Intravenous Pulse Cyclophosphamide Research Articles

Enteric-coated Mycophenolate Sodium therApy versus cyclophosphamide for induction of Remission in Microscopic PolyAngiitis (EMSAR-MPA trial): study protocol for a randomised controlled trial

IntroductionSeveral studies have demonstrated that mycophenolate mofetil (MMF) may be an excellent alternative to cyclophosphamide (CYC) or rituximab for the induction of remission in non-life-threatening anti-neutrophil cytoplasmic antibodies associated vasculitis...

Subarachnoid Hemorrhaging with Multiple Cerebral Artery Stenoses after Initiating Remission Induction Therapy for Eosinophilic Granulomatosis with Polyangiitis: a Case Report.

We encountered a 64-year-old Japanese woman who developed subarachnoid hemorrhaging (SAH) with multiple cerebral artery stenoses during remission induction therapy for eosinophilic granulomatosis and polyangiitis (EGPA). The treatment involved intensified steroid pulse therapy and continued intravenous cyclophosphamide pulse therapy, which led to beneficial effects. Given the rarity of multiple EGPA-associated cerebral artery stenoses and SAH, it is crucial to differentiate them from other diseases. The mortality rate of EGPA complicated by intracranial hemorrhagic lesions, including SAH, is high. When headache is present at the onset of EGPA, the possibility of SAH must be considered.

Aggressive multi-combination therapy for anti-MDA5 antibody-positive dermatomyositis-rapidly progressive interstitial lung disease.

To elucidate the efficacy and safety of aggressive multi-combination therapy with mycophenolate mofetil, rituximab, and plasma exchange or polymyxin B immobilized fiber column direct hemoperfusion followed by conventional therapy with corticosteroids, calcineurin inhibitors, and intravenous pulse cyclophosphamide in patients with rapidly progressive interstitial lung disease (RPILD) with anti-melanoma differentiation-associated gene 5 (MDA5)-antibody-positive dermatomyositis (DM). A total of 23 patients with anti-MDA5 antibody-positive DM-RPILD were enrolled, with nine patients in Group A (treated conventionally before March 2015) and 14 patients in Group B (received aggressive treatment after April 2015). Pretreatment severity of interstitial lung disease (ILD) did not differ between the two groups. However, Group B exhibited a higher cumulative survival rate at 48 weeks than Group A (64.3% vs. 33.3%). The corticosteroid dose, divided by the initial dose at 3 months and 12 months, was significantly lower in Group B than in Group A (p = .046 and .026, respectively). Among the ILD-related deaths in Group B, there was a tendency toward a higher proportion of males and more severe ILD. The incidence of infection did not differ between the groups, but leukopenia was more common in Group B. This aggressive multi-combination therapy may improve the survival outcome of patients with anti-MDA5 antibody-positive DM-RPILD. However, careful management of complications, such as opportunistic infections and leukopenia, is essential. Future refinement through longitudinal investigations tracking the long-term efficacy, safety, and cost-effectiveness of this treatment strategy is needed.

#6809 PULSE VERSUS DAILY ORAL CYCLOPHOSPHAMIDE IN ANCA-ASSOCIATED VASCULITIS WITH RENAL INVOLVEMENT: A SINGLE CENTER EXPERIENCE

Abstract Background and Aims We aimed to compare the risk of death, relapse and infections requiring hospital admission of ANCA-associated vasculitis (AAV) patients according to the induction of remission scheme used: daily oral (PO) cyclophosphamide or pulse intravenous (IV) cyclophosphamide. Method We identified all newly diagnosed AAV patients treated with PO or IV cyclophosphamide between January 1998 and December 2022 admitted to the CHVNGE Nephrology Department. Data were analyzed with SPSS v28® using parametric and non-parametric tests and Kaplan Meyer survival analysis. Results We identified 74 cases of de novo vasculitis, 50 of them received PO cyclophosphamide and 24 received IV cyclophosphamide. Median age at presentation was 68,50 ± 16,06 years PO and 68,00 ± 10,41 years IV. Median duration of follow-up was 3,8 years ± 2,98 for both groups, 6,21 years PO and 3,88 years IV. One-year survival was 84% in PO and 91,3% in IV patients; 15 (30%) PO and 5 (20,8%) pulse patients had at least one relapse. Neoplasms occurred in 3 (6%) patients in the PO group and 1 (4,2%) patient in the IV group. The number of patients admitted with one or more infections was 22 (44%) in the PO group and 9 (37,5%) in the IV group. Renal survival was 26 (52%) PO and 15 (62,5%) IV. There was no difference in survival (p = 0,176), renal survival (p = 0,113), risk of relapse (p = 0,283) and infection (p = 0,196) between the two groups. Conclusion There was no difference in renal or overall survival, confirming the previous published data. Contrasting with CYCLOPS, our analysis does not confirm an increased risk of relapse in the IV group. One particularly interesting data is that the number of infections in IV route was lower than PO, corroborating the data on lower cumulative doses and therefore lower risk of infection in previous studies. Potential bias of this study is the small sample of patients enrolled in the two groups and the duration of follow up. Despite the reduction in the cumulative dose of cyclophosphamide, we continue to have significant adverse effects, which can also be explained by the dose of corticosteroid previously used, therefore strategies to reduce the toxicity associated with treatment without compromising efficacy are important goals for future research. Treatments need to be optimized and customized according to the severity of the patient's disease and the risk of recurrence.

#4709 PERSONALISED INDUCTION THERAPY IN ANCA GLOMERULONEPHRITIS

Abstract Background and Aims Patient and kidney outcome in ANCA glomerulonephritis (GN) remains unsatisfactory. Rituximab use failed to reduce the rate of infectious complications and demonstrates a significant rate of hypogammaglobulinaemia in ANCA vasculitis. Adjusting the rituximab dosage to the individual patient's need promises a reduction in treatment toxicity. Method Retrospective analysis of a single centre cohort of ANCA GN patients with disease flares between 2019 – 2022 using a stratified induction immunosuppression with rituximab and cyclophosphamide. Treatment intensity was adjusted to resolution of systemic inflammation and microscopic haematuria, peripheral CD19 cell count depletion and immunoglobulin G (IgG) levels. Results 45 patients (median age 57 years, 55.7% female, median eGFR 27 mls/min) were treated with a median dose of 1.5 grams Rituximab during induction (interquartile range, IQR 1 – 2 grams). 18 patients received concomitant intravenous cyclophosphamide pulses to control the acute inflammation (median cumulative dose of 2 grams, IQR 1.65 – 3 grams). Peripheral B cell depletion was 91.4% at 3 months and 90.3% at 6 months (<3 CD19 cells/ul). During the initial 12 months treatment, IgG level fell below 7g/l in 20 patients, below 5g/l in nine patients and below 3g/l in one patient. Seven patients required renal replacement therapy at diagnosis (15.6%). Five patients recovered kidney function and three patients developed end stage kidney disease (6.7%). Twelve infections were reported requiring antibiotic treatment (26.7%), seven severe infections were documented requiring hospitalisation (13.3%) and one patient died (2.2%). Conclusion An early assessment of treatment response assists adjusting vasculitis therapy. Adjusting management to the patient's individual immunological and treatment response may result in better outcome with less treatment toxicity.

#5835 A LOW DOSE GLUCOCORTICOID, LOW DOSE CYCLOPHOSPHAMIDE, RITUXIMAB TREATMENT PROTOCOL AS INDUCTION THERAPY IN ANCA ASSOCIATED VASCULITIS PATIENTS

Abstract Background and Aims There has been a considerable improvement in the survival of patients with ANCA associated vasculitis (AAV) since the introduction of immunosuppressive therapy. Nowadays early deaths are attributable to infection while cardiovascular disease, infection and malignancy are the most common causes in long term mortality in these patients. High-dose glucocorticoids and cyclophosphamide have numerous dose-dependent adverse effects and are associated with those events. The aim of this study is to investigate the efficacy and safety a low dose glucocorticoids, low dose cyclophosphamide, rituximab treatment protocol in AAV patients. Method This is a single-centre cohort study of patients on a combination of reduced-dose oral glucocorticoids, rituximab and low-dose pulsed intravenous cyclophosphamide followed by a maintenance regimen of rituximab and tapered steroid for the treatment of AAV (table). Data shown as median (IQR). Results Nine patients (3 women) aged 62.4 (55/67.8) years, with serum creatinine (sCre) 2.15 (1.8/2.5) mg/dL, eGFR CKD-EPI 28 (20/39) ml/min/1.73 m2, albuminuria 0.98 (0.57/1.45) gr/24 h and BVAS 14 at baseline were treated with the mentioned protocol. Seven patients had MPO and 2 had double MPO/PR3 positivity. Two were already on dialysis and 4 had pulmonary involvement. The median follow-up was 19 (12.5/39) months. One patient required the addition of plasma exchange and extended treatment due to aggressive disease and one was lost to follow-up after four months. The rest of the 7 patients were dialysis free with a sCre 2.15 (1.8/2.5) mg/dL, eGFR 28 (20/39) ml/min/1.73 m2 at the end of follow-up. Patient and renal survival were 88% and 100% respectively. 85.7% of patients achieved ANCA-negative status and all remained B cell deplete at 6 and 18 months. There were no major relapses, while two patients had infection related hospitalization. No unexpected side effects were observed during follow-up. Conclusion These findings confirm the literature that a combined regimen provides early disease control with low relapse rates, without significant adverse effects from immunosuppression. A regimen like this may provide the basis for further refinement of remission induction protocols in AAV, potentially allowing early withdrawal of corticosteroids.

Clinical Image: Antineutrophil cytoplasmic antibody-associated vasculitis causing compressive cervicothoracic myelopathy.

The patient, a 64-year-old man, presented with a 6-week history of upper back pain and progressive lower-limb weakness and paraesthesia. Of particular note, he had a past history of chronic sinusitis and otitis media. Examination revealed a spastic paraparesis with sustained clonus, hyperreflexia, and medical research council grade 3/5 weakness in both lower limbs. Magnetic resonance imaging of his cervicothoracic spine revealed a circumferential mass–like lesion extending from C5 to T9 with compression of the spinal cord at T2-T3 (see image). Antineutrophil cytoplasmic antibody (ANCA) testing revealed a perinuclear pattern with a strongly positive myeloperoxidase antibody. Histologic examination demonstrated a dense lymphocytic infiltrate with fibrinoid necrosis of the blood vessel wall consistent with vasculitis. A diagnosis of ANCA-associated vasculitis causing compressive myelopathy was made. Treatment with high-dose glucocorticoids and pulsed intravenous cyclophosphamide was initiated, with almost immediate improvement seen in the patient's neurological status. This highlights the importance of including ANCA-associated vasculitis within the differential causes of spinal lesions. Disclosure form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Diagnostic and Management Strategies of IgA Vasculitis Nephritis/Henoch-Schönlein Purpura Nephritis in Pediatric Patients: Current Perspectives.

IgA vasculitis (IgAV) or Henoch-Schönlein purpura (HSP) is the most common vasculitis in children, and nephritis (IgAVN or HSPN) is the most important and only chronic manifestation of the disease. Despite this, there are no diagnostic criteria and we rely on the European League Against Rheumatism/Paediatric Rheumatology International Trials Organization/Paediatric Rheumatology European Society-endorsed Ankara 2008 classification criteria in our daily practice. Basic investigations that should be done in every patient with IgAVN include blood pressure measurement, estimated glomerular filtration rate and urinalysis. Kidney biopsy is still the gold standard for the diagnosis of IgAVN since noninvasive confirmation of nephritis is still pending. According to the Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) recommendations, the first-line treatment for with mild forms of IgAVN is oral glucocorticoids, for patients with moderate IgAVN parenterally administrated glucocorticoids in pulsed doses, while initial treatment for patients with the most severe forms of IgAVN include pulsed doses of glucocorticoids in combination with intravenous cyclophosphamide pulses. New therapeutic options are currently being tested, aiming to reduce the production of galactose-deficient IgA1 and autoantibodies or suppress the alternative or lectin complement pathway and blocking mesangial cell activation.

Pulmonary and Intestinal Involvement in a Patient with Myeloperoxidase-specific Antineutrophil Cytoplasmic Antibody-positive Hermansky-Pudlak Syndrome.

A 26-year-old Japanese woman was admitted with a 1-month history of diarrhea, a high fever for a few days, and exacerbation of dyspnea. She was treated with an antifibrotic drug and long-term oxygen therapy for Hermansky-Pudlak syndrome-related pulmonary fibrosis. New ground-glass attenuation appeared on chest computed tomography (CT), and a colon biopsy showed an inflammatory cell accumulation with a high titer of myeloperoxidase (MPO)-specific anti-neutrophil cytoplasmic antibodies (ANCA). Systemic inflammation related to MPO-ANCA titer elevation was suspected. Steroid pulse therapy and intravenous cyclophosphamide improved chest CT findings and diarrhea. Therefore, immunosuppressant treatment should be considered for systemic inflammation related to MPO-ANCA.

Effect of Sequential Intravenous Pulse Cyclophosphamide-Azathioprine in Systemic Sclerosis-Interstitial Lung Disease: An Open-Label Study

Systemic sclerosis (SSc) is a rare connective tissue disorder of unknown aetiology. Pulmonary involvement contributes substantially to its morbidity and mortality. Treatment of pulmonary disease due to SSc remains unsatisfactory. We examined the effect of sequential six-month intravenous pulse therapy with cyclophosphamide (CYC) followed by azathioprine and low-dose corticosteroids on SSc associated interstitial lung disease (SSc-ILD). In a single-centre, prospective, observational, open-labelled study; nine patients (eight females, one male) with SSc-ILD were treated with intravenous pulse CYC (600mg/m(2) body surface area) at monthly interval for six cycles with oral prednisolone 10mg daily. Subsequently, azathioprine (2-3mg/Kg) was administered while continuing with the same dose of prednisolone. Primary end-points were forced vital capacity (FVC) and high resolution computed tomography (HRCT) scan of thorax score. Secondary end-points were quality of life measured by health assessment questionnaire-disability index (HAQ-DI) and six-minute walk distance (6WMD) test. After one year of observation, the FVC showed significant improvement (p=0.003). The 6WMD also improved significantly (p=0.0028). However, change in HRCT scan scoring and HAQ-DI score was not significant. Intravenous, pulse CYC followed by azathioprine along with low-dose corticosteroids produces significant improvement in FVC and 6WMD at 12-month follow-up without significant change in radiological manifestations and health status.

Intravenous Cyclophosphamide Therapy for Anti-IFN-γ Autoantibody-Associated Talaromyces marneffei Infection.

High titers of anti-interferon-γ autoantibodies (AIGAs) are an important factor leading to persistent, relapsed, and refractory infections in HIV-negative hosts infected with Talaromyces marneffei (TM). We report 5 patients treated with pulses of high-dose intravenous cyclophosphamide (IVCY) who were followed for 2 years. Before IVCY therapy, all patients had multiple relapses, with a median (interquartile range [IQR]) of 2 (1-3) instances of relapse. The median serum AIGA titers (IQR) were 58 753 (41 203-89 605) ng/mL at diagnosis, 48 189.4 (15 537-83 375) ng/mL before IVCY therapy, and 10 721.2 (5637-13 245) ng/mL at the end of IVCY therapy (P < .05). After 3 months of follow-up, the median AIGA titers (IQR) rose gradually to 21 232.6 (9896-45 626) ng/mL, and to 37 464.2 (19 872-58 321) ng/mL at 24 months (P < .05). Five patients discontinued antimicrobial therapy within 3-12 months after completion of IVCY therapy, but only 1 patient had a relapse. In conclusion, pulses of short-term and high-dose IVCY can effectively reduce AIGA titers.

Incidence of acute exacerbation in patients with interstitial lung disease after COVID-19 vaccination

Acute exacerbations due to COVID-19 vaccination in patients with interstitial lung disease (ILD) have been reported, but their incidence is unknown. We investigated the incidence of exacerbations of ILD and respiratory symptoms due to the mRNA COVID-19 vaccines. A questionnaire survey was conducted on adverse reactions to the mRNA COVID-19 vaccination in 545 patients with ILD attending our hospital and retrospectively examined whether the eligible patients actually developed acute exacerbations of ILD induced by the vaccine. Of the 545 patients, 17 (3.1%) patients were aware of the exacerbation of respiratory symptoms, and four (0.7%) patients developed an acute ILD exacerbation after vaccination. Of the four patients who experienced exacerbations, two had collagen vascular disease-associated ILD, one had nonspecific interstitial pneumonia, another had unclassifiable idiopathic pneumonia, and none had idiopathic pulmonary fibrosis. Four patients were treated using steroid pulse therapy with a steroid taper, and two of the four also received intravenous cyclophosphamide pulse therapy. Tacrolimus was started in one patient with myositis-associated interstitial lung disease. Eventually, all patients exhibited improvement with immunosuppressive treatment and were discharged. COVID-19 vaccination for patients with ILD should be noted for developing acute exacerbations of ILD with low incidence, although manageable with early diagnosis and treatment.

Safety and effectiveness of mepolizumab therapy in remission induction therapy for eosinophilic granulomatosis with polyangiitis: a retrospective study

ObjectivesTo investigate the safety and effectiveness of mepolizumab (MPZ), an anti-interleukin-5 antibody, as remission induction therapy for severe eosinophilic granulomatosis with polyangiitis (EGPA).MethodsThe clinical courses of patients with severe EGPA over 6 months were retrospectively investigated and compared between patients treated with high-dose corticosteroid (CS) plus MPZ therapy (MPZ group, n = 7) and those treated with high-dose CS plus intravenous cyclophosphamide (IVCY) pulse therapy (IVCY group, n = 13). The primary endpoints were the MPZ retention rate and the IVCY completion rate. The secondary endpoints were adverse events and changes in the Birmingham Vasculitis Activity Score (BVAS), Vascular Damage Index (VDI), eosinophil counts, and concomitant CS doses, and the extent and rates of these changes were compared between the MPZ and IVCY groups.ResultsRegarding the primary endpoints, the MPZ retention rate was 100%, and the IVCY completion rate was 61.5%. Regarding the secondary endpoints, adverse events were detected in 2/7 patients (28.6%) in the MPZ group and 7/13 patients (53.8%) in the IVCY group. BVAS and eosinophil counts significantly decreased in both groups at and after month 1, but there was no significant difference in the magnitude of changes between the two groups. VDI scores did not significantly increase in either group, and the degree of changes did not significantly differ between the two groups. Although concomitant CS doses significantly decreased at and after month 1 in both groups, the rates of decrease in CS doses at and after month 3 were significantly higher in the MPZ group.ConclusionsThis study suggested that the use of MPZ as remission induction therapy for severe EGPA might be safe and effective for controlling disease activity and reducing CS doses.

Study on short term treatment response of connective tissue disease related interstitial lung disease

Background: Interstitial lung disease is a major cause of morbidity and mortality in patients suffering from connective tissue diseases. Early detection and prompt recognition of symptoms with appropriate treatment is necessary for effective control of the disease and for better prognosis and long-term survival. Aim: To study the short-term treatment response of patients with connective tissue disease-related interstitial lung disease. Objectives: The purpose of this study was to evaluate the treatment response of connective tissue disease-related interstitial lung disease patients treated with intravenous pulses of cyclophosphamide (CYP) based on improvements in lung function: forced vital capacity (FVC)% predicted, forced expiratory volume in the first second (FEV1)% predicted, dyspnea Borg scale and 6-minute walk test. To determine the factors affecting the treatment outcomes like age, sex, duration of the connective tissue disease, type of connective tissue disease, HRCT type, and presence of PAH. Methods: A cohort study was conducted in the Department of General Medicine, Rheumatology, and Pulmonology at the Amala Institute of Medical Sciences, Thrissur, and Kerala from November 2015 to June 2017 that evaluated 74 patients having connective tissue disease-related ILD. A detailed history and a thorough clinical examination were done.

Hypertrophic pachymeningitis with co-occurrence of anti-neutrophil cytoplasmic antibodies and immunoglobulin G4 seropositivity: Case report and literature review

We report an extremely rare case of hypertrophic pachymeningitis in which a 71-year-old man presented with an intractable recurrent headache for >1 year. During this period, he became positive for immunoglobulin G4 and proteinase 3-antineutrophil cytoplasmic antibodies. Contrast-enhanced magnetic resonance imaging showed characteristic diffuse thickening of the dura. Symptoms were improved by intravenous methylprednisolone (500 mg per day for 5 days) and cyclophosphamide pulse therapy during corticosteroid withdrawal; he remained symptom-free during 1-year follow-up. This case suggests that this disease can be treated by corticosteroids combined with immunosuppressive agents.

P055 Granulomatosis with polyangiitis presenting as compressive cervico-thoracic myelopathy

Abstract Background/Aims Granulomatosis with polyangiitis (GPA), a subgroup of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), is a small vessel vasculitis, characteristically associated with granulomatous inflammation. It demonstrates an increased propensity for pulmonary and renal involvement, in addition to ear, nose and throat disease. Central nervous system involvement is rare. Methods We present the case of a 64-year-old male who presented with a 6-week history of upper back pain and gradual deterioration in his gait, with associated lower limb paraesthesia and leg weakness. Results His background medical history is significant for a right sided mastoidectomy, in addition to recurrent episodes of sinusitis, with nasal crusting. He also had a history of frequent epistaxis requiring cauterisation. Neurological examination was significant for a spastic paraparesis, with MRC grade 3/5 weakness in lower limb flexors bilaterally, bilateral lower limb hypertonia, sustained clonus, hyperreflexia, and extensor plantar responses. Sensory examination revealed a mid-thoracic sensory level. Other systems examination were normal. Routine blood tests revealed normal full blood count, renal and liver indices. Inflammatory markers were elevated: C-reactive protein 43 mg/L (0-5 mg/L) and erythrocyte sedimentation rate 80 mm/hr (0-15 mm/hr). Gadolinium enhanced MRI spine and brain revealed a circumferential enhancing mass-like lesion extending from C5 to T9 with compression of the spinal cord at T2 and T3 levels, with normal brain parenchyma. There was evidence of mild sinusitis in the maxillary sinuses. CT of the thorax, abdomen and pelvis was normal. Urinalysis was normal, as was his urinary protein creatinine ratio, and there was no evidence of red cell casts. ANCA revealed a strongly positive perinuclear pattern (p-ANCA) with a markedly elevated myeloperoxidase (MPO) autoantibody, 117 (0-10 units/mL). Proteinase-3 (PR3) was negative. On identification of spinal cord compromise, the patient underwent urgent neurosurgical evaluation, and surgical exploration. During surgery, direct visualisation revealed the lesion to be solid and mass-like and samples of the tissue excised were sent for pathological analysis. Histopathological studies revealed a dense lymphocytic infiltrate, with fibrinoid necrosis of blood vessel wall consistent with vasculitis. There was no evidence of granuloma formation. A diagnosis of MPO positive GPA causing compressive myelopathy was made. He was commenced on high dose glucocorticoids which were tapered as per PEXIVAS reduced dose regimen. In tandem, he was commenced on pulsed intravenous cyclophosphamide. Within days of treatment initiation his neurological status improved, and he is currently engaging in rehabilitation. At his most recent review he was walking independently with crutches. Conclusion Our case highlights a rare cause of myelopathy but one that should enter the differential diagnosis when assessing a patient presenting with myelopathy, particularly with a mass-like lesion on neuroimaging. It should be treated aggressively and as part of the life-threatening organ involvement algorithm. Disclosure P. Harkins: None. R. Field: None. S. Hutchinson: None. R. Conway: None.

Benefits and risks of haematopoietic stem cell transplantation for systemic sclerosis: A systematic review and meta-analysis.

We aimed to evaluate the efficacy and safety of haematopoietic stem cell transplantation (HSCT) in patients with systemic sclerosis. A systematic literature review and meta-analysis were carried out. We compared survival outcomes using the Kaplan-Meier method with patient-level data between HSCT and intravenous pulse cyclophosphamide. Additionally, the incidence rate of treatment-related deaths with HSCT was pooled using a random-effect model. Of the 2091 articles screened, 22 were included: 3 randomized controlled trials and 19 observational studies. HSCT studies showed significant improvement in the skin thickness score and lung function. Despite treatment-related deaths being higher in HSCT than in intravenous pulse cyclophosphamide, the Kaplan-Meier analysis showed a high survival rate of 2 years post-transplant (log-rank, P = 0.004). The pooled frequency of transplant-related death from 700 systemic sclerosis patients was 6.30% (95% confidence interval 4.21-8.38). However, the estimated frequency of treatment-related deaths has been reducing over the last decade. HSCT is an effective treatment for systemic sclerosis, but the optimal indications must be carefully determined by balancing the risks.

Prognosis and Treatment of Myositis-Associated Severe Interstitial Lung Disease: A Descriptive Study Using a Nationwide Inpatient Database in Japan.

The aim of this study was to determine the prognosis, clinical course, and current management of severe interstitial lung disease (ILD) associated with myositis in Japan. We conducted a retrospective descriptive study using a nationwide database for inpatient care of acute illness in Japan. Among a total of ~66 million inpatient admissions, we identified patients with severe ILD associated with polymyositis (PM) or dermatomyositis (DM) who required mechanical ventilation and methylprednisolone pulse therapy (≥1 gm/day of methylprednisolone) from July 2010 to March 2018. We identified 155 patients with PM and 394 with DM who fulfilled the above criteria. The median age of patients was 65 years; DM patients were significantly younger than PM patients (64 versus 68 years; P < 0.001). The numbers of patients who were treated with calcineurin inhibitors, intravenous cyclophosphamide, and polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) were 403 (73.4%), 318 (57.9%), and 78 (14.2%), respectively. All these treatments were given significantly more frequently to the patients with DM compared with those with PM. The uses of other treatment options were much less frequent. The median periods after hospitalization when methylprednisolone pulse therapy, calcineurin inhibitors, mechanical ventilation, intravenous cyclophosphamide, and PMX-DHP were initiated and in-hospital death occurred among patients with DM were 2, 4, 7, 8, 17, and 36 days, respectively. In-hospital mortality was significantly higher in patients with DM than in those with PM (76.6% versus 56.8%; P < 0.001). The mortality of patients with myositis-associated severe ILD who require mechanical ventilation is extremely high despite aggressive and prompt interventions.

A case series of ocular involvement in bullous pemphigoid: clinical features, management, and outcomes

Ocular involvement in cases of bullous pemphigoid is rare and when present, the signs are usually subtle and in the form of fine tarsal scarring and dry eye disease. The current report aims to describe the clinical features and management protocols in a series of cases with aggressive ocular manifestations at presentation. All cases of bullous pemphigoid seen between 2017 and 2020 were included in this retrospective case series. Data regarding the clinical features, treatment administered, and outcomes was collected. Five cases (n=10 eyes) of bullous pemphigoid disease with ocular involvement were included. All eyes had significant cicatricial conjunctival changes in the form of symblephara, inferior forniceal shortening, and tarsal conjunctival scarring. Conjunctival granulomas were present in 3/10 eyes. Corneal involvement in the form of punctate keratitis was present in all eyes while 4/10 eyes had an epithelial defect as well. The management of these cases involved topical therapy with corticosteroids and lubricants (n=10 eyes) while pulse doses of intravenous methyl prednisolone were administered in 5/5 cases. Pulse intravenous cyclophosphamide was supplemented in 2/5 cases. Adequate control of the disease was noted in 3/5 cases while one case had a recalcitrant form of the disease and developed a dermalised ocular surface in both eyes. The last patient was lost to follow up during the course of therapy. Bullous pemphigoid can present with an aggressive form of cicatrizing conjunctivitis similar to other variants of autoimmune blistering disorders and must be considered as a differential in cases presenting with ocular cicatricial disease. Long-term intensive immunosuppression is required for the management of these cases to preserve the visual function and the integrity of the globe.

Prostate abscess with acute urinary retention as the initial presentation of granulomatosis with polyangitis

A 50-year-old male presented with acute urinary retention. He also had a history of cough, haemoptysis, exertional dyspnoea, loss of appetite, generalised weakness and left-ear discharge of 1-month duration. Prior episode of acute urinary retention had occurred 2 months ago; diagnostic evaluation revealed prostate abscess, and he had received treatment elsewhere for the same. He also had a history of hypertension. Physical examination revealed fever, pallor, bilateral parotid enlargement and left-ear serous discharge. Clinical examination, imaging of chest revealed consolidation with cavitation on the left side, bilateral pleural effusion. Laboratory testing revealed normocytic normochromic anaemia (haemoglobin 6.6 g/dL); neutrophilic leucocytosis (total leucocyte count 13,100 cells/mm3; polymorphs 87%); raised erythrocyte sedimentation rate (110 mm at the end of the first hour); elevated serum creatinine (2.69 mg/dL) and an active urine sediment. Flexible fibreoptic bronchoscopy showed alveolar haemorrhages. Bronchoalveolar lavage fluid Xpert MTB/RIF testing, cytopathology were negative. Computed tomography-guided biopsy from the lesion was suggestive of granulomatous vasculitis. Cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA) tested positive. The patient was diagnosed to have granulomatosis with polyangitis (GPA). As arterial hypoxaemia was evident, tracheal intubation and mechanical ventilatory support were initiated. Renal replacement therapy, intravenous (iv) methyl prednisolone and cyclophosphamide pulse therapy and five sessions of plasmapheresis were administered. As remission could not be achieved, iv rituximab was started. On the 36th day of admission, the patient developed septic shock and died. The present case documents the uncommon association of GPA with prostate abscess, acute urinary retention.