Efficacy and Safety of bimekizumab in elderly patients: real-world multicenter retrospective study - IL PSO (Italian Landscape Psoriasis)

Purpose of the article: The aim of this multicenter observational study is to report data from real world on the use of bimekizumab in patients aged ≥ 65 years with moderate-to-severe plaque psoriasis. Elderly patients are poorly represented in clinical trials on bimekizumab for plaque psoriasis, and real-world studies are important to guide clinical choices. Materials and methods: A retrospective multicenter study was conducted in 33 dermatological outpatient clinics in Italy. Patients aged ≥ 65 years, with moderate-to-severe plaque psoriasis and treated with bimekizumab were enrolled. No exclusion criteria were applied. Bimekizumab was administered following the Italian Guidelines for the management of plaque psoriasis and according to the summary of product characteristics, in adult patients who were candidates for systemic treatments. Overall, 98 subjects were included, and received bimekizumab up to week 36. Clinical and demographic data were collected before the initiation of treatment with bimekizumab. At baseline and each dermatological examination (4, 16, and 36 weeks), clinical outcomes were measured by the following parameters: (1) PASI score; (2) site-specific (scalp, palmoplantar, genital, nail) Psoriasis Global Assessment (PGA). At each visit, the occurrence of any adverse events (AEs) was recorded, including serious AEs and AEs leading to bimekizumab discontinuation. Results: The mean PASI score was 16.6 ± 9.4 at baseline and significantly decreased to 4.3 ± 5.2 after 4 weeks (p < 0.001), and 1.1 ± 1.7 after 16 week (p < 0.001). This level of improvement was maintained after 36 weeks (p < 0.001). PASI ≤2 was recorded in 36 (36.7%) at week 4, 68% and 69.4% at week 16 and 36, respectively. By week 16, 86/98 (87.8%) patients reached PASI75, 71/98 (72.4%) obtained PASI90, and 52/98 (53.1%) PASI100. Binary logistic regression tests showed a significant association of PASI100 by week 4 with lower PASI at baseline. PASI 100 at 16 or 36 weeks was not associated with baseline PASI, obesity, age, gender, previously naïve state, and presence of psoriatic arthritis. Patients naïve to biologics at baseline had similar response to bimekizumab as non-naïve subjects. Conclusions: Bimekizumab is a suitable option for elder patients as it is effective, tolerated and has a convenient schedule

Cross-reactions in patch testing and photopatch testing with ketoprofen, thiaprophenic acid, and cinnamic aldehyde

In the last 7 years, we have studied 123 patients with allergic reactions to topical arylpropionic anti-inflammatory drugs. We have investigated the rate of sensitization and the irritant potential of one of them, ketoprofen, and its cross-reactivity with such other derivatives as ibuproxam, ibuprofen, naproxen, fenoprofen, flurbiprofen, and thiaprofenic acid. Sensitization was single in most cases, and ketoprofen was the drug most often involved. The combination most frequently found was ketoprofen plus ibuproxam. The most frequent cross-reactions were to fragrance mix, especially cinnamic aldehyde and balsam of Peru, both contact and photocontact sensitizers. Because there is a ketonic group in the molecule of ketoprofen and cinnamic aldehyde and after conversion of thiaprofenic acid, this could be the trigger for this particular allergy and cross-reactivity

Immunohistologic evaluation of the effect of cyclosporine treatment on the lichen planus immune infiltrate

We have investigated immunohistologically the cutaneous immune infiltrate in the lesions of five patients with severe, extensive lichen planus of recent onset before and after 15 days of oral, low-dose cyclosporine therapy (3 mg/kg/day). Before therapy, we observed an abnormal bandlike cellular infiltrate localized in the papillary dermis, composed mostly of CD3+ cells, with a prevalence of CD4+ cells. Infiltrating lymphocytes showed markers of activation (HLA-DR antigens and interleukin 2 receptor), and there were many Langerhans (CD1+) cells in the dermal infiltrate. After 15 days of cyclosporine therapy, we observed a dramatic decrease in the total number of T cells and a corresponding decrease in interleukin 2 receptor-positive activated CD25+ cells and in antigen-presenting cells (CD1+ and CD14b+). These changes were concurrent with clinical improvement. Our results are compatible with the hypothesis that the inhibition of CD4 T cells by cyclosporine might explain the drug's therapeutic action and that the interaction between antigen-presenting cells and CD4 T cells is important in the pathogenesis of lichen planus

Allergic contact dermatitis prevalence in patients with otitis externa

A statistical analysis of the relationship between otitis externa and various clinical and etiological variables was carried out in 64 patients. Between 1988 and 1989, true eczema of the auditory canal was found in 43 of the 64 patients seen sequentially. 23.5% of all the patients found to have dermatitis could be regarded as having allergic contact dermatitis and the allergen identified. This incidence is less than the 40% and the 58% found in other previous studies. We did not find any specific difference in sex and age between the allergic and non-allergic groups. In the allergic group, topical drugs were the commonest sensitizing agents, followed by chemicals and resins found in the ear prosthesis. Twenty-one patients with negative patch tests were classified as seborrheic dermatitis and 11 as atopic dermatitis. The other 19 patients, who were discharged before patch testing, were diagnosed as having psoriasis (8) or chronic bacterial (6) or fungal infections (5), without true blister reaction. We think that accurately selected series must be used for these studies because of the low incidence of allergic contact dermatitis

Italian study of allergic contact photodermatitis: epidemiological aspects

A total of 1,050 patients with histories and clinical pictures suggestive of photoallergic contact dermatitis were seen. All the patients underwent photopatch tests with haptens proposed by the Gruppo Italiano Ricerca Dermatiti da Contatto plus other substances suggested by each patient's history. Two hundred fifty-nine patients (24.6%) were positive to at least one test substance of the standard series or to substances added. Typical photoallergic reactions were seen in 198 subjects (259 minus 40 toxic photodermatitis to chlorpromazine and 21 to promethazine), which represents 18.8% of the total population. Topical drugs represent the most involved substances in photodermatitis. The incidence in our population was about equal for antimicrobial agents, additives to fragrances, and fragrances themselves. Other allergens found were salicylanilides, whereas sun-screening agents were the fifth group of haptens but with clear-cut relevance. This study is a first attempt to organize the data about results of photopatch tests applied to Italian patients

Fluorescence Microscopy Studies of Plasma Membranes to Analyse the Molecular Machinery of Neuronal Exocytosis

Bei der regulierten Exocytose in Neuronen und neuroendokrinen Zellen führt ein intrazellulärer Anstieg der Calciumkonzentration zur Core-Komplexbildung zwischen den plasmamembranständigen SNAREs Syntaxin1A und SNAP-25 und dem vesikelassoziierten SNARE Synaptobrevin. Dadurch werden die gegenüberliegenden Membranen fusioniert. Neben den SNAREs ist auch Munc18-1, das zur Sec1/Munc18-Proteinfamilie gehört, ein essentielles Protein der neuronalen Exocytose. Der Munc18-1-Knockout führt zum Block der neuronalen Exocytose. In vitro bildet Munc18-1 mit Syntaxin1 einen Komplex, der Syntaxin1 in einer sogenannten geschlossenen Konformation hält. In diesem Komplex ist Syntaxin1 für Reaktionen mit SNAP-25 und Synaptobrevin2 unzugänglich, so dass keine Core-Komplexbildung mehr stattfinden kann. Wie diese Inhibition der Core-Komplexbildung mit der essentiellen Munc18-1-Funktion zusammenpasst ist bisher nicht verstanden. In der vorliegenden Arbeit wird gezeigt, dass Munc18-1 in intakten und exocytosekompetenten Plasmamembranpräparationen von PC12-Zellen mit membrangebundenem Syntaxin1 einen Komplex bildet. Aus diesem Komplex heraus kann Munc18-1 durch Zugabe von rekombinantem Synaptobrevin2, welches Core-Komplexe mit den endogenen SNAREs bildet, gelöst werden. Wurde das Experiment unter gleichen Bedingungen, jedoch statt unter Zugabe von Synaptobrevin2 unter Zugabe von rekombinantem Syntaxin1A bzw. SNAP-25, die keine Core-Komplexe an der Membran bilden, durchgeführt, verblieb Munc18-1 an Syntaxin1 gebunden. Zur Kontrolle wurde dieses Experiment auch an Membranen von SNAP-25-defizienten Mäusen durchgeführt. Da hier grundsätzlich keine Core-Komplexbildung stattfindet, konnte, wie erwartet, keine Freisetzung von Munc18-1 durch Synaptobrevin2 beobachtet werden. Dies untermauert, dass in der nativen Membran Syntaxin1 trotz seiner Munc18-1-Bindung für die Core-Komplexbildung zur Verfügung steht und dass sich Munc18-1 nach dieser Komplexbildung von Syntaxin1 löst. Daraus wird geschlossen, dass Munc18-1 die Bildung eines Komplexes zwischen Syntaxin1 und SNAP-25 erlaubt, der ein Akzeptor für vesikuläres Synaptobrevin ist und somit ein Intermediat der Exocytose darstellt. Die Munc18-1-Syntaxin-Bindung könnte ein räumlicher und zeitlicher Regulator dieses Intermediates sein und die Bildung unproduktiver SNARE-Komplexe in der Plasmamembran verhindern. Im Rahmen dieser Dissertation wurde außerdem untersucht, ob sich eine Erhöhung der Calciumkonzentration auf den Zustand der SNAREs auswirkt, welche unter Ruhebedingungen unkomplexiert und in Mikrodomänen aufkonzentriert sind. Es konnte gezeigt werden, dass bei erhöhten physiologischen Calcium-Konzentrationen eine starke Abnahme der Antigenizität der SNAREs zu beobachten ist: Für Syntaxin1 war bei gleichzeitiger Abnahme der Antigenizität eine gesteigerte Aufkonzentration in Domänen erkennbar. Für SNAP-25 wurde ein Abfall der Immunreaktivität um 90% beobachtet. Rekombinantes Synaptobrevin2 wurde deutlich schlechter in die Membran eingebaut. Diese Erkenntnisse lassen folgende Interpretationen zu: Durch Calcium kommt es zur Umorganisation von Syntaxin-Domänen. Da das Epitop zur Anfärbung von SNAP-25 innerhalb dessen SNARE-Motivs liegt, könnte die starke Abnahme der Immunreaktivität den Einbau von SNAP-25 in Syntaxin-SNAP-25-Komplexe widerspiegeln. Dies wird dadurch untermauert, dass nach Calciumbehandlung weniger rekombinantes Synaptobrevin mit den endogenen SNAREs reagiert

Gruppo Italiano Ricerca Dermatiti da Contatto ed Ambientali Italian Multicenter Study of Allergic Contact Photodermatitis: Epidemiological Aspects

A total of 1,050 patients with histories and clinical pictures suggestive of photoallergic contact dermatitis were seen. All the patients underwent photopatch tests with haptens proposed by the Gruppo Italiano Ricerca Dermatiti da Contatto plus other substances suggested by each patient's history. Two hundred fifty-nine patients (24.6%) were positive to at least one test substance of the standard series or to substances added. Typical photoallergic reactions were seen in 198 subjects (259 minus 40 toxic photodermatitis to chlorpromazine and 21 to promethazine), which represents 18.8% of the total population. Topical drugs represent the most involved substances in photodermatitis. The incidence in our population was about equal for antimicrobial agents, additives to fragrances, and fragrances themselves. Other allergens found were salicylanilides, whereas sun-screening agents were the fifth group of haptens but with clear-cut relevance. This study is a first attempt to organize the data about results of photopatch tests applied to Italian patients