Simultaneous occurrence of accelerated nodulosis in lungs, liver, and kidneys, and acute exacerbation of interstitial pneumonia in a patient with rheumatoid arthritis: an autopsy case report

Background Accelerated nodulosis (ARN) is a rare variant of rheumatoid nodules (RNs) that is characterized by a rapid onset or the worsening of RNs. It generally develops at the fingers in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX). Few case reports have described ARN at an extracutaneous location. Case presentation An elderly patient with long-standing RA was admitted to our hospital with acute respiratory failure. Computed tomography upon admission showed diffuse ground-glass opacities superimposed with subpleural reticular shadowing and honeycombing and multiple nodules in the lungs and liver. Despite the discontinuation of MTX and introduction of an immunosuppressive regimen with pulse methylprednisolone followed by a tapering dose of prednisolone and intravenous cyclophosphamide, the patient died due to the acute exacerbation (AE) of RA-related interstitial lung disease (ILD) following the parallel waxing and waning of a diffuse interstitial shadow and pulmonary and liver nodules. At autopsy, RNs were scattered throughout both lung fields in addition to extensive interstitial changes. RNs were also detected in the liver and kidneys. The foci of cryptococcosis were mainly identified in alveolar spaces. Based on the clinical and pathological findings, these nodules were most consistent with ARN because of acute increases in the size and number of previously detected pulmonary nodules. Conclusion The present case is noteworthy because ARN was concurrently detected in multiple internal organs and may be associated with the AE of RA-related ILD.

Hypertrophic pachymeningitis in eosinophilic granulomatosis with polyangiitis

ABSTRACT Eosinophilic granulomatosis with polyangiitis (EGPA) is one of the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), which is characterised by systemic small vessels vasculitis with associated eosinophilia. Hypertrophic pachymeningitis (HP) is an inflammatory disease in which the cerebral or spinal dura mater is thickened. AAV other than EGPA may sometimes develop HP; however, patients with EGPA rarely develop HP. This is the case of myeloperoxidase-ANCA-positive EGPA that presented with headache and blurred vision and was diagnosed with HP. It was successfully treated with pulsed steroid therapy and intravenous cyclophosphamide without any relapse for more than 4 years.

Treatment of Interstitial Lung Disease In Anti-MDA5-Positive Dermatomyositis: A Retrospective Study of 87 Patients

Objectives: The prognosis of anti-melanoma differentiation-associated gene (MDA5) antibody-positive dermatomyositis (DM)-interstitial lung disease (ILD) (anti-MDA5 -positive DM-ILD) is often poor, especially in rapidly progressive interstitial lung disease (RPILD). So far there is no established therapy. This study evaluated the efficacy and safety of pharmacological treatments for anti-MDA5-positive DM-ILD. Methods: This retrospective study comprised 87 anti-MDA5-positive DM-ILD patients. We reviewed the clinical characteristics, laboratory findings, lung function treatments, and outcomes of the 87 patients. Cox regression analysis was used to identify predictors of 6-month survival. The association between different combined immunosuppressive regimen and 6-month survival were evaluated.Results: High level of CYFRA21-1 and low PaO2/FiO2 ratio were associated with poor prognosis. Corticosteroid (CS) alone treatment group with higher CYFRA21-1 and lower PaO2/FiO2 ratio showed worse 6-month survival than the combination of CS with immunosuppressants group (p<0.01). In addition, tacrolimus/cyclosporine-treated anti-MDA5-positive DM Non-RPILD exhibited a better survival, comparing with tacrolimus/cyclosporine combined intravenous cyclophosphamide (IVCY)-treated patients (p<0.05). Conclusion: Addition of immunosuppressants to CS, were associated with better 6-month survival in anti-MDA5-positive DM-ILD. The triple regimen (CS, tacrolimus/cyclosporine and IVCY) was not superior to duple one (CS, tacrolimus/cyclosporine) in anti-MDA5-positive DM Non-RPILD.

Polyarteritis nodosa presenting with catastrophic involvement of the intra-abdominal arterial tree

We report a case of a 63-year-old female presenting with abdominal pain, who suffered a dramatic deterioration in her condition following a diagnosis of bilateral renal infarcts on imaging. Within days she had developed widespread aneurysmal dilatation, dissection and thrombosis of the intra-abdominal arterial tree, requiring emergency transfer to a tertiary vascular centre for treatment of polyarteritis nodosa. She responded well to intravenous cyclophosphamide and is now receiving treatment on an outpatient basis.

Remedial Effect of Intravenous Cyclophosphamide in Corticosteroid-Refractory Patients in the Acute Phase of Neuromyelitis Optica Spectrum Disorder-Related Optic Neuritis

Background: To investigate the remedial efficacy and safety of intravenous cyclophosphamide (CP) in the acute phase in patients with neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON) who are refractory to intravenous methylprednisolone (MP) treatment.Design: This study was a single-center, retrospective, observational case-control cohort study.Methods: Thirty-six patients who had acute NMOSD-ON attacks and were refractory to MP treatment were included. Patents were divided into two groups: the remedial CP group, and the MP group. The best-corrected visual acuity (BCVA), mean deviation (MD) of the visual field (VF), visual evoked potential amplitude (VEP-A), visual evoked potential latency (VEP-T), and average thickness of the retinal nerve fiber layer (RNFL) at onset, 1 month (m), 3 m, and 6 m after the attack were analyzed. Routine blood test results, liver and kidney function, routine urinalysis results and general condition were analyzed for safety issues at each follow-up. Fisher's exact test, the Mann-Whitney U test, the Kruskal-Wallis test and the Wilcoxon rank-sum test were used for statistical analysis.Results: The remedial CP group showed significant improvement over 6 m with regard to BCVA and MD (P &lt; 0.05),whereas MP group only showed significant improvement in MD (P &lt; 0.05). Regarding remedial CP intervention time window, the CP ≤ 30 days group showed significant improvement over 6 m with regard to BCVA (P = 0.002), MD (P = 0.003), and VEP-A (P = 0.036), while those CP &gt; 30 days group did not. Both two subgroups showed significantly RNFL thickness reduction, however, BCVA, MD, VEP-A, VEP-T, and RNFL thickness showed no significant differences between the two subgroups at any follow-up point (P &gt; 0.05).Conclusion: CP within 30 days of attack onset is safe and might have a beneficial degree of therapeutic efficacy for acute-phase treatment of NMOSD-ON that is refractory to MP treatment alone.

O23 Pulmonary emboli in a teenager with GPA: management dilemmas

Case report - Introduction 15 year old girl with the diagnosis of granulomatosis polyangiitis (GPA) managed with induction regimen of intravenous cyclophosphamide and whilst on maintenance mycophenolate mofetil (MMF) developed multiple cavitating lung lesions with the large cavity abutting pulmonary vein and bilateral segmental pulmonary embolism (PE) posing complex management dilemmas. Case report - Case description 15-year-old girl presented with being unwell for 3 months with malaise, lethargy, joint pains, significant weight loss (10 kg), mouth ulcer and significant hearing loss. Investigations showed anaemia, raised inflammatory markers, and impaired kidney function (estimated glomerular filtration rate eGFR 40). Her ANCA was positive, hearing test showed significant mixed hearing loss and CXR was normal. The renal biopsy confirmed pauci-immune ANCA associated glomerulonephritis with 70% crescents. She was initially managed with intravenous pulse of steroids followed by oral weaning regime, double filtration plasmapheresis and commenced on induction regimen of intravenous cyclophosphamide. She received 6 doses of cyclophosphamide 500 mg/m2 and following good recovery with normalising kidney function; was commenced on maintenance MMF. At this point she developed new onset earache, sore throat, and hoarseness of voice with raised inflammatory markers and worsening symptoms despite antibiotics. This was presumed to a flare of vasculitis and hence was given further pulse of steroids and increased the dose of MMF. The ENT assessment did not reveal any subglottic stenosis. After few weeks, symptoms recurred with cough/hoarseness of voice and associated tiredness. Bloods showed raised inflammatory markers; CXR revealed cavitating lung lesions and a CT chest was arranged. CT chest showed apical sub pleural lung nodule and a large thick-walled cavity measuring 6.6x 4.4 cm abutting the pulmonary vein on the right side and bilateral segmental pulmonary emboli. The child was systemically stable with no respiratory distress and oxygen saturations were 100% in air. Case report - Discussion The management of GPA was further complicated by the pulmonary embolism and cavitating lung lesions abutting pulmonary vein. The management included escalation of immunosuppression with pulse of steroids, further dose of cyclophosphamide and commence Rituximab .The key challenges with the immediate management were risk of bleeding associated with the anticoagulation, treating the pulmonary embolism, risk of diffuse alveolar haemorrhage and managing the patient in a safe setting equipped with all the expertise required. The child was screened for cardiolipin antibodies on multiple occasions and these were negative. An ECHO was done to look for evidence of clot at the end of central line tip, but this was normal. Deep venous thrombosis of legs was ruled out by Doppler scanning. There was no clear source of emboli identified. Although there is emerging evidence for increased incidence of vascular events in GPA adult patients, the data on vascular events in children with GPA is scarce. Merkel and co-workers reported a high occurrence of pulmonary embolism (PE) and deep venous thrombosis (DVT) among GPA patients included in a randomized therapeutic trial (WeCLOT study) 1 .FAURSCHOU et al. reported that GPA was associated with a much lower relative risk of stroke than of pulmonary embolism and deep venous thrombosis; the risk of venous thromboembolic events among GPA patients was increased during early as well as late follow up periods. Currently there are no significant data on the use of antiplatelet and/or anticoagulant therapy in AAV. Following extensive multidisciplinary discussion with respiratory, haematology, cardiology, cardiothoracic surgical and paediatric intensive care teams, and the child was anticoagulated with close monitoring in paediatric high dependency unit and immunosuppression escalated alongside. Case report - Key learning points This case highlights the risk of thromboembolic events in children with GPAProposed mechanisms in the literature for thrombosis in vasculitis at molecular level would probably explain the episode in the absence of source identifiedMultidisciplinary team approach is crucial for management of complex patientsThere were few challenges due to geographical location of the patient and the regional variation of subspecialty cover provided for their local District General HospitalFor discussion- Role of Rituximab early in GPA?

A refractory anti-NMDA receptor encephalitis successfully treated by bilateral salpingo-oophorectomy and intrathecal injection of methotrexate and dexamethasone: a case report

Introduction Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is an autoimmune-mediated disease that is common in young female patients with ovarian teratomas. With appropriate immunotherapy, most patients achieve a good prognosis. Nevertheless, some patients may be refractory to first- and second-line immunotherapy, thus alternative treatments are required for these patients. Case presentation: We present a case of anti-NMDA receptor encephalitis with ovarian teratoma. After the prompt removal of the teratoma and intense immunotherapy was administered, including an intravenous methylprednisolone pulse, intravenous immunoglobin, plasmapheresis, immunoadsorption, intravenous cyclophosphamide, and rituximab, the patient’s neurologic status did not improve. Bilateral salpingo-oophorectomy was then conducted, and intrathecal injection of methotrexate (MTX) and dexamethasone (DXM) was performed. The patient’s neurological symptoms improved dramatically, and she achieved a good prognosis after 23 months. Conclusions Intrathecal injection of MTX and DXM may be beneficial for treatment of refractory cases of anti-NMDA receptor encephalitis. Additional research is required to elucidate the mechanisms of intrathecal treatment with this therapy.