Churg-Strauss Syndrome

The functions ascribed to eosinophils have classically been limited to host defence against certain parasitic infections and potentially deleterious effects in the setting of specific diseases that are associated with elevated eosinophil counts in blood and/or tissue. The ability to induce eosinophil depletion either experimentally in animal models or through targeted therapies in humans has extended our understanding of the roles played by eosinophils in health and homeostasis as well as in disease pathogenesis. When associated with human disease aetiology, the eosinophil takes on a pathogenic rather than a protective role. This maladaptive response, called "eosinophilic immune dysfunction" herein, appears central to exacerbation pathogenesis and disease control in severe asthma and may be involved in the aetiology of other eosinophil-related conditions ranging from organ-system-limited diseases such as phenotypic subsets of chronic obstructive pulmonary disease and chronic rhinosinusitis with nasal polyposis to more broadly systemic diseases such as eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. In this review, we describe the evidence supporting eosinophilic functions related to health and homeostasis and explore the contribution of eosinophilic immune dysfunction to human disease.

Montelukast, a selective leukotriene receptor antagonist, is recommended in guidelines for the treatment of asthma in both children and adults. However, its effectiveness is debated, and recent studies have reported several adverse events such as neuropsychiatric disorders and allergic granulomatous angiitis. This study aims to obtain more insight into the safety profile of montelukast and to provide prescribing physicians with an overview of relevant adverse drug reactions in both children and adults. We retrospectively studied all adverse drug reactions on montelukast in children and adults reported to the Netherlands Pharmacovigilance Center Lareb and the WHO Global database, VigiBase® until 2016. Depression was reported most frequently in the whole population to the global database VigiBase® (reporting odds ratio (ROR) 6.93; 95% CI: 6.5-7.4). In the VigiBase® , aggression was reported the most in children (ROR, 29.77; 95% CI: 27.5-32.2). Headaches were reported the most frequently to the Dutch database (ROR, 2.26; 95% CI: 1.61-3.19). Furthermore, nightmares are often reported for both children and adults to the Dutch and the global database. Eight patients with allergic granulomatous angiitis were reported to the Dutch database and 563 patients in the VigiBase® . These data demonstrate that montelukast is associated with neuropsychiatric adverse drug reactions such as depression and aggression. Especially in children nightmares are reported frequently. Allergic granulomatous angiitis is also reported, a causal relationship has not been established.

Systemic necrotizing vasculitis comprises a group of diseases resembling polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA): granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. The definitive diagnosis is made in cooperation with a reference center for autoimmune diseases and rare systemic diseases or a competency center. The management goals are: to obtain remission and, in the long term, healing; to reduce the risk of relapses; to limit and reduce the sequelae linked to the disease; to limit the side effects and the sequelae linked to the treatments; to improve or at least maintain the best possible quality of life; and to maintain socio-professional integration and/or allow a rapid return to school and/or professional activity. Information and therapeutic education of the patients and those around them are an integral part of the care. All health professionals and patients should be informed of the existence of patient associations. The treatment of vasculitis is based on variable combinations of glucocorticoids and immunosuppressants, chosen and adapted according to the disease concerned, the severity and/or extent of the disease, and the underlying factors (age, kidney function, etc.). Follow-up clinical and paraclinical examinations must be carried out regularly to clarify the progression of the disease, detect and manage treatment failures and possible relapses early on, and limit sequelae and complications (early then late) related to the disease or treatment. A distinction is made between the induction therapy, lasting approximately 3-6 months and aimed at putting the disease into remission, and the maintenance treatment, lasting 12-48 months, or even longer. The role of the increase or testing positive again for ANCA as a predictor of a relapse, which has long been controversial, now seems to have greater consensus: Anti-myeloperoxidase ANCAs are less often associated with a relapse of vasculitis than anti-PR3 ANCA.

ObjectiveTo analyze the diagnostic pathway of patients with ANCA-associated vasculitis (AAV) and to identify factors associated with the time to diagnosis, including the role of referring and previously consulted medical specialties.MethodsThis retrospective single-center study analyzed patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) who received their diagnosis between 2014 and 2024. Data were extracted from medical records. Time to diagnosis was defined as the period between first AAV-related symptoms and confirmed diagnosis. Factors associated with diagnostic delay were analyzed using multivariate Cox regression. Temporal differences between subtypes were visualized using Kaplan-Meier curves.ResultsA total of 216 patients were included (GPA n = 128; MPA n = 70; EGPA n = 18). Median time to diagnosis was numerically longest in EGPA (455 days [IQR 144-924]) compared with GPA (120 days [IQR 61334]) and MPA (153 days [IQR 90-366]). Renal involvement was statistically associated with a shorter time to diagnosis (HR 1.65, 95% CI 1.18-2.31, p = 0.004), whereas prior consultations with dermatologists (HR 0.41, p = 0.004), pulmonologists (HR 0.58, p = 0.003), and rheumatologists (HR 0.63, p = 0.003) showed longer delays. Higher BVAS and CRP levels statistically correlated with shorter diagnostic intervals.ConclusionThe diagnostic delay in AAV varies by disease subtype and clinical presentation. EGPA shows the numerically longest time to diagnosis, while renal involvement seems to facilitate earlier diagnosis. Enhanced awareness among non is essential to reduce diagnostic delay and prevent organ damage, although outcome measures were not assessed in our study. Key Points • Diagnostic delay in ANCA-associated vasculitis varies between disease subtypes, organ involvement, and consulted specialties. • EGPA shows the numerically longest diagnostic delay, whereas renal involvement seems to facilitate earlier diagnosis. • Earlier recognition of AAV across specialties may reduce diagnostic delay and prevent organ damage.