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.

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.

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.

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.

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.

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.

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.

Treatment of Scleroedema Adultorum Buschke: A Systematic Review.

Scleroedema adultorum Buschke is a rare skin disease, which can be divided into 3 subtypes: classic type, occurring after respiratory infections; a type lacking association with infections; and a type associated with diabetes. Scleroedema adultorum Buschke is characterized by thickening and tightening of the skin, which typically starts at the neck. In half of patients, spontaneous remission may occur. The aim of this systematic review is to summarize all reported treatments for scleroedema adultorum Buschke, based on articles from PubMed database, using the query "scleroedema adultorum Buschke treatment", English and German, published between 1970 and 2016 and documenting adequate treatments. The results are based mainly on individual case reports, small case series, and retrospective studies often reporting unsuccessful results. Treatment options include topical as well as systemic treatments, and physical modalities. There is a need for randomized controlled trials and studies on long-term outcomes after treatment.

Treatment of acquired reactive perforating dermatosis - a systematic review.

Reactive perforating dermatosis is a rare chronic skin disease defined by the transepidermal elimination of collagen and/or elastin. In the acquired form in adults, it is frequently associated with diseases such as diabetes and chronic renal failure. No systematic reviews of treatment options are available for this disease. The aim of this systematic review is to summarize all reported treatment options for acquired reactive perforating dermatosis (ARPD). This is a systematic review based on a MEDLINE search of articles in English and German from 1990 to 2016. Most medical literature on the treatment of ARPD is limited to individual case reports and small series of patients. Various therapies that have been tried include antihistamines, topical keratolytics, corticosteroids, tretinoin, oral drugs such as allopurinol or antibiotics, and phototherapy or photochemotherapy. While there are no specific criteria for the evidence-based selection of treatment options for ARPD, the first priority in management of these conditions should be treatment of an underlying disease if present. None of the described modalities has been approved for first-line therapy. It is recommended to choose a combination of drugs that reduce itching and assist in the resolution of the skin lesions at the same time.

Position paper: Telemedicine in occupational dermatology - current status and perspectives.

Teledermatology is the use of telecommunication technologies to exchange medical information for diagnosis, consultation, treatment and teaching in dermatology. While its use has been evaluated in a wide range of dermatological diagnoses, only few studies exist on its validity, diagnostic precision, feasibility, and cost-effectiveness in occupational dermatology. However, these studies show a considerable potential for diagnosis, prevention, treatment support and follow-up of patients with occupational skin diseases. Asynchronous (store and forward; SAF) or synchronous dermatology teleconsults could assist occupational medicine specialists not only in occupational preventive care, but also in the context of skin cancer screening in outdoor workers. Thus, teledermatology might contribute to earlier prevention and notification of occupational skin diseases. Modern smartphone apps with artificial intelligence technologies may also facilitate self-monitoring in employees working in high-risk jobs.

Diagnostische Präzision der komponentenbasierten vs. der extraktbasierten In-vitro-Diagnostik von Insektengift-Allergien: Auswirkungen auf das klinische Management.

HINTERGRUND: Die Bestimmung von spezifischen IgE-Antikörpern spielt eine zentrale Bedeutung bei der Diagnostik von Bienen- und Wespengiftallergien. In den letzten Jahren wurden die komponentenbasierte Diagnostik (CRD) eingeführt, die die Bestimmung spezifischer IgE-Antikörper gegen die Allergene Api m 1, Ves v 1, Ves v 5 und Pol d 5 sowie kreuzreaktive Kohlenhydratdeterminanten (CCDs) erlaubt. Hierdurch soll vor allem bei Probanden mit Doppelsensibilisierungen die klinische Relevanz der einzelnen Sensibilisierungen besser beurteilt werden können. PROBANDEN UND METHODIK: Die spezifischen IgE-Antikörper-Bestimmungen an 143 Probanden mit Bienen- und/oder Wespengiftallergie erfolgten mit den extraktbasierten ImmunoCAP®-Allergenen i1 und i3 sowie den ImmunoCAP®-Allergenkomponenten i208-211 und o214 (Api m 1, Ves v 1, Ves v 5, Pol d 5, CCD). Bei Doppelsensibilisierten wurde zusätzlich ein Inhibitionstest durchgeführt. An einem Teilkollektiv der Studienpopulation erfolgten sIgE-Bestimmungen gegen Api m 1, Api m 4, Pol d 5 und Ves v 5 mittels Allergiechip (ISAC®, n  =  44). ERGEBNISSE: Die Sensitivität von Ves v 5 bei isolierten Wespengiftallergikern betrug 78,5 %, gemeinsam mit Ves v 1 stieg diese auf 92,3 %. Die Sensitivität von Api m 1 bei isolierten Bienengiftallergikern betrug 25 %. Die komponentenbasierte Diagnostik und Inhibitionstests bei Doppelsensibilisierten lieferten divergente Ergebnisse. Die CRD mittels ISAC®-Allergiechip erbrachte deutliche Unterschiede vor allem im Hinblick auf die Diagnostik von Api m 1 und CCDs. SCHLUSSFOLGERUNGEN: Die CRD bereichert das diagnostische Spektrum, sofern sie nicht allein sondern zusätzlich zu den etablierten Verfahren eingesetzt wird. Sie sollte neben Ves v 5 stets die Bestimmung der IgE-Antikörper gegen Ves v 1 umfassen.

Diagnostic precision of component-resolved vs. extract-based in vitro diagnosis of hymenoptera venom allergy: effects on clinical management.

BACKGROUND: The measurement of specific IgE (sIgE) antibodies plays a key role in the diagnosis of honeybee and wasp venom allergy. In recent years, component-resolved diagnosis (CRD) has been introduced, which allows for the measurement of sIgE antibodies against Api m 1, Ves v 1, Ves v 5, and Pol d 5, as well as cross-reactive carbohydrate determinants (CCDs). These tests are intended to help determine the clinical relevance of any given sensitization, especially in patients with dual sensitization. PATIENTS AND METHODS: Specific IgE antibody levels were measured in 143 patients with bee and/or wasp venom allergy using the extract-based ImmunoCAP® allergens i1 and i3 as well as the ImmunoCAP® allergen components i208-211 and O214 (Api m 1, Ves v 1, Ves v 5, Pol d 5, CCDs). In patients with dual sensitization, inhibition testing was also performed. In a subgroup of the study population, sIgE to Api m 1, Api m 4, Pol d 5, and Ves v 5 were determined using the ISAC® allergy microarray (n = 44). RESULTS: The sensitivity of Ves v 5 in patients with isolated wasp venom allergy was 78.5 %; in combination with Ves v 1, that figure increased to 92.3 %. The sensitivity of Api m 1 in individuals with isolated bee venom allergy was 25 %. CRD and inhibition testing in individuals with dual sensitization showed divergent results. CRD using the ISAC® allergy microarray showed marked differences, especially with regard to Api m 1 and CCDs. CONCLUSION: Component-resolved tests are a valuable addition to the diagnostic spectrum as long as they are used in combination with established procedures. Apart from Ves v 5, measuring IgE antibodies to Ves v 1 should always be included in the diagnostic workup.

Ultraviolet Exposure and Protection Behavior in the General Population: A Structured Interview Survey.

BACKGROUND: Exposure to solar ultraviolet (UV) radiation is a known and controllable risk factor for skin cancer. OBJECTIVE: To study the UV exposure and protection behavior of the general population. METHODS: Structured interview survey. RESULTS: A random sample of 865 volunteers from the EDEN (European Dermato-Epidemiology Network) Fragrance Study cohort was recruited. The individual skin type did not influence the occupation or leisure. The proportion of people who regularly used sunscreens was lower in the oldest age groups, where the risk of skin cancer is highest. Women used sunscreens significantly more frequently than men did and were more likely to have their moles checked by a specialist. CONCLUSIONS: A demand for public information on the risk factors for skin cancer and the role of protection was demonstrated by our study. The subpopulation of aged men represents a relevant target group for educational public campaigns on skin cancer risk avoidance.

Occupational contact urticaria caused by food - a systematic clinical review.

Food industry workers are at increased risk for occupational contact urticaria (CU). There are many foodstuffs that have been reported to cause occupational CU, including seafood, meat, vegetables, and fruits. The aim of this review is to summarize all reported occupational cases of CU in the food industry. This is a systematic review based on a MEDLINE search of articles in English and German and a manual search, between 1990 and 2014, to summarize the case reports and case series of occupational CU in the food industry. Many different foodstuffs have been implicated in CU. Occupational CU has been reported in many different occupations, mostly in individuals dealing with seafood, meat, vegetables, and fruits, such as chefs, cooks, bakers, butchers, slaughterhouse workers, and fish-factory workers. Foodstuffs that commonly induce occupational protein contact dermatitis include fish, seafood, meats, vegetables, and fruits. Food handlers may acquire CU resulting from occupational exposures. The prognosis varies widely. The diagnosis of immunological CU is based on the clinical history and on a positive prick test with the suspected substance and/or measurement of specific IgE.

A variant of the CXCL11 gene may influence susceptibility to contact allergy, particularly in polysensitized patients.

BACKGROUND: Hereditary factors may influence individual susceptibility to contact allergy. OBJECTIVES: To investigate genetic variants with impacts on early inflammatory reactions and T cell functions that possibly increase the risk of contact allergy. PATIENTS AND METHODS: Three hundred and seventy two patients undergoing patch testing were recruited from the Information Network of Departments of Dermatology (IVDK). Of these, 133 were monosensitized and 239 were polysensitized, defined as reacting to three or more unrelated sensitizers. Within the polysensitized individuals, a subgroup with at least one particularly strong patch test reaction (strong reactors; n = 194) was considered. Three hundred and forty-seven blood bank donors served as controls. Fifteen genetic variants in 13 genes were analysed. RESULTS: The homozygous variant CXCL11 AA genotype (rs6817952) was significantly more frequent among polysensitized patients (10 of 239 = 4.2%; p = 0.0048; odds ratio 7.49; 95%CI: 1.7-36.1) than among monosensitized patients (2.2%) and in the control group (0.6%). None of the remaining genetic variants investigated were characterized by similarly strong associations. However, the significance was lost after correction for multiple comparisons. CONCLUSIONS: The homozygous variant CXCL11 genotype is associated with an increased risk of contact allergy. To confirm this exploratory finding, further independent studies are needed.

Life of lesions in eosinophilic cellulitis (Wells' syndrome)-a condition that may be missed at first sight.

Eosinophilic cellulitis is an inflammation of, until now, unknown etiology that was first described by George Wells in 1971. Its dominating histological hallmarks are so-called "flame figures" and an eosinophilic infiltrate. Here, we report the case of a 46-year-old man who initially presented with excoriated papules that were histologically interpreted as consistent with "arthropod reactions." Later on, the clinical presentation changed to erythematous plaques, partially with cockade-like aspects. At this time, new biopsies were performed showing a superficial and deep perivascular lymphocytic and heavily eosinophilic infiltrate and flame figures, thus allowing to establish the diagnosis of Wells' syndrome. Under treatment with oral prednisolone and dapsone, the patient showed a rapid improvement of the condition. The presented case demonstrates both the clinical and histopathologic life of lesions of Well's syndrome in the course of the disease from unspecific to distinctive. The need for repeated biopsies is discussed. Current understanding of the pathogenesis of Wells' syndrome and its correlating histological features are elucidated.