Objective. Churg-Strauss syndrome (CSS) is classified among the so-called antineutrophil cytoplasmic antibody-associated systemic vasculitides (AASVs) because of its clinicopathologic features that overlap with the other AASVs. However, while antineutrophil cytoplasmic antibodies (ANCAs) are consistently found in 75-95% of patients with Wegener's granulomatosis or microscopic polyangiitis, their prevalence in CSS varies widely and their clinical significance remains uncertain. We undertook this study to examine the prevalence and antigen specificity of ANCAs in a large cohort of patients with CSS. Moreover, we evaluated the relationship between ANCA positivity and clinicopathologic features.Methods. Immunofluorescence and enzymelinked immunosorbent assay were used to determine the presence or absence of ANCAs in 93 consecutive patients at the time of diagnosis. The main clinical and pathologic data, obtained by retrospective analysis, were correlated with ANCA status.Results. ANCAs were present by immunofluorescence in 35 of 93 patients (37.6%). A perinuclear ANCA (pANCA) pattern was found in 26 of 35 patients (74.3%), with specificity for myeloperoxidase (MPO) in 24 patients, while a cytoplasmic ANCA pattern, with specificity for proteinase 3, was found in 3 of 35 patients (8.6%). Atypical patterns were found in 6 of 30 patients with anti-MPO antibodies (20.0%). ANCA positivity was associated with higher prevalences of renal disease (51.4% versus 12.1%; P < 0.001) and pulmonary hemorrhage (20.0% versus 0.0%; P ‫؍‬ 0.001) and, to a lesser extent, with other organ system manifestations (purpura and mononeuritis multiplex), but with lower frequencies of lung disease (34.3% versus 60.3%; P ‫؍‬ 0.019) and heart disease (5.7% versus 22.4%; P ‫؍‬ 0.042).Conclusion. ANCAs are present in ϳ40% of patients with CSS. A pANCA pattern with specificity for MPO is found in most ANCA-positive patients. ANCA positivity is mainly associated with glomerular and alveolar capillaritis.

Of the 21 patients, 13 (61.9%) had ENT involvement at asthma onset and 8 (38%) at diagnosis or during follow-up. The most common ENT manifestations were allergic rhinitis in 9 (42.8%) patients and nasal polyposis in 16 (76.1%). Three (14.2%) patients developed chronic rhinosinusitis without polyps, three (14.2%) had nasal crusting, one (4.7%) serous otitis media, one (4.7%) purulent otitis media, two (9.5%) progressive sensorineural hearing loss, and one (4.7%) unilateral facial palsy. Corticosteroid therapy associated with immunosuppressive drugs usually yielded improvement or stabilization.

Objective. To explore the association between HLA alleles and Churg-Strauss syndrome (CSS), and to investigate the potential influence of HLA alleles on the clinical spectrum of the disease.Methods. Low-resolution genotyping of HLA-A, HLA-B, and HLA-DR loci and genotyping of TNFA ؊238A/G and TNFA ؊308A/G single-nucleotide polymorphisms were performed in 48 consecutive CSS patients and 350 healthy controls.Results.

Peripheral neuropathy in WG occurs less frequently, later in the disease course and in a milder form than in CSS and MP. Single or multiple mononeuropathy associated with these subsets of vasculitis can often be painless.

Objectives: Churg‐Strauss syndrome (CSS) is a systemic vasculitic disorder of unknown etiology that affects small‐to‐medium‐size blood vessels. Patients affected by CSS frequently show ear, nose, and throat manifestations, which are often present at the time of disease onset. The purpose of this study was to determine the frequency of nasal polyposis in a series of 29 patients with CSS and to correlate the nasal findings to the total health situation of these patients. Study Design: Retrospective analysis. Setting: Department of Otolaryngology and Department of Clinical Medicine, Nephrology and Health Science, University of Parma. Methods: Twenty‐nine patients with CSS were identified. Of the 29 patients, 17 (58.6%) had nasal polyposis and were enrolled in this study. The nasal polyps were graded according to the Lund and Mackay endoscopic and radiological classifications. Results: At diagnosis, endoscopic intranasal evaluation identified nasal polyposis of grade 3 in nine cases (52.9%), grade 2 in six cases (35.2%), and grade 1 in the remaining case (5.8%). After corticosteroid and immunosuppressive therapy, clinical remission was achieved in 14 patients (82.3%), whereas 3 patients experienced a relapse. Posttreatment endoscopic evaluation showed a permanent disappearance (grade 0) of nasal polyps in eight patients (47%). The other nine patients (52.92%) were found to have a small polyp situated in the middle meatus (grade 1). Conclusions: Nasal polyposis in patients with CSS may represent the initial phase of the syndrome, though patients often have concurrent pulmonary disease. Corticosteroid therapy either alone or combined with immunosuppressive drugs usually yielded improvement or stabilization.

Toll-like receptor 4 (TLR4) activation is pivotal to innate immunity and has been shown to regulate proliferation and differentiation of human neural stem cells (hNSCs) in vivo. Here we study the role of TLR4 in regulating hNSC derived from the human telencephalic-diencephalic area of the fetal brain and cultured in vitro as neurospheres in compliance with Good Manifacture Procedures (GMP) guidelines. Similar batches have been used in recent clinical trials in ALS patients. We found that TLR2 and 4 are expressed in hNSCs as well as CD14 and MD-2 co-receptors, and TLR4 expression is downregulated upon differentiation. Activation of TLR4 signaling by lipopolysaccharide (LPS) has a positive effect on proliferation and/or survival while the inverse is observed with TLR4 inhibition by a synthetic antagonist. TLR4 activation promotes neuronal and oligodendrocyte differentiation and/or survival while TLR4 inhibition leads to increased apoptosis. Consistently, endogenous expression of TLR4 is retained by hNSC surviving after transplantation in ALS rats or immunocompromised mice, thus irrespectively of the neuroinflammatory environment. The characterization of downstream signaling of TLR4 in hNSCs has suggested some activation of the inflammasome pathway. This study suggests TLR4 signaling as essential for hNSC self-renewal and as a novel target for the study of neurogenetic mechanisms.

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A 51-year-old Caucasian man was hospitalized because of myalgia and fever. He had been suffering from chronic rhinitis since the age of 18 years and from asthma since the age of 45 years. Three months before hospitalization, he had received an influenza vaccine. On admission, he also complained of fatigue and paresthesias involving the lower limbs, and reported the recent onset of palpable purpura at both legs ( Figure 1a). Laboratory tests are summarized in Table 1. The patient's HLA-DRB1 genotype was positive for *04-*07 alleles, both belonging to the HLA-DRB4 gene. Chest computed tomography (CT) scan was normal, whereas head CT showed diffuse sinusitis (Figures 1c and d). Electroneurography disclosed sensorimotor polyneuropathy with signs of axonal damage affecting the right peroneal and left sural nerves. A biopsy of the purpuric lesions was performed, and histology showed leukocytoclastic vasculitis ( Figure 1b). As an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis was suspected and urinary abnormalities persisted, renal biopsy was performed. On light microscopy (Figure 2), the biopsy specimen included 24 glomeruli, 3 of which were obsolescent. Segmental necrosis was found in 30% of the glomeruli, whereas four showed extracapillary proliferation. The tubulointerstitium, arterioles, and venules were normal, with no eosinophilic infiltration. Immunofluorescence showed no immune deposits. Churg-Strauss syndrome (CSS) was diagnosed on the basis of histological findings showing vasculitis and the presence of asthma, eosinophilia, sinusitis, and polyneuropathy. Prednisone therapy (initial dose 1 mg/kg/ day) induced rapid symptom remission, normalization of the eosinophil count, and urinary abnormalities. Prednisone was stopped 9 months later but was resumed soon after withdrawal because of relapsing asthma.