisole-adulterated cocaine-induced mucous membrane pemphigoid. This study is a review of case reports and literature. Two patients presented with bilateral severe purulent conjunctivitis, corneal ulceration, and rapidly progressive forniceal shortening. Both patients were active cocaine users. A complete blood analysis showed a positive antineutrophil cytoplasmic antibody immunofluorescence with a mixed perinuclear antineutrophil cytoplasmic antibody and cytoplasmic-staining antineutrophil cytoplasmic antibody pattern. Direct immunofluorescence examination of conjunctival tissue showed linear deposition of component 3 and immunoglobulins at the basal membrane. A diagnosis of levamisole-adulterated cocaine-induced mucous membrane pemphigoid was made. In case 1, this suspicion was confirmed by investigating remnants of cocaine on the patient's debit card using mass spectrometry, which contained traces of levamisole. In both cases, aggressive immunosuppressive therapy combining systemic corticosteroids and rituximab was able to control the disease. However, by the time these therapies were initiated, significant corneal injury had occurred requiring corneal grafts in both patients. Given the rising abuse of cocaine, it is important that ophthalmologists are made aware of its association with severe atypical cicatricial conjunctivitis. To the best of our knowledge, we present the first case proving the causal relationship between levamisole and ocular cicatricial pemphigoid.

Sterile granulomatous panuveitis in dogs in the United Kingdom: A review of 33 cases.

To describe the clinical and histopathological features of a sterile granulomatous panuveitis syndrome in 33 dogs that underwent enucleation and ocular histopathology. Retrospective review of the medical records and ocular histopathology reports of 33 cases. Inclusion criteria were enucleation in conjunction with characteristic clinical and histopathological features. Thirteen breeds were represented (including crossbreeds). Panuveitis was acute and fulminating, and secondary glaucoma was common (n = 27). Interval from initial presentation to enucleation was 99 days (median 33 days, range 5-605 days). The mean age at enucleation was 6.7 years. Ocular signs were initially unilateral (n = 18) or bilateral (n = 15). The disease became bilateral in 18/25 cases that initially underwent unilateral enucleation, resulting in enucleation or euthanasia in 9/18 (mean interval of 168 days). Seven out of 59 eyes had a good outcome following topical anti-inflammatory and systemic immunosuppressive therapy. None of the dogs had travel history nor relevant systemic signs from presentation to follow-up (mean 619 days, range 16-3012 days). Histopathology revealed histiocytic and lymphoplasmacytic panuveitis with pigment dispersion, and no infectious agents were identified on light microscopy. To the authors' knowledge, this is the first report of a sterile granulomatous panuveitis syndrome in dogs in the UK. The clinical signs are severe, with rapid progression, and can result in bilateral enucleation or euthanasia in affected dogs. There does not appear to be an age or breed predisposition, however further research is necessary in this regard. Early and aggressive intervention, with both topical and systemic immunosuppressive therapy, is recommended to reduce the risk of blindness, enucleation, and euthanasia.

Magnetic Resonance Imaging/cerebrospinal Fluid-negative Myelitis Following COVID-19 with a Dramatic Response to Early Aggressive Immunosuppressive Therapy.

A 57-year-old man presented with subacute-onset paraparesis, bilateral dysesthesia in his lower extremities, and bladder/bowel disturbance six weeks after being infected with SARS-CoV-2 infection (COVID-19). A neurological examination suggested transverse myelitis at the level of the lower thoracic spinal cord. However, repeated spinal magnetic resonance imaging (MRI) showed no abnormalities in the spinal cord. Laboratory and cerebrospinal fluid (CSF) tests ruled out other etiologies of myelitis, eventually suggesting COVID-19-associated myelitis. Aggressive immunosuppressive therapy, started soon after hospitalization, dramatically improved his symptoms. Early aggressive immunosuppressive therapy should therefore be considered in cases of MRI/CSF-negative myelitis associated with COVID-19.

Immunotherapy of acquired hemophilia A.

Acquired hemophilia A (AHA) is an autoimmune disorder characterized by the formation of autoantibodies that neutralize the function of coagulation factor VIII. Immunosuppressive therapy (IST) with glucocorticoids, cyclophosphamide, rituximab, or combinations thereof is the standard of care to suppress autoantibody formation and induce remission of AHA. About 80% of patients achieve remission over the course of a few weeks to several months. However, patients with AHA are often elderly and frail and have adverse events from IST. Therefore, guidelines suggest an individualized approach using caution in elderly and frail patients. Prophylaxis with emicizumab may reduce the need for early and aggressive IST in the future.

Myositis-associated interstitial lung disease

Introduction/ObjectiveTo review the epidemiology, general clinical aspects and diagnosis, impact on morbidity and mortality, and general treatment approaches for myositis-associated ILD. Materials and methodsThe relevant literature was reviewed. ResultsThe clinical, radiographic, and histopathological features of interstitial lung disease (ILD) in idiopathic inflammatory myopathies (IIM) are similar to idiopathic ILD. Patients with a known diagnosis of myositis require prompt clinical evaluation including the determination of myositis-associated autoantibodies. Patients possessing autoantibodies associated with ILD or those with any pulmonary symptoms should undergo a pulmonary function test and high-resolution CT (HRCT) scanning of their lungs. ConclusionDespite the lack of placebo-controlled trials, systemic glucocorticoids are considered the mainstay of initial treatment of myositis-associated ILD. Glucocorticoid-sparing agents are often concomitantly administered, particularly in patients with severe disease. The first-line conventional immunosuppressive drugs include either mycophenolate mofetil or azathioprine. If these agents fail or if the pulmonary features are severe or rapidly progressive, then more aggressive immunosuppressive or immunomodulatory therapy including cyclophosphamide, tacrolimus or cyclosporine, rituximab, IVIg, or tofacitinib can be considered. Further investigations are required to assess the role of novel therapies in the treatment of myositis-associated ILD.

Risk of end-stage renal disease in patients with early-onset lupus nephritis: A population-based cohort study

ObjectiveTo compare the risk of end-stage renal disease (ESRD) between patients with early-onset lupus nephritis (EOLN) and those with delayed-onset LN (DOLN). MethodsThis retrospective study of incident cases of systemic lupus erythematosus (SLE) used nationwide Korean claims databases and data from 2008 through 2018. We divided LN patients into two groups: the EOLN group (with LN onset within 12 months of SLE diagnoses) and the DOLN group (with LN onset later than 12 months after SLE diagnoses). Patients were observed from the date of LN diagnosis to the development of ESRD, death, or the last follow-up. Cox proportional hazards modeling was used to predict hazard ratios (HRs) for progression to ESRD with death as a competing risk. ResultsWe identified 3779 incident SLE patients who developed LN during follow-up: 60 % (n = 2281) had EOLN, and 40 % (n = 1489) had DOLN. Sixty-nine patients with EOLN (3.0 %) and 29 patients with DOLN (1.9 %) progressed to ESRD. After adjusting for confounders, the ESRD risk associated with EOLN was comparable to the risk associated with DOLN (HR 1.10, 95 % confidence interval [CI] 0.57 to 2.11). In the subgroup of patients on aggressive immunosuppressive therapy (670 with EOLN and 179 with DOLN), the ESRD risk was higher in the DOLN group (HR 2.6, 95 % CI 1.11 to 6.10). ConclusionThe risk of ESRD was comparable between patients with EOLN and DOLN. However, among patients on aggressive immunosuppressive therapy, compared with EOLN, DOLN was associated with a higher risk of progression to ESRD.

Total Lymphoid Irradiation in the Treatment of Heart Transplant Rejection: Single Institution Long-Term Results

Acute cardiac allograft rejection is a major cause of morbidity and mortality post-transplant. Total lymphoid irradiation (TLI) has been shown to cause long-lasting alterations in lymphocyte sub-sets, and thereby induces a state of partial response that is useful to prevent organ transplant rejection. In our previous report, treatment with TLI resulted in decreased episodes of acute rejection and steroid dosage requirements for up to 9.1 years post cardiac transplantation. In this study, we report an update on the short- and long-term effects of TLI in the treatment of cardiac transplant rejection. We performed a retrospective analysis of patients with intractable cardiac allograft transplantation evaluated in the department of radiation oncology at our institution over 23 years (1998-2021). Cardiac allograft rejection was defined as multiple or persistent episodes of rejection despite aggressive immunosuppressive therapy. The prescribed dose was 8 Gy in 10 fractions to be delivered over 5 weeks. All episodes of pathologic acute cardiac rejection, duration of immunosuppression, and episodes of acute infection requiring treatment before and after TLI were documented. Overall survival (OS) was analyzed using Kaplan-Meier method. The median time to first cardiac allograft rejection and the median time to first acute rejection was monitored. Of the 29 patients included, 21 (72.4%) had ISHLT grade 1R, 5 (17.2%), grade 2R, and 2(6.9%) grade 3R rejection. Rejection grade was unknown for 1 patient. The mean number of acute rejections after transplant was 14.4 episodes per patient (range 1-44) with median time to first rejection of 0.63 months. The median radiation dose was 8 Gy (range 7.2-8 Gy) delivered over a mean of 31 days. Treatment was stopped early in 2 (6.5%) patients (after 7.2 Gy and 7.9 Gy) for severe bone marrow suppression and drop in CD4 counts, respectively. The number of rejections dropped from 14.2 to 3.97 per patient over a median time of 29.0 months vs 28.1 months pre and post TLI (p = 0.01). The frequency of ISHLT acute grade 3R rejections decreased from 0.58 to 0.06 episodes per patient pre and post TLI (p = 0.02). Immunosuppressant requirements decreased from 2.83 before TLI to 2.69 after TLI (p = 0.71). Infection rates per patient were 0.71 pre TLI and remained at 0.63 post TLI. Treatment was well tolerated with 4 (13.8%) grade 2 or higher radiation toxicity. Median follow up was 76.3 months. Median and 3-year OS were 53.4 months and 60.9%, respectively. TLI is a safe and effective treatment for control of intractable cardiac rejection. The episodes of acute rejection and immunosuppressant requirements are decreased, but with long-term follow up, these patients continue to experience rejection. However, TLI lowers the frequency of ISHLT moderate to severe rejection episodes for up to 6.4 years. There was no increased risk of severe infections and there were only minimal short- and long-term grade 2 or higher radiation toxicities.

Presence of uveitis as indicator of juvenile idiopathic arthritis severity: results of a retrospective cohort study

BACKGROUND: Juvenile idiopathic arthritis is the most common rheumatic disease in children. A frequent extra-articular manifestation of juvenile idiopathic arthritis is uveitis, which is a serious clinical diagnostic problem in routine pediatric practice. Among the known risk factors for uveitis are the early age of the juvenile idiopathic arthritis onset, oligoarticular subtype, seropositivity by antinuclear factor.
 AIM: to evaluate the influence of presence of uveitis on the course of juvenile idiopathic arthritis.
 MATERIALS AND METHODS: A single-center retrospective study included 520 patients with uveitis. The analysis was carried out among patients who developed (n = 116) and did not develop (n = 404) uveitis. The minimum follow-up period was 2 years, for patients who did not develop uveitis.
 RESULTS: Uveitis was diagnosed in 116 (22.3%) children with juvenile idiopathic arthritis. Most often, uveitis occurred in patients with oligoarthritis and psoriatic arthritis. When comparing the features of the articular status of patients with juvenile idiopathic arthritis who developed and did not develop uveitis, a lower frequency of involvement of the cervical spine, temporomandibular, shoulder, elbow, wrist, proximal and distal interphalangeal joints, hip, talus-heel joint, as well as a smaller number of active joints in children with uveitis was found. Patients with uveitis received methotrexate therapy more often, cumulative doses of corticosteroids were lower, the frequency of prescribing genetically engineered biological drugs was approximately the same in both groups. Remission of arthritis was achieved more often, but the proportion of children who developed an exacerbation was higher. When calculating the risk factors of uveitis by binary logistic regression, it was found that the main predictors of uveitis were oligoarthritis, the number of active joints 8, seropositivity by antinuclear factor and recurrent course of arthritis. The difference in the frequency of achieving remission may be due to more aggressive systemic therapy in the presence of uveitis.
 CONCLUSIONS: Children with uveitis have a more severe course of juvenile idiopathic arthritis and may require more aggressive immuno-suppressive therapy. Further studies are required to determine the prognostic role of uveitis in the course and outcomes of juvenile idiopathic arthritis.

Immunomodulatory Therapy for Giant Cell Myocarditis: A Narrative Review.

Giant cell myocarditis (GCM) is a rare, often rapidly progressive, and potentially fatal disease because of myocardium inflammation due to the infiltration of giant cells triggered by infectious as well as non-infectious etiologies. Several studies have reported that GCM can occur in patients of all ages but is more commonly found in adults. It is relatively more common among African American and Hispanic patients than in the White population. Early diagnosis and treatment are critical. Electrocardiogram (EKG), complete blood count, erythrocyte sedimentation rate, C-reactive protein, and cardiac biomarkers such as troponin and brain natriuretic peptide (BNP), echocardiogram, cardiac magnetic resonance imaging (MRI), myocardial biopsy, and myocardial gene profiling are useful diagnostic tools. Current research has identified several potential biomarkers for GCM, including myocarditis-associated immune cells, cytokines, and other chemicals. The standard of care for GCM includes aggressive immunosuppressive therapy with corticosteroids and immunomodulatory agents like rituximab, cyclosporine, and infliximab, which have shown promising results in GCM by balancing the immune system and preventing the attack on healthy tissues, resulting in the reduction of inflammation, promotion of healing, and decreasing the necessity for cardiac transplantation. Without immunosuppression, the chance of mortality or cardiac surgery was 100%. Multiple studies have revealed that a treatment combination of corticosteroids and immunomodulatory agents is superior to corticosteroids alone. Combination therapy significantly increased transplant-free survival (TFS) and decreased the likelihood of heart transplantation, hence improving overall survival. It is important to balance the benefits of immunosuppression with its potentially adverse effects. In conclusion, immunomodulatory therapy adds significant long-term survival benefits to GCM.

Successful treatment of rapidly progressive interstitial lung disease complicated by a refractory pneumomediastinum in a patient with anti‐MDA5 antibody‐positive dermatomyositis

AbstractIntroductionAnti‐melanoma differentiation‐associated gene 5‐positive dermatomyositis (anti‐MDA5+ DM) is a distinct subtype of DM, which is characterized by typical cutaneous features, minimal or no muscle involvement and notable interstitial lung disease, which typically progresses rapidly and has a high mortality. Spontaneous pneumomediastinum (PNM), a relatively unusual but serious complication of anti‐MDA5+ DM, further increases mortality. Currently, there is no generally accepted treatment regimen for anti‐MDA5+ DM‐associated PNM.Case DescriptionA 53‐year‐old man with anti‐MDA5+ DM presented with rapidly progressive interstitial lung disease that progressed to diffuse subcutaneous emphysema and PNM despite aggressive immunosuppressive therapies. He responded well to combined anti‐infection treatments, moderate immunotherapy, and continuous oxygen therapy.ConclusionComprehensive screening for potential infections, as well as close monitoring of the patient's immune status is essential for individualizing treatment and maximizing prognosis.

Novel Antifungals and Aspergillus Section Terrei with Potpourri Susceptibility Profiles to Conventional Antifungals.

The epidemiology of invasive fungal infections (IFIs) is currently changing, driven by aggressive immunosuppressive therapy, leading to an expanded spectrum of patients at risk of IFIs. Aspergillosis is a leading cause of IFIs, which usually affects immunocompromised patients. There are a limited number of antifungal medications available for treating IFIs, and their effectiveness is often hindered by rising resistance rates and practical limitations. Consequently, new antifungals, especially those with novel mechanisms of action, are increasingly required. This study assessed the activity of four novel antifungal agents with different mechanisms of activity, namely, manogepix, rezafungin, ibrexafungerp, and olorofim, against 100 isolates of Aspergillus section Terrei, containing amphotericin-B (AmB)-wildtype/non-wildtype and azole-susceptible/-resistant strains, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method. In general, all tested agents showed potent and consistent activity against the tested isolates, exhibiting geometric mean (GM) and minimum effective concentration (MEC)/minimum inhibitory concentration (MIC) ranges, respectively, as follows: manogepix (0.048 mg/L, 0.032-0.5 mg/L), rezafungin (0.020 mg/L, 0.016-0.5 mg/L), ibrexafungerp (0.071 mg/L, 0.032-2 mg/L), and olorofim (0.008 mg/L, 0.008-0.032 mg/L). In terms of MIC90/MEC90, olorofim had the lowest values (0.008 mg/L), followed by rezafungin (0.032 mg/L), manogepix (0.125 mg/L), and ibrexafungerp (0.25 mg/L). All the antifungals tested demonstrated promising in vitro activity against Aspergillus section Terrei, including A. terreus as well as azole-resistant and AmB-non-wildtype cryptic species.

Modern approaches to the diagnosis and treatment of cardiac sarcoidosis: results of a cohort study

Aim. To analyze clinical and paraclinical data in patients with documented cardiac sarcoidosis, outlining the key points of diagnosis and selection of the optimal treatment.Material and methods. For the period from 2016 to 2021, 63 patients (50,4±14,1 years) were included in the cohort study on negotiability. Based on a standard examination, 15 patients (41±13 years old) were selected, who continued the examination to confirm the diagnosis of cardiac sarcoidosis. Contrast-enhanced cardiac magnetic resonance imaging (MRI) was performed in 10 patients, while endomyocardial biopsy in 7 patients. All patients underwent 18F-fluorodeoxyglucose positron emission tomography (PET).Results. The most common (53%) electrocardiographic abnormality was right bundle branch block. Ventricular arrhythmias and high-grade atrioventricular block were recorded mainly in patients with documented activity. Regional contractility disorders were predominantly detected in patients with cardiac fibrosis. Delayed contrast enhancement according to cardiac MRI was recorded mainly intramurally in the interventricular septum and subepicardial area of left ventricular (LV) lateral wall. When analyzing the PET results, we found the predominant radiopharmaceutical accumulation in the interventricular septum (56%), lateral (44%) and anterior (33%) LV walls. There was no significant improvement in global LV contractility against the background of immunosuppressive therapy, especially in patients with reduced ejection fraction: initially 49,2±10,1% vs 46,9±14,9% during therapy (p=0,658).Conclusion. A certain apprehensive attitude of the doctor and adherence to the algorithm for early diagnosis of cardiac sarcoidosis allows minimizing the risks of fatal cardiovascular events. On the contrary, in the case of late diagnosis, even the use of aggressive immunosuppressive therapy does not lead to an improvement in global myocardial contractility, and fibrosis zones can cause life-threatening bradyarrhythmias and ventricular arrhythmias.

Efficacy and Safety of Plasma Exchange as an Adjunctive Therapy for Rapidly Progressive IgA Nephropathy and Henoch-Schönlein Purpura Nephritis: A Systematic Review.

Patients with IgA nephropathy (IgAN), including Henoch-Schönlein purpura nephritis (HSP), who present with rapidly progressive glomerulonephritis (RPGN) have a poor prognosis despite aggressive immunosuppressive therapy. The utility of plasmapheresis/plasma exchange (PLEX) for IgAN/HSP is not well established. This systematic review aims to assess the efficacy of PLEX for IgAN and HSP patients with RPGN. A literature search was conducted using MEDLINE, EMBASE, and through Cochrane Database from inception through September 2022. Studies that reported outcomes of PLEX in IgAN or HSP patients with RPGN were enrolled. The protocol for this systematic review is registered with PROSPERO (no. CRD42022356411). The researchers systematically reviewed 38 articles (29 case reports and 9 case series articles) with a total of 102 RPGN patients (64 (62.8%) had IgAN and 38 (37.2%) had HSP). The mean age was 25 years and 69% were males. There was no specific PLEX regimen utilized in these studies, but most patients received at least 3 PLEX sessions that were titrated based on the patient's response/kidney recovery. The number of PLEX sessions ranged from 3 to 18, and patients additionally received steroids and immunosuppressive treatment (61.6% of patients received cyclophosphamide). Follow-up time ranged from 1 to 120 months, with the majority being followed for at least 2 months after PLEX. Among IgAN patients treated with PLEX, 42.1% (n = 27/64) achieved remission; 20.3% (n = 13/64) achieved complete remission (CR) and 18.7% (n = 12/64) partial remission (PR). 60.9% (n = 39/64) progressed to end-stage kidney disease (ESKD). Among HSP patients treated with PLEX, 76.3% (n = 29/38) achieved remission; of these, 68.4% (n = 26/38) achieved CR and 7.8% achieved (n = 3/38) PR. 23.6% (n = 9/38) progressed to ESKD. Among kidney transplant patients, 20% (n = 1/5) achieved remission and 80% (n = 4/5) progressed to ESKD. Adjunctive plasmapheresis/plasma exchange with immunosuppressive therapy showed benefits in some HSP patients with RPGN and possible benefits in IgAN patients with RPGN. Future prospective, multi-center, randomized clinical studies are needed to corroborate this systematic review's findings.

Management of autoimmune factor XIII deficiency in a frail, elderly patient.

Autoimmune factor XIII/13 deficiency (aFXIII deficiency) is a rare hemorrhagic disorder, for which typical guideline-directed treatment is aggressive immunosuppressive therapy. Approximately 20% of patients are over 80 years old; however, and optimum management of such patients has not reached consensus. Our elderly patient had massive intramuscular hematoma, and aFXIII deficiency was diagnosed. The patient opted against aggressive immunosuppressive therapy, so he was managed with conservative treatment only. Thorough survey of other correctable causes of bleeding and anemia is also required in similar cases. Our patient's serotonin-norepinephrine reuptake inhibitor use and multivitamin deficiency (vitamin C, B12 and folic acid) were revealed to be aggravating factors. Fall prevention and muscular stress prevention are also important in elderly patients. Our patient had two relapses of bleeding within 6 months, which were improved spontaneously by bed rest without factor XIII replacement therapy or blood transfusion. Conservative management may be preferred for frail and elderly patients with aFXIII deficiency when they opt against standard therapy.

Relapsing Polychondritis and Aseptic Meningoencephalitis.

We herein report a 49-year-old Japanese man with relapsing polychondritis (RP) and aseptic meningoencephalitis. Four years ago, the patient was diagnosed with RP. Prednisolone (PSL) was started at 30 mg/day, and the symptoms promptly disappeared. However, cognitive impairment gradually appeared from six months before hospitalization. Methylprednisolone pulse therapy was immediately initiated, followed by administration of PSL at 1 mg/kg/day. Intravenous cyclophosphamide was combined with PSL. After treatment, the patient's cognitive impairment clearly improved. In conclusion, RP rarely causes aseptic meningoencephalitis, highlighting the need for prompt and aggressive immunosuppressive therapy.