Treatment of mucocutaneous leishmaniasis - A systematic review.

Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities. It is caused by protozoa of the genus Leishmania spp. transmitted to humans by sandflies. Mucocutaneous leishmaniasis occurs after untreated or inadequately treated cutaneous leishmaniasis and is more common in immunocompromised patients. The aim of this systematic review is to summarize all reported treatment options for mucocutaneous leishmaniasis. This review is based on all English, German, French, Spanish and Portuguese articles published in the databases "PubMed" and "Lilacs" from 1995 to 2020. Most of the medical literature is limited to case reports, small case series, retrospective studies, and a few randomized controlled trials. Various treatment options include pentavalent antimonates such as meglumine antimonate or sodium stibogluconate, amphotericin B (liposomal, deoxycholate, lipid complex, colloidal dispersion), miltefosine, and pentamidine. Other therapeutic options include itraconazole, fluconazole, ketoconazole, aminosidine sulfate, and azithromycin. The choice of drug depends primarily on its availability in the endemic area and the patient's comorbidities.

European patch test results with audit allergens as candidates for inclusion in the European Baseline Series, 2019/20: Joint results of the ESSCAA and the EBSB working groups of the ESCD, and the GEIDACC.

BACKGROUND: In 2019, a number of allergens (haptens), henceforth, "the audit allergens," were considered as potential additions to the European Baseline Series (EBS), namely, sodium metabisulfite, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, imidazolidinyl urea, Compositae mix II (2.5% or 5% pet), linalool hydroperoxides (lin-OOH), limonene hydroperoxides (lim-OOH), benzisothiazolinone (BIT), octylisothiazolinone (OIT), decyl glucoside, and lauryl glucoside; Evernia furfuracea (tree moss), was additionally tested by some departments as well. OBJECTIVES: To collect further data on patch test reactivity and clinical relevance of the audit allergens in consecutive patients across Europe. METHODS: Patch test data covering the audit allergens in 2019 and 2020 were collected by those departments of the European Surveillance System on Contact Allergies testing these, as well as further collaborators from the EBS working group of the European Society of Contact Dermatitis (ESCD), and the Spanish Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea. As patch test outcome, reactions between day (D) 3 and D5 were considered. RESULTS: Altogether n = 12 403 patients were tested with any of the audit allergen. Positive reactions were most common to lin-OOH 1% pet. (8.74% [95%CI: 8.14-9.37%]), followed by lin-OOH 0.5% pet., and lim-OOH 0.3% pet (5.41% [95% CI: 4.95-5.89%]). Beyond these terpene hydroperoxides, BIT 0.1% pet. was the second most common allergen with 4.72% (95% CI: 4.2-5.28%), followed by sodium metabisulfite 1% pet. (3.75% [95%CI: 3.32-4.23%]) and Compositae mix 5% pet. (2.31% [95% CI: 1.84-2.87%]). For some allergens, clinical relevance was frequently difficult to ascertain. CONCLUSIONS: Despite many positive patch test reactions, it remains controversial whether lin- and lim-OOH should be tested routinely, while at least the two preservatives BIT and sodium metabisulfite appear suitable. The present results are a basis for further discussion and ultimately decision on their implementation into routine testing among the ESCD members.

The pan-JAK inhibitor delgocitinib in a cream formulation demonstrates dose response in chronic hand eczema in a 16-week randomized phase IIb trial.

BACKGROUND: Chronic hand eczema (CHE) is a burdensome disease, and new well-documented, safe and efficacious treatments are warranted. In a recent CHE phase IIa trial, the pan-Janus kinase (JAK) inhibitor delgocitinib in an ointment formulation was found to be efficacious and well tolerated. OBJECTIVES: This trial assessed the dose response, efficacy and safety of delgocitinib cream in CHE. METHODS: In this double-blind, phase IIb dose-ranging trial, adults with CHE and a recent history of inadequate response or contraindication to topical corticosteroids were randomized to delgocitinib cream 1, 3, 8, 20 mg g-1 or vehicle treatment twice daily for 16 weeks. The primary endpoint was the Investigator's Global Assessment for CHE (IGA-CHE) treatment success [0 (clear) or 1 (almost clear) with a ≥ two-point improvement from baseline to week 16]. Secondary endpoints were the time to IGA-CHE treatment success and changes in Hand Eczema Severity Index (HECSI); other endpoints were itch and pain numerical rating scale (NRS) scores, and Patient's Global Assessment (PaGA) at week 16. RESULTS: Patients (n = 258) were randomized 1 : 1 : 1 : 1 : 1 to delgocitinib cream 1, 3, 8, 20 mg g-1 or vehicle. A significant dose-response relationship was established for IGA-CHE (P < 0.025). IGA-CHE treatment success at week 16 was achieved in 21.2% (1 mg g-1 ), 7.8% (3 mg g-1 ), 36.5% (8 mg g-1 ), 37.7% (20 mg g-1 ) and 8.0% (vehicle) of patients. Delgocitinib 8 and 20 mg g-1 showed a treatment effect against vehicle (P < 0.001). Similarly, there were improvements in HECSI, itch and pain NRS scores, and PaGA. Delgocitinib cream was well tolerated with the majority of adverse events being mild or moderate and considered unrelated to treatment. The most frequently reported adverse events were nasopharyngitis (17.3-29.4% in delgocitinib groups vs. 40% in vehicle group), eczema (5.8-11.3% in delgocitinib groups vs. 16.0% in vehicle group) and headache (3.8-11.5% in delgocitinib groups vs. 4.0% in vehicle group). CONCLUSIONS: In this trial, delgocitinib cream showed a dose-response relationship in terms of efficacy and was well tolerated.

Prevalence of contact allergies in the population compared to a tertiary referral patch test clinic in Jena/Germany.

BACKGROUND: The contact allergy prevalences in patch-tested patients are usually higher than those in the population, owing to morbidity-driven selection. OBJECTIVES: To examine the differences between two samples, one from the population, one from the patch test clinic, in one area of Germany (Jena, Thuringia). METHODS: Between August 2008 and October 2011, a total of 519 participants of the population-based european dermato-epidemiology network (EDEN) fragrance study were patch tested in Jena using a TRUE Test baseline series extended with some pet.-based (fragrance) allergen preparations. Between 2007 and 2012 (inclusive), 1906 routine patients were patch tested for suspected allergic contact dermatitis (ACD) in the Jena University Hospital Department; of these 1694 (83.2%) with the German baseline series using pet./aq.-based, investigator-loaded allergens. RESULTS: In the population (clinical) sample, 19.6% (41.1%) were sensitized to at least one of the allergens considered. The most common baseline series allergens in the population/clinical sample were nickel (10.5%/13.2%), fragrance mix (FM) II (2.9%/6.7%), FM I (2.3%/8.3%), and cobalt (1.6%/5%). The clinical sample was slightly older (71.5% vs 55.9% age 40+) and included less males (36% vs 49.3%). CONCLUSIONS: Results are quite similar, although prevalences are usually higher in the clinical setting, with the exception of p-tert-butylphenol formaldehyde resin.

Doppelblinde, randomisierte repetitive In-vivo-Wirksamkeitsstudie zu kommerziellen Hautschutzprodukten gegen Natriumlaurylsulfat (SLS).

HINTERGRUND: In der Primär- und Sekundärprävention von Berufsdermatosen werden Hautschutzprodukte eingesetzt, die eine präexpositionelle Schutzwirkung aufweisen sollen. Insbesondere finden sich auf dem Markt zahlreiche Produkte, die zum Einsatz bei Feuchtarbeit ausgelobt werden. Eine objektive Qualitätsbeurteilung dieser Produkte für Anwender ist auf Grund fehlender vergleichender Wirksamkeitsstudien oft nicht möglich. MATERIAL UND METHODIK: In einer doppelblinden, randomisierten und kontrollierten In-vivo-Studie wurden sechs kommerzielle Hautschutzexterna in einem repetitiven Irritationsmodell untersucht. Sie wurden hinsichtlich ihrer präexpositionellen Schutzwirkung vor dem durch Natriumlaurylsulfat (SLS) induzierten irritativen Kontaktekzem mittels hautphysiologischer Methoden getestet. Es wurde ein Wirkindex anhand des transepidermalen Wasserverlustes (TEWL) gemäß des Protokolls der multizentrischen Studie des Forschungsprojektes FP 275 der Deutschen Gesetzlichen Unfallversicherung DGUV berechnet. ERGEBNISSE: Die untersuchten Externa zeigten eine Schutzwirkung gegen SLS im Vergleich zum unbehandelten Kontrollfeld, wiesen allerdings signifikante Wirkunterschiede auf. Die Auswertung der Nebenparameter Corneometrie und visueller Score erbrachte ebenfalls Unterschiede zwischen den Externa. SCHLUSSFOLGERUNGEN: Die zwischen den untersuchten Externa festgestellten Unterschiede hinsichtlich der Wirkgüte ermöglichten eine Einteilung der Produkte, welche als Grundlage für die Auswahl geeigneter Schutzpräparate dienen kann.

Double blind randomized repetitive efficacy test of various occupational skin protection preparations against sodium lauryl sulphate.

BACKGROUND: Skin protection products, formerly named as barrier creams, are being used as primary and secondary prevention measures against occupational dermatoses. Many of these cosmetic products are claimed by manufacturers to be efficacious against wet work-induced skin barrier impairment if applied prior to exposure. However, results of validated and standardized in vivo efficacy tests allowing the comparison of different products are lacking. MATERIAL AND METHODS: Efficacy of six skin protection products against sodium lauryl sulphate-induced irritant contact dermatitis was investigated in a double blind, randomized and controlled repetitive irritation study in healthy volunteers using skin physiological methods. Transepidermal water loss (TEWL) results were used to calculate an efficacy index of protection by mathematical/statistical means according to a protocol developed in a German Statutory Accident Insurance (DGUV) multicenter study (research project FP 275). RESULTS: All tested products had a demonstrable, protective effect against SLS compared to controls, but their relative efficacy varied significantly. Differences were also seen upon evaluation of other parameters such as corneometry and clinical irritation score (visual score). CONCLUSIONS: Product ranking as a result of the established differences allows improved selection of appropriate skin protection products based on objective parameters, as compared to heterogenous product claims.

Expert consensus on practical aspects in the treatment of chronic urticaria.

BACKGROUND: Chronic urticaria (CU) is a common disease which represents a considerable burden for many patients. The current urticaria guideline describes the evidence-based diagnosis and treatment of CU. In addition, however, questions often arise in everyday practice that are not addressed by the guideline. METHODS: In May 2020, a digital meeting with German urticaria experts was held, in which practical aspects of CU treatment were discussed and supporting aids for everyday clinical treatment formulated. The resulting advice in this document focus on practical questions and the available literature and experiences of the participants. RESULTS: The diagnosis of CU can be made in a short time by means of a thorough anamnesis, a physical examination, and a basic laboratory chemical diagnosis. For this purpose, practical recommendations for everyday practice are given in this paper. An extended diagnosis is only indicated in a few cases and should always be carried out in parallel with an effective therapy. In general, CU should always be treated in the same way, regardless of whether wheals, angioedema or both occur. Symptomatic therapy should be carried out according to the treatment steps recommended by the guidelines. This publication provides practical advice on issues in everyday practice, such as the procedure in the current coronavirus disease 2019 (COVID-19) pandemic, the cardiac risk under higher dosed H1 antihistamines, the self-administration of omalizumab as well as vaccination under omalizumab therapy. In addition to treatment recommendations, topics such as documentation in the practice and family planning with urticaria will be discussed. DISCUSSION: These supporting treatment recommendations serve as an addendum to the current CU guideline and provide support in dealing with CU patients in everyday practice. The aim is to ensure that patients suffering from CU achieve complete freedom of symptoms with the help of an optimal therapy. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s40629-021-00162-w) contains supplementary material, which is available to authorized users.

European Surveillance System on Contact Allergies (ESSCA): Characteristics of patients patch tested and diagnosed with irritant contact dermatitis.

BACKGROUND: Irritant contact dermatitis (ICD) is caused by the acute locally toxic effect of a strong irritant, or the cumulative exposure to various weaker physical and/or chemical irritants. OBJECTIVES: To describe the characteristics of patients with ICD in the population patch tested in the European Surveillance System on Contact Allergies (ESSCA; www.essca-dc.org) database. METHODS: Data collected by the ESSCA in consecutively patch-tested patients from January 2009 to December 2018 were analyzed. RESULTS: Of the 68 072 patients, 8702 were diagnosed with ICD (without concomitant allergic contact dermatitis [ACD]). Hand and face were the most reported anatomical sites, and 45.7% of the ICD was occupational ICD (OICD). The highest proportions of OICD were found in metal turners, bakers, pastry cooks, and confectionery makers. Among patients diagnosed with ICD, 45% were found sensitized with no relevance for the current disease. CONCLUSIONS: The hands were mainly involved in OICD also in the subgroup of patients with contact dermatitis, in whom relevant contact sensitization had been ruled out, emphasizing the need for limiting irritant exposures. However, in difficult-to-treat contact dermatitis, unrecognized contact allergy, or unrecognized clinical relevance of identified allergies owing to incomplete or wrong product ingredient information must always be considered.