Eosinophilia Syndrome Research Articles

32626 Addition of intravenous immunoglobulin therapy to facilitate resolution of steroid-refractory DRESS syndrome

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening cutaneous adverse reaction with risk of visceral organ involvement. Timely management is necessary to reduce morbidity and prevent mortality. Rarely, DRESS syndrome may be refractory to standard treatment with high-dose systemic corticosteroids, prompting use of supplementary therapies.

Identification of novel signal of clobazam-associated drug reaction with eosinophilia and systemic symptoms syndrome: A disproportionality analysis.

Clobazam is a well-known benzodiazepine used as an anti-anxiety drug as well as an anti-epileptic, particularly for patients who are not responding to first-line treatments. Recent case reports have indicated the association of clobazam with drug reaction with eosinophilia systemic symptoms syndrome (DRESS Syndrome). However, DRESS syndrome is not known to be associated with clobazam. Thus, the main objective of the current study was to identify the potential signal of clobazam-associated DRESS Syndrome. US FDA Adverse event reporting system (US FAERS), pharmacovigilance data 2004Q1-2021Q3 was extracted using OpenVigil 2.1-MedDRA-v24. The Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR) with a Chi-Square value (95% confidence interval), and number of cases (≥3) were used as disproportionality analysis parameters. A total of 141 drug-event combinations were reported and results of disproportionality analysis indicate the positive signal of DRESS syndrome with clobazam. The signal strength was decreased after removing the cases of concomitantly administered drugs (phenytoin, levetiracetam, and valproic acid); however, the association of clobazam with DRESS syndrome remains statistically significant. The subgroup analysis results have shown a greater number of cases in the age group (18-64 years) as compared to other age groups whereas the number of cases in the male and female groups is almost similar. The DRESS syndrome is identified as a novel signal with clobazam. However, further causality assessment is required.

DRESS syndrome by sulfonamides, about a case

Among the most feared toxico-dermas is drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, a rare drug dermatitis that occurs after acute exposure to drugs whose clinical impact is based on multiple organs (skin, liver, kidneys, lungs, heart) and cell lines (eosinophils and lymphocytes). It is an entity with high mortality if it is not identified early, its treatment consists of the immediate suspension of the responsible drug and the administration of steroids, these being the therapeutic protagonists. A 64-year-old male patient with clinical, biochemical and histopathological criteria compatible with DRESS syndrome. It is essential to suspect the clinical course of DRESS syndrome before the appearance of dermatosis with multisystem involvement associated with the use of drugs, emphasis is placed on its early identification and the establishment of timely treatment to modify its prognosis.

Prolonged Drug-Induced Hypersensitivity Syndrome/DRESS With Alopecia Areata and Autoimmune Thyroiditis.

Drug-induced hypersensitivity syndrome (DIHS), also called drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, is a potentially fatal drug-induced hypersensitivity reaction that is characterized by a cutaneous eruption, multiorgan involvement, viral reactivation, and hematologic abnormalities. We present a case of lamotrigine-associated DIHS/DRESS complicated by an unusually prolonged course requiring oral corticosteroids and narrow-band ultraviolet B treatment and with development of extensive alopecia areata and autoimmune thyroiditis. DIHS/DRESS is a severe cutaneous adverse reaction that may require prolonged treatment until symptoms resolve. Oral corticosteroids are the mainstay of treatment, but long-term use is associated with significant adverse effects. Alternative therapies, such as cyclosporine, look promising, but further studies are needed to determine safety profile and efficacy. DIHS/DRESS patients also should be educated and followed for potential autoimmune sequelae.

Phenytoin Induced Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome: A Clinical Case Report

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially life-threatening hypersensitivity reaction with cutaneous presentation and internal organ involvement. We herein present a case of phenytoin induced DRESS syndrome in a 56- year-old male who presented with high-grade fever and chills, cough with expectoration and generalized maculopapular rash. Laboratory findings revealed eosinophilia, leukocytosis, thrombocytopenia, transaminitis and elevated inflammatory markers. Further clinical, radiological and histopathological assessments confirmed the diagnosis. Phenytoin was discontinued, and patient was started on intravenous dexamethasone, which was later switched to oral prednisone. Rapid resolution of fever, eosinophilia and progressive improvement in skin rash and liver dysfunction was observed. Our report highlights the importance of prompt recognition of DRESS syndrome and the need for a guideline directed therapy for the management of this adverse drug reaction.

Calprotectin in nasal secretion: a new biomarker of non-type 2 inflammation in CRSwNP.

SUMMARYObjectiveWe analysed calprotectin in sinonasal secretions of different chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes to assess its role as a biomarker of non-type 2 inflammation.MethodsWe included primary diffuse CRSwNP patients (n = 41) and three different control groups [non-allergic rhinitis (NAR) (n = 13), non-allergic eosinophilic syndrome (NARES) (n = 10) and healthy subjects (n = 12)]. Calprotectin levels were detected in nasal secretions using a chemiluminescent immunoassay (CLIA).ResultsCalprotectin levels in nasal secretions were significantly higher in all non-type 2 endotypes of CRSwNP compared to healthy controls (p < 0.05). In contrast, in type-2 CRSwNP calprotectin was significantly lower compared to controls (p < 0.05). A significant correlation between calprotectin levels and neutrophilic count/HPF was found in CRSwNP (p < 0.01). Clinically, mean levels of calprotectin and neutrophilia were significantly higher in patients who previously underwent 3 or more endoscopic sinus surgeries (p < 0.05).ConclusionsCalprotectin in nasal secretions may be a biomarker of non-type 2 inflammation. Low levels of calprotectin are indicative of a type-2 immune response in both CRSwNP and non-allergic rhinitis. We observed that calprotectin levels significantly increased based on the number of previous surgeries.

174 Oblique earlobe crease as a physical examination finding in drug reaction with eosinophilia and systemic symptoms

Introduction: While drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is known to be associated with facial swelling, this edema can be challenging to identify. This study evaluates the utility of a physical examination finding, the oblique earlobe crease, to support the diagnosis of DRESS. Design: This is a retrospective case-control study in which dermatologists evaluated for the presence of an oblique earlobe crease in patients diagnosed with DRESS syndrome compared to unmatched controls with morbilliform drug reactions, Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN), or acute generalized exanthematous pustulosis (AGEP).

A typical presentation of moxifloxacin-induced DRESS syndrome with pulmonary involvement: a case report and review of the literature

BackgroundDrug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a kind of hypersensitivity drug reaction involving the skin and multiple internal organ systems. Moxifloxacin has rarely been reported to be a drug that is associated with DRESS syndrome. Lungs are less frequently involved in DRESS syndrome, but their involvements may herald more serious clinical processes. We present a rare typical case of moxifloxacin-induced DRESS syndrome with lungs involved. Valuable clinical data such as changes in the pulmonary imaging and pulmonary function tests was recorded. This case is important for the differential diagnosis of DRESS syndrome with lungs involved by providing clinical manifestations, CT imaging, pulmonary function tests, and biopsy pathological characteristics. The changes in pulmonary imaging and pulmonary function tests may help us understand the mechanism of DRESS syndrome further.Case presentationWe report a case of a 47-year-old woman who was treated with oral moxifloxacin for community-acquired pneumonia. The patient subsequently developed a cough, fever, liver injury, skin rash, hematologic abnormalities, and shortness of breath (SOB) followed by pharyngeal herpes and peripheral neuritis. These symptoms, clinical lab index, and CT scan of the lungs improved after the withdrawal of moxifloxacin. The probability of moxifloxacin-induced DRESS syndrome was rated as “Definite”, with 7 scores graded by RegiSCAR. A literature search was also performed with “fluoroquinolones,” “moxifloxacin,” “ciprofloxacin,” “levofloxacin,” “delafloxacin,” and “DRESS” or “drug-induced hypersensitivity syndrome (DIHS)” as the keywords that were put into PubMed. The overall pulmonary involvement was approximately 9.1% (1/11). It is a rare reported case of DRESS syndrome with pulmonary involvement induced by moxifloxacin. We summarized detailed clinical data, including pulmonary imaging and pulmonary function changes.ConclusionThis is a rare reported case of DRESS syndrome with pulmonary involvement induced by moxifloxacin. Prompt recognition and correct diagnosis can promote appropriate treatment and accelerate recovery. This case is important for us as a reference in the differential diagnosis of DRESS syndrome and helps us further understand the mechanism of DRESS syndrome.

Phenytoin Induced Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome: A Case Report

Published on:June 2022 Journal of Young Pharmacists, 2022; 14(2):253-255 Case Report | doi:10.5530/jyp.2022.14.48 Authors: Meghna Gosi1, Sujit Kumar Sah1,*, Arya Merin1, Siddartha Ningappa Dhurappanavar1, Ashwini Padubidri Kombettu2 1Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education and Research, SS Nagar, Mysuru, Karnataka, INDIA. 2Department of Dermatology, JSS Hospital, JSS Academy of Higher Education and Research, SS Nagar, Mysuru, Karnataka, INDIA. Abstract: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an idiosyncratic and rare drug reaction that can be severe and life‑threatening if untreated. We present a 34 year old male patient, who developed DRESS syndrome after receiving phenytoin for 8 weeks and presented with rapidly progressive erythematous rash on trunk, face and upper extremities, fever and facial swelling. Abnormal laboratory findings, RegiSCAR score, and Naranjo’s probability scale revealed the association between phenytoin and DRESS syndrome. Phenytoin was withdrawn and adequately managed with systemic corticosteroids, antihistamine, and other symptomatic treatments. DRESS syndrome can be cured completely by early detection and removal of culprit drug along with other adequate symptomatic treatments.Key words: DRESS syndrome, Naranjo probability, Hypersensitivity reaction, Scale, Phenytoin, RegiSCAR score.

Co-occurrence of clozapine-related DRESS syndrome core clinical manifestations: results of a systematic review

IntroductionDrug reaction with eosinophilia and systemic symptoms (DRESS) syndrome refers to a cluster of clinical symptoms/signs related to drug hypersensitivity. The main clinical features include fever, skin rash, eosinophilia, enlarged lymph nodes, atypical lymphocytosis, and involvement of at least one internal organ. Clozapine-related DRESS syndrome has been rarely reported, but this may be due to a different clinical presentation pattern compared to DRESS for other culprit drugs.ObjectivesWe aimed to assess clusters of main clinical features of clozapine-related DRESS.MethodsWe ran a network analysis for clinical manifestations in the pooled sample of all previous published cases of clozapine-related DRESS.ResultsWe observed a triad of core symptoms (i.e., organ implication, fever, and eosinophilia) among DRESS criteria co-occurring in 59.3% (n=16) of 27 patients. The organs most likely to be involved in clozapine-related DRESS included lungs, liver, heart, and kidneys. Fever was also present in almost all cases (n=25 patients), while eosinophilia was observed in two thirds of the sample (n=18 patients).ConclusionsRegarding clinical manifestations clozapine-related DRESS may differ from DRESS for other culprit drugs as skin reaction is not very typical; thus, clinicians need to consider DRESS as a potential diagnosis even in absence of a skin reaction. When managing clozapine-treated patients with the core triad of organ implication, fever, and eosinophilia clinicians should consider guidelines for DRESS treatment.DisclosureNo significant relationships.

Interim analysis of a single-center, single-arm, prospective phase 2 study to evaluate the efficacy and safety of benralizumab for alpelisib rash in metastatic PIK3CA-mutant, hormone receptor–positive breast cancer.

12100 Background: Rash associated with increased peripheral eosinophils develops in approximately 50% of metastatic breast cancer patients receiving alpelisib. Antihistamines and corticosteroids have limited benefit. Refractory rash may lead to decreased dose intensity and affect clinical outcome. Benralizumab is an anti-IL-5Rα chimeric monoclonal antibody that depletes peripheral eosinophils and has demonstrated benefit in eosinophilic asthma and hypereosinophilic syndrome. We investigate the efficacy and safety of benralizumab for the treatment of alpelisib rash. Methods: We performed a single-center, single-arm, prospective phase 2 study to evaluate the efficacy and safety of benralizumab in cancer patients who developed CTCAE grade 2/3 skin events resulting from immunotherapy or targeted therapies with absolute blood eosinophil counts of ≥300/mcl. While remaining on culprit drugs, patients were treated with benralizumab 30mg once every 4 weeks for the first 3 doses followed by once every 8 weeks for 3 additional doses (approved dosing for eosinophilic asthma). Primary endpoint was clinical response measured as reduction in CTCAE grade 2/3 skin event to grade ≤1 by week 4. Secondary endpoints were patient quality of life (QoL) measured by skindex16, safety data, need for supportive oral corticosteroids, and changes in cytokines and eosinophil biomarkers. This interim analysis focuses on patients with PIK3CA-mutant metastatic breast cancer receiving alpelisib. Results: Between September 16th 2020 and January 1st 2022, we enrolled 10 metastatic breast cancer patients with grade 2/3 rash attributed to alpelisib (5 pts with G3). All patients had a reduction of rash to grade ≤1 (n = 10, p &lt; 0.0001), and a decrease in peripheral absolute eosinophils (mean 500/mcl to 0, p &lt; 0.0001). Of these, 6 patients had been on prophylactic oral antihistamines and 2 had oral steroid coadministration. QoL significantly improved (Skindex16 mean score 58 to 16, p = 0.0001) and eosinophils in skin histology decreased per HPF (mean 6.25 to 0.25, n = 8, p = 0.2) by week 4. An increase in IL-5 &gt; 600% and reduction IL-6 and TNF-α &gt; 50% were reported by week 4 and 8. Grade 1/2 mucositis in 4 patients were reported as adverse events. Conclusions: Our findings suggest that benralizumab is safe and effective for the treatment of grade 2/3 rash with eosinophilia related to alpelisib in patients with breast cancer. A reduction in rash severity was evidenced in all patients, along with improved QoL. Larger controlled studies are in development to evaluate the efficacy of benralizumab for the prevention of alpelisib rash. Clinical trial information: NCT04552288.

Calprotectin in nasal secretion: a new biomarker of non-type 2 inflammation in CRSwNP

Objective. We analysed calprotectin in sinonasal secretions of different chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes to assess its role as a biomarker of non-type 2 inflammation. Methods. We included primary diffuse CRSwNP patients (n = 41) and three different control groups [non-allergic rhinitis (NAR) (n = 13), non-allergic eosinophilic syndrome (NARES) (n = 10) and healthy subjects (n = 12)]. Calprotectin levels were detected in nasal secretions using a chemiluminescent immunoassay (CLIA). Results. Calprotectin levels in nasal secretions were significantly higher in all non-type 2 endotypes of CRSwNP compared to healthy controls (p &lt; 0.05). In contrast, in type-2 CRSwNP calprotectin was significantly lower compared to controls (p &lt; 0.05). A significant correlation between calprotectin levels and neutrophilic count/HPF was found in CRSwNP (p &lt; 0.01). Clinically, mean levels of calprotectin and neutrophilia were significantly higher in patients who previously underwent 3 or more endoscopic sinus surgeries (p &lt; 0.05). Conclusions. Calprotectin in nasal secretions may be a biomarker of non-type 2 inflammation. Low levels of calprotectin are indicative of a type-2 immune response in both CRSwNP and non-allergic rhinitis. We observed that calprotectin levels significantly increased based on the number of previous surgeries.

Screening the European pharmacovigilance database for reports of clozapine-related DRESS syndrome: 47 novel cases

Clozapine-related drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare adverse reaction. We aimed to screen a large pharmacovigilance database to identify clozapine-related DRESS cases, even if otherwise reported and provide a clinical overview. We screened spontaneous reports of clozapine-related DRESS syndrome in EudraVigilance database applying the European Registry on Severe Cutaneous Adverse Drug Reactions (RegiSCAR) criteria and scores to identify probable/definite DRESS syndrome cases. Clinical and demographic characteristics of included cases were provided and associations between RegiSCAR scores, and time to develop/recover DRESS were assessed. In a total of 262,146 adverse drug reactions reports for 75,190 clozapine-treated patients, 596 cases fulfilled RegiSCAR criteria; ultimately, 51 cases were rated as probable/definite DRESS according to RegiSCAR scores, of which 4 were previously published as case reports. The mean age of patients was 41.06 years (43.1% females), with 13 patients (25.5%) receiving reported co-medication with other DRESS culprit drugs. Median time between clozapine initiation and DRESS symptoms was 25 days. Clozapine dose was associated with days to develop symptoms (Spearman's ρ 0.40, p = 0.03). Organ involvement was reported in all cases followed by fever (n = 49; 96.1%) and eosinophilia (n = 47; 92.2%). Treatment involved clozapine discontinuation for 37 patients (72.5%), while 3.9% (n = 2) of cases ended fatally. Clozapine rechallenge was undertaken in 25 patients (49.0%). The screening of the EudraVigilance database revealed 47 novel clozapine-related DRESS cases, and only one was originally reported as DRESS. Clozapine-related DRESS may occur with clozapine monotherapy not only during dose titration, but also during maintenance treatment.

Time is skin: What does the emergency physician need to know about DRESS?

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome, also known as Drug Induced Hypersensitivity Syndrome (DIHS), is an acute drug-induced hypersensitivity reaction. The pathogenesis of this syndrome, which can develop due to many drugs, especially antiepileptic agents, is not known exactly. This syndrome, which was denominated “hydantoin hypersensitivity” in 1950, was renamed as “DRESS syndrome” by Bocquet and his colleagues in 1996 and the first diagnostic criteria were determined. Unlike syndromes that may develop due to other drugs, DRESS syndrome customarily commences 2-8 weeks after the commencement of the drug, and symptoms perpetuate to progress after discontinuation of the responsible drug. Symptoms such as fever, lymphadenopathy, hematological disorders, maculopapular rash and internal organ involvement are common in this syndrome. Diagnosis of DRESS syndrome is often difficult, as the clinical manifestations are varied and the latent period after the initiation of drug use can be up to 3 months. Thus, it is thought that the diagnosis of DRESS should be in the minds of all doctors, especially emergency physicians.

54-Year-Old Man With Acute Dyspnea on Exertion

54-Year-Old Man With Acute Dyspnea on Exertion

The challenge of antibiotic selection in prosthetic joint infections due to Corynebacterium striatum: a case report

BackgroundCorynebacterium striatum is a gram-positive facultative anaerobe found in the environment and human flora that has historically been considered a contaminant. More recently, Corynebacterium striatum has been implicated in human infections, including respiratory infections, endocarditis, and bone and joint infections, particularly those involving hardware or implanted devices.Case presentationA 65-year-old man presented for washout of his left total knee arthroplasty following a revision 20 days prior. The patient underwent debridement of his left total knee and revision of the left total femur arthroplasty. Daptomycin was initiated empirically due to a previous rash from vancomycin. Operative tissue cultures grew Staphylococcus haemolyticus, Staphylococcus epidermidis and Corynebacterium striatum. Given concern for daptomycin resistance and the reliability of vancomycin susceptibility, daptomycin was discontinued and vancomycin initiated following a graded challenge. Within a few days, the patient developed a diffuse, blanching, erythematous, maculopapular rash and daptomycin was restarted. Over the next 72 h, his rash progressed and he met criteria for drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Daptomycin was stopped and oral linezolid initiated; rash improved. C. striatum returned with susceptibility to gentamicin, linezolid, vancomycin and daptomycin. Due to concern for adverse effects on long-term linezolid, daptomycin was restarted and was tolerated for 20 days, at which point purulent drainage from incision increased. The patient underwent another arthroplasty revision and washout. Operative cultures from this surgery were again positive for C. striatum. Repeat C. striatum susceptibilities revealed resistance to daptomycin but retained susceptibility to linezolid. Daptomycin was again changed to linezolid. He completed six weeks of linezolid followed by linezolid 600 mg daily for suppression and ultimately opted for disarticulation.ConclusionsC. striatum has historically been regarded as a contaminant, particularly when grown in tissue culture in the setting of prosthetic joint infection. Based on the available literature and susceptibility patterns, the most appropriate first-line therapy is vancomycin or linezolid. Treatment with daptomycin should be avoided, even when isolates appear susceptible, due to the risk of development of high-level resistance (MIC > 256 µg/mL) and clinical failure.

Eosinophilic Syndromes Associated With Daptomycin Use: Re-exposure Hypersensitivity Pneumonitis and Prior Peripheral Eosinophilia.

BackgroundDaptomycin pulmonary eosinophilia (DPE) has been well described in case reports and reporting from the Food and Drug Administration. We report 3 eosinophilic syndromes associated with daptomycin use.MethodsThis is a retrospective review of all patients who received daptomycin (inpatient or outpatient) from 2010 to 2020 at the Veterans Affairs Portland Healthcare System. Patients who developed DPE while receiving daptomycin were evaluated to determine risk factors. Data collected included daptomycin dose and duration, body mass index, creatinine clearance, and peripheral eosinophilia.ResultsOf 330 patients who received daptomycin, 81.5% developed a peripheral eosinophilia, with 109 (33%) developing peripheral eosinophilia ≥5%. Fifty-one (16%) met criteria for DPE. Primary DPE occurred in 38 of the 51 patients with a median 26 days of treatment, and 49% had peripheral eosinophilia ≥5%. Re-exposure DPE occurred in the other 13 patients and occurred a median of 3 days after initiation of daptomycin. The presence of an elevated peripheral eosinophilia of ≥5% during daptomycin usage was significantly associated with primary (odds ratio [OR], 2.23; 95% CI, 1.2–4.09; P = .008) and re-exposure DPE (OR, 12; 95% CI, 1.6–103; P = .003). All patients recovered after withdrawal of daptomycin without complications.ConclusionsThere are 3 daptomycin eosinophilic syndromes: peripheral eosinophilia, primary DPE occurring about 4 weeks into therapy, and re-exposure DPE. Elevated peripheral eosinophilia ≥5% was a risk factor for both primary and re-exposure DPE, but still identified about half the cases. Peripheral eosinophilia should be carefully monitored during daptomycin treatment, and clinicians should be aware that prior eosinophilia may predict an acute pulmonary reaction upon daptomycin re-exposure.

COVID-19 infection in hypereosinophilic syndrome: A survey-based analysis

COVID-19 infection in hypereosinophilic syndrome: A survey-based analysis

Sulfasalazine induced atypical drug reaction with eosinophilia and systemic symptoms syndrome: a case report

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a type IV b hypersensitivity reaction characterized by cutaneous manifestations, fever, lymphadenopathy, hematologic abnormalities, and multiple organ manifestations. We report a case of sulfasalazine induced DRESS syndrome who was admitted with a complaint of morbilliform rash all over the body, a fever of 100oF, and severe abdominal pain. Initially the patient did not mention about intake of sulfasalazine while taking the drug history as he could not remember the past medication. The laboratory investigations revealed elevated eosinophils, WBC, and liver function tests. The patient was treated with antibiotics assuming tropical infection, but the patient’s condition was not improving. Later while taking proper drug history from a patient representative over the telephone revealed that the patient was in 4th week of tablet sulfasalazine 500 mg treatment for polyarthritis. Further, the J-SCAR scale was used to diagnose it as Sulfasalazine induced atypical DRESS syndrome. The patient was treated with topical and intravenous corticosteroids and antihistamine; the patient exhibited surprising symptomatic improvement. The patient was given a tapering dose of oral corticosteroid tablet prednisolone 20 mg for three weeks and topical corticosteroid mometasone lotion for two weeks upon discharge.

Clinical Evidence of Type 2 Inflammation in Non-allergic Rhinitis with Eosinophilia Syndrome: a Systematic Review.

Non-allergic rhinitis (NAR) includes different subtypes, among which NAR with eosinophilia syndrome (NARES) is the most important because of severity of symptoms and the high risk of comorbidities. Its pathophysiology is still object of debate, but a crucial role of chronic eosinophilic inflammation has been recognized. The aim of this review is to critically analyze the current evidence regarding the hypothesis that NARES may be considered a type 2 inflammatory disorder. The definition and diagnostic criteria for NARES are not universally shared and adopted, thus generating difficulties in reproducing the results. At present, there is extreme heterogeneity in sampling methods and disagreement in the cut-off of local eosinophilic count to determine a diagnosis of NARES. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standard was applied to identify English-language experimental and clinical articles regarding NARES. The search was performed in April 2021. Twenty-six articles were included. Our data suggest a particular heterogeneity regarding sampling and specific cut-offs adopted for diagnosis of NARES and consensus should be reached. We suggest that eosinophil count should be reported as an absolute value for at least 10 observed rich fields in order to increase the level of standardization. Consensus among authors on this topic should be reached with particular attention to the cut-off for diagnosis. In the future, this limitation may be overcome by the identification of repeatable biomarkers to refine diagnosis and prognosis of NARES. Furthermore, our data strongly suggest that NARES have numerous similarities with clinical features of the most common type 2 diseases such as eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP): late onset, association with type 2 comorbidities, selective eosinophilic tissue infiltration, remarkable response to oral and intranasal corticosteroids, and progression in a type 2 CRSwNP.