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Basophils are granulocytes involved in parasite immunity and allergic diseases, known for their potent secretion of type 2 cytokines. Identifying their functions has proven to be controversial due to their relative rarity and their complex lineage phenotype. Here, we show that the expression of basophils lineage markers CD200R3 and FcεRIα is highly variable in inflammatory settings and hinders basophils identification by flow cytometry across multiple disease states or tissues. Fluorophore-conjugated antibody staining of these lineage markers strongly activates basophil type 2 cytokine expression, and represents a potential bias for coculture or in vivo transfer experiments. The Basoph8 is a mouse model where basophils specifically express a strong fluorescent reporter and the Cre recombinase. Basophils can be identified and FACS sorted unambiguously by their expression of the enhanced yellow fluorescent protein (eYFP) in these mice. We show that the expression of the eYFP is robust in vivo during inflammation, and in vitro on living basophils for at least 72 h, including during the induction of anaphylactoid degranulation. We bred and characterized the Basoph8xiDTR mice, in which basophils specifically express eYFP and the simian diphtheria toxin receptor (DTR). This model enables basophils conditional depletion relatively specifically ex vivo and in vivo during allergic inflammation and their detection as eYFP+ cells. In conclusion, we report underappreciated benefits of the commercially available Basoph8 mice to study basophils function.

Background: Asthma is a chronic inflammatory disease characterized by airway inflammation and airway hyperresponsiveness (AHR). IL-33 is considered as one of the most critical molecules in asthma pathogenesis. IL-33 is stored in nucleus and passively released during necrosis. But little is known about whether living cells can release IL-33 and how this process is regulated. Objective: We sought to investigate the role of polymerase I and transcript release factor (PTRF) in IL-33 release and asthma pathogenesis. Methods: Ovalbumin (OVA)-induced asthma model in PTRF+/− mice were employed to dissect the role of PTRF in vivo. Then, further in vitro experiments were carried out to unwind the potential mechanism involved. Results: In OVA asthma model with challenge phase, PTRF+/− mice showed a greater airway hyper-reaction, with an intense airway inflammation and more eosinophils in bronchoalveolar lavage fluid (BALF). Consistently, more acute type 2 immune response in lung and a higher IL-33 level in BALF were found in PTRF+/− mice. In OVA asthma model without challenge phase, airway inflammation and local type 2 immune responses were comparable between control mice and PTRF+/− mice. Knockdown of PTRF in 16HBE led to a significantly increased level of IL-33 in cell culture supernatants in response to LPS or HDM. Immunoprecipitation assay clarified Y158 as the major phosphorylation site of PTRF, which was also critical for the interaction of IL-33 and PTRF. Overexpression of dephosphorylated mutant Y158F of PTRF sequestered IL-33 in nucleus together with PTRF and limited IL-33 extracellular secretion. Conclusion: Partial loss of PTRF led to a greater AHR and potent type 2 immune responses during challenge phase of asthma model, without influencing the sensitization phase. PTRF phosphorylation status determined subcellular location of PTRF and, therefore, regulated IL-33 release.

BackgroundMicroscopic polyangiitis (MPA) is a necrotizing vasculitis that involves small- and medium-sized vessels and is associated with the presence of antineutrophil cytoplasmic antibodies with a perinuclear staining pattern (p-ANCA). The kidney and lungs are the organs primarily affected. MPA is rare in children and is easily misdiagnosed. Below is a complete case history of the course of the disease.Case presentationAn 11-year-old girl with a 1-month history of cough and hemoptysis showed no improvement after imipenem-cilastatin treatment. p-ANCA and microscopic hematuria and proteinuria were positive, and a chest CT revealed an area of shadow in the bilateral lower lobe of the lungs. Renal biopsies showed crescentic glomerulonephritis, and MPA was diagnosed based on these criteria. The patient exhibited dramatic clinical and imaging improvements after immunosuppressive treatment.ConclusionThe organs most commonly involved in MPA in children are the lungs, kidneys, skin, nervous system organs, and organs of the gastrointestinal tract. Careful examination should be carried out in these patients while biopsies of the kidney or any other organs remain the gold standard for diagnostic purposes. Pulmonary involvement may be the initial symptom of the disease and should not be confused with pneumonia. A urinalysis should be performed in patients with hemoptysis. Antibiotics should be used with caution.

Intractable chronic inflammatory diseases, including autoimmune diseases, autoinflammatory diseases and allergic diseases, are caused by disruption or failure of the immune system. Pathogenic immune cells are presumed to be closely related to the pathogenesis of intractable diseases, but the precise cellular and molecular mechanisms underlying the pathogenesis of these diseases remain unclear. The balance between the T helper type 1 (Th1) and Th2 cell fractions has been believed to be responsible for the differences among inflammatory diseases. However, an analysis of the cells infiltrating inflammatory lesions in mice and humans revealed the generation of pathogenic Th cells with different characteristics at the memory T-cell stage in the peripheral tissues in various inflammatory diseases. In this review, we will summarize and discuss recent progress regarding the characteristics of pathogenic Th cells, their mode of action, and the molecular mechanisms that regulate the pathology of intractable chronic inflammatory diseases, particularly those with tissue fibrosis. We hope this article will help clarify the pathogenesis of these diseases and propose a future direction for research.

Aim of the work To assess the outcome of planned pregnancies in patients with systemic lupus erythematosus (SLE). Patients and methods: The study was conducted on 32 patients. The medical management included pre-pregnancy planning at the quiescent phase of the disease and after at least six months of clinical remission. The patients had a monthly visit during pregnancy and three months post-delivery. Disease flare was characterized by the recurrence of symptoms and signs in different organs, as well as the need for an increase in medication dose. Results: There were 36 planned pregnancies in 32 patients, of which 15 and 17 cases were primiparous and multiparous, respectively. The SLE flares were observed in 36.1% of the cases, 8.3% of which developed postpartum; moreover, they were moderate in severity and mostly involved the kidneys and joints. Pregnancy outcomes included18 (50%) cases ended in term labor; 13 (36.1%) pregnancies had preterm labor, and 5 (13.8%) pregnancies terminated with abortions. Furthermore, obstetric complications included 2(6.5%) patients with premature rupture of membranes, 5(15.6%) fetuses with intrauterine growth retardation, and 2(6.4%) mothers with preeclampsia. 10(27.7%) pregnancies occurred in patients with lupus nephritis. Cesarean section was performed on 24(77.4%) patients, and low birth weight was observed in 7(21.8%) infants. None of the infants had neonatal lupus, congenital deformities or infection. Conclusion: Pre-pregnancy planning in patients with SLE can considerably improve pregnancy outcomes. Neonatal lupus, congenital anomalies or infection were not present. SLE patients intending to become pregnant should be provided with close medical supervision for a safe maternal and fetal outcome.

Aim of the work: To measure the levels of serum calprotectin (CLP) in rheumatoid arthritis (RA) patients and to assess its association with disease activity, functional status, ultrasonographic findings, and radiological damage. Patients and methods: This study included 47 RA patients and 33 controls. The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), C-reactive protein (CRP), disease activity score (DAS28), health assessment questionnaire (HAQ), modified Larsen radiological score, musculoskeletal ultrasound and serum CLP levels were assessed. Results: The mean age of the patients was 42.5 ± 12.8 years; 34 females and 13 males (F:M 2.6:1) with a mean disease duration of 2.6 ± 1.1 years. RF was positive in 72%. CLP level was significantly increased in patients compared to control (2.78 ± 0.89 μg/ml vs. 0.84 ± 0.5 μg/ml; p

Background HIV status disclosure facilitates access to HIV-related prevention and treatment services and increases opportunities for social support, HIV risk reduction with partners, and index testing for sexual partners or children. This study assessed the effect of a program model of community-based social welfare volunteers on HIV status disclosure among caregivers of orphans and vulnerable children (OVC). Methods This was a longitudinal study, which was based on OVC caregivers who were beneficiaries of the USAID Kizazi Kipya project in Tanzania. They were enrolled (baseline) by community social welfare volunteers during 2017–2018, received services, and reassessed at midline in 2019. Caregivers who reported having been HIV tested, were asked to voluntarily report the status in order for the volunteers to establish and provide needed services. Those who reported their HIV status as negative or positive were grouped as “disclosed”, and those who knew their status but did not report it were documented as “undisclosed”. McNemar’s tests compared disclosure rates at baseline and midline. Multivariable analysis was conducted using generalized estimating equation (GEE). Results The study analyzed 140,664 caregivers (72% female) from 81 district councils of Tanzania. Their mean age at enrollment was 47.4 years. Overall, 81.3% of the caregivers disclosed their HIV status to the project staff at baseline; this increased significantly to 96.1% at midline (p 0.05). In the multivariable analysis, caregivers’ likelihood of HIV status disclosure was nearly 6 times higher at midline than at baseline, when baseline characteristics were adjusted for (OR = 5.76, 95% CI 5.59–5.94, p Conclusions This study detected an increased caregivers’ HIV status disclosure to the USAID Kizazi Kipya project staff by 14.8%, from 81.3% at baseline to 96.1% at midline within an average project exposure period of 1.4 years. The observed loss of sociodemographic differences in HIV status disclosure rate at midline implies that community-based interventions may be well-positioned to successfully address and eliminate sociodemographic barriers to service uptake and consequently improve services coverage and health outcomes.

Background Entheseal involvement is a frequent and distinctive feature of psoriatic arthritis (PsA). It is detected clinically but lacks sensitivity and reliability. Musculoskeletal ultrasound (MSUS) is an important tool for accurate detection of enthesitis. Aim of the work To determine the frequency and distribution of subclinical entheseal abnormalities at lower limbs using MSUS in patients with psoriasis for early detection of PsA, and to evaluate its relation to disease severity. Patients and methods 80 patients with psoriasis were studied. Psoriasis Area and Severity Index (PASI) was assessed. High-resolution MSUS assessment of quadriceps, patellar and Achilles tendons, and plantar fascia entheses was performed. Glasgow Ultrasound Enthesitis Scoring System (GUESS) was assessed. Results The median (interquartile range; difference between 75th and 25th quartile) age of the patients was 46(26.3) years and were 42 males. The disease duration was 9(12) years, PASI was 10.9(18.9), and GUESS 6(4). Nail dystrophy was found in 48(60%). Clinical enthesitis was found in 15(18.8%) patients; MSUS revealed lower limb enthesopathy in at least one enthesis in 76(95%) patients, and abnormality in 421 of 800 entheses (52.6%). Distal insertion of the patellar tendon was the most frequently involved (68.8%). GUESS significantly correlated with the age, body mass index (BMI), and PASI. Conclusion Psoriasis is associated with a relevant frequency of asymptomatic entheseal abnormalities. MSUS is a valuable, simple, and noninvasive tool in early detection of enthesopathy in psoriatic patients, especially in the presence of older age, high BMI, and high PASI as potential parameters for detection of psoriatic enthesitis.

Aim of the work: To assess sleep quality in Egyptian patients with rheumatoid arthritis (RA) and its relationship with disease activity, depression and functional status. Patients and methods: This cross-sectional study included 133 RA patients and 76 age and sex matched controls. Sleep using the Pittsburg Sleep Quality Index (PSQI), Beck depression inventory (BDI), functional status using health assessment questionnaire (HAQ), visual analogue scale-pain (VAS), and disease activity score (DAS28) were assessed. Results: Patients were 125 females and 8 males with a mean age of 42.5 ± 9.5 years and disease duration of 3.9 ± 1.3 years. 76 age and sex matched control were also included. Poor sleep quality was detected in 54.1% of patients. Patients had significantly higher scores in the subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, day-time dysfunction domains and in terms of the total PSQI score compared to the control (p

Suguru Sato, Junpei Saito, Atsuro Fukuhara, Manabu Uematsu, Yasuhito Suzuki, Mami Rikimaru, Takaya Kawamata, Takashi Umeda, Tatsuhiko Koizumi, Ryuichi Togawa, Yuki Sato, Takefumi Nikaido, Hiroyuki Minemura, Kenya Kanazawa, Yoshinori Tanino, Yoko Shibata Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, 960-1295, JapanCorrespondence: Suguru SatoDepartment of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Hikarigaoka-1, Fukushima, 960-1295, JapanTel +81-24-547-1360Fax +81-24-548-9366Email suguru@fmu.ac.jpBackground: Nocturnal asthma symptoms are a well-known feature of sleep disturbance. However, there are few reports on the association between sleep-related characteristics and asthma exacerbation. The aim of the current prospective observational study was to explore the factors while sleeping associated with future asthma exacerbation.Materials and Methods: At baseline, adult asthmatics underwent home sleep monitoring by a Watch-PAT instrument and then they were prospectively followed-up for the occurrence of exacerbations. The number of asthma exacerbation was observed over a period of one year, and multivariable analyses of the factors associated with asthma exacerbation were performed.Results: A total of 62 asthmatic subjects were enrolled (mean age 62.1 years), 59 of whom were finally included in the prospective observational study. Obstructive sleep apnea (defined by an apnea-hypopnea index based on peripheral arterial tone more than 5 times/hour) were observed in 81% of the subjects. During the one-year monitoring period, 14 of the 59 subjects (24%) used occasional systemic corticosteroids for their exacerbation asthma (worsened group) while the other 45 subjects did not experience asthma exacerbation (stable group). A comparison of the baseline clinical characteristics and sleep-related data between the two groups, mean forced expiratory volume one second percent (FEV1/FVC), mean baseline Asthma Control Test (ACT) score, median pAHI value, and median oxygen desaturation index value were significantly lower in the worsened group than those in the stable group. Additionally, mean prevalence of the left lateral decubitus (LLD) position in sleep monitoring were significantly higher in the worsened group than that in the stable group. Among the independent variables, baseline asthma severity, ACT score, and the LLD position showed significant associations with asthma exacerbation.Discussion/Conclusion: The present study identified that sleeping in the LLD position was also associated with asthma exacerbation.Keywords: asthma, asthma control, sleep position, asthma exacerbation

Ying-Jhen Huang,1 Yi-Chi Chu,1 Hung-Ling Huang,2– 4 Jing-Shiang Hwang,5 Ta-Chien Chan1,6 1Research Center for Humanities and Social Sciences, Academia Sinica, Taipei, Taiwan; 2Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 4Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Institute of Statistical Science, Academia Sinica, Taipei, Taiwan; 6Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, TaiwanCorrespondence: Ta-Chien ChanResearch Fellow, Research Center for Humanities and Social Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 115, TaiwanTel +886 2-2785-7108 ext. 312Email dachianpig@gmail.comBackground: Asthma and obesity are important public health issues around the world. Obesity is considered a risk factor associated with the severity and incidence of asthma. We investigated the relationships between poor pulmonary function (defined by forced vital capacity (FVC) and percentage of predicted FVC (FVC%)) and obesity.Methods: This is a retrospective longitudinal study using the MJ health examination database in Taiwan from 2000 to 2015. There were 160,609 participants aged ≥ 20 years with complete obesity indicators and lung function data, and having at least two visits. A generalized estimation equation (GEE) model was applied to estimate the association between lung function and obesity.Results: BMI was the best indicator to predict poor pulmonary function for our participants. Results of BMI are presented as an example: Obesity (body mass index (BMI) ≥ 27.0 kg/m2) is significantly associated with lower FVC [adjusted coefficients (β) for asthmatics: -0.11 L (95% CI: -0.14, -0.08); adjusted β for non-asthmatics: -0.08 L (-0.09, -0.08)] and FVC% [adjusted β for asthmatics: -1.91% (95% CI: -2.64, -1.19); adjusted β for non-asthmatics: 1.48% (-1.63, -1.33)]. Annual change of BMI (ΔBMI/year) is an independent risk factor for decreased FVC [adjusted β for asthmatics: -0.030 L (-0.048, -0.013); adjusted β for non-asthmatics: -0.019 L (-0.022, -0.016)] and FVC% [adjusted β for non-asthmatics: -0.603% (-1.063, -0.142); adjusted β for non-asthmatics: -0.304% (-0.393, -0.214)], and is significantly associated with accelerated FVC decline [adjusted β of ΔFVC/year and ΔFVC %/year for asthmatics: -0.038 L (-0.054, -0.022) and -0.873% (-1.312, -0.435); adjusted β of ΔFVC/year and ΔFVC %/year for non-asthmatics: -0.033 L (-0.042, -0.024) and -0.889% (-1.326, -0.452)].Conclusion: Obesity is significantly associated with decreased lung function, and asthmatics had a higher risk than non-asthmatics.Keywords: asthma, obesity, BMI, pulmonary function, FVC

Aim of the work: Spironolactone with its anti-inflammatory and immunomodulatory properties due to inhibition of nuclear factor kappa B could have a therapeutic potential in ankylosing spondylitis (AS). The aim was to study the impact of spironolactone in active AS patients with an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARDs). Patients and methods: Sixty AS patients were randomized to receive 24 weeks of treatment with spironolactone (n = 30, 2 mg/kg/day) or placebo (n = 30) as an adjunct to existing stables DMARDs. Therapy results evaluated by assessment of inflammatory measures erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath AS disease activity index (BASDAI), AS disease activity score (ASDAS) and Bath AS functional index (BASFI), and proinflammatory cytokines (TNF-α,IL-6 and IL-1). Endothelial progenitor cells (EPCs), flow-mediated dilatation (FMD), oxidative measures (TBARS and serum nitrite) were assessed as surrogates for cardiovascular endpoints. Results: After 24 weeks: inflammatory and disease activity measures ESR, CRP, ASDAS, BASDAI, and BASFI (All p 0.05). Proinflammatory cytokines, TNF-α and IL-6, significantly reduced after treatment (both p

Aim of the work: To investigate the value of neutrophil- lymphocyte ratio (NLR), platelet- lymphocyte ratio (PLR), red blood cell distribution width (RDW), mean platelet volume (MPV) as biomarkers of disease severity and clinical manifestations in systemic sclerosis (SSc). Patients and methods: This study included 35 SSc patients, together with 45 controls. Disease severity was assessed by Medsger severity score (MSS). NLR, PLR, MPV, RDW were measured by COULTER LH 750 assay analyzer. Results: The mean age of SSc patients and controls was 42.8 ± 12.6 and 40.8 ± 9.7 years respectively. MPV, RDW, NLR, PLR were significantly higher in patients compared to controls (p = 0.03, < 0.001

Background The rate at which patients are accurately diagnosed with hereditary angioedema (HAE), as well as diagnosed patients access to modern treatments differs greatly among countries. Moreover, the severity and burden of HAE on patients have been reported mostly on the basis of physician-reported surveys. To gain insight into the real-world conditions of patients with HAE through a patient-reported survey in Japan and identify any unmet needs. Methods A questionnaire was distributed to 121 patients with HAE via a Japanese HAE patient organization during 2016–2017. Responses were collected from 70 patients (57.9%) and subjected to analysis. Results The average periods from the initial appearance of symptoms (e.g. edema) to a HAE diagnosis was 15.6 years (min–max, 0–53). Patients visited an average of 4.6 different departments until receiving a definitive diagnosis. The average age at the first visit was 25.6 years (3–73) and at diagnosis 32.8 years (0–73). Patients reported an average of 15.7 (0–100) attacks per year, but only 53.1% of attacks were treated. The days of hospitalization due to severe attacks was 14.3 (0–200) before diagnosis, but these declined to 4.3 (0–50) after diagnosis. In the treatment for attacks, 82% of the patients were treated with the plasma-derived C1 inhibitor concentrate, and 69% of the patients reported experiencing a therapeutic effect. Conclusions There is a long gap between first attack and diagnosis of HAE, and the number of non-treated attacks is high in Japan. Steps are needed to improve the diagnostic and treatment environments to address these issues.

Aim of the work: To measure the levels of serum survivin in rheumatoid arthritis (RA) patients and to assess its relation to disease activity, functional impairment, and radiological damage. Patients and methods: This study included 58 RA patients and 34 controls. The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), C-reactive protein (CRP), disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), modified Larsen radiological score and serum survivin level were assessed. Results: The mean age of the patients was 43.5 ± 11.5 years; 43 females and 15 males (F:M 2.9:1) with a mean disease duration of 2.6 ± 1.13 years. RF was positive in 79% Survivin level was significantly increased in patients compared to the controls (171.8 ± 74.4 pg/ml vs. 98.7 ± 16 pg/ml, p

Background Chronic granulomatous disease (CGD) is a rare immunodeficiency disorder that manifested by recurrent severe bacterial and fungal infection. It may be associated with non-infectious inflammatory complications that affect gastrointestinal tract, lung and skin. Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterizes by painful cutaneous ulceration. The coexistence of PG and CGD is very rare and the treatment is challenging; only few cases have been reported. Aim of the work To describe the features and management of a challenging case of PG associated with CGD. Case report A 20-year old male with a long history of recurrent bacterial and fungal infections due to CGD presented to the Rheumatology and Immunology outpatient clinic at Mansoura University hospital with an ulcerative cutaneous lesion with exudation and crusting on the left lateral malleolus. There were elevated inflammatory markers: erythrocyte sedimentation rate (ESR) 130 mm/1st h and C-reactive protein (CRP) 52 mg/dl. Histological examination of the lesion revealed diffuse dermal infiltrate of neutrophils and nuclear dust admixed with some histiocytes, lymphocytes and plasma cells, a picture suggestive of PG. Systemic and musculoskeletal examination were unremarkable except for low grade fever (37.7 °C). Conventional immunosuppressives were not satisfactory and adalimumab (40 mg/2 weeks) was added showing significant improvement of the lesion (ESR 7 mm/h, CRP 3 mg/dl). Conclusion CGD is a rare primary immunodeficiency disorders that can be associated with PG. The coexistence of these two conditions requires judicious use of immunosuppressive agents. However; adalimumab may be an effective and safe treatment option.

Background: Obesity is a risk factor for severe and difficult-to-treat asthma. However, the impact of different physiques on long-term outcomes is poorly understood. We aimed to investigate the correlation between obesity and asthma-associated long-term mortality in Japanese adults. Methods: From the data on 3146 individuals with air pollution-related respiratory diseases in the Omuta City Air Pollution-Related Health Damage Cohort Program, 697 adult patients with asthma were analyzed. Hazard ratios for long-term all-cause and respiratory disease -related mortality were compared in patients with different physiques using the Cox proportional hazard models. The classification of physiques was based on the WHO obesity criteria. Results: Of the 697 patients, 439 died during the median observation period of 26.3 years. The number (% of total) of underweight, normal-weight, pre-obese, and obese class I–III individuals were 75 (10.8%), 459 (65.9%), 140 (20.1%), and 23 (3.3%), respectively. The Cox proportional hazard model (adjusted hazard ratio [95% confidence interval], P value) showed that pre-obese group had a significantly reduced risk for all-cause (0.65 [0.51 to 0.83], P

Background Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease. Few states in developing countries have an adequate management of HAE, but none of them belongs to the former USSR area. This study analyses data from C1-INH-HAE patients from Belarus. Methods Data about clinical characteristics, genetics, access to diagnosis and treatment were collected from 2010 by the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology in Minsk. A questionnaire about attacks, prophylactic (LTP) and on-demand therapy (ODT) was administered to patients. Results We identified 64 C1-INH-HAE patients belonging to 26 families, 27 (42.2%) of which were diagnosed in the last 3 years. The estimated minimal prevalence was 1:148,000. Median age at diagnosis was 29 years, with diagnostic delay of 19 years. Thirty-eight patients answered a questionnaire about therapy. Eleven patients did not use any treatment to resolve HAE attacks. Twenty-seven patients underwent ODT: 9 with appropriate treatments, and 18 with inappropriate treatments. Nine patients used LTP with attenuated androgens and 1 with tranexamic acid. Thirty-two patients answered a questionnaire about attacks and triggers: 368 angioedema attacks were reported, with an average of 10 attacks per year. We found 24 different SERPING1 variants: 9 missenses, 6 in splice sites, 6 small deletions, 2 nonsense, 1 large deletion; 7 have not been previously described. De novo variants were found in 11 patients. Conclusions C1-INH-HAE diagnosis and management in Belarus is improved as seen from the high number of new diagnosis in the last 3 years. Next steps will be to reduce the diagnostic delay and to promote the LTP and ODT.

Background Inflammatory diseases can interfere with adequate nutrition and even lead to a malnourished state. Nutritional deficiency manifestations may be similar to rheumatologic manifestations. Aim of the work To assess whether malnutrition is an associated feature of rheumatic diseases (RDs). Patients and methods A multicenter study included Egyptian patients with different RDs; nutrition measurements and common features of deficiency were assessed; general appearance, skin, hair/nail changes, spooning of nails, night blindness, mouth problems, edema, tetany, dysphagia, diarrhea, thyromegaly, loss of appetite and weight loss. Results The study included 284 patients with various RDs: rheumatoid arthritis (RA) (n = 128), systemic lupus erythematosus (n = 120), Behcet’s disease (n = 17), spondyloarthritis (n = 6), systemic sclerosis (n = 5), dermatomyositis (n = 2), relapsing polychondritis (n = 2), and one patient each with familial Mediterranean fever, Gout, Still's disease and undifferentiated connective tissue disease. Muscle wasting was present in 44(15.5%) patients, spooning of nails in 26(9.2%), night blindness in 38(13.4%), glossitis in 48(16.9%), tetany in 32(11.3%) and loss of appetite in 51(18%). Although there was significant differences among RDs in some nutritional deficiency signs, the type and their durations did not significantly affect symptoms or signs of nutritional deficiency, while age was associated with peripheral edema (p = 0.014) and tetany (p = 0.009); azathioprine was associated with hair/nail changes (p = 0.04); methotrexate with peripheral edema and hair/nail changes (p = 0.002, p = 0.01 respectively); and hydroxychloroquine was negatively associated with skin rash, wasting and hair/nail changes (p = 0.011, p = 0.001 and p Conclusion Nutritional deficiency is common among RD patients especially elderly and should be monitored frequently regardless type and onset.

Jun Yang,1 Lina Geng,2 Yongmin Ma,3 Xinyi Tang,1 Huiyong Peng,1 Jie Tian,2 Huaxi Xu,2 Shengjun Wang1,2 1Department of Laboratory Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, People’s Republic of China; 2Institute of Laboratory Medicine, Jiangsu Key Laboratory for Laboratory Medicine, Jiangsu University School of Medicine, Zhenjiang, People’s Republic of China; 3Department of Otorhinolaryngology-Head Surgery, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, People’s Republic of ChinaCorrespondence: Shengjun WangDepartment of Laboratory Medicine, The Affiliated People’s Hospital, Jiangsu University, No. 8, Dianli Road, Zhenjiang, 212002, People’s Republic of ChinaTel +86-511-8891-5573Fax +86-511-8503-8483Email sjwjs@ujs.edu.cnBackground: Allergic rhinitis (AR) is characterized by type I hypersensitivity that is mediated by IgE-induced humoral responses. Follicular helper T cells (Tfh) comprise the key helper T cell (Th) subset that promotes antibody production. Signaling lymphocytic activation molecules (SLAMs) participate in regulation of the differentiation and function of Tfh cells, but whether this regulation is involved in the pathogenesis of AR is unknown.Methods: CD4+CXCR5+ Tfh-like cells from peripheral blood were detected by flow cytometry. The IL-21 and IgE levels in serum were measured by an ELISA. Blood CD4+CXCR5+ Tfh-like cells were sorted and cultured with anti-SLAM mAb in vitro.Results: The frequencies of circulating CD4+CXCR5+ Tfh-like cells appeared virtually unchanged in AR patients, but the expression of SLAMs and SLAM-associated protein (SAP) on circulating Tfh-like cells was significantly decreased. Meanwhile, the level of serum IL-21 was increased in AR patients, and a negative correlation was found between the IL-21 level and SLAM or SAP expression on CD4+CXCR5+ T cells. Treatment with anti-SLAM mAb resulted in reduced IL-21 production by Tfh-like cells in vitro. Additionally, SLAM expression on B cells was significantly decreased, although the percentages of B cells were increased in AR patients.Conclusion: SLAMs negatively regulate IL-21 production in CD4+CXCR5+ Tfh-like cells, which contributes to the pathogenesis of AR.Keywords: AR, circulating Tfh-like cells, SLAM, IL-21

Background To compare the incidence of osteoporotic fractures in patients with rheumatoid arthritis (RA) with matched controls from a university hospital. Methods Consecutive RA patients (n = 100) were matched (age and sex) with controls (1:2). The follow-up period began at the index date, defined as the date of diagnosis for RA patients and the date of the first medical claim at the Health Management Organization (HMO) for non-RA patients. Fracture incidence rates per 1000 persons-years (PY) for distinct types of fractures were calculated. Multivariate cox regression analysis was performed to identify factors associated with fractures. Results One hundred RA patients were followed for a total of 975.1 patients-years and 200 controls for 1485.7 patients-years. No difference was found in the overall fracture incidence rate per 1000 PY between RA and controls (19.5, 95% CI 12.7–28.6 vs 12.1, 95% CI 7.7–18.7, p = 0.07). In the Cox regression analysis, only age (HR 1.06, 95% CI 1.02–1.11, p = 0.006) and history of a prior fracture (HR 9.85, 95% CI 2.97–32.64, p p = 0.01). Conclusion Patients with RA didn’t show an overall increased risk of osteoporotic fractures compared with matched controls, but vertebral fractures were more frequently observed in patients with RA.

Background Mugwort and house dust mite (HDM) are two of the most common inhalant allergens in Asia, however, whether mugwort affects polysensitized HDM+ allergic rhinitis (AR) patients has not been elucidated. Methods Overall, 15,884 AR outpatients were assessed for clinical status. Amino acid sequences of mugwort were determined by mass spectrometry. Afterward, cross-reactivity between mugwort tropomyosin and Dermatophagoides pteronyssinus 10 (Der p10) was analysed by ELISA inhibition and basophil activation experiments. To compare immunologic responses eliciting by two different tropomyosins, peripheral blood mononuclear cells (PBMCs) of HDM-monosensitized patients were stimulated by mugwort, HDM, Der p10 and synthetic peptides representing mugwort tropomyosin respectively. Results Polysensitized HDM+AR patients were mainly sensitized to cat and mugwort, and the positive rate of monosensitized HDM+AR out-clinic patients was increased during the mugwort pollen season. Tropomyosin protein was able to find in mugwort. Synthetic tropomyosin peptide of mugwort activated basophils which were primed by HDM-specific IgE; ELISA inhibition experiment showed synthetic tropomyosin peptide of mugwort inhibited IgE binding to HDM tropomyosin, Der p10. Unlike HDM and Derp 10, mugwort and mugwort tropomyosin mainly induced IFN-γ and IL-17 release in PBMCs of monosensitized HDM+AR patients, but not IL-5. Conclusions Pan-allergen tropomyosin accounts for the cross-reactivity between mugwort and HDM, which reminds HDM+ patients to reduce mugwort exposure in mugwort pollen season in virtue of the tropomyosin induced mild inflammation.

Background: Infection is a leading cause of morbidity, mortality and hospital admission in systemic lupus erythematosus (SLE) patients. Aim of the work: To study infection in SLE patients regarding site of infection, pathogenic organism, hospitalization and/or intensive care unit (ICU) admission. Patients and methods: This study included 79 patients. SLE disease activity index (SLEDAI-2K) and damage index were evaluated. Detailed information about the site of infection and pathogens were reported. Results: 71 females and 8 male patients (F:M 8.9:1), with a mean age of 29 ± 9.6 years (17–55 years) and disease duration of 5.9 ± 5.7 years, 55 (69.6%) patients had infection at time of study while 24 (30.4%) did not. The SLEDAI-2 k and damage index were significantly higher in SLE patients with infection (14.2 ± 11.8 and 3.7 ± 3.7) compared to those without infection (5.9 ± 5.03 and 1.8 ± 1.3) (p = 0.03 and p = 0.045 respectively). Those with infection had a shorter disease duration (4.9 ± 5.2 vs 8.3 ± 6.2; p = 0.005), received more cyclophosphamide (56.4% vs 16.7%; p = 0.001), higher erythrocyte sedimentation rate (ESR) (75.5 ± 27.1 vs 35.8 ± 24.7 mm/1sthr) (p

Lateral epicondylitis, 'tennis elbow', is a common condition seen in general practice. Patients present with lateral elbow pain radiating distally and exacerbated by wrist and finger extension against resistance. Pain is also accompanied with functional impairment of the upper limb and hand. High intensity laser therapy (HILT) is a relatively new pain management modality used for treating musculoskeletal disorder. Aim of the work: To compare the efficacy of therapeutic HILT and ultrasound (US) in pain reduction and functional improvement in patients with chronic lateral epicondylitis. Patients and methods: 45 patients were randomly distributed into three equal groups: Group I treated by HILT and US; Group II treated by HILT only and Group III by US only. Patients were treated day after day for 12 sessions. The hand grip-strength was assessed by the dynamometry, pain measured by visual analogue scale (VAS) and the disorder of arm, shoulder and hand (DASH) scored. The HILT emitted a double wave length (915 nm and 808 nm) at a power of 3.2 Watt (W) and energy density of 5 Joule/cm2 while the US was used at an intensity of 1.5 W/cm2. Results: Patients were 24 females and 21 males with mean age of 44.9 ± 7.3 years. There was a significant improvement in the VAS, DASH and grip-strength for the three groups after sessions (p

Background: Many patients report questionable drug hypersensitivity reactions (DHR) to betalactam antibiotics. A workup is required for objectivation. Direct drug provocation tests (DPTs) omitting a prior allergy workup are increasingly recommended as the primary diagnostic approach. However, apart from the risk of severe side effects, DPTs often are a scarce resource in overloaded healthcare-systems. We investigated how many cases can be solved by drug-specific history, drug-specific IgE, and skin tests obviating the need for DPT. Methods: We conducted a chart review in a retrospective cohort of 932 patients in an allergy outpatient centre from 2016 to 2017. Patients had been submitted to drug-specific history and specific IgE-, skin prick-, intradermal- and patch-tests with early and late readings with a series of penicillins and cephalosporins but DPTs were no option. Results: Overall, positive in vitro and/or skin tests were found in 96/932 (10.3%) patients. Drug-specific IgE was detected in 40/932 (4.3%) patients, 61/787 (7.8%) patients had positive skin tests. In vitro tests to Pencillin V showed the highest rate of positivity 24/479 (5.0%) and early readings of ampicillin the highest amongst the skin tests (3/49, 6.1%). Immediate skin tests were more often positive than delayed ones (75:45). The combination of all parameters including drug-specific history solved 346/932 (37.1%) cases while 586/932 (62.9%) remained unresolved. Self-reported DHR could be less often confirmed in females and young children (p

Aim of the work: To investigate the association between IL and 16 genetic (rs4072111) single nucleotide polymorphism (SNP) and susceptibility to primary knee osteoarthritis (KOA) and to elaborate its connection with clinical and radiographic severity of KOA. Patients and methods: 80 primary KOA patients and 35 matched healthy controls. IL-16 gene rs4072111 SNP was genotyped in KOA patients and control using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique and verified by direct DNA sequencing. Western Ontario and McMaster Universities Arthritis Index (WOMAC) was used to assess the clinical severity of KOA and Kellgren lawrence (K/L) radiographic grading was evaluated. Results: The 80 KOA patients were 60 female and 20 male patients with mean of 55.8 ± 8.9 years (38–71 years), BMI 25.5 ± 1.8 (16.5–27) and disease duration 5.8 ± 4.3 years (1–20 years). The mean WOMAC index was 52.9 ± 17.9 and the K/L score was 2.49 ± 0.73. Patients carrying the wild (CC) genotype had a significantly higher WOMAC index compared those carrying the TT and CT genotypes (p = 0.0.046) also, KL sore had tendency to increase in patient carrying the wild (CC) compared to patients carrying the TT and CT genotypes (p = 0.08), However, no direct genetic association was detected between the SNP and KOA. On performing a regression with WOMAC as the dependant factor only the triglycerides (p = 0.001) and K/L (p

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening disorders characterized by widespread epidermal necrosis of the skin and mucosa. The severity-of-illness scoring system for TEN (SCORTEN) was widely used since 2000 as a standard prognostic tool consisting of seven clinical values. Methods: To evaluate the prognosis using current treatments and risk factors for mortality, we retrospectively analyzed 59 cases of TEN, including SJS/TEN overlap treated in two university hospitals from January 2000 to March 2020. Results: The mortality rate of TEN was 13.6% (8/59). All patients treated with high-dose steroid administration in combination with plasma exchange and/or immunoglobulin therapy recovered. Logistic regression analysis showed nine clinical composite scores, namely: heart rate (≧120 bpm), malignancy present, percentage of body surface area with epidermal detachment (>10%), blood urea nitrogen (>28 mg/dL), serum bicarbonate level (252 mg/dL), age (≧71 years), the interval between disease onset and treatment initiation at the specialty hospital (≧8 days), and respiratory disorder within 48 h after admission. The receiver operating characteristic curves confirmed a high potential for predicting the prognosis of TEN. Conclusions: Recent developments in treatment strategies have contributed to the improved prognosis of TEN patients. A modified severity scoring model composed of nine scores may be helpful in the prediction of TEN prognosis in recent patients. Further large-scale studies are needed to confirm mortality findings to improve prognostication in patients with TEN.

IgE antibodies play a protective role against parasites and environmental toxins by its strong effector functions. However, aberrant IgE production can contribute to the development of allergic disorders, and thus is tightly regulated. Beside its very short half-life, IgE is normally produced only transiently and its affinity maturation is limited under physiological immune responses. Although such distinct characteristics of IgE among Ig classes are well-known, the underlying molecular mechanisms have not been understood until recently. Somatic or genetic defects of such mechanisms can lead to pathogenesis of allergic diseases. In this review, we summarize recent advances in our understanding of the mechanisms that control the production of IgE and formation of IgE-type humoral memory, focusing on the B cell immune responses.

Aim of the work: To assess whether there is seasonality in the internet search volume related to gout and whether this reflects the seasonal variation of the actual number of gout cases in South Korea according to the nationwide insurance data. Patients and Methods: The number of gout cases was obtained from the Health Insurance Review and Assessment Service (HIRA) in South Korea between January 2015 and December 2019. Internet search query data for the search terms “gout” and “uric acid” were obtained from a publicly available search engine database, Google Trends, during the same period. The cosinor analysis was conducted to assess a potential seasonality in the number of gout cases and gout-related search volumes (RSV) in Google Trends. Results: There was a significant seasonality in the number of gout cases and RSV for the search terms “gout” and “uric acid”. For both analyses, summer was the peak season, and winter was the trough season. The month with the most gout cases was July with February having the least number of cases. The RSV of the terms “gout” (r = 0.47; p

Zinc is an essential micronutrient in human body and a vital cofactor for the function of numerous proteins encoded by the human genome. Zinc has a critical role in maintaining many biochemical and physiological processes at the molecular, cellular, and multiple organ and systemic levels. The alteration of zinc homeostasis causes dysfunction of many organs and systems. In the immune system, zinc regulates the differentiation, proliferation and function of inflammatory cells, including T cells, eosinophils, and B cells, by modifying several signaling pathways such as NFκB signaling pathways and TCR signals. An adequate zinc level is essential for proper immune responses and decreased zinc levels were reported in many allergic inflammatory diseases, including atopic dermatitis, bronchial asthma, and chronic rhinosinusitis. Decreased zinc levels often enhance inflammatory activation. On the other hand, the inflammatory conditions alter the intracellular homeostasis of zinc, often decreasing zinc levels. These findings implied that there could be a vicious cycle between zinc deficiency and inflammatory conditions. In this review, we present recent evidence on the involvement of zinc in atopic dermatitis, bronchial asthma, and chronic rhinosinusitis, with insights into the involvement of zinc in the underlying molecular and cellular mechanisms related to these allergic inflammatory diseases.

Hydrogen sulfide (H2S) has recently been recognised as the third important gas-signalling molecule, besides nitric oxide and carbon monoxide. H2S has been reported to be produced by many cell types in mammalian tissues and organs throughout the actions of H2S-generating enzymes or redox reactions between the oxidation of glucose and element of sulfur. Although the pathological role of H2S has not yet been fully elucidated, accumulative data suggest that H2S may have biphasic effects. Briefly, it mainly has anti-inflammatory and antioxidant roles, although it can also have pro-inflammatory effects under certain conditions where rapid release of H2S in tissues occur, such as sepsis. To date, there have been several clinical studies published on H2S in respiratory disorders, including asthma and chronic obstructive pulmonary disease (COPD). According to previous studies, H2S is detectable in serum, sputum, and exhaled breath, although a gold standard method for detection has not yet been established. In asthma and COPD, H2S levels in serum and sputum can vary depending on the underlying conditions such as an acute exacerbation. Furthermore, sputum H2S in particular correlates with sputum neutrophils and the degree of airflow limitation, indicating that H2S has potential as a novel promising biomarker for neutrophilic airway inflammation for predicting current control state as well as future risks of asthma. In the future, concurrent measures of H2S with conventional inflammatory biomarkers (fractional exhaled nitric oxide, eosinophils etc) may provide more useful information regarding the identification of inflammatory phenotypes of asthma and COPD for personalised treatment.

Background Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but serious delayed hypersensitivity reaction that can be caused by antibiotic exposure. The reaction typically develops in 2 to 6 weeks. The pathophysiology is thought to involve toxic drug metabolites acting as a hapten, triggering a systemic response. The diagnosis is made clinically but can be confirmed using assays such as the lymphocyte toxicity assay (LTA), which correlates cell death upon exposure to drug metabolites with susceptibility to hypersensitivity reactions. Case presentations Case 1 involves a previously healthy 11-month-old male with first exposure to amoxicillin-clavulanate, prescribed for seven days to treat a respiratory infection. The patient developed DRESS fourteen days after starting the drug and was successfully treated with corticosteroids. LTA testing confirmed patient susceptibility to hypersensitivity reactions with amoxicillin-clavulanate. Parental samples were also tested, showing both maternal and paternal susceptibility. Neither parent reported prior hypersensitivity reactions. Lifelong penicillin avoidance for the patient was advised along with the notation in medical records of penicillin allergy. The parents were advised to avoid penicillin class antibiotics and be monitored closely for DRESS if they are exposed. Case 2 involves an 11-year-old female with atopic dermatitis with first exposure to amoxicillin-clavulanate, prescribed for ten days to treat a secondary bacterial skin infection. She developed DRESS eleven days after starting antibiotics and was successfully treated with corticosteroids. LTA testing confirmed patient susceptibility to hypersensitivity reactions with amoxicillin-clavulanate. Maternal samples were also tested and showed sensitivity. The mother reported no prior hypersensitivity reactions. Lifelong penicillin avoidance for the patient was advised along with the notation in medical records of penicillin allergy. Conclusions Amoxicillin-clavulanate is a commonly used antibiotic and the cases we have described suggest that it should be recognized as a potential cause of DRESS in pediatric patients. Furthermore, these cases contribute to current literature supporting that there may be a shorter latent period in DRESS induced by antibiotics. We have also shown that the LTA can be a helpful tool to confirm DRESS reactions, and that testing may have potential implications for family members.

Aim of the work To investigate the frequency and types of pulmonary involvement using high resolution computed tomography (HRCT) and pulmonary function tests (PFTs) and to identify different disease parameters as predictors of lung involvement. Patients and Methods One hundred RA patients were recruited from El-Maadi Armed Forces Rheumatology clinic. Spirometry, plain X-ray chest, and HRCT were performed. Disease activity score (DAS28) and Larsen score were assessed. Results They were 77 females and 23 males with a mean age of 55.7 ± 11.4 years and disease duration of 14.9 ± 6.8 years. Extra-articular manifestations included pleura-pulmonary involvement (33%), eye dryness (30%) and skin nodules (13%). PFTs showed abnormalities in 38%. X-ray chest abnormalities were found in 12 patients as follows: pleural effusion (3%), atelectasis in (6%), pulmonary nodules (2%) and hyperinflated chest (3%). Abnormal HRCT findings were found in 68% of the patients: ground glass opacity (GGO) in 36 (52.9%), air trapping in 26 (38.2%), thickened septal/non-septal lines in 21 (30.9%), nodules in 17 (25%), Caplan’s syndrome in 8 (11.8%) and bronchial wall thickening in 8 (11.8%) while 3 (4.4%) showed honey combing and bronchiectasis. Passive smoking, chronic cough, Larsen score and anti-cyclic citrullinated peptide (anti-CCP) titre were significant predictors of lung involvement as detected by HRCT. Conclusion HRCT of the chest was found to be a more sensitive measure than spirometry to diagnose pulmonary abnormalities. Passive smoking, chronic cough, disease severity and high anti-CCP titre were significant independent predictors of lung involvement as detected by PFT and HRCT among rheumatoid patients.

Background Some patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) or wheat allergy showed negative ω-5 gliadin-specific IgE test and high level of grass pollen-specific IgE. It was presumed that these patients developed allergic reaction upon cross-reaction of their IgE antibodies raised against grass pollen allergens to wheat allergens. This study aimed to clarify clinical characteristics and wheat allergens of this phenotype of WDEIA/wheat allergy, which were tentatively diagnosed as grass pollen-related wheat allergy (GPWA). Methods A total of six patients with GPWA were enrolled, and controls were 17 patients with grass pollen allergy but no episode of wheat allergy, and 29 patients with other wheat allergies: 18 with conventional WDEIA and 11 with hydrolyzed wheat protein allergy. Sensitization to wheat proteins was determined by basophil activation test (BAT). IgE-binding proteins in wheat flour were identified by immunoblotting followed by mass spectrometry. Wheat allergen-specific IgE tests were established by CAP-FEIA system. Results All the six patients with GPWA were sensitized to water-soluble wheat proteins in BAT and IgE-immunoblotting, and peroxidase-1 (35 kDa) and beta-glucosidase (60 kDa) were identified as specific IgE-binding wheat proteins. The binding of patient IgE to these proteins was inhibited by pre-incubation of patient sera with grass pollen. The peroxidase-1- and beta-glucosidase-specific IgE tests identified three and four of six patients with GPWA, respectively, but only two of 29 controls, indicating high specificity of these tests. Conclusions Peroxidase-1 and beta-glucosidase are specific wheat allergens for GPWA among grass pollen allergy and other types of wheat-induced food allergies.

Gabriella Gálffy,1 Melanie Emmeluth,2 Arkady Koltun,3 Ferdinand Kopietz,2 Duc Tung Nguyen,2 Hans Christian Kuhl2 1Onco-Pulmonology Department, Pest County Pulmonology Hospital, Törökbálint, Hungary; 2Global Medical Affairs, MEDA Pharma GmbH & Co. KG (A Mylan Company), Bad Homburg, Germany; 3Global Medical Affairs, Mylan, Inc, Canonsburg, PA, USACorrespondence: Gabriella GálffyHead of the Onco-Pulmonology Department and Research and Education Director of Pest County Pulmonology Hospital, Törökbálint 70, Munkácsy Mihály Street, Törökbálint, 2045, HungaryFax +36-23511598Email ggalffy@hotmail.comBackground: Allergic rhinitis (AR) is characterized by nasal and ocular symptoms, and substantially impacts the quality of life. Therapy selection for patients with AR depends on several factors, including symptom severity, age, patient preference, patient adherence, and cost.Methods: The purpose of this multicenter, noninterventional, cross-sectional survey was to evaluate current therapy decisions in routine clinical practice for patients with symptomatic AR, and to determine how these decisions are linked to experiences with previous treatments and current symptom severity as assessed by aVAS. The survey included patients aged 18 years or older in Spain and 12 years or older in Hungary whoconsulteda physician fortreatment of AR symptoms. Physicians recorded AR symptom burden in the previous 7 days, previous AR treatments, and the current AR therapy decision made at the visit.Results: Overall, 72.9% of 181 patients (Spain) and 67.1% of 228 patients (Hungary) had received treatment in the previous 7 days. Among patients who had received step 3 treatment, 82.9% (Spain) and 75.8% (Hungary) received a free combination of intranasal corticosteroid (INCS) and antihistamines. Despite the high number of pretreated patients in both countries, 72.9% and 78.9% in Spain and Hungary, respectively, reported uncontrolled symptoms (VAS ≥ 50 mm). Of pretreated patients, 58.3% (Spain) and 61.4% (Hungary) received a step-up in treatment during the visit. Physicians more often prescribed a fixed combination of INCS and intranasal antihistamine than a free combination. However, of patients with uncontrolled symptoms whoreceived previous therapy, 28.0% (Hungary) and 40.6% (Spain) did not receive a step-up as suggested by the guidelines.Conclusion: Many patients suffering from acute AR symptoms consulted with their physician because of insufficient medications. Not all patients with uncontrolled symptoms received a step-up in treatment, underscoring the need for improved physician education to enhance AR management and control in accordance with consensus treatment guidelines.Keywords: allergic rhinitis, therapy, decision-making, guidelines, intranasal corticosteroid, antihistamine, visual analog scale, noninterventional

Background We aimed to report the clinical characteristics, immunological features, and treatment of one patient with a de novo STAT3 gain-of-function mutation identified by next generation sequencing. We investigated the efficacy of tocilizumab therapy in immune dysregulation diseases caused by STAT3 mutation. Results The patient was a 16-year-old girl. She presented with recurrent respiratory infections and chronic diarrhea after birth. She had life-threatening autoimmune pancytopenia at 14 years old. After receiving glucocorticoid therapy, she developed diabetes. However, her pancytopenia relapsed when the glucocorticoid was tapered. Next-generation sequencing showed a de novo heterozygous mutation in the STAT3 gene, c.1261G > A (p. G421R), which was previously described as a gain-of-function mutation. After tocilizumab therapy, her pancytopenia fully resolved, and insulin and glucocorticoid therapies were gradually discontinued within 12 months. She had lymphopenia and an inverted CD4/CD8 ratio before therapy. Lymphocyte subpopulation analysis indicated an expansion of effector memory CD4+, effector memory CD8+ and central memory CD4+ T cells. The proportions of memory B cells and naive CD4+ T cells were decreased, and the proportion of naïve B cells was increased. None of the abnormal lymphocytic changes improved significantly. STAT3 GOF mutations were identified by next gene sequencing in those with early-onset multi-organ autoimmunity. Including our patient, 13 patients with STAT3 GOF mutations received targeted treatment. Twelve of them were treated with tocilizumab alone or combination tocilizumab with JAK inhibitor, and ten patients improved. Conclusions Gene sequencing should be performed for patients with early-onset refractory or multiorgan immune dysregulation diseases. Targeted drugs can effectively improve the clinical problems associated with STAT3 gain-of-function mutations, while nontargeted immunosuppressive therapy is usually insufficient.

Background This study identified whether Functional Index for Hand Osteoarthritis (FIHOA) is associated with pain, hand muscle strength, health-related quality of life, and radiographic severity in hand osteoarthritis (OA). Methods We consecutively recruited 95 patients with hand OA. The FIHOA was used to assess questionnaire-based physical function in hand OA. Health-related quality of life was evaluated using EuroQol-5 dimension (EQ-5D). Radiographic changes of hand joints were measured by Kellgren-Lawrence (K-L) grade, which was determined based on total radiographic severity score and number of affected joints. Other measures included patient’s visual analogue scale (VAS) score for pain and performance-based function indexes such as grip and pinch strength. Statistical analysis was performed using Mann-Whitney U test, Spearman’s correlation analysis, and multivariate logistic regression analysis. Results FIHOA score was negatively associated with grip and pinch hand strength and EQ-5D and positively correlated to VAS pain (p 4) (p 4) was related with increased VAS pain and with lower EQ-5D index (p = 0.008 and p = 0.013, respectively). There was no association between FIHOA score and measures of total radiographic severity score and number of affected joints. Conclusion This study observes that FIHOA score is associated with patient-reported VAS pain, hand muscle strength indexes, and EQ-5D but not radiographic severity in hand OA.

Taoming Liu, Juan Bai, Su Wang, Shuni Ying, Sheng Li, Jianjun Qiao, Hong Fang Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Jianjun Qiao; Hong FangDepartment of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, People’s Republic of ChinaTel/Fax +86-571-87236706Email qiaojianjun@zju.edu.cn; fanghongzy@zju.edu.cnAbstract: Prurigo nodularis (PN) is an intense pruritic skin condition. Treatment of PN is challenging. We described an elderly patient with PN who had contradictions of cyclosporine or methotrexate and achieved significant improvement after treatment with dupilumab. We also reviewed published cases of elderly patients with PN who were refractory to traditional therapy.Keywords: prurigo nodularis, dupilumab, elderly patient, targeted therapy

Objective Emerging articles have profiled the relations between microRNAs and viral myocarditis. This research was unearthed to explore the capacity of miR‐425‐3p on cardiomyocyte apoptosis in mice with viral myocarditis and its mechanism. Methods A total of 120 mice were classified into 4 groups in a random fashion (n = 30). The mice were intraperitoneally injected with coxsackievirus type B3 (CVB3) to induce myocarditis. On the 7th day after CVB3 infection, 10 mice in each group were euthanized to assess the heart function indices of mice, observe the pathological conditions, detect myocardial tissue apoptosis, and measure the inflammatory factor levels in myocardial tissues. Expression of miR‐425‐3p, transforming growth factor (TGF‐β1), and apoptosis‐associated proteins in myocardial tissues was determined. The remaining 20 mice in each group were used for survival observation. The luciferase activity assay was implemented to validate the relationship between miR‐425‐3p and TGF‐β1. miR‐425‐3p mimic was transfected into mouse cardiomyocytes HL‐1 and then infected with CVB3 to further verify the regulatory effect of miR‐425‐3p on the cardiomyocyte apoptosis in viral myocarditis. Results miR‐425‐3p was lowly expressed in myocardial tissues of mice with viral myocarditis. Overexpressed miR‐425‐3p improved the cardiac function, alleviated pathological conditions, reduced cardiomyocyte apoptosis, decreased Bax and cleaved Caspase‐3 expression, elevated Bcl‐2 expression, decreased levels of inflammatory factors and improved survival rate of mice with viral myocarditis. Luciferase activity assay verified that miR‐425‐3p could bind to TGF‐β1, and overexpressed miR‐425‐3p suppressed TGF‐β1, p‐smad2/smad2 and p‐smad3/smad3 expression. In vitro experiments further verified that overexpression of miR‐425‐3p inhibited the apoptosis of CVB3‐HL‐1 cells, and the addition of TGF‐β1 would reverse this effect. Conclusion Our research indicates that miR‐425‐3p is poorly expressed in myocardial tissues of mice with viral myocarditis. Overexpressed miR‐425‐3p inhibits cardiomyocyte apoptosis and myocardial inflammation in mice with viral myocarditis as well as improves their survival rates through suppressing the TGF‐β1/smad axis., The left ventricular function in mice was assessed by the observation of transthoracic echocardiography (Figure 1A‐E): CVB3‐induced viral myocarditis presented elevated LVEDd and LVESd and reduced LVEF and LVFS. HE staining observation showed that on the 7th day after CVB3 infection, increased number of inflammatory cell infiltration (Figure 1G) and higher pathological score of myocardial tissues (Figure 1H) were found in mice with CVB3‐induced viral myocarditis. Then we detected that miR‐425‐3p was downregulated in mice with CVB3‐induced viral myocarditis (Figure 1I, P < .001).

Background Peer education and HIV risk perception are related to HIV testing uptake among key populations. We aimed to examine the association between peer education, HIV risk perception, and HIV testing uptake, as well as to evaluate the mediated effect of HIV risk perception in the relationship between peer education and HIV testing uptake. Methods We conducted a cross-sectional survey among 1188 HIV-uninfected or unknown participants from populations of men who have sex with men (MSM), female sex workers (FSWs), and drug users (DUs) in seven cities of China. Partial correlation analysis and regression analysis were employed to examine the associations among peer education, HIV risk perception, and HIV testing uptake. Mediation analysis was conducted to assess whether HIV risk perception mediated the hypothesized association. Results Receiving peer education was associated with higher odds of HIV testing uptake among MSM, FSWs and DUs. Perceiving risk of HIV infection was associated with higher odds of HIV testing uptake among MSM and DUs. Among MSM, the relationship between peer education and HIV testing uptake was mediated by moderate risk perception of HIV (indirect effect: 0.53, 95% CI 0.07 to 1.21), and by high risk perception of HIV (indirect effect: 0.50, 95% CI 0.01 to 1.17). Among DUs, the relationship between peer education and HIV testing uptake was mediated by moderate risk perception of HIV (indirect effect: 1.80, 95% CI 0.57 to 3.45). Conclusions Participants who received peer education tended to perceive their risk of HIV infection, which in turn was associated with increased HIV testing uptake among MSM and DUs. Therefore, in addition to peer education interventions, more report about HIV epidemic and risk assessment should also be scaled up to enhance HIV risk perception among key populations.

Giulia Brindisi,1,* Valentina De Vittori,1,* Rosalba De Nola,2,3 Antonio Di Mauro,4 Giovanna De Castro,1 Maria Elisabetta Baldassarre,4 Ettore Cicinelli,2 Bianca Cinicola,1 Marzia Duse,1 Anna Maria Zicari1 1Pediatrics Department, Umberto I Hospital, Sapienza University, Rome, 00161, Italy; 2Department of Biomedical Science and Human Oncology, Gynecology and Obstetrics Section, “Aldo Moro” University of Bari, Bari, 70124, Italy; 3Department of Tissues and Organs Transplantation and Cellular Therapies, “Aldo Moro” University of Bari, Bari, 70124, Italy; 4Department of Biomedical Sciences and Human Oncology-Neonatology and Neonatal Intensive Care Unit, “Aldo Moro” University of Bari, Bari, 70124, Italy*These authors contributed equally to this workCorrespondence: Giulia BrindisiPediatrics Department, Umberto I Hospital, Sapienza University, Viale Regina Elena 324, Rome, 00161, ItalyTel +39 06 49979333Email giulia.brindisi@gmail.comBackground: Allergic rhinitis (AR) and asthma are two common atopic diseases, often associated with a common ethiopathogenesis characterized by a Th2 inflammatory response with the release of many biomarkers, such as nitric oxide (NO).Purpose: To evaluate and compare inflammatory (nFeNO and eFeNO) and functional (mNF and FEV1) parameters in AR children with or without asthma in comparison to controls. Secondly, we aimed to identify nFeNO cut-off values and verify their reliability to predict the presence of rhinitis or asthma alone or in combination.Patients and Methods: We enrolled 160 children (6– 12 years of age) with AR and/or asthma divided into four groups: controls, AR, asthma, and AR + asthma. All children underwent the following inflammatory and functional measurements: nFeNO, eFeNO, mNF and FEV1.Results: We observed that levels of nFeNO were extremely higher in children with AR and even more in those with AR + asthma in respect to controls. Notably, all the pathological conditions, especially AR + asthma, showed significantly lower values of mNF compared to healthy children. A negative correlation linked mNF and nFeNO. Then, we found eFeNO values significantly higher in all the pathological groups compared to controls, with major values of this marker in patients affected by asthma and AR + asthma, as well as FEV1 values significantly lower in all the disease groups, especially in children with asthma and AR+ asthma. ROC curve analysis showed that nFeNO was a great predictor for rhinitis alone or with asthma, revealing an accurate cut-off of 662 ppb.Conclusion: nFeNO measurement is non-invasive, easy to perform, economic and a valuable test in case of AR alone or in association with asthma. Thus, it should be used in patients with rhinitis, together with anterior active rhinomanometry (AAR) to diagnose and estimate the degree of nasal obstruction but also in children with asthma to assess their nasal involvement and improve the therapeutic management.Keywords: nasal nitric oxide, exhaled nitric oxide, anterior active rhinomanometry, allergic rhinitis, asthma, children

Introduction The ubiquitously expressed nonhistone nuclear protein high‐mobility group box protein 1 (HMGB1) has different functions related to posttranslational modifications and cellular localization. In the nucleus, HMGB1 modulates gene transcription, replication and DNA repair as well as determines chromosomal architecture. When the post‐transcriptional modified HMGB1 is released into the extracellular space, it triggers several physiological and pathological responses and initiates innate immunity through interacting with its reciprocal receptors (i.e., TLR4/2 and RAGE). The effect of HMGB1‐mediated inflammatory activation on different systems has received increasing attention. HMGB1 is now considered to be an alarmin and participates in multiple inflammation‐related diseases. In addition, HMGB1 also affects the occurrence and progression of tumors. However, most studies involving HMGB1 have been focused on adults or mature animals. Due to differences in disease characteristics between children and adults, it is necessary to clarify the role of HMGB1 in pediatric diseases. Methods and Results Through systematic database retrieval, this review aimed to first elaborate the characteristics of HMGB1 under physiological and pathological conditions and then discuss the clinical significance of HMGB1 in the pediatric diseases according to different systems. Conclusions HMGB1 plays an important role in a variety of pediatric diseases and may be used as a diagnostic biomarker and therapeutic target for new strategies for the prevention and treatment of pediatric diseases.

Introduction The pathophysiology and temporal dynamics of affected tissues in chronic rhinosinusitis (CRS) remain poorly understood. Here, we present a multiomics‐based time‐series assessment of nasal polyp biopsies from three patients with CRS, assessing natural variability over time and local response to systemic corticosteroid therapy. Methods Polyp tissue biopsies were collected at three time points over two consecutive weeks. Patients were prescribed prednisone (30 mg daily) for 1 week between Collections 2 and 3. Polyp transcriptome, proteome, and microbiota were assessed via RNAseq, SWATH mass spectrometry, and 16S ribosomal RNA and ITS2 amplicon sequencing. Baseline interpatient variability, natural intrapatient variability over time, and local response to systemic corticosteroids, were investigated. Results Overall, the highly abundant transcripts and proteins were associated with pathways involved in inflammation, FAS, cadherin, integrin, Wnt, apoptosis, and cytoskeletal signaling, as well as coagulation and B‐ and T‐cell activation. Transcripts and proteins that naturally varied over time included those involved with inflammation‐ and epithelial–mesenchymal transition‐related pathways, and a number of common candidate target biomarkers of CRS. Ten transcripts responded significantly to corticosteroid therapy, including downregulation of TNF, CCL20, and GSDMA, and upregulation of OVGP1, and PCDHGB1. Members of the bacterial genus Streptococcus positively correlated with immunoglobulin proteins IGKC and IGHG1. Conclusions Understanding natural dynamics of CRS‐associated tissues is essential to provide baseline context for all studies on putative biomarkers, mechanisms, and subtypes of CRS. These data further our understanding of the natural dynamics within nasal polypoid tissue, as well as local changes in response to systemic corticosteroid therapy., The pathophysiology and temporal dynamics of affected tissues in chronic rhinosinusitis (CRS) remain poorly understood. This study comprised a comprehensive multiomics analysis of polyp biopsies from three patients with chronic rhinosinusitis with nasal polyps, assessing natural variability over time as well as local response to systemic corticosteroids. Overall, these data provide further support for current hypotheses of CRS and polyposis pathogenesis, provide essential temporal context to studies on biomarkers and mechanisms of polyposis, and highlight areas of focus for future targeted therapeutic options.

Background Chemokine receptors and their corresponding ligands are key players of immunity by regulation of immune cell differentiation and migration. CXCR1 is a high‐affinity receptor for CXCL8. Differential expression of CXCR1 is associated with a variety of human pathologies including cancer and inflammatory diseases. While various studies have highlighted the importance of CXCR1‐mediated CXCL8‐sensing for neutrophil trafficking and function, its role in B‐cell responses remains unsolved. Therefore, our aim was to investigate innate and adaptive antibody responses in CXCR1‐deficient mice. Methods Cell populations of the spleen and the peritoneal cavity were identified and quantified via flow cytometry. To investigate thymus‐independent (TI) and thymus‐dependent (TD) antibody responses, mice were immunized intraperitoneally with TNP‐Ficoll, Pneumovax23, and TNP‐Chicken Gamma Globulin. Mice were bled before as well as 7 and 14 days after vaccination to collect serum. Serum antibody levels overtime were analyzed according to their specificity by enzyme‐linked immunosorbent assay. B‐1 cell functionality was examined by IL‐5/IL‐5Rα‐dependent stimulation of peritoneal and splenic cells in vitro. To analyze CXCR1/2‐expression, CD19+ splenocytes were enriched by magnetic‐activated cell sorting before isolation of total RNA contents, followed by reverse transcription and real‐time polymerase chain reaction. Results The distribution of natural B‐1 cell populations was disturbed in the absence of CXCR1, while their responsiveness towards TI antigens and in vitro stimulation remained functional. Besides, CXCR1‐deficiency was accompanied by increased frequencies of follicular B‐2 cells in the spleen. Interestingly, these mice produced elevated levels of antigen‐specific IgG1 upon TD immunization and harbored a significantly enlarged proportion of CXCR5‐expressing T helper (H) cells. CXCR1‐expression was detectable in CD19+ splenocytes derived from wild‐type, but not CXCR1‐deficient mice. Conclusion Our data demonstrate a previously unknown relevance of CXCR1 for the production of specific IgG1 in response to vaccination. These findings identify CXCR1 as a promising candidate for future studies on the regulation of adaptive antibody responses.

Veronica Storino,1 Juliana Muñoz-Ortiz,2 Valeria Villabona-Martinez,3 Juan Diego Villamizar-Sanjuán,3 William Rojas-Carabali,3 Alejandra de-la-Torre3 1Faculty of Medicine, Universidad de los Andes, Bogotá, Colombia; 2Escuela Barraquer, Research Group, Escuela Superior de Oftalmología, Instituto Barraquer de América, Bogotá, Colombia; 3Neuroscience Research Group “NeURos”, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, ColombiaCorrespondence: Alejandra de-la-TorreNeuroscience Research Group “NeURos”, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Carrera 24 # 63C - 69, Bogotá, ColombiaTel +57 3102482196Email alejadelatorre@yahoo.comPurpose: To report the case of a patient with multiple food allergies comorbid with multiple chemical sensitivity (MCS) who was misdiagnosed on various occasions, resulting in a negative impact on the patient’s personal and social life.Case Report: We present the case of a 43-year-old Colombian women with multiple food allergies concomitant with MCS. Symptoms started with a mild reaction to insecticides, car exhaust smoke, and perfumes and gradually evolved into a severe reaction to her environment. She also presented recurrent episodes of clinical reactivity to foods and persistent elevated IgE levels, as well as several life-threatening anaphylactic reactions. Alternative and allopathic therapies were applied, but her symptoms persisted. Various diagnoses were made before the definitive diagnosis.Conclusion: MCS is an unusual entity of unknown pathophysiology that can, on rare occasions, coexist with food allergies. Early recognition and multidisciplinary treatment are required as these entities have a major impact on the patient’s quality of life. We present the first Latin American case regarding the association of the two diseases.Keywords: type I hypersensitivity, idiopathic environmental intolerance, environmental exposure, food allergy

Rationale The Environmental Exposure Unit (EEU), a controlled allergen exposure model of allergic rhinitis (AR), has traditionally utilized seasonal allergens. We sought to clinically validate the use of house dust mite (HDM), a perennial allergen, in the HDM-EEU, a specially designed facility within the larger EEU. Methods Forty-four HDM-allergic and eleven non-allergic participants were screened and deemed eligible for one of two 3-h exposure sessions in the HDM-EEU. Participants were exposed to a modest or higher HDM target, with blood and nasal brushing samples collected before and after allergen exposure. Symptomatic data, including Total Nasal Symptom Score (TNSS), Total Ocular Symptom Score (TOSS), Total Rhinoconjunctivitis Symptom Score (TRSS), and Peak Nasal Inspiratory Flow (PNIF) were collected at baseline, every 30 min until 3 h, on an hourly basis for up to 12 h, and at 24 h following the onset of HDM exposure. Results The modest and higher HDM target sessions respectively featured cumulative total particle counts of 156,784 and 266,694 particles (2.5–25 µm), Der f 1 concentrations of 2.67 ng/m3 and 3.80 ng/m3, and Der p 1 concentrations of 2.07 ng/m3 and 6.66 ng/m3. Allergic participants experienced an increase in symptoms, with modest target participants plateauing at 1.5 to 2 h and achieving a mean peak TNSS of 5.74 ± 0.65, mean peak TOSS of 2.47 ± 0.56, and mean peak TRSS of 9.16 ± 1.32. High HDM-target allergics reached a mean peak TNSS of 8.17 ± 0.71, mean peak TOSS of 4.46 ± 0.62, and mean peak TRSS of 14.08 ± 1.30 at 3 h. All allergic participants’ symptoms decreased but remained higher than baseline after exiting the HDM-EEU. Sixteen participants (37.2%) were classified as Early Phase Responders (EPR), eleven (25.6%) as protracted EPR (pEPR), seven (16.3%) as Dual Phase Responders (DPR), and nine (20.9%) as Poor Responders (PR). Allergic participants experienced significant percent PNIF reductions at hours 2 and 3 compared to healthy controls. Non-allergics were asymptomatic during the study period. Conclusions The HDM-EEU is an appropriate model to study HDM-induced AR as it can generate clinically relevant AR symptoms amongst HDM-allergic individuals.

Wei Fu, Shanshan Xu, Xiang Dong, Qing Xie, Yadong Gao Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Yadong Gao; Wei FuDepartment of Allergology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of ChinaTel +86 15071384536Email gaoyadong@whu.edu.cn; fuwei0511@163.comAbstract: Aspirin is clinically widely used to inhibit platelet aggregation after coronary intervention. Herein we describe a case of aspirin-induced thrombocytopenia that may be related to allergy to aspirin. A 47‐year‐old man developed a delayed hypersensitivity reaction to aspirin, with pruritus, purpura and thrombocytopenia, increased peripheral blood eosinophils and enlarged inguinal lymph node. All the symptoms disappeared in 2 years after stopping aspirin. Aspirin-induced thrombocytopenia related to allergy is rarely reported. Aspirin hypersensitivity should be taken into consideration in case of unexplained thrombocytopenia in patients taking aspirin. Aspirin “allergy”-induced thrombocytopenia may involve both aspirin related IgG and IgE antibodies.Keywords: aspirin, allergy, thrombocytopenia, platelets

Background The impact of childhood food allergy on household costs has not been examined in Canada. The current study sought to examine differences in direct, indirect, and intangible costs among Canadian families with and without a food-allergic child. Methods Families with a child with a specialist-diagnosed food allergy (cases) were recruited from two tertiary pediatric allergy clinics in the Province of Manitoba, Canada, and matched, based on age and sex, to families without a food-allergic child (controls). Cost data for the two groups were collected via an adapted version of the Food Allergy Economic Questionnaire (FA-EcoQ). Consideration was given to income, defined as above vs. below the provincial annual median income. Results Results from 35 matched case/control pairs revealed that while total household costs did not significantly differ between cases and controls, food-allergic families did incur higher direct costs ($12,455.69 vs. $10,078.93, p = 0.02), which were largely attributed to spending on food. In contrast, cases reported lower, but not statistically significant, total indirect costs compared to controls ($10,038.76 vs. $12,294.12, p = 0.06). Families also perceived their food-allergic child as having poorer quality of life relative to their healthy peers. Lastly, stratification of the analyses by annual income revealed several differences between the higher and lower income groups. Conclusions Relative to families without a food-allergic child, food-allergic families incurred higher direct costs across a number of different areas.

BackgroundGood adherence to antiretroviral therapy (ART) and retention in care are essential for the effectiveness of an HIV care program. With the current increase in numbers of people living with HIV taking second-line ART in sub-Saharan Africa, there is a need to establish their treatment outcomes and the rate of loss to follow up. In this study, we determined the incidence and predictors of loss to follow up among patients taking second-line ART at an experienced HIV treatment center in southwestern Uganda.MethodsThis was a retrospective review of an electronic database at Mbarara Regional Referral Hospital HIV clinic in southwestern Uganda. Second-line ART included at least two of the nucleoside reverse transcriptase inhibitors and a boosted protease inhibitor. Loss to follow-up was defined as failure to return to the health facility for care or treatment refill for 180 days or more from the previous visit. After excluding children less than 15 years, we pooled data that included socio-demographic, clinical, and laboratory data for patients who started second-line ART between 2002 and 2017. Multiple imputation was done for variables with missing data. Variables that had a p ResultsBetween 2002 and 2017, 1121 patients had been initiated on second-line ART. We included data from 924 participants and of these, 518 (56.1%) were female, the mean age (SD) was 38.4 (± 10.5) years, and 433 (52.4%) had a CD4 count less than 100 cells/µl at the start of second-line ART. The incidence of loss to follow-up was 26.7 per 100 person-years. Male gender (Adjusted risk ratio (ARR) = 1.8, 95% CI 1.5–2.0) p ConclusionsThere is a high incidence of loss to follow up among patients taking protease-inhibitor based second-line ART at a tertiary HIV center in southwestern Uganda. There is a need to routinely measure hemoglobin during clinic reviews, and establish mechanisms to retain males initiated on second-line ART in care. The association of anemia and loss to follow up needs to be investigated.