Update on reslizumab for eosinophilic asthma

The cellular uptake of oligomeric nucleic acid-based tools and drugs including small-interfering RNA (siRNA) represents a major technical hurdle for the biologic effectiveness and therapeutic success in vivo. Subsequent to cellular delivery it is crucial to direct siRNA to the cellular location where it enters the RNA interference pathway. Here the authors summarise evidence that functionally active siRNA represents a minor fraction in the order of 1% of total siRNA inside a given target cell. Exploiting possibilities of steering intracellular release or trafficking of siRNA bears the potential of substantially increasing the biological activity of siRNA. The recently described phosphorothioate stimulated cellular delivery of siRNA makes use of the caveolar system ending in the Golgi apparatus, which contrasts all other known delivery systems. Therefore, it represents an attractive alternative to study whether promoted intracellular release is related to increased target suppression and, thus, increased phenotypic biologic effectiveness.     

Calls to Poison Centers for hookah smoking exposures

Over the past decade, smoking behaviors have changed in the US. Hookah or waterpipe smoking is increasing, especially among youth and young adults. Social media sites describe the “hookah high” or “buzz”, which may be related to nicotine, carbon monoxide, or other inhalants in hookah smoke. Most important is the risk of carbon monoxide poisoning. Case reports include a high number of victims presenting with loss of consciousness from either syncope or seizures. Anaphylaxis and a very rare respiratory hypersensitivity reaction, acute eosinophilic pneumonia, have also been reported from hookah smoking in previously healthy young adults. This article provides background information on hookah smoking, describes hookah-induced acute injuries that could precipitate poison center calls, and offers suggestions for exposure characterization.     

Clinical features of eosinophilic esophagitis: Ten Japanese cases

Aim: We studied eosinophilic esophagitis (EE) to clarify the clinical and endoscopic features of a Japanese case series. Methods: Records of 10 patients diagnosed with EE at our hospital between May 2010 and December 2011 were examined for age, sex, symptoms, allergic disorder, endoscopic findings, and treatment received. Esophageal wall thickness was measured by endoscopic ultrasonography (EUS). Results: Patients were seven males and three females with a mean age of 48 years. Symptoms included dysphagia, heartburn, food impaction, and chest pain. Nine patients had a history of allergic diseases. Increased peripheral eosinophil count was observed in one patient whereas increased immunoglobulin E level was observed in eight patients. Endoscopic findings included longitudinal furrows in all patients, mucosal edema in nine patients, loss of vascular pattern in nine patients, white exudates in six patients, cobblestone‐like appearance in five patients, and concentric rings in three patients. EUS revealed thickening of the esophageal wall in one patient. Histopathological examination revealed eosinophilic infiltration (≥15 eosinophils/high‐powered field) in the esophageal epithelium of all patients. Treatment was required in six patients. Proton pump inhibitor (PPI) therapy was given as the first‐line treatment but was ineffective in four patients and effective in two patients. Steroid therapy was given to three patients unresponsive to PPI therapy and was effective. Conclusions: EE was common among relatively young men and was associated with allergic diseases. Longitudinal furrows were observed as the most characteristic endoscopic finding. Esophageal wall thickening was not commonly observed by EUS.     

The role of TNF‐α in eosinophilic inflammation associated with RSV bronchiolitis

Choi J, Callaway Z, Kim HB, Fujisawa T, Kim CK. The role of TNF‐α in eosinophilic inflammation associated with RSV bronchiolitis.
Pediatr Allergy Immunol 2010: 21: 474–479.
© 2009 John Wiley & Sons A/S The purpose of our study was to investigate whether tumor necrosis factor (TNF)‐α correlates with eosinophilic inflammation that occurs during a lower respiratory tract infection with the respiratory syncytial virus (RSV) in children. Sixty children with RSV bronchiolitis (RSV group) and 20 healthy children with no respiratory symptoms (Control group) were enrolled. We measured the nasal lavage fluid (NLF) Th2 cytokine (IL‐5), proinflammatory cytokine (TNF‐α, IL‐8), eosinophil‐active cytokine [granulocyte‐macrophage colony stimulating factor (GM‐CSF), IFN‐γ], and eosinophil‐active chemokine (eotaxin, regulated on activation normal T cell excreted and secreted) levels for both groups. We also measured serum eosinophil‐degranulation product (eosinophil‐derived neurotoxin; EDN, eosinophil cationic protein; ECP) levels from RSV group. TNF‐α, IL‐8, GM‐CSF, IFN‐γ, and eotaxin levels were significantly higher in the RSV group compared with the Control group. TNF‐α correlated with GM‐CSF (r = 0.87, p < 0.0001), IFN‐γ (r = 0.92, p < 0.0001), eotaxin (r = 0.64, p < 0.0001), and IL‐8 (r = 0.84, p < 0.0001). TNF‐α may have an important role in eosinophilic inflammation of airways in children with RSV bronchiolitis.     

Eosinophilic fascitis: a report of two cases treated with ultraviolet A1 phototherapy

Eosinophilic fascitis (EF) (synonyms: Shulman's syndrome, diffuse fascitis with eosinophilia) is a disease characterized by a complex set of symptoms with scleroderma-like skin lesions, the absence of Raynaud's phenomenon and other non-mandatory symptoms including eosinophilia, elevated erythrocyte sedimentation rate, hypergammaglobulinemia and high levels of circulating immune complexes. EF is probably not a separate disease entity, but an acute variant of localized scleroderma. This rare disease of unknown etiology is usually seen in middle-aged adults. Sclerodermiform indurations without Raynaud's symptoms develop rapidly usually on the extremities and more rarely on the trunk or the face. The skin becomes hard, tightly bound to the underlying structures, so that contractures can develop in as little as a few weeks. The course of the disease is usually chronic but spontaneous remission is possible. Standard therapy includes high doses of corticosteroids, immunosuppressive drugs such as methotrexate, cyclosporin A, cyclophosphamide or azathioprine and others such as psoralen and ultraviolet A radiation.     

Prostaglandin E2 and cysteinyl leukotriene concentrations in sputum: association with asthma severity and eosinophilic inflammation

Background Inflammation of the airways in asthma is associated with the production of cysteinyl leukotrienes (cysLT), prostaglandin (PG)E₂, 8‐isoprostane, nitric oxide and other mediators. However, the relationship between asthma severity or eosinophilic inflammation and the concentrations of mediators in sputum is unclear. Objective To assess sputum PGE₂, cysLT, 8‐isoprostane and nitrate concentrations, as well as urinary leukotriene (LT)E₄ and 9α,11β‐prostaglandin (PG)F₂ concentrations, in patients with differing severities of asthma and eosinophilic or non‐eosinophilic airway inflammation. Methods Inflammatory cells in sputum were assessed in 12 patients with mild, 14 with moderate and 12 with severe persistent asthma, as well as in 13 control subjects. Asthmatic patients were categorized into those with eosinophilic or non‐eosinophilic airway inflammation. Sputum PGE₂, cysLT and 8‐isoprostane, and urinary LTE₄ were extracted on immunoaffinity sorbents, and the concentrations of all mediators were measured using enzyme immunoassays. Sputum nitrate concentrations were measured on a chemiluminescence analyzer. Results Sputum PGE₂ concentrations were higher in both moderate (1710 pg/mL) and severe asthmatic (1590 pg/mL) compared with control subjects (827 pg/mL) (P<0.05). CysLT concentrations were higher in moderate asthmatic compared with control or severe asthmatic subjects (P<0.05). Sputum PGE₂ concentrations were lower in patients with eosinophilic (1180 pg/mL) compared with non‐eosinophilic airway inflammation (2520 pg/mL) (P=0.02). In contrast, sputum cysLT and urinary LTE₄ concentrations were higher in those with eosinophilic airway inflammation (P<0.05). Forced expiratory volume in 1 s was inversely correlated with sputum eosinophils in all asthmatic patients (r_s=?0.5, P=0.002). There were no significant differences in sputum 8‐isoprostane or nitrate concentrations. Conclusions Increased airway concentrations of PGE₂ are consistent with the hypothesis that PGE₂ has a bronchoprotective and anti‐inflammatory role in patients with more severe asthma. A reduced PGE₂ to cysLT ratio in the airways may adversely affect lung function and contribute to persistence of symptoms and airway remodelling in patients with eosinophilic airway inflammation. Cite this as: S. Aggarwal, Y. P. Moodley, P. J. Thompson and N. L. Misso, Clinical & Experimental Allergy, 2010 (40) 85–93.     

Langerhans' cell histiocytosis of the frontal bone

Two cases of Langerhans' cell histiocytosis of the frontal bone are presented. This condition was previously known as eosinophilic granuloma and rarely involves the orbit but may be associated with widespread and life-threatening disease. Clinical, radiological and histopathological features are presented. A discussion of the light and electron microscopic appearances, investigation and management follows.     

Extracorporeal photochemotherapy in the treatment of eosinophilic fasciitis

BACKGROUND: Eosinophilic fasciitis (EF) is a rare connective tissue disorder characterized clinically by symmetrical swelling, induration and thickening of the skin and histologically by thickening of the fascia with chronic inflammatory infiltrate containing eosinophils. The disease is classified in the spectrum morphea/systemic sclerosis and treated with systemic steroids and other immunosuppressant drugs. OBJECTIVE: The purpose of this study was to use extracorporeal photochemotherapy (ECP) in patients with EF to evaluate the effectiveness of this therapy. SUBJECTS AND METHODS: Three patients affected by EF were treated with ECP because they failed to respond or with contraindications to immunosuppressant treatment. The patients underwent ECP with a UVAR XTS apparatus. Subjects were treated on two consecutive days at 2-week intervals for the first 3 months and thereafter every 4 weeks on the basis of clinical response. The patients were assessed before therapy and then monthly by means of a clinical score. Changes in affected areas were evaluated at predetermined points by computerized skin elastometry (Cutometer SEM 474). RESULT: After 1 year of therapy we found considerable improvement of clinical parameters in two cases. There was less striking improvement in the other case. These clinical results were confirmed by the elastometry measurements. All patients reported improved quality of life, which enabled a reduction in the dose of immunosuppressants. CONCLUSION: ECP emerged as a safe and effective therapy in association with low doses of immunosuppressants in our three patients. A randomized comparative multicentre study between ECP as single therapy and ECP plus immunosuppressants and conventional therapies is required to firmly establish photopheresis as a possible basic treatment to combine with conventional therapies for EF.     

郎格罕细胞组织细胞增生症46例临床研究

目的 探讨郎格罕细胞组织细胞增生症的临床特点，提高临床诊治水平。方法 对近8年来我院46例郎格罕细胞组织细胞增生症进行临床回顾性研究分析。结果 46例病人中最小发病年龄为1个月，勒雪氏综合征的发病年龄都在3岁以下；骨嗜酸性肉芽肿最小发病年龄16个月。男多于女，但年龄在12个月以下发病男女无差异。临床以发热，皮疹，骨损害，突眼，尿崩，耳溢等表现为主。病情轻重和预后与发病年龄密切相关。46例中发现1例伴海洋性贫血，1例伴G-6PD缺陷症。结论 郎格罕细胞组织细胞增生症临床表现多样化，病情轻重不一，典型皮疹印片有诊断意义。治疗采用手术刮除和化疗，合并尿崩时联合抗利尿激素使用。取得较好疗效。     

Langerhans cell histiocytosis of the skull on cytologic squash preparations

We present a case in which a primary cytodiagnosis of Langerhans cell histiocytosis (LCH) of the skull was made using squash preparations. The patient, a 25-year-old male, presented with raised intracranial pressure and decreased visual acuity. Magnetic resonance imaging revealed a large skull lesion with osteolytic features in the left frontal bone. The patient underwent surgical resection by the extended basal frontal epidural approach. The squash preparation smears were cellular and demonstrated a mixed population of small, mature lymphocytes, eosinophils, and a high histiocytes content. The histiocytes occurred as isolated or loosely cohesive and clustered. They possessed abundant cytoplasm with rounded cell shape and had characteristic nuclear features, composed of fine chromatin and delicate nuclear membranes. The cytologic features of these histiocytes were consistent with Langerhans cells (LCs). A final impression of LCH of the skull was rendered. Subsequent histopathology confirmed the diagnosis. LCs reacted with both S-100 protein and CD1a immunohistochemically. The demonstration of Birbeck granules on electron microscopic study was also noted. Whenever squash preparation yields a mixed population of mature lymphocytes, eosinophils, and histiocytes, the cytologists should be aware of and consider LCH as a diagnostic possibility.