Skin manifestations and clinical features of drug reaction with eosinophilia and systemic symptoms: a retrospective multicentre study of 125 patients.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction generally accompanied by skin manifestations as the first and most frequent symptoms. However, skin manifestations and associated clinical features of DRESS have not been fully explored and evaluated. OBJECTIVES: This study aimed to describe the skin manifestations of DRESS in detail and analyse their association with demographic characteristics and extra-cutaneous clinical features. METHODS: We conducted this retrospective study on patients with DRESS diagnosed between September 2009 and August 2021 at three medical institutes and validated using the RegiSCAR score. Data regarding demographics, skin manifestations and clinical characteristics were retrieved through thorough chart reviews. RESULTS: Among 182 potential cases of DRESS, the validated 125 cases were analysed. A widespread rash extending over more than 50% of the body surface area was observed in 122 patients (97.6%) and typical facial oedema was experienced by 67 patients (53.6%). Polymorphous maculopapules were the most common rash morphology (106, 84.8%): specifically, exfoliative (59, 47.2%), urticarial (57, 45.6%) and purpuric forms (39, 31.2%) were common. Mucosal involvement was observed in 41 patients (32.8%). Patients with carboxamide antiepileptics (carbamazepine and oxcarbazepine) experienced more oedema (P = 0.014) and typical facial oedema than those with allopurinol (P = 0.021). The RegiSCAR score was higher in patients with purpura (P < 0.01). CONCLUSIONS: Skin manifestations of DRESS exhibit a wide range of skin lesions and can vary according to the culprit drugs. Early suspicion and prompt intervention are needed to improve prognosis.

Incidence and Risk Factors of Immediate Hypersensitivity Reactions Associated With Low-Osmolar Iodinated Contrast Media: A Longitudinal Study Based on a Real-Time Monitoring System.

OBJECTIVES: We investigated the incidence of immediate hypersensitivity reaction (HSR) caused by different types of low-osmolar contrast media (LOCM) and cumulative exposure to LOCM. METHODS: This cohort study included all consecutive patients who underwent LOCM-enhanced computed tomography from 2012 through 2014. We assessed 5 LOCM (iobitridol, iohexol, iomeprol, iopamidol, and iopromide). All patients were monitored for adverse events, and new symptoms and signs were recorded in real time using the Contrast Safety Monitoring and Management System (CoSM2oS). RESULTS: The overall incidence of immediate HSR to LOCM was 0.97% (2004 events resulting from 205 726 exposures). Incidence differed significantly depending on whether the patient had a previous history of HSR to LOCM (0.80% in patients with no history and 16.99% in patients with a positive history of HSR to LOCM, P=.001). The incidence of HSR to individual LOCM ranged from 0.72% (iohexol) to 1.34% (iomeprol), although there were no significant differences across the 5 LOCM. A longitudinal analysis demonstrated that the incidence of HSR increased gradually with more frequent previous exposure to LOCM (HR=2.006 [95%CI, 1.517-2.653], P<.001). However, this cumulative increase in risk was observed in patients who had experienced HSR to LOCM, but not in those who had not. CONCLUSION: The incidence of HSR did not differ significantly across the 5 LOCM assessed in the study. Repeated exposure to LOCM did not increase the risk of HSR among patients who had never experienced HSR to LOCM.

Severe Asthma Phenotypes Classified by Site of Airway Involvement and Remodeling via Chest CT Scan.

OBJECTIVES: This study aimed to establish a system that can classify severe asthma on the basis of airway remodeling patterns visualizedusing computed tomography (CT) images and to evaluate the clinical characteristics of individual image-based subtypes. METHODS: Chest CT images from severe asthma patients were retrospectively evaluated to classify phenotypes by site of airway involvement and remodeling. The association between radiologic subtypes and clinical characteristics was assessed. RESULTS: Of 91 patients with severe asthma, 74 (81.3%) exhibited abnormal radiologic findings, including bronchial wall thickening (BT), mucus plugging (MP), and bronchiectasis (BE). The severity of BT and the extent of MP were independently associated with peripheral blood eosinophil count (P=.012, r2=0.112) and sputum eosinophil count (P=.022, r2=0.090), respectively. The large-to-medium airway remodeling type, which showed diffuse BT combined with MP and BE, accounted for 44% of patients and revealed higher peripheral blood eosinophil counts than other types. In the small airway remodeling type, which accounted for 6.6% of patients, we observed a higher rate of fixed airflow obstruction, along with a predominance of males and smokers and more frequent use of controller medication than other phenotypes. In 26% of patients with severe asthma, no prominent airway remodeling was observed (near-normal type); the near-normal type required oral corticosteroids less frequently than the large-to-medium airway and small airway remodeling types. CONCLUSIONS: Depending on the site of airway involvement and remodeling pattern, 3 different structural types can be distinguished in chest CT findings from patients with severe asthma. Remodeling in large-to-medium sized airways revealed an association with systemic eosinophilic inflammation in patients with severe asthma.

Incidence of cephalosporin-induced anaphylaxis and clinical efficacy of screening intradermal tests with cephalosporins: A large multicenter retrospective cohort study.

BACKGROUND: Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests. METHODS: In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins. RESULTS: We identified 76 cases of cephalosporin-induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06). CONCLUSIONS: The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Screening IDT showed no clinical efficacy at a population level.

Immunologic regulatory effects of human umbilical cord blood-derived mesenchymal stem cells in a murine ovalbumin asthma model.

BACKGROUND: Mesenchymal stem cells (MSCs) have multiple immunomodulatory properties and hold therapeutic potential for inflammatory diseases. However, the therapeutic and immunologic effects of human umbilical cord blood-derived MSCs (huMSCs) remain largely unexamined for asthma. OBJECTIVE: This study was to investigate the immunomodulatory properties of huMSCs in an ovalbumin (OVA)-induced murine asthma model. METHODS: Mice were injected intraperitoneally with OVA and an aluminium hydroxide adjuvant. huMSCs were administered via the tail vein (5×105 cells/100 uL) to female BALB/c mice prior to the initial OVA challenge. The effects of huMSCs were assessed by investigating airway hyperresponsiveness, histological changes, inflammatory cell numbers, serum allergen-specific antibodies, cytokine production in spleen, lung tissue, and bronchoalveolar lavage (BAL) fluid as well as expansion of regulatory T cells. RESULTS: Administration of huMSCs significantly reduced methacholine bronchial hyperresponsiveness and eosinophil counts in BAL cells. Similarly, there was a significant decrease in serum OVA-specific IgE and IgG1 levels along with Th2 cytokine production (IL-4, IL-5, and IL-13) in the lung and spleen tissues, whereas increased percentage of regulatory T cells was observed after treatment with huMSCs. CONCLUSIONS: Our results suggest that huMSC treatment reduces OVA-induced allergic inflammation, which could be mediated by regulatory T cells.

Skin tests in patients with hypersensitivity reaction to iodinated contrast media: a meta-analysis.

BACKGROUND: Patients with a previous history of hypersensitivity reaction (HSR) to iodinated contrast media (ICM) are at high risk of the development of HSR to ICM. Many studies have tried to evaluate the diagnostic potential of skin tests in this population but have not yet reached a common conclusion. We investigated the role of skin tests in patients with HSR to ICM in terms of positive rate, cross-reactivity rate, and tolerability to skin test-negative ICM according to the type of HSR. METHODS: We performed literature searches of the MEDLINE and EMBASE databases and included studies where skin tests were performed in patients with HSR to ICM, with extractable outcomes. Outcomes were pooled using a random-effects model. RESULTS: Twenty-one studies were included. Pooled per-patient positive rates of skin tests were 17% (95% CI, 10-26%) in patients with immediate HSR, and up to 52% (95% CI, 31-72%) when confined to severe immediate HSR. Among patients with nonimmediate HSR, the positive rate was 26% (95% CI, 15-41%). The pooled per-patient cross-reactivity rate was higher in nonimmediate HSR (68%; 95% CI, 48-83%) than that in immediate HSR (39%; 95% CI, 29-50%). Median per-test cross-reactivity rates between pairs of ICM were 7% (IQR, 6-9%) in immediate HSR and 38% (IQR, 22-51%) in nonimmediate HSR. Pooled per-patient recurrence rates of HSR to skin test-negative ICM were 7% (95% CI, 4-14%) in immediate HSR and 35% (95% CI, 19-55%) in nonimmediate HSR. CONCLUSION: Skin tests may be helpful in diagnosing and managing patients with HSR to ICM, especially in patients with severe immediate HSR.

Staphylococcal enterotoxin sensitization in a community-based population: a potential role in adult-onset asthma.

BACKGROUND: Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult-onset asthma in community-based populations. OBJECTIVE: We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community-based adult populations. METHODS: The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age = 60.2 years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin-specific IgE using ImmunoCAP. RESULTS: Staphylococcal enterotoxin sensitization (≥ 0.35 kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (≥ 61 years), and inhalant allergen sensitization. Current asthma was mostly adult onset (≥ 18 years old) and showed independent associations with high enterotoxin-specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin-specific IgE level was identified as the major determinant factor for total IgE level. CONCLUSIONS AND CLINICAL RELEVANCE: Staphylococcal enterotoxin sensitization was independently associated with adult-onset asthma in adult community populations. Strong correlations between the enterotoxin-specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis.

Normal C1 inhibitor mRNA expression level in type I hereditary angioedema patients: newly found C1 inhibitor gene mutations.

BACKGROUND: C1 esterase inhibitor (C1INH) plays a key role in the classical pathway of the complement cascade. Mutations in this gene cause a decreased level of antigenic (type I hereditary angioedema, HAE) or functional (type II HAE) C1INH. OBJECTIVE: To find novel mutations in C1INH and evaluate the expression of C1INH gene in HAE patients. METHODS: Direct sequencing mutation analysis was performed for genomic DNA from three unrelated families (14 HAE patients and 18 family members). Genomic DNA from one family was also analyzed for larger genomic rearrangements, using Southern blotting analysis. We used real-time quantitative polymerase chain reaction (PCR) to evaluate C1INH mRNA expression level. RESULTS: Four mutations in exons (2,311 T-->C, 14,034 G-->A, 16,830 G-->A, and 16,979-16,980 G insertion) and four in introns (738 G-->A, 8,531 A-->G, 14,254 A-->G, and 14,337-14,378 TT deletion) were found. Interestingly, all of the nine patients in one family share the same mutation of Gly345Arg (14,034 G-->A) in the seventh exon. In another family, a single base mutation near the splice site (14,254 A-->G) was found in all of the three patients. In the last family, although a significant mutation was not found by direct sequencing, patients showed an abnormal 16 kb fragment in addition to the normal allele (21 kb Bcl I fragment). The C1INH mRNA expression of HAE patients in two families was not significantly different compared with that of normal controls. CONCLUSION: The two novel exonal mutations (G-->A and A-->G) and one large gene deletion were associated with the clinical phenotypes of HAE. Considering the normal C1INH mRNA levels but below normal protein levels in two families, their phenotypes would be associated with the post-translational defect.

Systemic lupus erythematosus complicated with cerebral venous sinus thrombosis : a report of two cases.

A rare manifestation of systemic lupus erythematosus (SLE) is cerebral venous sinus thrombosis (CVST), in which early diagnosis and aggressive therapy are of prime importance for favorable outcome. The pathogenesis of CVST is largely unknown, but it is thought to be caused by cerebral vasculitis, antiphospholipid antibodies or other conditions associated with enhanced coagulability. We describe two cases of SLE with CVST which were not associated with antiphospholipid antibodies. Both cases were treated with immunosuppressants (intravenous methylprednisolone and cyclophosphamide pulse therapy) and anticoagulant drugs (heparin and subsequent maintenance therapy with warfarin). There was a marked improvement of neurologic symptoms with the disappearance of thrombus in a follow-up MRI. The possibility of CVST should be considered in any patients with SLE who show neuropsychiatric manifestations.

Rheumatoid arthritis associated with myelodysplastic syndrome: a case report.

Myelodysplastic syndromes (MDS) are a group of refractory anemias resulting from a clonal stem cell disorder often associated with cytogenetic abnormalities. There is increasing recognition of immunological abnormalities in patients with MDS, including defective B- and T-cell function, hyper- or hypogammaglobulinemia and monoclonal gammopathy. MDS have been associated with Sjögren's syndrome, polymyalgia rheumatica, relapsing polychondritis and systemic lupus erythematosus. Although there may be various rheumatologic features, including acute arthritis in MDS, chronic inflammatory arthritis is uncommonly combined. There have been a few reports that described cases of rheumatoid arthritis (RA) concurrent with MDS, but advanced rheumatoid arthritis with typical joint deformities has rarely been reported. We report a case of rheumatoid arthritis with atlantoaxial subluxation combined with refractory anemia in a 31-year-old woman.