Clinical Characteristics of Peripheral Neuropathy in Eosinophilic Granulomatosis with Polyangiitis: A Retrospective Single-Center Study in China.

OBJECTIVE: To investigate clinical features, independent associated factors, treatment, and outcome of patients with peripheral neuropathy (PN) in eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: We retrospectively analyzed clinical data of 110 EGPA patients from 2007 to 2019 in Peking Union Medical College Hospital. The independent factors associated with PN in EGPA were analyzed with univariate and multivariate logistic regressions. RESULTS: In EGPA with PN, paresthesia and muscle weakness were observed in 82% and 33% of patients, respectively. Both the upper and lower limbs were involved in 51% of patients. 30% of EGPA patients had symmetrical multiple peripheral neuropathy, whereas only 16.4% presented with mononeuritis multiplex. Compared to patients without PN, patients with PN had a higher erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, Birmingham vasculitis activity score (BVAS), and positivity of myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA). Regarding manifestations, patients with PN tended to develop weight loss and arthritis or joint pain. Notably, ANCA positivity, arthritis or joint pain, and higher BVAS were found to be independent associated factors for PN in EGPA. Patients with PN more frequently need glucocorticoid pulses and intravenous infusion of cyclophosphamide. With the longest follow-up of 11.0 years, we found that age and cardiac involvement were risk factors for survival, and female was the protective factor. CONCLUSION: PN in EGPA frequently displays with symmetrical multiple peripheral neuropathy in China. Positive ANCA, arthritis or joint pain, and higher BVAS are the independent associated factors of PN in EGPA. Glucocorticoids with immunosuppressants are vital therapeutic strategy.

Updates for the treatment of EGPA.

Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) is the least frequent antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). Major advances of our knowledge on its pathophysiology have revealed features of both AAV and eosinophilic disorders. The development of targeted biotherapies for both diseases opened new possibilities for EGPA management. In this review, we highlight the rationale underlying the routine treatment strategy, which relies mainly on corticosteroids, with immunosuppressant adjunction for severe disease. However, novel therapies are still needed for refractory/relapsing disease and to alleviate the corticosteroid-dependence of asthma and chronic rhinosinusitis. At present, the most promising biotherapies target either eosinophil biology, like mepolizumab, an anti-interleukin-5, or the B-cell compartment, with rituximab. Recent clinical data on new treatment options are discussed and therapeutic strategies are proposed.

Antineutrophil cytoplasmic antibody-associated vasculitis in Taiwan: A hospital-based study with reference to the population-based National Health Insurance database.

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS), comprises a group of diseases with significant morbidity and mortality. The incidence and relative frequency of GPA/MPA/CSS are different all over the world. The epidemiology of AAV in Taiwan is still not clear. METHODS: The current study aimed to provide a population-based estimate of the annual incidence of GPA using the Taiwan National Health Insurance (NHI) research database and a single hospital-based estimate of the relative frequency of AAV in Taiwan. RESULTS: The annual incidence of GPA in Taiwan was 0.37 per million patient-years (95% Poisson rate confidence interval: 0.30-0.45) from 1997 to 2008, according to the NHI database. In our hospital, 24 patients were newly diagnosed with AAV between 2003 and 2011, including eight patients with GPA, 14 with MPA, and two with CSS. The ratio of the number of patients with GPA to that of MPA was 0.57. CONCLUSION: The current results provide an estimate of the annual incidence of GPA and the relative frequency of AAV in the Chinese Han community in Taiwan. Such geoepidemiology information may help illuminate the interaction between ethnic background and environment in these autoimmune diseases.

Proteinase 3, the autoantigen in granulomatosis with polyangiitis, associates with calreticulin on apoptotic neutrophils, impairs macrophage phagocytosis, and promotes inflammation.

Proteinase 3 (PR3) is the target of anti-neutrophil cytoplasm Abs in granulomatosis with polyangiitis, a form of systemic vasculitis. Upon neutrophil apoptosis, PR3 is coexternalized with phosphatidylserine and impaired macrophage phagocytosis. Calreticulin (CRT), a protein involved in apoptotic cell recognition, was found to be a new PR3 partner coexpressed with PR3 on the neutrophil plasma membrane during apoptosis, but not after degranulation. The association between PR3 and CRT was demonstrated in neutrophils by confocal microscopy and coimmunoprecipitation. Evidence for a direct interaction between PR3 and the globular domain of CRT, but not with its P domain, was provided by surface plasmon resonance spectroscopy. Phagocytosis of apoptotic neutrophils from healthy donors was decreased after blocking lipoprotein receptor-related protein (LRP), a CRT receptor on macrophages. In contrast, neutrophils from patients with granulomatosis with polyangiitis expressing high membrane PR3 levels showed a lower rate of phagocytosis than those from healthy controls not affected by anti-LRP, suggesting that the LRP-CRT pathway was disturbed by PR3-CRT association. Moreover, phagocytosis of apoptotic PR3-expressing cells potentiated proinflammatory cytokine in vitro by human monocyte-derived macrophages and in vivo by resident murine peritoneal macrophages, and diverted the anti-inflammatory response triggered by the phagocytosis of apoptotic cells after LPS challenge in thioglycolate-elicited murine macrophages. Therefore, membrane PR3 expressed on apoptotic neutrophils might amplify inflammation and promote autoimmunity by affecting the anti-inflammatory "reprogramming" of macrophages.

Successful treatment of calcific uremic arteriolopathy in a pediatric dialysis patient.

Calcific uremic arteriolopathy (CUA) is a rare, life-threatening disease, typically affecting patients with end-stage renal disease. It is characterized by widespread vascular calcification, endothelial fibrosis and end-organ ischemia. The mortality rate is high with infection and sepsis being the most common causes of death. Common therapies include restoration of calcium and phosphorous homeostasis, wound care and pain control. Although soft tissue calcification is a known complication in children with advanced renal disease, the incidence of CUA in pediatrics remains unknown. Additionally, current literature regarding its management in pediatric patients is lacking. We report the case of a 17-year-old African-American male patient with end-stage renal disease secondary to Wegener's granulomatosis who developed CUA after 3 years on peritoneal dialysis. Treatment with sodium thiosulfate (STS) and hyperbaric oxygen (HBO) therapy alone was ineffective, forcing the patient to undergo bilateral below the-knee-amputation (BKA) 5 months after presentation. It was not until peritoneal dialysis had been changed to daily hemodialysis, while continuing STS and HBO therapy, that the patient demonstrated complete resolution of CUA on repeat bone scan. Based on these findings, and the extremely high mortality rate associated with this disease, CUA management requires early and aggressive intervention with multi-faceted therapy, including prompt conversion from peritoneal dialysis to hemodialysis, STS infusions and hyperbaric oxygen therapy.