[Experience of biological therapy in severe forms of chronic rhinosinusitis with nasal polyps in the conditions of regional healthcare]. / Opyt biologicheskoi terapii pri tyazhelykh formakh khronicheskogo polipoznogo rinosinusita v usloviyakh regional'nogo zdravookhraneniya.

Recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) with a predominant Th2 endotype of inflammation, including associated with bronchial asthma and/or allergic rhinitis, aspirin triad, refers to diseases with an insufficient level of control, despite the use of a wide range of options for conservative and surgical treatment. OBJECTIVE: To analyze our own experience, clinical and organizational features of the application of the method of biological therapy in patients with severe forms of recurrent CRSwNP. MATERIAL AND METHODS: 25 patients with severe and moderate forms of CRSwNP were examined, who, in a round-the-clock hospital (model CSG 36.018) was treated with Dupilumab, in the form of subcutaneous injections of 300 mg/2 ml 1 every two weeks. The diagnosis was confirmed on the basis of anamnestic data, SNOT-22 quality of life questionnaires, visual endoscopic examination, evaluation of CT data (Lund-Mackay scale), laboratory data. The effectiveness of treatment was monitored after 16 weeks, based on endoscopic examination data, evaluation of CT and SNOT-22 data. In 3 observations, a study of pathomorphological material for tissue eosinophilia was performed. RESULTS: The duration of the course of treatment ranged from 10 to 56 weeks. The most striking clinical effect was observed for signs such as sense of smell and nasal breathing (in some cases-after the first injection). The degree of regression of polyps according to CT and endoscopic examination was more prolonged in time, the same dynamics was observed in the level of total IgE. In a number of patients, the phenomenon of eosinophilia growth was observed against the background of treatment (with regression of clinical symptoms). Pathomorphological examination confirmed a high level of tissue eosinophilia as one of the fundamental signs of Th2 inflammation. One patient with concomitant chronic tubar dysfunction had an improvement in hearing. All patients with AD noted a subjective improvement in disease control (a decrease in the frequency and severity of choking attacks). The cancellation (break in treatment) of treatment was accompanied by a gradual return of symptoms in all patients at various times. CONCLUSIONS: Patients who have not achieved an acceptable level of control of CRSwNP,that meets the criteria of Th2 inflammation can be considered as candidates for the use of targeted biological therapy. With strict compliance with the selection criteria, there is a good clinical effect, primarily in relation to nasal symptoms (sense of smell and nasal breathing) and improved control of asthma symptoms.

Do Biologic Therapies Decrease Mucus Plugging in Asthma?

Asthma researchers have long recognized that abnormal mucus production and clearance play a role in the pathophysiology of asthma.1 Mucus plugs are known to be common in patients with severe asthma, and mucus plug scores, for which higher scores indicate more severe plugging, are directly correlated with airflow obstruction and markers of eosinophilic airway inflammation (i.e., higher scores or marker levels are associated with more severe obstruction). Other work has shown that mucus plugs were associated with distal deficits in regional ventilation as delineated by hyperpolarized gas magnetic resonance imaging.2,3.

Partial Response to Sorafenib in a Child With a Myeloid/Lymphoid Neoplasm, Eosinophilia, and a ZMYM2-FLT3 Fusion.

Dysregulated tyrosine kinases in myeloid/lymphoid neoplasms with eosinophilia are rare, but do occur in children. To increase awareness of this diagnosis, we present a child who was diagnosed after a 3-year disease history. The patient was initially treated according to a T-cell lymphoblastic lymphoma protocol, but genetic analyses at recurrence revealed microdeletions resulting in an in-frame fusion of ZMYM2 and FLT3. Treatment with sorafenib, an FLT3 tyrosine kinase inhibitor, rapidly resulted in significant reduction of lymphadenopathy and normalization of white blood cell and eosinophil counts. At 17 months of treatment, he remains in complete hematologic, but not molecular remission.

Effects of Anti-T2 Biologic Treatment on Lung Ventilation Evaluated by MRI in Adults With Prednisone-Dependent Asthma.

BACKGROUND: The functional consequence of airway obstruction in asthma can be regionally measured using inhaled gas MRI. Ventilation defects visualized by MRI persist post-bronchodilator in patients with severe asthma with uncontrolled sputum eosinophilia and may be due to eosinophil-driven airway pathology that is responsive to "anti-T2" therapy. RESEARCH QUESTION: Do anti-T2 therapies that clear eosinophils from the airway lumen decrease ventilation defects, measured by inhaled gas MRI, in adults with prednisone-dependent asthma? STUDY DESIGN AND METHODS: Inhaled hyperpolarized gas MRI was performed before and after bronchodilation in 10 prednisone-dependent patients with asthma with uncontrolled eosinophilic bronchitis (sputum eosinophils ≥3%) at baseline and 558 (100-995) days later when their eosinophilic bronchitis had been controlled (sputum eosinophils <3%) by additional anti-T2 therapy. The effect of anti-T2 therapy on ventilation defects, quantified as the MRI ventilation-defect-percent (VDP), was evaluated before and after bronchodilation for all patients and compared between patients dichotomized based on the median percentage of sputum eosinophils at baseline (15.8%). RESULTS: MRI VDP was improved pre- (ΔVDP+anti-T2: -3% ± 4%, P = .02) and post-bronchodilator (ΔVDP+anti-T2: -3% ± 4%; P = .04) after additional anti-T2 therapy that controlled eosinophilic bronchitis (n = 2 mepolizumab, n = 2 reslizumab, n = 3 benralizumab, n = 1 dupilumab, n = 2 increased daily prednisone). A greater post-bronchodilator ΔVDP+anti-T2 was observed in those patients with median or higher percentage of sputum eosinophils at baseline (≥15.8%; P = .01). In 7 of 10 patients with asthma, residual ventilation defects persisted despite bronchodilator and anti-T2 therapy. INTERPRETATION: Controlling sputum eosinophilia with anti-T2 therapies improves ventilation defects, measured by inhaled gas MRI, in adults with prednisone-dependent asthma.

Protein losing enteropathy caused by eosinophilic gastroenteritis: A case report.

Protein losing enteropathy (PLE), a very rare disease with hypoproteinemia and edema as its characteristics, is caused by various diseases resulting in protein depletion from the gut. The diagnosis is relatively difficult due to its complex pathogeneses. The present paper reported a case whose symptom started with acute diarrhea and hypoproteinemia. Gastrointestinal endoscopies showed digestive ulcers and colon polyp. The treatments contained albumin infusion, Chinese herbal decoction and other symptomatic therapies. The hypoproteinemia become even worse and edema occurred after 4 days' treatment. A larger dose of albumin infusion (40-60 g/d) and modified herbal decoctions were prescribed. A final diagnosis of eosinophilic gastroenteritis (EG) complicated with PLE was confirmed by histopathological examination of a repeated gastroscopy. After three weeks' treatment, the serum albumin level was raised and the edema subsided gradually. In conclusion, herbs may have an effect on PLE patients, but PLE resulting from EG is very complex and easy to misdiagnose, especially in atypical conditions. Further studies are required to find the exact mechanisms.

Hematochezia caused by eosinophilic proctocolitis in a newborn before oral feeding: a case report.

BACKGROUND: Hematochezia is a frequent symptom in early infancy. However, it occurs very rarely within the immediate neonatal period, and its occurrence before any oral intake is particularly rare. Because of the "congenital" presentation of hematochezia in our patient, we initially considered our case to be a non-classical, potentially severe type of food protein-induced allergic proctocolitis. This diagnosis needs to be confirmed by an abnormal oral challenge test once the hematochezia has disappeared. If such a challenge cannot demonstrate an allergic origin, then the etiology of the hematochezia could be a neonatal transient eosinophilic colitis. Only two similar cases have been described so far. CASE PRESENTATION: We report the case of a black baby boy of African origin born at 36 weeks 5 days of gestational age who presented with massive hematochezia immediately after birth. A rectosigmoidoscopy revealed a severe inflammation associated with diffuse eosinophilic infiltration on biopsy. His clinical outcome was favorable after introduction of an amino acid formula diet. We initially considered our case to be a non-classical, potentially severe type of food protein-induced allergic proctocolitis but reintroduction of standard formula milk at the age of 3 months was successful. So, our patient is the first newborn in Europe who fits the diagnosis of "neonatal transient eosinophilic colitis." CONCLUSIONS: We discuss the possible etiology of "congenital" eosinophilic inflammation of the distal colon and conclude that hematochezia in well-looking neonates, in the absence of negative challenge tests later on, is more likely to be a neonatal transient eosinophilic colitis than an allergic proctocolitis. This new entity could be more frequent than previously thought, changing our medical care strategies for this kind of neonatal symptom.

Conjugated Alpha-Alumina nanoparticle with vasoactive intestinal peptide as a Nano-drug in treatment of allergic asthma in mice.

Asthma is a chronic respiratory disease characterized by airway inflammation, bronchoconstriction, airway hyperresponsiveness and recurring attacks of impaired breathing. Vasoactive intestinal peptide (VIP) has been proposed as a novel anti-asthma drug due to its effects on airway smooth muscle relaxation, bronchodilation and vasodilation along with its immunomodulatory and anti-inflammatory properties. In the current study, we investigated the therapeutic effects of VIP when conjugated with α-alumina nanoparticle (α-AN) to prevent enzymatic degradation of VIP in the respiratory tract. VIP was conjugated with α-AN. Balb/c mice were sensitized and challenges with ovalbumin (OVA) or PBS and were divided in four groups; VIP-treated, α-AN-treated, α-AN-VIP-treated and beclomethasone-treated as a positive control group. Specific and total IgE level, airway hyperresponsiveness (AHR), bronchial cytokine expression and lung histology were measured. α-AN-VIP significantly reduced the number of eosinophils (Eos), serum IgE level, Th2 cytokines and AHR. These effects of α-AN-VIP were more pronounced than that seen with beclomethasone or VIP alone (P<0.05). The current data indicate that α-AN-VIP can be considered as an effective nano-drug for the treatment of asthma.

Rivaroxaban-induced drug reaction with eosinophilia and systemic symptoms

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Assessment of Tumor Associated Tissue Eosinophilia (TATE) in Oral Squamous Cell Carcinoma Using Carbol Chromotrope Stain / Evaluación de la Eosinofilia Tisular Asociada al Tumor (TATE) en el Carcinoma Oral de Células Escamosas Mediante la Tinción de Carbol Cromótropo

Tumor related tissue eosinophilia (TATE) is a known phenomenon but its role in prognostics and correlation with size of the primary tumor is still controversial. Using a stain, like Carbol chromotrope, that targets eosinophils exclusively and vividly, offers an advantage over haematoxylin and eosin, which was used in most of the studies. Forty-nine cases of oral squamous cell carcinoma, where the TNM staging has been recorded in their history, was taken and stained with Lendrum's carbol chromotrope. Significant difference in the eosinophil count with varying size of the tumor and a parallel increase in the number noted, with increase in size. There is a corresponding increase in the number of eosinophils infiltrating the tumor with increase in size of oral squamous cell carcinoma.

La eosinofilia tisular asociada a tumores (TATE) es un fenómeno conocido, sin embargo su pronóstico y correlación con el tamaño del tumor primario aún es tema de controversia. El uso de cromotropo como tinción dirigida exclusivamente a los eosinófilos, ofrece una ventaja sobre la hematoxilina-eosina, que ha sido utilizada en la mayoría de los estudios. Se estudiaron células escamosas en 49 casos de carcinoma oral, con registro del estadio TNM. Las células fueron teñidas con carbol cromotropo de Lendrum. Se observó una diferencia significativa en el recuento de eosinófilos con el tamaño del tumor y un aumento paralelo en número, con el aumento de tamaño. Hay un aumento correspondiente en el número de eosinófilos que infiltran el tumor con aumento en el tamaño de carcinoma de células escamosas orales.

Fecal microbiota transplantation and prednisone for severe eosinophilic gastroenteritis.

Eosinophilic gastroenteritis is a rare disease of unknown etiology. It is characterized by patchy or diffuse eosinophilic infiltration of the bowel wall to a variable depth and various gastrointestinal manifestations. We describe a case of severe eosinophilic gastroenteritis presenting as frequent bowel obstruction and diarrhea in a 35-year-old man. The patient was misdiagnosed and underwent surgery because of intestinal obstruction when he was first admitted to a local hospital. Then he was misdiagnosed as having Crohn's disease in another university teaching hospital. Finally, the patient asked for further treatment from our hospital because of the on-going clinical trial for treating refractory Crohn's disease by fecal microbiota transplantation. Physical examination revealed a slight distended abdomen with diffuse tenderness. Laboratory investigation showed the total number of normal leukocytes with neutrophilia as 90.5%, as well as eosinopenia, monocytopenia and lymphocytopenia. Barium radiography and sigmoidoscopy confirmed inflammatory stenosis of the sigmoid colon. We diagnosed the patient as having eosinophilic gastroenteritis by multi-examinations. The patient was treated by fecal microbiota transplantation combined with oral prednisone, and was free from gastrointestinal symptoms at the time when we reported his disease. This case highlights the importance of awareness of manifestations of a rare disease like eosinophilic gastroenteritis.

A severe case of rat lungworm disease in Hawa'i.

A 23-year-old man living on the island of Hawa'i developed a life threatening case of eosinophilic meningitis caused by infection with Angiostrongylus cantonensis (rat lungworm disease: RLWD). He was comatose for 3 months, incurring brain and nerve damage sufficiently extensive that he was not expected to recover. The case was complicated by secondary infections of methicillin-resistant Staphylococcus aureus, Clostridium difficile, and pneumonia, which resulted in an empyema requiring a thoracoscopy and decortication. He was treated with prednisone, mebendozal, and pain medication for RLWD, and antibiotics and antifungal medications for the secondary infections. The administration of herbal supplements was requested by the family and approved, and these were administered through a gastric tube. Less than a month after being declared in a persistent vegetative state the man was able to talk, eat, and had regained some muscle functions. After release from the hospital he continued the use of supplements and received treatments of intravenous vitamin therapy. Four years after onset of the illness he is able to ride a bicycle, is a part time student, plays guitar, and is fluent in two foreign languages. RLWD is an emerging tropical disease of growing importance in Hawa'i.

DRESS syndrome induced by acenocoumarol with tolerance to warfarin and dabigatran: a case report.

Drug reaction with eosinophlia and systemic symptoms (DRESS) syndrome describes a severe medication-induced adverse reaction, which shows skin, blood and solid-organ features. Up to 50 drugs have been described to cause DRESS. The main responsible drugs are carbamazepine and allopurinol. There are no previous reports associated with acenocoumarol. A 85-year-old white male, who was treated with acenocoumarol for the prevention of venous thromboembolism due to atrial fibrillation, presented 6 weeks later a maculopapular exanthema of the trunk and limbs as well as purple lesions and blisters on distal parts of his legs. Elevated creatinine, glucose, urea, International Normalized Ratio, gamma-glutamyl-transpeptidase (GGT) and eosinophilia levels were observed. Acenocoumarol was removed and enoxaparine, systemic corticosteroids, antihistamines were used as treatment with a favorable clinical evolution: 1 month later, the skin lesions had disappeared and laboratory parameters were normalized. Patch tests with warfarin and dabigatran were carried out. Two simple-blind, placebo-controlled oral challenges with warfarin and dabigatran were performed. Patch tests were negative, and single-blind, placebo-controlled oral challenges with warfarin and dabigatran were achieved without immediate or delayed reactions. We firstly describe a DRESS syndrome induced by acenocoumarol. Patch test was useful to assess alternative therapies. Tolerance to other anticoagulants (warfarin and dabigatran) was demonstrated.

Treatment of DIHS/DRESS syndrome with combined N-acetylcysteine, prednisone and valganciclovir--a hypothesis.

BACKGROUND: Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a rare and severe adverse drug reaction with an associated mortality of 10-20%. Clinical worsening despite discontinuation of the culprit drug is considered a characteristic feature of DIHS/DRESS. Besides the early recognition of the syndrome and discontinuation of its causative drug, the mainstay of treatment is systemic corticosteroids. Nevertheless, treatment of severe DIHS/DRESS is not well defined, as corticosteroids may sometimes not be effective, and decreasing the dose may be associated with flaring of the disease. CASE REPORT: A 38-year-old woman with high fever, malaise, abdominal pain, rash, and elevated liver enzymes received immediate high-dose N-acetylcysteine, because acetaminophen hepatotoxicity was suspected. N-acetylcysteine administration was associated with a significant clinical improvement. However, within the next week DIHS/DRESS syndrome was diagnosed, which explained all the symptoms, and which was subsequently treated with prednisone and valganciclovir. CONCLUSIONS: New options necessary to improve treatment of severe DIHD/DRESS have to consider its sequential pathogenetic mechanisms. N-acetylcysteine might neutralize the drug-derived reactive metabolites, which are responsible for protein adduct formation and specific T cell stimulation, and replete the glutathione stores that counterbalance oxidative stress. Prednisone might inhibit lymphoproliferation and valganciclovir might prevent complications related to HHV-6 reactivation. We therefore propose the unprecedented combination of N-acetylcysteine, prednisone and valganciclovir as a treatment option for DIHS/DRESS.

Eosinophilic gastrointestinal disorders in infants: a Japanese case series.

BACKGROUND: Eosinophilic gastrointestinal disorders (EGIDs) are disorders characterized by primary eosinophil inflammation in the gastrointestinal tract. There are a small number of reports of eosinophil infiltration in gastrointestinal tracts presenting as EGIDs in infants. In this study, we present Japanese cases of EGIDs in infants. METHODS: Five patients diagnosed with or strongly suspected to have EGIDs in our hospital from 2008 to 2010 were reviewed. Radiographic contrast enema examinations and/or endoscopies were performed in 4 and 3 patients, respectively. RESULTS: There were patients with eosinophilic colitis (1 suspected and 2 biopsy-proven), a patient who was suspected of having allergic eosinophilic enterocolitis, and a patient with eosinophilic gastroenteritis associated with pediatric hypereosinophilic syndrome. CONCLUSIONS: The causes and clinical findings of patients with intestinal eosinophil inflammation vary. Therefore, deliberate examination and observation are important for patients with infantile EGID.

Eosinophilic vasculitis: an inhabitual and resistant manifestation of a vasculitis.

A 55-year-old woman was referred because of diffuse pruritic erythematous lesions and an ischemic process of the third finger of her right hand. She was known to have anaemia secondary to hypermenorrhea. She presented six months before admission with a cutaneous infiltration on the left cubital cavity after a paravenous leakage of intravenous iron substitution. She then reported a progressive pruritic erythematous swelling of her left arm and lower extremities and trunk. Skin biopsy of a lesion on the right leg revealed a fibrillar, small-vessel vasculitis containing many eosinophils.Two months later she reported Raynaud symptoms in both hands, with a persistent violaceous coloration of the skin and cold sensation of her third digit of the right hand. A round 1.5 cm well-delimited swelling on the medial site of the left elbow was noted. The third digit of her right hand was cold and of violet colour. Eosinophilia (19 % of total leucocytes) was present. Doppler-duplex arterial examination of the upper extremities showed an occlusion of the cubital artery down to the palmar arcade on the right arm. Selective angiography of the right subclavian and brachial arteries showed diffuse alteration of the blood flow in the cubital artery and hand, with fine collateral circulation in the carpal region. Neither secondary causes of hypereosinophilia nor a myeloproliferative process was found. Considering the skin biopsy results and having excluded other causes of eosinophilia, we assumed the diagnosis of an eosinophilic vasculitis. Treatment with tacrolimus and high dose steroids was started, the latter tapered within 12 months and then stopped, but a dramatic flare-up of the vasculitis with Raynaud phenomenon occurred. A new immunosuppressive approach with steroids and methotrexate was then introduced. This case of aggressive eosinophilic vasculitis is difficult to classify into the usual forms of vasculitis and constitutes a therapeutic challenge given the resistance to current immunosuppressive regimens.

A pilot study to assess the efficacy of biofeedback-assisted relaxation training as an adjunct treatment for pediatric functional dyspepsia associated with duodenal eosinophilia.

OBJECTIVES: To conduct a pilot study examining whether adding biofeedback-assisted relaxation training (BART) to medication treatment results in better clinical outcomes than medication treatment alone for children with functional dyspepsia (FD) associated with duodenal eosinophilia, a subgroup of children with recurrent abdominal pain. METHODS: Twenty children were randomly assigned to receive a standardized medication treatment or medication plus 10 sessions of BART. Children and parents completed psychosocial functioning and quality of life measures at baseline, posttreatment, and 6 months. Children rated pain daily via PDA. Physicians provided biweekly assessments of clinical improvement. RESULTS: Children receiving medication plus BART demonstrated better outcomes on pain intensity, duration of pain episodes, and clinical improvement than children receiving medication alone. CONCLUSIONS: BART is a promising adjunctive treatment for pediatric FD associated with duodenal eosinophilia. Electronic daily diaries appear to be a useful approach to assessing changes in self-reported pain ratings in this population.

Carbamazepine induced DRESS syndrome.

We present here an 18-yr-old male who presented with intermittent fever of moderate grade and of 15 days duration, followed by maculopapular erythematous rashes over upper and lower extremities, face, and trunk developing over 10-12 days. He was suffering from recurrent seizures since last 3 months for which he was started on carbamazepine 200mg twice daily for the past 6 weeks. He was febrile on admission. Generalized lymphadenopathy with discreet, non-matted, firm and tender inguinal lymph nodes. Patch test with 1% and 5% solution of carbamazepine was strongly positive.

DRESS syndrome with mild manifestations as a diagnostic and therapeutic problem: case report.

The group of severe cutaneous drug reactions with systemic symptoms includes several syndromes: toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS). These reactions occur several days to six weeks after introducing the incriminating drug. The skin and internal organs (liver, kidneys, lungs, etc.) are usually involved. A great possibility of lethal outcome is a critical characteristic of these syndromes. A patient with pyelonephritis diagnosed during emergency room workup is described. Ciprofloxacin was prescribed and the patient was discharged. After ten days, the patient came back with worsening condition, general inflammatory response, skin changes, liver and kidney damage, and eosinophilia. DRESS syndrome was diagnosed based on clinical and other findings. The diagnosis and treatment of severe drug reactions with cutaneous and systemic symptoms pose a medical challenge.