History Of Atopic Dermatitis Research Articles

Severe herpes simplex virus − 1 Kaposi varicelliform eruption and SARS-CoV-2 infection in atopic dermatitis treated with dupilumab

Herpes Simplex Virus-1 (HSV-1) Kaposi varicelliform eruption (KVE) is a rare and severe cutaneous manifestation, clinically characterized by the presence of widespread vesicles and pustules. A case report details a patient with a history of Atopic Dermatitis (AD) and recent SARS-CoV-2 infection who developed a severe KVE subsequent to the viral illness. The patient, a 35-year-old male, presented with severe atopic dermatitis (AD) subsequent to a SARS-CoV-2 infection. In a period of four months, the dermatological eruption underwent a rapid progression to a severe state, characterised by the presence of extensive vesicles and pustules, in addition to the emergence of symptoms. In conjunction with a chest CT scan, plasma and antigen testing, the patient was confirmed to be positive for HSV-1 positive. The patient exhibited elevated levels of IgE and a notable reduction in the absolute number of immune cells. The patient was treated with valaciclovir, piperacillin-tazobactam, IVIG at the same time. Within seven days of treatment, the blisters had dried up and the scabs had fallen off without any pain, pruritus, or fever. This case highlights the potential for severe viral eruptions, such as KVE in individuals with underlying dermatological conditions following viral infections.

Karakteristik Pasien Dermatitis Kontak (Iritan dan Alergi) di Puskesmas Tarowang Kabupaten Jeneponto Provinsi Sulawesi Selatan Tahun 2022-2023

Contact dermatitis is a general term for an acute or chronic inflammatory reaction to a substance that stimulates the skin. This disease can cause work discomfort and reduce worker productivity. Women, babies, the elderly, and those with atopic tendencies are more susceptible to irritant contact dermatitis, while allergic contact dermatitis has risks including age, occupation, and a history of atopic dermatitis. The aim of this study was to determine the characteristics of contact dermatitis patients (irritants and allergies) at the Tarowang Community Health Center, Jeneponto Regency in 2022-2023. This research is a quantitative descriptive study with a research sample of all patients diagnosed with contact dermatitis (irritant and allergic) at the Tarowang Community Health Center and 455 samples were obtained from medical record data. The results of this study show that the incidence of DKA is greater than DKI at the Tarowang Community Health Center in 2022-2023 with the general occupational characteristics of DKI patients being housewives while DKA are fishermen in the 26-45 year age category with the highest number of lesion locations on the hands of this type. The most common gender is female and the therapy used in DKI patients is an antihistamine type cetrizine while in DKA it is an antihistamine type mebihydroline napadisylate.

A-147 Transcriptomic and Genomic Profiling as Diagnostic and Prognostic Markers in CTCL Patients with a History of Atopic Dermatitis

A-147 Transcriptomic and Genomic Profiling as Diagnostic and Prognostic Markers in CTCL Patients with a History of Atopic Dermatitis

The Effect of Topical 100% Sunflower Seed Oil (SSO) Extract on Trans Epidermal Water Loss (Tewl) and Skin PH Levels in a History of Atopic Dermatitis

The skin barrier function can be disturbed in various conditions, one of which is atopic dermatitis (AD). Efforts to improve the skin barrier can be done by using various types of moisturizers. Natural oil from sunflower seed oil (SSO) can be used as "skin barrier therapy" by reducing trans epidermal water loss (TEWL) and skin pH levels. A randomized single blind clinical trial with a two parallel group pre and post design was conducted on subjects with a history of AD who were treated at the Skin and Venereology Polyclinic at Sunan Kalijaga Hospital, Demak. Samples were randomized into 2 groups to receive 100% SSO or petrolatum as a control. TEWL and pH assessments were carried out at the beginning of the study and at week 4. Bathing habits and complaints about using moisturizers were also assessed. TEWL values ​​decreased in the SSO and petrolatum groups (-5.8±1.93 vs -6.1±9.08, p = 0.9). The pH value in AD patients also decreased after administration of SSO extract and petrolatum (-0.4±0.10 vs -0.2±0.75, p = 0.2). The decrease in TEWL and pH in both groups was not statistically significant. This may be related to differences in bathing habits and moisturizer use in the two groups. Most of the samples in the SSO group stated that they had no complaints regarding usage. The entire sample completed the study without any reports of allergic reactions or hypersensitivity. Administration of SSO extract was effective in reducing TEWL and pH in DA with the majority of samples stating that they had no complaints about use.

The Effect of Topical 0.1% Pomegranate Extract (Punica Granatum) on Trans Epidermal Water Loss (Tewl) and Skin Ph Levels in Patients with a History of Atopic Dermatitis

Repairing the skin barrier with moisturizers is one of the five main pillars of treating atopic dermatitis. Petrolatum is considered the gold standard, but its consistency is too thick and oily making it less comfortable to use. Moisturizers containing pomegranate extract (Punica granatum) can be an alternative choice that is more comfortable to use. The effectiveness of this pomegranate extract can be eval__uated using TEWL and pH examinations which are considered accurate indicators for changes in skin barrier conditions. Effectiveness of topical administration of 0.1% pomegranate extract in reducing TEWL and skin pH in sufferers with a history of AD.Single blind randomized clinical trial with two parallel group pre and post design. 34 sufferers with a history of AD were randomly divided into treatment groups (topical 0.1% pomegranate extract, 17 subjects) and control group (topical 100% petrolatum, 17 subjects). Moisturizer was applied twice daily to the volar area of ​​the forearm for 4 weeks. Both groups showed a significant decrease in TEWL after 4 weeks with a TEWL delta of -5.2±2.31g/m2/hour (p<0.001) in the pomegranate extract group and-7.0±7.95g/m2/hour(p=0.003) in the petrolatum group. There was no significant difference in TEWL reduction between the two study groups.The pomegranate extract group showed a significant decrease in pH after 4 weeks with a pH delta of -0.5±0.10(p<0.001), while the petrolatum group actually showed a slight increase with a pH delta of0.0±0.59 (p=0.6). The pomegranate extract group showed a significantly greater decrease in pH (p<0.001).Topical 0.1% pomegranate extract is as effective as 100% petrolatum in reducing TEWL, but more effective in lowering skin pH.

Risk factors associated with the incidence of asthma among adolescents in Ukraine

Background. Asthma is a common disease among children and adolescents. The purpose of this study was to describe the detailed characteristics of adolescents with asthma, identify risk factors associated with the development of asthma and to evaluate medical care for patients with asthma. Materials and methods. Asthma patients (n = 80) aged 12 to 18 years from the Allergology Department of the Kyiv City Children’s Clinical Hospital 2, the clinical base of the Department of Pediatrics 2 of the Bogomolets National Medical University, were included in the study. The control group consisted of 120 children without asthma. In the group of interviewed children, asthma was diagnosed based on clinical data and objective measurement of lung function. All children underwent spirometry and skin prick test with aeroallergens. During the clinical examination, weight and height were measured, and body mass index was calculated. The survey was conducted by a research doctor using a Google form. Results. Parents of 80 children with asthma were involved in our survey between September 2023 and May 2024. Asthma occurred more often in boys than in girls: odds ratio (OR) = 7.3 (95% confidence interval (CI) 3.84–14.16, P < 0.0001). 31.25 % respondents reported a history of atopic dermatitis, 26.25 % had atopic dermatitis at the time of the study. Food allergy was detected in 25 % children. 48.75 % children had concomitant allergic rhinitis, of which 33.75 % had seasonal, 15 % had perennial. We found that children living in the city had asthma more often: OR = 7.3 (95% CI 3.26–16.62, P < 0.0001). Having an older sibling was associated with a lower risk of asthma: OR = 3.6 (95% CI 1.86–6.92, P < 0.0001). Also, we found that cat owners were significantly more likely not to have asthma: OR = 7.7 (95% CI 3.96–14.99, P < 0.0001). Such data are most likely related to the refusal to own a cat due to the prevalence of cat allergy among children with asthma or at risk of cat allergy. We have not found a statistically significant difference in the group of children with asthma and in the control group in relation to the exposure to tobacco smoke in the atmosphere (passive smoking): OR = 1.4 (95% CI 0.79–2.59, P > 0.05). Conclusions. Treatment of allergies and atopic conditions should be considered an important component of asthma treatment, which may affect the frequency and severity of the disease. In adolescents and adults, smoking cessation, in particular, as a factor in the impact of passive smoking on a sick child can also significantly reduce the number of hospitalizations. Confirming the diagnosis of asthma, demonstrating good inhaler technique, and emphasizing adherence to preventive therapies such as inhaled glucocorticosteroids can improve asthma control and reduce overreliance on short-acting bronchodilators.

A case with Gianotti-Crosti syndrome with a history of atopic dermatitis

Gianotti-Crosti syndrome (GCS) is characterized by the sudden onset of a papular or papulovesicular rash with a symmetrical distribution. This rash mainly appears on the extensor surfaces of the limbs, buttocks, and face. GCS is most frequently observed in children aged 1 to 6 years. In this case, we present the diagnosis of GCS in an 8-month-old male patient who also has a history of atopic dermatitis. Symmetrical, multiple, monomorphic, raised, red, and itchy lesions were identified on the patient’s face, trunk, arms, and legs. The presence of atopic dermatitis was notably more common in individuals with GCS, suggesting a significant association with a family history of atopy. GCS is a syndrome that demands a high degree of clinical suspicion as it can be mistaken for other childhood exanthematous diseases.

Comparison of the Effectiveness of Platelet-Rich Plasma Versus Tranexamic Acid Plus Vitamin C Mesotherapy in the Treatment of Periorbital Hyperpigmentation: A Split-Site, Randomized Clinical Trial.

Periorbital hyperpigmentation (POH) is a common cosmetic problem with a negative impact on the patient's self-confidence, leading to a decrease in the quality of life. Current treatments include topical agents and mesotherapy, but research remains limited. Due to the undesirable effect of the available treatments, the present study was designed to compare the effectiveness of platelet-rich plasma (PRP) injection and intradermal injection of tranexamic acid plus vitamin C mesotherapy as a therapeutic method to treat POH. Patients received an intradermal injection of PRP randomly on one side and an intradermal injection of tranexamic acid + vitamin C on the other side of their face, for three sessions with an interval of 3 weeks. Digital photography was taken, and data were assessed based on physician global assessment (PGA) and patient satisfaction. Eighteen patients were studied. Among all, 12 patients had a positive family history, 2 had asthma, and 4 had a history of atopic dermatitis. Even though patient satisfaction was higher in the PRP group than in mesotherapy, it was not statistically significant. Both groups showed similar rates of improvement. However, improvement rates did not significantly differ based on various factors including gender, skin type, family history, or medical history. Age and the age of disease onset also did not significantly affect the improvement rates. Both methods revealed successful results in the reduction of POH. Comparing the efficacy of these two methods showed that both treatments had similar improvements.

Type I Kounis syndrome in a young woman without chest pain: a case report

BackgroundKounis syndrome is defined as the concurrence of acute coronary syndromes in the setting of allergic or anaphylactic reactions. It primarily affects men aged 40–70 years and is often associated with chest pain. This syndrome is often unrecognized and undiagnosed in clinical practice due to a low level of awareness. Herein, we present a case of type I Kounis syndrome in a young woman without chest pain.Case presentationA 28-year-old Japanese woman with a history of atopic dermatitis received a glycyrrhizin, glutathione, and neurotropin preparation (a preparation of inflamed skin extract from rabbits inoculated with vaccinia virus) at a dermatology clinic to treat pruritus caused by atopic dermatitis. Immediately after the administration, the patient developed abdominal pain and generalized body wheals. The patient was diagnosed with anaphylaxis and was transported to our hospital. She had no chest pain on arrival at our hospital; however, a 12-lead electrocardiogram showed ST elevation in leads I, aVL, V2, and V3, and an echocardiogram showed decreased wall motion in the anterior and lateral walls of the left ventricle. Sublingual nitroglycerin administration improved ST-segment elevation and left ventricular wall motion abnormalities. The patient underwent emergency coronary angiography, which revealed no significant stenosis, and was diagnosed with type I Kounis syndrome.ConclusionKounis syndrome without chest pain is rare in young women. Since it can be fatal in cases with severe allergic symptoms such as anaphylaxis, the possibility of concurrent acute coronary syndrome should be considered when treating systemic allergic reactions, regardless of age, sex, or the presence or absence of chest symptoms.

Eczematous reactions in patients with plaque psoriasis receiving biological therapy: an observational study.

The use of biologic agents, mainly tumor necrosis factor (TNF)-α and interleukin (IL)-17A inhibitors, was associated with cutaneous side effects, but the factors associated with eczematous reactions occurring during biologic treatments are not completely known. An observational, retrospective, multicentre Italian study evaluated the clinical features and the management of eczematous eruptions in 54 patients with chronic plaque psoriasis who developed eczema after treatment with biological agents (anti-IL-17 or 23). Many of these patients had personal and family history of atopy. Eczematous reactions developed between a few days and 3 years after initiation of the biologic drug. The highest proportion of cases associated with eczematous reactions during biologic treatments was seen in patients on anti-IL-17 agents, including brodalumab. We observed that eczema rapidly remitted without relapse in all patients who switched to anti-IL-23 agents. Among our cases, fast responders to psoriasis therapy seem to have more persistent eczematous reactions. Patients with psoriasis and a history of atopic dermatitis should be treated with an IL-23 inhibitor due to its efficacy in psoriasis and the rarely reported eczematous reaction.

Periocular Manifestation in Acute Atopic Dermatitis in a Paediatric Patient. A Case Report

Atopic dermatitis is a chronic skin condition characterized by itchy, scaly, and crusted lesions, most commonly affecting infants and children. The condition presents with intense pruritus and a chronic course with exacerbations. Periorbital involvement is expected due to the thin and sensitive skin in this area, and the inflammation can be exacerbated by rubbing or scratching. This case reports a 5-year-old girl with bilateral periorbital inflammation that had been present for 4 hours. She had a history of atopic dermatitis and no known surgical history or medication allergies but was allergic to shellfish. No medication or topical cream was administered for the described episode. Upon waking up, she presented with newly developed periorbital inflammation. She had not consumed any food to which she was known to be allergic, and there had been no increase in eyelid scratching. There was no recollection of contact with any toxic agents. During the physical examination, erythematous scaly plaques were observed on both cheeks, chin, and neck, and periorbital inflammation accompanied by eyelid and periorbital Dennie-Morgan fold. The primary diagnosis was periorbital atopic dermatitis in the context of an acute atopic dermatitis flare-up. The prescribed treatment included prednisolone acetate (Estilsona) for five days and pimecrolimus for the atopic dermatitis. Atopic dermatitis is a complex condition with a multifactorial aetiology, and its management can be challenging. Further research is needed to develop more effective treatments for atopic dermatitis.

Allergic Contact Dermatitis to Octyl Cyanoacrylate Skin Glue After Surgical Wound Closure: A Systematic Review.

The rising incidence of allergic contact dermatitis (ACD) after cyanoacrylate adhesive use necessitates a comprehensive understanding of its clinical presentations, risk factors, and management. In this systematic review, we conducted an exhaustive search following PRISMA guidelines within Medline and PubMed databases to identify studies reporting cases of ACD resulting from cyanoacrylate adhesive application in wound closure. A total of 47 studies, covering 193 ACD cases, were included in our analysis. These cases involved 35 male, 120 female patients, and 38 cases without gender information (M:F ratio = 1:3.43), with ages ranging from 7 to 92 years (mean age 43.9 years). The majority of cases (n = 140) were part of 6 orthopedic studies, focusing on joint replacements (n = 68), orthopedic surgeries (n = 38), and breast surgeries (n = 29). The remaining 58 cases encompassed various surgical procedures. Common clinical manifestations included swelling, pruritic rash, erythema, vesicles, and itching around the surgical sites, typically appearing around 10 days post-adhesive application (within a range of 6 hours to 6 weeks). Patients with prior exposure to 2-octyl cyanoacrylate tended to exhibit earlier symptoms. Similar rates of dermatitis were observed across different adhesive brands, suggesting brand independence. Treatment strategies involved adhesive removal, administration of steroids and antihistamines, meticulous wound care, and, in some cases, surgical intervention. Notably, 3.1% of the 193 cases required surgical intervention. Risk factors, including a history of atopic dermatitis, high body mass index, diabetes, prior adhesive exposure, and surgical history, were identified in the studies. Patch tests confirmed 2-octyl cyanoacrylate as the allergen in 21 studies. Our review aims to enhance health care professionals' understanding of ACD resulting from the use of cyanoacrylate adhesive, facilitating improved postsurgical management and prevention strategies. Recognizing diverse risk factors, understanding varying clinical presentations, distinguishing ACD from infection, and employing appropriate treatment approaches are essential for achieving optimal outcomes in such cases.

P33 A lichenoid eruption and severe eczema in association with IMAGe syndrome

Abstract IMAGe syndrome is a rare genetic disorder. IMAGe is an acronym for; (1)Intrauterine restricted growthMetaphyseal dysplasiaCongenital adrenal hypoplasiaGenitourinary abnormalities in males (cryptorchidism, micropenis, and hypospadias) Diagnosis is established by molecular genetic testing with heterozygous CDKN1C pathogenic mutation or a proband with suggestive findings in the PCNA (proliferating cell nuclear antigen)- binding domain of the maternally expressed allele. Additional features include characteristic facies (frontal bossing), developmental delay, immunodeficiency, osteoporosis and scoliosis. Severe, early onset eczema has been described in association with this syndrome. (2) We present the case of a 15-year-old boy with proven IMAGe syndrome, longstanding history of atopic dermatitis, and new onset lichenoid eruption on the forearms.

A CHILD CASE OF EGOMA (PERILLA FRUTESCENS) ALLERGY DUE TO SCHOOL LUNCH, PROBABLY CAUSED BY PERCUTANEOUS SENSITIZATION

Herein, we report the case of a 7-year-old girl with a history of atopic dermatitis because of infancy. Her grandfather grew Egoma (Perilla frutescens), and her family frequently consumed food items prepared using Egoma; however, she never consumed them because she did not enjoy these food items; she experienced vomiting, facial swelling, and oral discomfort upon ingesting Egoma during school lunch for the first time. Her food oral challenge test was positive, as well as a skin-prick test with sesame powder. Egoma antigen protein was extracted and reacted with patient serum by immunoblotting, which detected a positive band of approximately 26kDa. She was brought up in an environment with high exposure to Egoma; hence, she most likely developed an allergy to Egoma because of percutaneous sensitization. This is the first time an Egoma allergen analysis has been conducted in Japan, and we consider it to be a valuable case.

Mycosis fungoides unveiled following dupilumab treatment in a patient with a history of atopic dermatitis. Usefulness of HFUS in monitoring skin features. A review with a case report

Mycosis fungoides unveiled following dupilumab treatment in a patient with a history of atopic dermatitis. Usefulness of HFUS in monitoring skin features. A review with a case report

Early-Life Risk Factors and Clinical Features of Food Allergy Among Thai Children.

Background: Food allergy affects 1%-10% of children under five worldwide, with genetic and early-life factors playing a primary role. Reported factors include a family history of allergic diseases, personal atopic dermatitis, cesarean section, dietary restrictions during pregnancy and lactation, and the timing of introducing solid foods. This study was aimed at identifying various factors associated with food allergy and evaluate each food allergy's clinical features. Methods: We conducted a case-control study with a participant ratio of 1:2 between cases and controls. Data were gathered from both groups of participants, and questionnaires included living area, sex, and natal history (birth details, maternal diet during pregnancy and breastfeeding, feeding history during infancy, family history of atopic diseases, and household smoking). Results: All 72 cases with food allergy and 145 controls were included in the study. Term birth comprised a protective factor for developing food allergy (adjusted odds ratio [aOR] 0.213, p value 0.022). In contrast, personal atopic dermatitis (aOR 20.097, p value 0.001) and a family history of allergic disease constituted risks (aOR 3.183, p value 0.002). Food allergy was unrelated to cesarean section, low birth weight, dietary restrictions during lactation and pregnancy, exclusive breastfeeding, or the early introduction of complementary foods. The three most common food allergens were egg white (40.2%), wheat (34.7%), and cow's milk (30.5%), respectively. Conclusions: In this study, risk factors associated with food allergy comprised a personal history of atopic dermatitis and a family allergic disease, which may be used as predictive factors for developing food allergy among Thai children.

Atopic Dermatitis Associated Retinal Detachment and Retinal Vasculitis: A Case Report

Atopic dermatitis is usually associated with various ocular complications. We report a 21-year-old Chinese male who presented to our ophthalmology clinic with bilateral retinal detachment and cataracts. The patient had a clear medical history of atopic dermatitis, which had been diagnosed eight years earlier and had been treated with loratadine and pimecrolimus. Cataract surgery was performed for both eyes, combined with scleral buckling for the right eye and pars plana vitrectomy for the left eye. During postoperative follow-up, fundus fluorescein angiography showed retinal vasculitis in both eyes and macular edema in the left eye, which coincided with an exacerbation of atopic dermatitis. Macular edema improved after four months of regular dupilumab treatment in the dermatology department. The ocular condition remained stable three years postoperatively.

A case of unilateral epidermal nevi complicated by atopic dermatitis treated with dupilumab

Epidermal Nevus Syndrome (ENS) is a congenital disorder characterized by skin lesions called epidermal nevi. This condition typically appears at birth or in infancy. However, a case of adult‐onset epidermal nevi was reported in a 36‐year‐old male with a history of atopic dermatitis (AD) and skin abnormalities on the right side of his body. He had been using topical steroids for AD but eventually started dupilumab treatment at age 41. The treatment led to significant improvements in his skin condition, including a reduction in erythema and scaling. Laboratory tests also showed improvement in serum Immunoglobulin E (IgE) levels and other markers. We report with a literature review.

Lung sound analysis for predicting recurrent wheezing in preschool children

BackgroundIn young healthy children, assessing airflow limitation may be difficult because of the narrowing of the airways, which is a pathology of asthma, and responsiveness to bronchodilators. ObjectiveWe investigated whether lung sound analysis could predict the development of recurrent wheezing (RW), one of the signs of asthma. MethodsIn healthy children aged 3 to 24 months, we recorded and analyzed lung sounds before and after inhalation of bronchodilators and conducted a questionnaire survey. The children were followed up and assessed for the development of RW at 3 years of age. ResultsOf the 62 patients analyzed, 19 (30.6%) developed RW. The parameters RPF50 and RPF75, calculated by lung sound analysis, were lower in the RW group, with odds ratios (95% CI) of 0.77 (0.61–0.98) and 0.81 (0.66–0.99), respectively. The change rate of lung sound analysis parameters after bronchodilator inhalation was not different among all participants; however, in the subgroup of children with a history of atopic dermatitis, B4/AT and ΔRPF50 were elevated in the RW group (P = .015 and P = .041, respectively). In the subgroup of children with total IgE >20 kUA/L, the sensitivity and specificity (95% CI) for predicting the development of RW were 85.7% (48.7-99.3) and 68.8% (44.4-85.8), respectively, when the cutoff value of ΔRPF50 was set at 10.5%. ConclusionThe lung sound analysis method allows noninvasive assessment of the airway, including airway hypersensitivity, in young children and may predict the risk of developing RW.

Real-world effectiveness of dupilumab in patients with asthma: Findings from the US ADVANTAGE study

BackgroundDupilumab is approved as an add-on maintenance therapy for patients (≥6 years) with moderate-to-severe asthma. Better understanding of real-world effectiveness is needed. ObjectiveTo characterize the real-world effectiveness of dupilumab in asthma management. MethodsThis retrospective study included patients (≥12 years of age) diagnosed with asthma, initiating dupilumab between November 2018 and September 2020. The study used a US electronic medical record database (TriNetX Dataworks, Cambridge, Massachusetts). Asthma exacerbation rates before and after the initiation of dupilumab were analyzed using generalized estimating equations models with Poisson probabilistic link to estimate incidence rate ratios (IRRs). Sensitivity analyses were conducted based on previous exacerbation data, eosinophil levels, history of atopic dermatitis or chronic rhinosinusitis with nasal polyps, previous use of biologics, and presence of SARS-CoV-2 (COVID-19). ResultsA total of 2400 patients initiating dupilumab met all study criteria. After initiation of dupilumab, risk of asthma exacerbation was reduced by 44% (IRR, 0.56; 95% CI, 0.47-0.57; P = <0.0001) and systemic corticosteroid prescriptions by 48% (IRR, 0.52; 95% CI, 0.48, 0.56; P = <0.0001) compared with those before initiation of dupilumab. Adjustment for COVID-19 showed a greater reduction in asthma exacerbations (IRR, 0.50; 95% CI, 0.45-0.55; P = <0.0001). ConclusionCurrent real-world efficacy evidence indicates that dupilumab reduces asthma exacerbations and total systemic corticosteroid prescriptions in clinical practice. The effectiveness of dupilumab was observed independent of exacerbation history, eosinophil levels, or COVID-19 impact.