Mepolizumab -- therapeutic strategy for a paediatric patient with eosinophilic granulomatosis with polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) is classified as an anti-neutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis. It is a multisystem disorder and can affect every organ system. EGPA is a rare disease, with an estimated prevalence of 1/70,000–100,000 in Europe. As its onset usually occurs in adulthood, data from paediatric patients are limited. We present here a very rare practical EGPA clinical case involving a paediatric patient. Presently, data on mepolizumab usage in paediatric patients are limited, with only a few case reports published.

KL-6 in ANCA-Associated Vasculitis Patients with and without ILD: A Machine Learning Approach

Background: ANCA-associated vasculitis (AAV) are small vessel vasculitis distinguished between microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). The former may have interstitial lung disease (ILD) associated with high morbidity and mortality. Here, Krebs von den Lungen-6 (KL-6), a marker of fibrotic ILD, was assessed for distinguishing AAV patients with ILD from those without ILD, and whether its changes over time are correlated with disease activity. Materials and Methods: Thirteen AAV patients (eight females, mean age 61 ± 14.8 years) were enrolled: six MPA and six GPA. Serum samples were assayed for KL-6 concentrations (Fujirebio Europe, Belgium). To investigate potential binary classifiers for diagnosis of AAV-ILD, we constructed a regression decision tree model. Results: Higher serum KL-6 were in AAV-ILD compared with those without ILD (972.8 ± 398.5 vs 305.4 ± 93.9, p = 0.0040). Area under the receiver operating characteristics curve showed 100% of the diagnostic performance of KL-6 for identifying the ILD involvement (accuracy 91.7%) and the best cutoff value of 368 U/mL (sensitivity 100% and specificity 87.5%). The decision tree model showed a 33% improvement in class purity using a cut-off value of 513 U/mL to distinguish AAV patients with and without ILD. Stratifying AAV patients as MPA and GPA with and without ILD considering T0 and T1 KL-6, the model obtained an improvement of 40% for classifying GPA non-ILD with a T0 serum KL-6 cut-off value of 513 U/mL and a T1 KL-6 cut-off of 301 U/mL. A direct correlation was found between serum T0 KL-6 and T0 BVAS (r = 0.578, p = 0.044). Conclusion: Our multicenter study demonstrated KL-6 as a reliable, non-invasive, and easy-to-perform marker of ILD in AAV patients and its helpfulness for disease activity assessment. Changes in serum concentrations of KL-6 over time could be useful for monitoring AAV patients. Further study of KL-6 as a marker of response to therapy during long-term follow-up would also be worthwhile.

Organ Manifestation and Systematic Organ Screening at the Onset of Inflammatory Rheumatic Diseases

Background: Inflammatory rheumatic diseases (IRD) are often associated with the involvement of various organs. However, data regarding organ manifestation and organ spread are rare. To close this knowledge gap, this cross-sectional study was initiated to evaluate the extent of solid organ manifestations in newly diagnosed IRD patients, and to present a structured systematic organ screening algorithm. Materials and Methods: The study included 84 patients (63 women, 21 men) with newly diagnosed IRD. None of the patients received any rheumatic therapy. All patients underwent a standardised organ screening programme encompassing a basic screening (including lungs, heart, kidneys, and gastrointestinal tract) and an additional systematic screening (nose and throat, central and peripheral nervous system) on the basis of clinical, laboratory, and immunological findings. Results: Represented were patients with connective tissue diseases (CTD) (72.6%), small-vessel vasculitis (16.7%), and myositis (10.7%). In total, 39 participants (46.5%) had one or more organ manifestation(s) (one organ, 29.7%; two organs, 10.7%; ≥three organs, 6.0%). The most frequently involved organs were the lungs (34.5%), heart (11.9%), and kidneys (8.3%). Lastly, a diagnostic algorithm for organ manifestation was applied. Conclusion: One-half of the patients presented with a solid organ involvement at initial diagnosis of IRD. Thus, in contrast to what has been described in the literature, organ manifestations were already present in a high proportion of patients at the time of diagnosis of IRD rather than after several years of disease. Therefore, in IRD patients, systematic organ screening is essential for treatment decisions.

Sudden Cardiac Death Caused by Cardiac Small Vessel Vasculitis after COVID-19 Vaccination (BNT162b2 nCov-19): A Case Report

This study presents a case of sudden cardiac death due to cardiac small vessel vasculitis after coronavirus disease 2019 (COVID-19) mRNA vaccination (BNT162b2). The deceased was a 76-year-old woman with diabetes mellitus (DM) and chronic hypertension (HTN), who experienced generalized pain for a month after the first dose of vaccination, and unexpectedly died. Postmortem examination revealed small vessel vasculitis in the heart, lungs and vaccinated site of the left arm. These features were similar to those observed in a previously reported case of a patient with COVID-19 and cardiac endotheliitis and multisystem inflammatory syndrome. In addition, DM and HTN may contribute to vaccine-induced immunologic changes and vascular dysfunction. However, further studies with additional cases are needed.

Causes of acute respiratory failure in patients with small-vessel vasculitis admitted to intensive care units: a multicenter retrospective study

Rationale Acute respiratory failure (ARF) in patients admitted to the intensive care unit (ICU) with known or de novo small-vessel vasculitis (Svv) may be secondary to the underlying immune disease or to other causes. Early identification of the cause of ARF is essential to initiate the most appropriate treatment in a timely fashion. Methods A retrospective multicenter study in 10 French ICUs from January 2007 to January 2018 to assess the clinical presentation, main causes and outcome of ARF associated with Svv, and to identify variables associated with non-immune etiology of ARF in patients with known Svv. Results During the study period, 121 patients [62 (50–75) years; 62% male; median SAPSII and SOFA scores 39 (27–52) and 6 (4–8), respectively] were analyzed. An immune cause was identified in 67 (55%), and a non-immune cause in 54 (45%) patients. ARF was associated with several causes in 43% (n = 52) of cases. The main immune cause was diffuse alveolar hemorrhage (DAH) (n = 47, 39%), whereas the main non-immune cause was pulmonary infection (n = 35, 29%). The crude 90-day and 1-year mortality were higher in patients with non-immune ARF, as compared with their counterparts (32% and 38% vs. 15% and 20%, respectively; both p = 0.03), but was marginally significantly higher after adjusted analysis in a Cox model (p = 0.053). Among patients with a known Svv (n = 70), immunosuppression [OR 9.41 (1.52–58.3); p = 0.016], and a low vasculitis activity score [0.84 (0.77–0.93)] were independently associated with a non-immune cause, after adjustment for the time from disease onset to ARF, time from respiratory symptoms to ICU admission, and severe renal failure. Conclusions An extensive diagnosis workup is mandatory in ARF revealing or complicating Svv. Non-immune causes are involved in 43% of cases, and their short and mid-term prognosis may be poorer than those of immune ARF. Readily identified predictive factors of a non-immune cause could help avoiding unnecessary immunosuppressive therapies.

Focal Seizures and Posterior Reversible Encephalopathy Syndrome as Presenting Signs of IgA Vasculitis/Henoch-Schoenlein Purpura—An Educative Case and Systematic Review of the Literature

Background: IgA vasculitis/Henoch-Schoenlein purpura (IgAV/HSP) is a systemic small vessel vasculitis of unknown pathogenesis predominantly affecting children. While skin, GI tract, joints, and kidneys are frequently affected and considered, central nervous system (CNS) involvement of this disease is underestimated.Methods: We provide a case report and systematically review the literature on IgAV, collecting data on the spectrum of neurological manifestations.Results: We report on a 7-year-old girl with IgAV who presented with diplopia and afebrile focal seizures, which preceded the onset of purpura. Cranial magnetic resonance imaging was consistent with posterior reversible encephalopathy syndrome (PRES), showing typical focal bilateral parietal swelling and cortical and subcortical high signal intensities on T2-fluid attenuated inversion recovery (FLAIR) images predominantly without diffusion restriction. Cerebrospinal fluid analysis and blood tests excluded systemic inflammation or vasculitis. Interestingly, hypertension was not a hallmark of the developing disease in the initial phase of PRES manifestation. Renal disease and other secondary causes for PRES were also excluded. Supportive- and steroid treatment resulted in restitution ad integrum. Reviewing the literature, we identified 28 other cases of IgAV with CNS involvement. Severe CNS involvement includes seizures, cerebral edema, or hemorrhage, as well as PRES. Thirteen patients fulfilled all diagnostic criteria of PRES. The mean age was 11.2 years (median 8.0, range 5-42 years), with no reported bias toward gender or ethnic background. Treatment regimens varied from watchful waiting to oral and intravenously steroids up to plasmapheresis. Three cases showed permanent CNS impairment.Conclusion: Collectively, our data demonstrate that (I) severe CNS involvement such as PRES is an underappreciated feature of IgAV, (II) CNS symptoms may precede other features of IgAV, (III) PRES can occur in IgAV, and differentiation from CNS vasculitis is challenging, (IV) pathogenesis of PRES in the context of IgAV remains elusive, which hampers treatment decisions. We, therefore, conclude that clinical awareness and the collection of structured data are necessary to elucidate the pathophysiological connection of IgAV and PRES.

Anti-glomerular basement membrane disease in children: a brief overview

Anti-glomerular basement membrane disease (Anti-GBM), previously known as Goodpasture syndrome, is an extremely rare cause of rapidly progressive glomerulonephritis and chronic kidney disease stage 5 (CKD5) in children. It is associated with acute pulmonary haemorrhage and it has a poor prognosis. It is classified as an autoimmune, small-vessel vasculitis caused by autoantibody formation against the alpha-3 chain in type IV collagen found in the glomerular basement membrane. Evidence of anti-GBM antibodies in serum or histologically are required for diagnosis. Treatment in children is based on very limited adult data and often involves the use of acute apheresis to rapidly remove circulating factors coupled with intensive immunosuppression such as cyclophosphamide and intravenous corticosteroids. There is also an emerging role for the use of biologic agents such as B cell depletion. The evidence base in children with anti-GBM disease is extremely limited. Multi-centre international collaboration is required to provide insight into this disease, better describe its prognosis and work towards improving outcomes. This review article summarises the key features of this disease in children, highlights treatment options and considers areas of unmet need.

Vasculitic Tibial Mononeuropathy Associated with Inherited Immune Dysregulation: A Review of Tibial Mononeuropathies with Electrodiagnostic Considerations

Compressive tibial mononeuropathies are uncommon and can be caused by conditions including posterior compartment syndrome, soleal sling syndrome, and tarsal tunnel syndrome. Therefore, it is critical to consider noncompressive etiologies when a tibial mononeuropathy is suspected. This is a patient with a history of rare inherited immune dysregulation that presented to the electrodiagnostic laboratory with severe neuropathic pain in the right foot associated with plantarflexion weakness, concerning for a tibial mononeuropathy. However, the patient’s clinical presentation and results on electrodiagnostic testing were not consistent with any of the above entities. Therefore, noncompressive etiologies of tibial mononeuropathies such as vasculitis had to be considered. The patient subsequently underwent sural nerve biopsy which confirmed small-vessel vasculitis as the cause of the tibial mononeuropathy. She was then started on appropriate immunosuppressive treatment which resulted in significant pain relief and was discharged home. This case highlights the importance of considering noncompressive causes of tibial nerve injury. Compressive and vasculitic tibial mononeuropathies along with their electrodiagnostic considerations are reviewed. Furthermore, this case highlights the critical role of the electromyographer and ability to maximize the impact on patient care through a solid foundation in anatomy, pathophysiology, and electrodiagnosis blended with clinical acumen.