Publications by authors named "Kanokvalai Kulthanan"

117 Publications

Adrenaline autoinjector is under-prescribed in typical cold urticaria patients living in tropical climate countries.

Qatar Med J 2022 24;2022(2):19. Epub 2022 Mar 24.

Allergy Unit, Second Department of Dermatology and Venereology, Urticaria Center of Reference and Excellence (UCARE), National and Kapodistrian University of Athens, University General Hospital "Attikon", Athens, Greece.

The diagnosis of typical cold urticaria (ColdU) relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). Till date, it is largely unclear how often patients with ColdU receive adrenaline treatment and are provided with an adrenaline autoinjector (AAI). An international, cross-sectional study, COLD-CE (i.e., comprehensive evaluation of ColdU and other cold-induced reactions), was carried out at 32 UCAREs. Detailed histories were taken and CST with an ice cube and/or TempTest performed. ColdA was defined as an acute cold-induced (i.e., by cold water, air, or surfaces) involvement of the skin and/or visible mucosal tissue and at least one of the symptoms (cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms). Of the 551 ColdU patients, 75% ( = 412) had a positive CST. Of them, concomitant chronic spontaneous urticaria was diagnosed in 10%. Of 372 patients with stand-alone ColdU, 69% were women and 91% adults. Their median age was 36 (IQR 26 - 48) years. Patients were also categorized into residents of countries with a tropical ( = 33), temperate ( = 264), or cold ( = 75) climate (Table 1: R13C1, R17C1, R21C1). AAI was more often prescribed to residents of temperate than tropical countries (30% vs. 12%,  = .038; Table 1: R31C1), although the frequency of ColdA did not significantly differ between these countries (44% vs. 42%,  = 1.000; R29C2). Residents of tropical countries had a higher frequency of ColdA induced by cold air than residents of temperate (36% vs. 12%,  = .001; R29C4) or cold (36% vs. 12%,  = .007; R25C4) countries. Cardiovascular manifestations induced by cold air were diagnosed in 33% ( = 11) of residents of tropical countries, but only 18% ( = 2) and 36% ( = 4) of them had received adrenaline and AAI, respectively (R13 - 15C7). Furthermore, hypotension and/or loss of consciousness induced by cold air occurred in 18% ( = 6) of patients, but only 17% ( = 1) received adrenaline (R13 - 14C10). ColdA was induced by complete cold water immersion in 9% ( = 3) of patients, and none of them received adrenaline treatment nor AAI (R13 - 15C3). Our findings suggest that ColdA is undertreated and call for changes in ColdU management.
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http://dx.doi.org/10.5339/qmj.2022.fqac.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284591PMC
March 2022

Differential cytokine profiles produced by anti-epileptic drug re-exposure of peripheral blood mononuclear cells derived from severe anti-epileptic drug patients and non-allergic controls.

Cytokine 2022 Sep 27;157:155951. Epub 2022 Jun 27.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reactions with eosinophilia and systemic symptoms (DRESS) are the most common severe cutaneous adverse drug reactions (SCARs). Anti-epileptic drugs are one of the most common drugs causing SCARs. Cytokine profiles of SCARs during culprit drug exposure have never been characterized. This study aimed to identify cytokine patterns between SCARs and non-SCARs in epilepsy patients and the patterns of DRESS and SJS/TEN. Epilepsy patients that showed allergic responses to anti-epileptic drugs that manifested as SJS/TEN or DRESS were recruited. Epilepsy patients with no drug allergy symptoms and healthy people were also recruited as control groups. Peripheral blood mononuclear cells (PBMCs) were isolated and co-cultured with assigned anti-epileptic drugs according to the lymphocyte transformation test (LTT). LTT and measurement of cytokine levels in supernatants were performed on day six of cell cultivation. This study identified different cytokine expression patterns between SCAR and non-SCAR in epilepsy patients. Significant levels of IL-10, IL-12, IL-17, and GM-CSF were detected in non-SCAR epilepsy. However, the levels of IL-2, IL-5, IL-13, and IFN-gamma were significantly higher in supernatants of PBMCs of DRESS cultivated with AEDs relative to those of SJS/TEN. These cytokine levels were positively correlated with the cell proliferation index. Production of IL-5 and IL-13 was a unique characteristic of DRESS PBMCs. This study was the first to demonstrate distinct differences in cytokine levels between SCAR and non-SCAR PBMCs in epilepsy, which could help explain the immune-pathomechanism of drug hypersensitivity in SCARs. Different patterns of cytokine production and cell proliferation between DRESS and SJS/TEN in AED hypersensitivity were also demonstrated. Production of IL-5 and IL-13 might be a promising marker to define drug hypersensitivity in DRESS.
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http://dx.doi.org/10.1016/j.cyto.2022.155951DOI Listing
September 2022

Food-Dependent Exercise-Induced Wheals, Angioedema, and Anaphylaxis: A Systematic Review.

J Allergy Clin Immunol Pract 2022 Jun 22. Epub 2022 Jun 22.

Institute of Allergology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany. Electronic address:

Background: Food-dependent exercise-induced wheals, angioedema, and anaphylaxis remain insufficiently characterized.

Objective: We systematically reviewed the literature on clinical manifestations, laboratory investigations, culprit foods, triggering exercise, comorbidities, and treatment outcomes.

Methods: Using predefined search terms and Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) recommendations, we searched 3 electronic databases to identify relevant literature published before July 2021.

Results: Of 722 patients (median age 25 years; 55.4% male) from 231 studies (43 cohort studies, 15 cases series, and 173 case reports), 79.6% and 3.7% had anaphylaxis with and without wheals and/or angioedema, respectively. The remaining 16.6% had wheals and/or angioedema without anaphylaxis. The duration from eating to exercising and from exercising to symptom onset ranged from 5 minutes to 6 hours (median 1 hour) and from 5 minutes to 5 hours (median 30 minutes), respectively, and virtually all patients exercised within 4 hours after eating and developed symptoms within 1 hour after exercising. Wheat was the most common culprit food. Running was the most common trigger exercise. Most patients were atopic, and 1 in 3 had a history of urticaria. Aspirin and wheat-based products were the most frequent augmenting factors. On-demand antihistamines, corticosteroids, and epinephrine were commonly used and reported to be effective. Patients who stopped eating culprit foods before exercise no longer developed food-dependent exercise-induced allergic reactions.

Conclusions: Food-dependent exercise-induced allergic reactions are heterogeneous in their clinical manifestations, triggers, and response to treatment. Patients benefit from avoidance of culprit foods before exercise, which highlights the need for allergological diagnostic workup and guidance.
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http://dx.doi.org/10.1016/j.jaip.2022.06.008DOI Listing
June 2022

A web-based survey on the behavior of moisturizer used in adults with and without atopic dermatitis in Thailand.

Asian Pac J Allergy Immunol 2022 May 22. Epub 2022 May 22.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Moisturizers play an important role in restoring the skin barrier. They should be used to treat and prevent eczema, especially in atopic dermatitis (AD).

Objective: To evaluate the factors that influence selection of moisturizers in adult patients with AD and without it. Usage behavior between the two groups was also determined.

Methods: A cross-sectional web-based survey was performed.

Results: A total of 1,195 participants with mean age of 46.5 ± 14.5 were enrolled. Fifty participants (4.2%) met the William's criteria for AD diagnosis. Most participants reported using moisturizer every day or two times per day. A non-sticky moisturizer, followed by pleasant odor were considered important properties. For choosing a moisturizer, personal satisfaction was the most common answer given by participants. The most common locations that participants applied moisturizer were the extremities (85.1%) and face (84.9%). Physicians' suggestion was also a significant factor that led to moisturizer use by AD patients but it was not significant in the non-AD group (29.2% vs 14.7%, p = 0.007, OR 2.4). A pH of 5.5 and the anti-inflammatory property were important factors in choosing a moisturizer in the AD group. Both AD and non-AD participants preferred liquid soap over bar soap in daily life.

Conclusions: Our results showed that most participants have basic knowledge of how to use a moisturizer. Physicians' suggestion influenced the selection of moisturizer in AD patients. Thus, physicians should continue to educate in order to achieve good clinical outcomes.
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http://dx.doi.org/10.12932/AP-291221-1291DOI Listing
May 2022

A Systematic Review of Aquagenic Urticaria-Subgroups and Treatment Options.

J Allergy Clin Immunol Pract 2022 Aug 6;10(8):2154-2162. Epub 2022 May 6.

Institute of Allergology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany. Electronic address:

Background: Aquagenic urticaria (AquaU) is a rare variant of chronic inducible urticaria where wheals occur after skin contact with water. Information on clinical manifestations and treatment outcomes is limited, which makes the management of AquaU challenging.

Objective: To systematically review disease features and relevant triggers of AquaU and patients' response to treatment.

Methods: Related articles were searched by use of the terms "aquagenic urticaria" and "aquagenic angioedema" until June 2021 and reviewed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations.

Results: A total of 77 patients with AquaU were investigated in 59 studies including 47 case reports and 12 case series. AquaU predominantly presented in women (47 patients, 61%), and the mean age of onset of the disease was 19.6 ± 10.8 years (range: 0-54 years). Wheals commonly occurred in localized areas and regardless of the water temperature. Based on the reviewed evidence, AquaU can be classified as familial AquaU (FAquaU, 18.2%) and acquired AquaU (AAquaU, 81.8%). Although many treatments were used in both subtypes of AquaU, the use of second-generation H antihistamines (2AH) was reported most often to achieve marked improvement in both subtypes. The use of topical therapies in AquaU, which most commonly use hydrophobic vehicles, is poorly documented and of controversial efficiency.

Conclusions: AquaU is proposed to be classified into 2 subtypes, FAquaU and the more common AAquaU. Treatment with a 2AH is recommended as the first-line treatment for both types of AquaU. Further studies are required to fill knowledge gaps.
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http://dx.doi.org/10.1016/j.jaip.2022.04.033DOI Listing
August 2022

Rituximab-induced psoriasis in a patient with pemphigus foliaceous: A case report and literature review.

J Dermatol 2022 08 5;49(8):e251-e252. Epub 2022 Apr 5.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

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http://dx.doi.org/10.1111/1346-8138.16367DOI Listing
August 2022

Development and Evaluation of an In-House ELISA to Detect Anti-FcR1 IgG Autoantibodies in Chronic Spontaneous Urticaria Patients.

J Immunol Res 2022 25;2022:6863682. Epub 2022 Feb 25.

Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Association between chronic spontaneous urticaria (CSU) and autoimmunity has been well documented. Autologous serum skin testing could support the autoimmune etiology of CSU, whereas it is difficult to interpret and could not be performed on antihistamine omitted patients. It was found that immunoglobulin G (IgG) autoantibodies (autoAbs) against high-affinity IgE receptor (FcR1) were suggested as a potential trigger in the pathogenesis of CSU. Although many ELISA protocols have been developed to detect these autoAbs, they lacked validation or a reliable cut-off point. We, therefore, aimed to develop a validated ELISA with a reliable cut-off point to quantitate IgG anti-FcR1 autoAbs for CSU.

Methods: We developed an in-house ELISA to quantitate IgG anti-FcR1 autoAbs. Sera from 233 CSU patients and 25 healthy people were used to test with ELISA. The cut-off point was obtained from the results subjected to analyze with receiver operating characteristic (ROC) analysis. ELISA was validated with 116 CSU patients and 150 healthy donors.

Results: ELISA revealed that healthy people had a basal level of IgG anti-FcR1 autoAbs, whereas their levels were significantly lower than autoAbs levels in CSU patients. ROC analysis of ELISA determined the cut-off point at 936.7 ng/ml. Our ELISA was validated and provided excellent sensitivity and specificity at 98.28% and 92.67%, respectively.

Conclusion: Our ELISA could detect significant levels of IgG anti-FcR1 autoAbs in CSU, supporting that these autoAbs were associated with CSU etiology. Our validated ELISA with the reliable cut-off point provided excellent accuracy at 95.11% (98.28% sensitivity and 92.67% specificity). Our ELISA could be an alternative test benefit for the patient who is unable to omit antihistamine treatment.
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http://dx.doi.org/10.1155/2022/6863682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8896930PMC
April 2022

Risk factors for systemic reactions in typical cold urticaria: Results from the COLD-CE study.

Allergy 2022 Jul 23;77(7):2185-2199. Epub 2021 Dec 23.

Urticaria Center of Reference and Excellence (UCARE), Center of Allergy and Immunology, Clinical State Hospital 52, Moscow Ministry of Healthcare, Moscow, Russian Federation.

Background: Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU.

Methods: An international, cross-sectional study COLD-CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest performed. ColdA was defined as an acute cold-induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms.

Results: Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold-induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes.

Conclusion: ColdA is common in typical ColdU. High-risk patients require education about their condition and how to use an adrenaline autoinjector.
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http://dx.doi.org/10.1111/all.15194DOI Listing
July 2022

Recommendations for Using Over-The-Counter Products as Adjunctive Acne Care in Asian Phototypes: Improving Treatment Outcomes and Managing Side Effects.

J Drugs Dermatol 2021 Nov;20(11):1213-1221

Background: Acne vulgaris (acne) is a common inflammatory skin disorder prevalent among all ethnic groups. This review aimed to investigate the current literature regarding the potential benefit of over-the-counter (OTC) adjuncts (eg, moisturizers, cleansers) for acne patients focusing on Asian phenotypes.

Methods: An online procedure was employed to review the role of adjunctive OTC acne treatment. A panel consisting of dermatologists with expertise in treating Asian acne patients participated in a pre-meeting survey that collected information regarding their recommendation habits for OTC products in acne patients. Recommendations on using OTC products as an adjunct for treating acne in Asians are based on the pre-meeting survey results, evidence from literature presented during a series of plenary lectures, and discussions conducted during a stepwise program of sessions.

Results: Many topical treatments have been associated with adverse events (AEs) (eg, skin dryness, erythema, scaling, stinging, burning, pruritus). Multiple studies on topical acne treatments have found that Asians display greater sensitivity and less tolerability than Caucasians to acne treatment. Skincare as an adjunct to acne treatment may reduce dryness or irritation, particularly important in Asians with acne.

Conclusions: Advisors agreed that cleansers and moisturizers should be considered for their beneficial adjunctive role in the armamentarium of acne treatment and maintenance strategies. J Drugs Dermatol. 2021;20(11): 1213-1221. doi:10.36849/JDD.6259.
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http://dx.doi.org/10.36849/jdd.6259DOI Listing
November 2021

The Correlations between Clinical Features, Dermoscopic and Histopathological Findings, and Treatment Outcomes of Patients with Pitted Keratolysis.

Biomed Res Int 2021 25;2021:3416643. Epub 2021 Oct 25.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Pitted keratolysis (PK) is a superficial bacterial infection diagnosed mainly by clinical manifestations. Current data on its dermoscopic and histopathological findings, and the correlation of those findings, are limited.

Objectives: To evaluate the clinical manifestations, dermoscopic, and histopathological findings of PK and to determine the correlations.

Methods: Forty naval cadets with PK and five cadets with normal feet were enrolled this cohort study and provided informed consent. Dermoscopy was independently applied and evaluated by 2 dermatologists. Shave biopsies were performed on 37 patients with PK.

Results: Pits were the most common dermoscopic finding (88.1%). The dermoscope had more sensitivity for the detection of PK than the naked eye examinations. Apart from the pits and the presence of bacteria, the most common histopathological finding for PK was color alteration of keratin. The presence of bacteria correlated with interrupted dermatoglyphic lines and the color alteration of keratin. Moreover, the presence of bacteria at the base of pits was related to worse treatment outcomes.

Conclusions: Dermoscopy is a useful tool for PK diagnosis. Color alteration of keratin is another histopathological finding for PK. The presence of bacteria is associated with worse treatment outcomes.
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http://dx.doi.org/10.1155/2021/3416643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560252PMC
January 2022

The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria.

Allergy 2022 03 20;77(3):734-766. Epub 2021 Oct 20.

Service d'allergie, Centre Hospitalier Université Laval/Centre Hospitalier Universitaire de Québec, Québec, Quebec, Canada.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
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http://dx.doi.org/10.1111/all.15090DOI Listing
March 2022

Adult female acne: Clinical characteristics and factors significantly associated with polycystic ovary syndrome.

Australas J Dermatol 2021 Nov 23;62(4):e532-e538. Epub 2021 Aug 23.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Adult female acne (AFA) may be different from adolescent acne, and may be a sign of polycystic ovary syndrome (PCOS). The objective of the study was to investigate the clinical characteristics of AFA, and the factors significantly associated with PCOS in AFA.

Methods: AFA patients aged 25 years or older were enrolled. History taking and dermatologic examinations were performed by dermatologists. PCOS was diagnosed by gynaecologists. Perimenopausal acne (aged 45 years or older) and the Dermatology Life Quality Index (DLQI) were also evaluated.

Results: Among 208 patients, mean age was 31.8 ± 7.1 years and 47.1%, 26.9%, and 26% had persistent, late-onset, and recurrent acne, respectively. The common aggravating factors included pre-menstruation (72.6%) and stress (53.8%). Recurrent acne was significantly aggravated by cosmetic products. Higher body mass index (BMI) was positively correlated with acne severity. Acne lesions were predominately located on both cheeks (87.0%) and at the perioral area (81.7%). PCOS was identified in 48.1%. Younger age (≥25 to <33 years), premenstrual flare, and irregular menstruation, but not hirsutism or androgenetic alopecia, were associated with PCOS in univariate and multivariate analysis. Perimenopausal acne was identified in 6.7%. The total mean DLQI score was 8.0 ± 5.4 (range from 0 to 23).

Conclusions: Persistent acne with moderate severity was common in AFA patients and higher BMI was associated with acne severity. PCOS should be screened in AFA patients with younger age, premenstrual flare, and irregular menstruation.
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http://dx.doi.org/10.1111/ajd.13700DOI Listing
November 2021

Use of facial care products and frontal fibrosing alopecia: Coincidence or true association?

J Dermatol 2021 Oct 15;48(10):1557-1563. Epub 2021 Jul 15.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

The increasing incidence of frontal fibrosing alopecia (FFA) suggests that environmental factors may be related to the pathogenesis. Recent studies reported potential association between the use of facial care products and FFA. The aim of this study was to investigate the possible association between the use of facial care products and FFA in Asian females. A total of 250 females (50 FFA patients, 100 pattern hair loss [PHL] patients, and 100 normal controls) were recruited and completed a questionnaire to obtain information approximately facial care products and various environmental factors. Our study revealed the use of moisturizer to be significantly higher in the FFA group compared to normal controls (p < 0.001), and sunscreen use was significantly higher in the PHL group than in the control group (adjusted p < 0.001). Subjects with FFA or PHL reported significantly higher use of both sunscreen and moisturizer compared to normal controls (p < 0.001). This study focused on Asian populations. Our results revealed a high frequency of moisturizer and sunscreen use in both FFA and PHL among Asian females. Therefore, the use of facial care products appears not to be linked to the true disease mechanism of FFA, but rather to appearance-related concerns of patients.
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http://dx.doi.org/10.1111/1346-8138.16063DOI Listing
October 2021

Patient Recovery from COVID-19 Infections: Follow-Up of Hair, Nail, and Cutaneous Manifestations.

Biomed Res Int 2021 19;2021:5595016. Epub 2021 Jun 19.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: COVID-19 is a pandemic disease worldwide. Although cutaneous manifestations may present in affected patients, there have been limited studies on the cutaneous findings and hair and nail abnormalities after discharge.

Objective: To establish the cutaneous manifestations, hair and scalp disorders, and nail abnormalities in patients who recovered from COVID-19 infections.

Methods: A retrospective chart review and telephone interviews were conducted to determine the cutaneous manifestations, hair and scalp disorders, and nail abnormalities of patients aged over 18 years who were diagnosed with COVID-19 infections at Siriraj Hospital, Bangkok, Thailand, between January and June 2020.

Results: Ninety-three patients with prior COVID-19 infections participated in the study. The COVID-19 severity had been mild for most (71%). Cutaneous manifestations were reported in 8 patients (8.6%), with the common skin conditions being maculopapular rash and urticaria. The onsets of the skin conditions were before admission (1%), during admission (4.3%), and after discharge (3.2%). Increased hair shedding was also reported in 22 patients (23.7%), with a female predominance. Three patients were affected during admission, while the others were affected after discharge. The patients with moderate, severe, and critical COVID-19 infections experienced significantly more hair shedding than those with asymptomatic and mild diseases. Only 2 patients with mild COVID-19 disease reported nail abnormalities (chromonychia and brittle nails).

Conclusions: Cutaneous manifestations, hair disorders, and nail abnormalities can occur in patients with COVID-19 after their discharge from hospital. Patients should therefore be followed up in anticipation of dermatological problems.
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http://dx.doi.org/10.1155/2021/5595016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238562PMC
July 2021

Clinical practice guidelines for the diagnosis and management of atopic dermatitis.

Asian Pac J Allergy Immunol 2021 Sep;39(3):145-155

Division of Dermatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Atopic dermatitis (AD), a chronic, relapsing dermatitis, is characterized by dry and pruritus skin in patients with a personal or family history of atopy. It affects up to 20% of children and 1-3% of adults in most countries worldwide, and leads to significant treatment costs and morbidity. These guidelines are developed in accordance with evidence-based publications and expert opinions. Following simple algorithms, the guidelines aim to assist adult and pediatric physicians in the better care of patients with AD. As with other diseases, there have been several diagnosis criteria proposed over time. Nonetheless, the classical Hanifin and Rajka criterion with no pathognomonic laboratory biomarkers is still the most widely used worldwide for the diagnosis of AD. The management of AD must be considered case by case to provide suitable care for each patient. Basic therapy is focused on avoiding specific/unspecific provoking factors and hydrating skin. Topical anti-inflammatory treatments such as glucocorticoids and calcineurin inhibitors are suggested for disease flare, and proactive therapy is best for long-term control. Other therapies, including antimicrobial agents, systemic antihistamines, systemic anti-inflammatory agents, immunotherapy, phototherapy, and psychotherapy, are reviewed in these guidelines. Crisaborole, a new topical phosphodiesterase 4 inhibitor, can be used twice daily in AD patients over three months old. Dupilumab, a biological drug for patients with moderate-to-severe AD, may be considered in patients with no improvement from other systemic treatments.
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http://dx.doi.org/10.12932/AP-010221-1050DOI Listing
September 2021

Reply to "Proposal for a new classification of vibratory urticaria/angioedema".

J Allergy Clin Immunol Pract 2021 06;9(6):2543-2544

Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany (corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2021.02.037DOI Listing
June 2021

The Pathogenesis of Chronic Spontaneous Urticaria: The Role of Infiltrating Cells.

J Allergy Clin Immunol Pract 2021 06 3;9(6):2195-2208. Epub 2021 Apr 3.

Divison of Pulmonary and Critical Care Medicine and Allergy and Immunology, Department of Medicine, The Medical University of South Carolina, Charleston, SC. Electronic address:

Chronic spontaneous urticaria is characterized by a perivascular non-necrotizing cellular infiltrate around small venules of the skin. It consists primarily of CD4(+) lymphocytes, a prominence of the T helper (Th)2 subtype but also Th1 cells, with Th17 cell-derived cytokines elevated in plasma. There are also neutrophils, eosinophils, basophils, and monocytes. Chemokines derived from mast cells and activated endothelial cells drive the process. Although the role of the cellular infiltrate has not previously been addressed, each constituent can contribute to the overall pathogenesis. It is of interest that CSU responds to corticosteroid, yet, short-term steroids do not affect autoimmunity or degranulation of mast cells, and act on margination of cells along the endothelium and chemotaxis to enter the surrounding dermis. In this review, we address each cell's contribution to the overall inflammatory response, as it is currently understood, with a view toward development of therapeutic options that impede the function of critical cells and/or their secretory products.
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http://dx.doi.org/10.1016/j.jaip.2021.03.033DOI Listing
June 2021

A randomized controlled trial to compare the effectiveness and safety of adsorbent lotion containing tapioca starch, spent grain wax, Butyrospermum parkii extract, argania spinosa kernel oil, aloe barbadensis, rosehip oil, and allantoin with a low-potency topical corticosteroid in the treatment of intertrigo.

J Cosmet Dermatol 2022 Feb 18;21(2):679-688. Epub 2021 Apr 18.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Intertrigo is an inflammatory skin-fold condition. Candida infections may occur concurrently or afterward. Topical corticosteroids may reduce inflammation but exacerbate Candida infections. The treatment is contentious.

Objective: To evaluate the efficacies and safety of adsorbent lotion containing tapioca starch, spent grain wax, Butyrospermum parkii extract, argania spinosa kernel oil, aloe barbadensis, rosehip oil, and allantoin for the treatment of mild-to-moderate intertrigo, relative to 1% hydrocortisone cream.

Methods: This randomized, double-blinded study enrolled 40 intertrigo patients. Twice daily, 20 patients applied adsorbent lotion while the remainder used 1% hydrocortisone cream. Efficacy evaluation, skin biophysical measurements, skin tolerability, safety, and visual analog scale (VAS) patient-satisfaction scores were evaluated at baseline and Week 2.

Results: The adsorbent lotion showed higher complete cure rates for color, partial epidermal loss, papules/pustules/vesicles/patches, dryness, and scaling than the corticosteroid without statistical significance. Adsorbent lotion demonstrated significantly higher reduction in pruritus than the corticosteroid treatment. Reduction of erythema level using Mexameter and VAS patient-satisfaction scores were not statistically different between adsorbent lotion and hydrocortisone cream. No adverse effects or superimposed infections were reported.

Conclusions: The anti-inflammatory efficacies of adsorbent lotion and low-potency steroid were equivalent. The lotion was safe and produced excellent pruritus reduction. Patient satisfaction was high.
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http://dx.doi.org/10.1111/jocd.14125DOI Listing
February 2022

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.

Allergy 2021 03 29;76(3):816-830. Epub 2020 Dec 29.

Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology and Venereology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Introduction: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown.

Aim: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19.

Materials And Methods: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences.

Results: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19.

Conclusions: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.
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http://dx.doi.org/10.1111/all.14687DOI Listing
March 2021

Cold urticaria - What we know and what we do not know.

Allergy 2021 04 24;76(4):1077-1094. Epub 2020 Dec 24.

Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Cold urticaria (ColdU) is a common form of chronic inducible urticaria characterized by the development of wheals, angioedema or both in response to cold exposure. Recent research and guideline updates have advanced our understanding and management of ColdU. Today, its pathophysiology is thought to involve the cold-induced formation of autoallergens and IgE to these autoallergens, which provoke a release of proinflammatory mediators from skin mast cells. The classification of ColdU includes typical and atypical subtypes. We know that cold-induced wheals usually develop on rewarming and resolve within an hour and that anaphylaxis can occur. The diagnosis relies on the patient's history and cold stimulation testing. Additional diagnostic work-up, including a search for underlying infections, should only be done if indicated by the patient's history. The management of ColdU includes cold avoidance, the regular use of nonsedating antihistamines and the off-label use of omalizumab. However, many questions regarding ColdU remain unanswered. Here, we review what is known about ColdU, and we present important unanswered questions on the epidemiology, underlying pathomechanisms, clinical heterogeneity and treatment outcomes. Our aim is to guide future efforts that will close these knowledge gaps and advance the management of ColdU.
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http://dx.doi.org/10.1111/all.14674DOI Listing
April 2021

A Double-Blinded, Randomized, Vehicle-Controlled Study of the Efficacy of Moisturizer Containing Licochalcone A, Decanediol, L-Carnitine, and Salicylic Acid for Prevention of Acne Relapse in Asian Population.

Biomed Res Int 2020 16;2020:2857812. Epub 2020 Oct 16.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Many topical agents are available for treating the acute phase of acne; however, few agents have been proven beneficial during the maintenance phase. To evaluate the efficacy and safety of moisturizer containing licochalcone A, 1,2-decanediol, L-carnitine, and salicylic acid during the maintenance phase of mild to moderate acne in Thai patients. One hundred and ten patients with mild to moderate acne vulgaris were initially treated with a fixed combination of adapalene 0.1%/benzoyl peroxide 2.5% gel once daily for 8 weeks. Fifty patients who achieved at least 50% reduction in lesion counts or at least a 2-grade improvement in the Investigator's Global Assessment (IGA) grade from baseline were enrolled in the maintenance phase, which was an investigator-masked, left-right comparison, randomized, controlled, intraindividual study. Moisturizers with and without the active study ingredients were applied twice a day to each side of the face, respectively, for 12 weeks. Assessments included acne lesion counts, acne severity by IGA scoring, skin bioengineering measurements, and skin tolerability as assessed by both patient and physician. The treatment group had a significant reduction in the mean counts of noninflammatory, inflammatory, and total lesions compared to the vehicle group at week 12 and also between baseline and week 12. There was no significant difference in the mean scores for skin dryness, stinging/burning, or pruritus at any time point between groups. Moisturizer containing licochalcone A, 1,2-decanediol, L-carnitine, and salicylic acid reduced acne lesions and prevented the development of new lesions during the maintenance phase. This trial is registered with ClinicalTrials.gov registration no. NCT04002024.
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http://dx.doi.org/10.1155/2020/2857812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603542PMC
May 2021

A double-blinded, randomized, split-side, vehicle-controlled study of the efficacy of cleanser containing Acanthus ebracteatus Vahl., Suregada multiflora, and Acacia concinna in patients with atopic dermatitis: A pilot study.

Asian Pac J Allergy Immunol 2020 Oct 17. Epub 2020 Oct 17.

Center of Applied Thai Traditional Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Barrier repair therapy is the key management approach for both eczematous and non-lesional skin of atopic dermatitis. The use of appropriate cleansers to enhance skin hydration is an adjunctive treatment that increases topical drug penetration. Anti-inflammatory properties of various medicinal plants in tropical Asia have been reported.

Objective: Investigate the efficacy of herbal cleanser containing a combination of herbal extracts from Acanthus ebracteatus Vahl., Suregada multiflora, and Acacia concinna on seemingly intact skin in patients with atopic dermatitis by measuring improvements in the skin barrier function.

Methods: This 2-week pilot study was a split-side, randomized, double-blinded, vehicle-controlled trial. All patients (n = 30) were asked to use both a cleanser with an active formulation containing the herbal extracts and a vehicle- controlled cleanser on each side of mid-volar forearm. Biophysical assessments including transepidermal water loss (TEWL), skin hydration, skin pH, and skin roughness were performed at baseline and upon study completion.

Results: Compared to baseline, the median percentage change in TEWL at the end of the study was significantly greater for the active side 10.4 (-19, 20.7) g/m2h than the control side -13.2 (-28.7, 9.1) g/m2h; p = 0.01. The median percentage change of skin hydration, skin pH, and skin roughness of the active side compared to the control side had no a statistical significance.

Conclusions: This cleanser is beneficial when used as adjunctive therapy. Further studies should evaluate its anti- sinflammatory properties in the remedy or active phase of atopic dermatitis or other inflammatory skin diseases.
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http://dx.doi.org/10.12932/AP-050519-0554DOI Listing
October 2020

Vibratory Angioedema Subgroups, Features, and Treatment: Results of a Systematic Review.

J Allergy Clin Immunol Pract 2021 02 19;9(2):971-984. Epub 2020 Sep 19.

Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany. Electronic address:

Background: Vibratory angioedema (VA) is a subtype of chronic inducible urticaria that manifests with erythematous wheals or angioedema after skin exposure to vibration. Because the condition is rare, the available information is limited.

Objective: To systematically review the clinical manifestations and treatment options of VA.

Methods: Relevant literature published until August 2020 was searched using the terms "vibratory urticaria," "vibratory angioedema," "vibratory-induced angioedema," and "vibratory-induced urticaria." Preferred Reporting Items for Systematic Reviews and Meta-analysis recommendations were applied to this systematic review.

Results: On the basis of review of 22 studies (16 case reports, 4 case series, and 2 cohort studies) that had a combined total of 83 patients, we propose that VA be classified as hereditary VA (33.7%) and acquired VA (66.3%). Vibration-induced itching was frequent in both subgroups. Patients with hereditary VA more commonly had wheals and systemic symptoms, whereas patients with acquired VA more frequently had angioedema, burning, pain, or tingling. Although many VA treatments are used, there is little information on their efficacy. Most patients do not achieve complete control.

Conclusions: The novel VA classification proposed could help clinicians with the diagnostic workup of patients with VA. Because of the paucity of reported cases, firm recommendations for the treatment of VA are currently not possible. For patients with acquired VA, we suggest second-generation H-antihistamines as the first-line treatment. Controlled therapeutic trials are needed and should be performed.
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http://dx.doi.org/10.1016/j.jaip.2020.09.009DOI Listing
February 2021

Relationship Between Depression and Quality of Life Among Vitiligo Patients: A Self-assessment Questionnaire-based Study.

Clin Cosmet Investig Dermatol 2020 4;13:511-520. Epub 2020 Aug 4.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Vitiligo is a common chronic autoimmune disease that is characterized by progressive loss of skin color due to melanocyte destruction. In addition to the physical effects of vitiligo, this condition exerts adverse psychological effects and causes social stigmatization. Earlier studies reported that individuals with vitiligo suffer from poor quality of life (QoL), but data about the QoL of Thai vitiligo patients is scarce.

Objective: This study aimed to investigate the QoL and prevalence of depression in Thai vitiligo patients, association between QoL and depression, and factors associated with QoL and depression among Thai people with vitiligo.

Methods: This cross-sectional self-assessment questionnaire-based study was conducted at the phototherapy and vitiligo clinics of the Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University (Bangkok, Thailand). QoL was assessed using the Dermatology Life Quality Index (DLQI) questionnaire, and depression was evaluated via the Patient Health Questionnaire (PHQ-9).

Results: Among the 104 vitiligo patients that were recruited, the mean DLQI score was 7.46, and the prevalence of depression (PHQ-9 ≥9) was 13.5%. Factors significantly associated with a higher mean DLQI score were skin phototype IV compared to phototype III, active disease, new lesions within the last three months, lesions involving upper extremities, and PHQ-9 ≥9 (<0.05). Moderate correlation was found between DLQI score and PHQ-9 score (Pearson's correlation coefficient: 0.524, <0.001). Factors significantly associated with depression were working status and developing new lesions within the last three months (<0.05). Patients with new lesions were 4.12 times more likely to be depressed than those without new lesions (OR: 4.12, 95%CI: 1.20-14.16; =0.025).

Conclusion: Developing new lesions, active disease, dark skin phototype (IV), and lesion on upper extremity had significant adverse effects on QoL. Vitiligo patients who were employed and who had new vitiligo lesions are significantly more likely to be depressed.
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http://dx.doi.org/10.2147/CCID.S265349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414931PMC
August 2020

Cholinergic Urticaria: Clinical Presentation and Natural History in a Tropical Country.

Biomed Res Int 2020 24;2020:7301652. Epub 2020 May 24.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Cholinergic urticaria (CholU) is a subset of chronic inducible urticaria characterized by the recurrent pinpoint-sized wheals that are induced by exercising or increasing core body temperature. Currently, the data of CholU in tropical climate is still limited.

Objective: To investigate the clinical features and natural course of CholU in a tropical country.

Materials And Methods: This retrospective chart review study analyzed the data of CholU patients aged over 18 years who visited Siriraj Urticaria Clinic, Siriraj Hospital, Bangkok, Thailand, between January 2007 and September 2019. Demographic data, clinical presentations, and results of provocation tests and other laboratory investigations were evaluated and compared with other studies reported in temperate zones.

Results: Sixteen out of 2,175 chronic urticaria patients (0.7%) were diagnosed with CholU. The median age of CholU patients was 28.0 ± 11.7 years with male predominance (56.3%). Three patients (18.8%) had a history of atopy. Fifteen patients (93.8%) were positive to the exercise provocation test. Nonsedating antihistamine drugs were a main treatment (73.8%). Six patients (37.5%) were in remission at the time of the study, with a mean duration 4.3 years. The Kaplan-Meier survival analysis demonstrated that 12.5%, 35.5%, and 67.9% of patients would have disease remission within 1 year, 5 years, and 13 years, respectively.

Conclusions: The prevalence of CholU differs in each geographic region and is found to be low in tropical countries with a median duration 4.3 years. The prevalence of atopy and anaphylaxis with CholU is also lower in tropical countries than in temperate.
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http://dx.doi.org/10.1155/2020/7301652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273400PMC
March 2021

Symptomatic Dermographism: A Systematic Review of Treatment Options.

J Allergy Clin Immunol Pract 2020 10 28;8(9):3141-3161. Epub 2020 May 28.

Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany. Electronic address:

Background: Symptomatic dermographism (SD), the most common form of chronic inducible urticaria, presents with transient wheals accompanied by itching in response to scratching. Little is known about available treatment options and their efficacy in SD.

Objective: To systematically review the efficacy of treatment options for patients with SD.

Methods: Using predefined search terms, we searched for relevant literature published until September 2019. The systematic review process was consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations.

Results: The 23 studies identified included 15 randomized controlled trials; 22 and 17 assessed treatment responses in patients with SD by provocation/threshold testing and patient/physician clinical assessment, respectively. Thirteen different treatments were investigated in a total of 430 adult patients. The most frequently studied therapy, first-generation H-antihistamines, showed variable efficacy and significant side effects. In contrast, second-generation H-antihistamines (2AH), in all studies, were effective and well tolerated. Monotherapy with an H-antihistamine (AH) was not effective, whereas adding an AH increased the efficacy of treatment with an H-antihistamine (AH). SD improved with omalizumab. All other treatments were only investigated in small, unrepeated, and/or uncontrolled studies. There are no studies on updosing of 2AH.

Conclusions: The available SD studies are heterogeneous, mostly monocentric, old, small, and unrepeated, pointing to a high need for more and better studies. We suggest that 2AH should be the first-line treatment. In uncontrolled cases, the combination of AH and AH may be tried. Even though there is no evidence of its efficacy over standard dosage, updosing of 2AH may be considered based on the extrapolation of evidence from chronic spontaneous urticaria; omalizumab should be added in recalcitrant patients.
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http://dx.doi.org/10.1016/j.jaip.2020.05.016DOI Listing
October 2020

Clinical characteristics and management of chronic spontaneous urticaria in patients refractory to H-Antihistamines in Asia, Middle-East and Africa: Results from the AWARE-AMAC study.

World Allergy Organ J 2020 Apr 30;13(4):100117. Epub 2020 Apr 30.

Novartis Pharma AG, Basel, Switzerland.

Background: Chronic urticaria (CU) is a condition characterized by recurrent itchy hives and/or angioedema for ≥6 weeks. Most of the data about CU come from western countries with very little information available about CU in Asia, Africa, and the Middle East.

Methods: AWARE-AMAC is a 24-month prospective, observational, real-world, non-interventional study in patients aged ≥18 years from Asia, the Middle East, and Africa (AMAC) with CU refractory to H1-antihistamines (H1-AH). The main objective was to describe the real-world experience with CU, including clinical characteristics, presence of angioedema, treatment patterns (shifts between treatment classes and changes within a treatment class), investigator-assessed disease control, and the impact on quality of life. Subgroups of interest were type of CU at Baseline and treatment class (based on 2013 urticaria guidelines). There were no mandatory visits and diagnostic/monitoring procedures additional to routine practice, except the patient diary (7-day Urticaria Activity Score) and patient reported outcome assessments.

Results: The focus of the current manuscript is on patients with chronic spontaneous urticaria (CSU), who formed 98% of the sample. Patients were predominantly female (69.6% female, mean age ± SD 39.8 ± 13.29 years). Time since current diagnosis (Mean ± SD) was 28.6 ± 49.06 months. Amongst patients with CSU, 31.0% had comorbid chronic inducible urticaria (CINDU) and 46.4% had a history of angioedema. 91.9% received H1-AH therapy (±other treatments). The most frequently prescribed treatment classes at Baseline were any/combination of medications, not classified under the other 7 treatment classes, named "Others" (30.5%) followed by, omalizumab (OMA; 23.6%) and second-generation H1-AH monotherapy (sgAH; 15.1%). At Month 12, the most prescribed treatment classes (>15%) for patients were OMA (23.5%) and "Other" (21.3%); 19.7% received "No drug". At Month 24, OMA (22.5%), and "Other" (17.9%) were most frequently prescribed; 28.6% received "No drug". Overall, 79.5% of patients had some type of change in treatment. Over the study period, improvement in self-reported QoL increased, which was mirrored by better disease control.

Conclusion: In AMAC countries, the non-recommended "Other" treatment class played a major role in the initial management of CU patients. High usage of H1-AH (±other treatments) and OMA was observed. Treatment changes were observed in a majority of patients. Treatment escalation from sgAH was mostly via OMA. Improvement of disease control and QoL was achieved during the study period.

Trial Registration: Observational study (NA).
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http://dx.doi.org/10.1016/j.waojou.2020.100117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200453PMC
April 2020
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