Monica Corazza, Federica Baldo, Maria Michela Lauriola, Maria Rosaria Zampino, Annarosa Virgili
I patch test convenzionali con prodotti d?uso oftalmici sono spesso negativi. Per la diagnosi di dermatite allergica da contatto da topici oftalmici la letteratura ha proposto metodiche alternative quali lo stripping, lo scratching, l?uso di Large Finn Chamber. Recentemente è stato proposto anche il pre-trattamento della cute con sodio lauril solfato (SLS). In questo studio 22 pazienti con sospetta dermatite da contatto da prodotti oftalmici sono stati testati con le diverse metodiche per valutarne la sensibilità diagnostica. Tutte sono risultate avere maggiore sensibilità rispetto alla tecnica convenzionale. Si suggerisce l?esecuzione di patch test con topici oftalmici utilizzando dapprima Large Finn Chamber, in quanto metodica pratica, semplice e di facile gestione ambulatoriale. L?esecuzione di patch test con metodiche più impegnative dal punto di vista organizzativo (pre-trattamento con SLS) o, seppur minimamente, invasive (stripping e scratching) potrebbero essere riservate ai casi di forte sospetto diagnostico e risultati negativi con le altre tecniche.
The diagnosis of allergic contact dermatitis from ophthalmic products often gives discouraging results, as patch tests with patients? own products are often negative. Alternative procedures of performing patch tests with topical ophthalmic medicaments such as previous stripping or scratching of the skin or the use of Large Finn Chambers have been proposed in the past. Recently, we performed patch tests on previously pre-treated skin with sodium lauryl sulphate (SLS). This method seems promising as it reveals more positive responses than the conventional patch tests. In the present study we performed patch tests with patients? own products using different methods in the same patients, with the aim of comparing the sensitivity of the dif- ferent procedures proposed until now in the literature. Twenty-two patients with periorbital dermatitis were investigated. We suspected the dermatitis had been caused by topical ophthalmic products due to a highly indicative history or positive stop-restart test. Clinically, 13 subjects had eyelid eczema and 9 had persistent erythematous-edematous reaction with conjunctival hyperemia. In all patients, patch tests were performed with the SIDAPA standard series and the antimicrobials series, containing the most frequent preservatives of ophthalmic products like benzalkonium chloride, phenylmercuric acetate and thimerosal. An integrative series of excipients of topical ophthalmic medicaments (sodium EDTA 1% pet, monobasic sodium phosphate 1% aq, hydroxypropylcellulose 25% alc, hydroxyethylcellulose 25% alc, dibasic sodium phosphate 1% aq) was added. We also carried out patch tests with patients? own eyedrops and ocular ointments as is, with different procedures: using normal Finn Chambers, using Large Finn Chambers, on stripped skin (skin stripped for 10 times), on scarifed skin (scratching), on previously treated skin with SLS. Conventional patch test revealed 7.3% of allergies (5 out of 68), while Large Finn chambers 13.8% (9 out of 65) and SLS pre-treatment 14.5% (9 out of 62). Percentages of positive reactions obtained with stripping and scratching were higher: 20.8% (5 out of 24) and 19.2% (5 out of 26) respectively. We conclude that all these procedures increase patch test sensi- tivity and may enhance response intensity making evaluation and scoring of the reactions easier. In clinical practice we suggest performing patch test with ophthalmic topical products using Large Finn Chambers (a practical, easy-to-perform method which does not require so many visits to the outpatients? clinic). We be- lieve that methods that require more time (pre-treatment with SLS) or that are slightly invasive (stripping and scratching) should be chosen only in the case of highly indicative suspect and negative results obtained with other methods.
Gianni Cadario, Antonella Appino, Massimo Milani
Obiettivo: valutare in uno studio prospettico l?effcacia e la tollerabilità della immunoterapia sublinguale (ITSL) con estratti standardizzati di acari della polvere (Dermatophagoides pteronyssinus e Dermatophagoides farinae; SLITone®, ALK-Abellò S.p.A., Milano) in pazienti con dermatite atopica (DA) lieve-moderata e sensibilizzazione agli acari della polvere. Materiali e metodi: sono stati arruolati 86 pazienti con DA (53 donne e 33 uomini; età : 18-60 anni) con sensibilizzazione agli acari della polvere (IgE specifche > Classe 2) e sottoposti a ITSL per almeno 12 mesi. Obiettivo primario dello studio è stato la valutazione delle variazioni dello SCORAD e dell?utilizzo dei farmaci sintomatici. Risultati: al basale il valore dello SCORAD era di 43,3±13,7 (range: 18-84). Dopo un anno di trattamento, lo SCORAD si è ridotto a 23,7±13,3 (range: 0-65; p=0,0001). Il trattamento con ITSL si è accompagnato ad una riduzione signifcativa dei livelli delle IgE specifche (p=0,001) e dell?utilizzo dei farmaci topici. Non sono stati osservati eventi avversi gravi. Conclusioni: questo studio evidenzia che l?ITSL specifca riduce in modo rilevante lo SCORAD in soggetti adulti con DA e sensibilizzazione agli acari della polvere. Futuri studi in doppio cieco verso placebo potranno valutare il reale ruolo dell?immunoterapia specifca nel trattamento della DA.
Background: specifc subcutaneous immunotherapy with house dust mite (HDM) preparations has recently been shown to improve skin lesions in patients with atopic dermatitis (AD). So far, there is less data regarding the effcacy and safety of specifc sublingual immunotherapy (SLIT) in patients with AD. Objective: evaluate in an open non-controlled, non-randomized pilot trial the effetcs of SLIT with HDM allergen extracts preparation (Dermatophagoides pteronyssinus and Dermatophagoides farinae; SLITone®, ALK-Abellò S.p.A., Milan, Italy) on SCORAD in adult patients with mild-moderate AD. Materials and Methods: 86 subjects (53 women and 33 men; between 18 and 60 years of age) with AD and IgE-proved HDM sensitivity (Class >2) were enrolled in the trial after their informed consent. Exclusion criteria were severe asthma and treatment with systemic or high potent topical corticosteroids or immunosuppressant agents. Patients were treated with SLIT for at least 12 months. SCORAD was evaluated at baseline and after 12 months of treatment. Results: baseline SCORAD value (mean ± SD) was 43.3±13.7 (range: 18-84). After 1 year of SLIT, SCORAD value was reduced to 23.7±13.3 (range: 0-65; p=0.0001; unpaired T-Test vs baseline). This was a 46% reduction in SCORAD in comparison with baseline time. A signifcant improvement, defned as a SCORAD reduction of >30%, was observed in 51 out of 86 patients (59.2%). In 5 patients (5.9%) the SCORAD value did not change at the end of the observation period. In 30 patients (34.9%) the SCORAD reduction after SLIT was ≤30% in comparison with baseline. Specifc-IgE serum levels were signifcantly (p=0.001) reduced after SLIT. No severe adverse events were observed during the trial. Conclusions: in this open non-controlled trial the SLIT with HDM extracts in patients with mild-moderate AD was effective in reducing the SCORAD after 1 year of SLIT treatment. In addition, the treatment was very well tolerated. Treatment with SLIT, furthermore, has allowed a gradual and relevant reduction of concomitant therapies with corticosteroids and immunosuppressants. Present results require further controlled trials in order to confrm the potential clinic beneft of SLIT in this clinical setting.
Giuseppe De Panflis, Elena Tognetti, Carla Antonella Pepe, Chiara Cortelazzi
Il rischio ambientale legato alle radiazioni ultraviolette (RUV) viene considerato in grado di sca- tenare una catena di eventi che, a partire dalla esposizione solare, coinvolge la realizzazione di danni del DNA, la successiva insorgenza di mutazioni e lo sviluppo, infne, di tumori cutanei. Dal canto loro, le risposte biologiche cutanee al danno del DNA, intese a prevenire l?insorgenza di mutazioni geniche RUV-indotte, sono rappresentate dall?arresto del ciclo cellulare, dalla riparazione del danno del DNA consentito da tale arre- sto, dall?apoptosi della cellula irreparabilmente danneggiata e dalla melanogenesi. Le RUV sono in grado, infne, di favorire la generazione di cellule ?T regolatrici? immunosoppressive e pro-tumorali, le quali sono state recentemente riscontrate sia nell?infltrato di epiteliomi cutanei sia, nel nostro laboratorio, nel micro- ambiente del melanoma cutaneo primitivo, nel contesto del quale rivestono un ruolo predittivo della gravità del melanoma medesimo.
Environmental risk linked to ultraviolet radiations (UVRs) is believed to be a major factor promoting the onset of skin cancer. UVRs, in fact, are able to trigger a pathophysiological chain of biological phenomena that starts with sun exposition, cause DNA damage, mutations and at the end skin cancer. On the other hand, UVR-exposed skin is able to develop a series of protective biological mechanisms, which are often capable to avoid the progres- sion of the bio-molecular events involved in the above-mentioned pathophysiological chain. Specifcally, DNA damage can be prevented by UVR-induced thickening of the epidermis, pigmentation and anti-oxidant factors. In addition, UVR-induced mutations can be prevented by a series of p-53-dependent changes associated to DNA damage, including the possible cell cycle arrest, the repair of the damaged DNA, and if such a repair is impos- sible to realize an apoptosis. Even melanogenesis may be viewed in this context, because it can be envisaged as a p53-dependent phenomenon, eventually linked to DNA damage itself. Finally, UVR-mutated cells can be destroyed by a series of mechanisms belonging to the activity of effectors linked to cutaneous immunosurveillance, including the recently described role played by IL-12. UVR, however, are known to be capable to block cutaneous immunosurveillance due to a series of well recognized immunosuppressive activities, including altered presentation of tumoral molecules, release of IL-10 by keratinocytes, conversion within the epidermis of trans-urocanic acid into cis-urocanic acid. Recently, UVRs were shown to promote a RANKL-mediated activation, sustained by UVR-irradiated keratinocytes, of Langerhans cells, which after such a stimulation they were able to trigger a suppressive T lymphocytic polarization. Such regulatory T cells (Treg), indeed, infltrate cutaneous cancers, including epithelial cancers and, as shown in our laboratory, primary cutaneous melanoma, in signifcantly related clinical phases and stages of melanoma itself. Thus, since stage- and phase-related proportions of Treg occurr within the melanoma microenvironment, such Treg may suppress in vivo the local effector anti-melanoma immune response. For this immunotherapeutic strategies aimed to counteract in vivo the action of Treg might have a crucial impact on the design of effcient vaccination protocols to the treatment of melanoma patients. In conclusion, the environmental UVR-linked risk is able not only to trigger damaged DNA and UVR-associated mutations, but also to promote the onset of skin cancer from UVR-mutated skin cells: this last capacity seems strongly related to UVR-triggered development of Treg, that are able to suppress anti-tumoral responses.
Nicoletta Cassano, Valeria Lattanzi, Nicola Arpaia, Gino Antonio Vena
Gli agenti infettivi possono essere coinvolti nel determinismo dell?orticaria acuta e cronica. Mentre l?orticaria acuta si riscontra spesso in associazione a sintomi suggestivi di infezione, il ruolo delle infezioni nell?orticaria cronica è piuttosto complesso e controverso. In alcuni casi l?orticaria cronica correlata ad infezioni riconosce una natura vasculitica e meno frequentemente è rappresentata da un?orticaria da freddo. I meccanismi potenzialmente implicati sono di tipo immunologico o extraimmunologico. Sono possibili reazioni di tipo allergico, che in realtà rendono conto soltanto di una minoranza dei casi. Nelle forme croniche possono essere innescate risposte cellulari sovrapponibili alle ?late-phase reactions?, o reazioni non immunologiche di vario tipo. Possibile, ma non comprovato nell?orticaria, lo scatenamento di autoimmunità in corso di alcune particolari infezioni, come quelle da Helicobacter pylori e da virus dell?epatite C. Le possibili noxae patogene sono numerose: parassiti, coinvolti nell?orticaria cronica, più raramente, come nel caso di Anisakis simplex, in quella acuta; virus, soprattutto quelli implicati nelle infezioni a carico delle vie aeree superiori, ma anche i virus epatitici, quello dell?immunodefcienza acquisita ed altri ancora; batteri, responsabili di infezioni croniche, ed in particolare Helicobacter pylori, implicati soprattutto nell?orticaria cronica; miceti, il cui ruolo nel determinismo di alcuni casi di orticaria cronica è tuttora controverso
Infections agents can be implicated in both acute and chronic urticaria. While in the case of acute urticaria are frequently found infection symptoms, the role of infectious agents in chronic urticaria is still controversial and very complex. Infection-related chronic urticaria has sometimes a vasculitic nature or, more rarely, can present as cold-induced urticaria. The pathogenic mechanisms triggered by the infectious agent may be both immunological and non immunological. Also immediate-type hypersensitivity reactions are likely to occur but only in a limited number of cases. In chronic forms, cell-mediated pathways resembling ?late-phase-reactions? or other non immunological responses can be activated. The development of autoimmunity has been associated with some infectious agents, such as Helicobacter pylori and hepatitis C virus, but its role in chronic urticaria is unknown. Several infectious agents have been associated with urticaria: parasites, a factor for chronic urticaria and, more rarely, for acute urticaria, as Anisakis simplex; several viruses, in particular those responsible for upper respiratory tract infections, but also hepatitis viruses and human immunodefciency virus; bacteria that can cause chronic infections, in particular Helicobacter pylori, implicated very often in chronic urticarias; fungi, whose role in chronic urticaria is still controversial
Achille Sertoli, Maria Cristina Acciai, Emilia Vanni, Vincenzo Maria Calabretta, Carlo Carnevali
Vengono discussi alcuni aspetti dei patch test (PT) forse un po? trascurati anche se particolarmente importanti, quali: l?esecuzione dei PT con i materiali ed i prodotti forniti dal paziente in rapporto al Fenomeno paradosso, alla Compound allergy ed al Fenomeno del quenching; le reazioni positive a comparsa tardiva (da ?Flare up? e da ?Pseudo-fare up?), tardive propriamente dette, persistenti e discordanti; l?Angry back syndrome; le reazioni dubbie; la rilevanza delle reazioni positive; la tolleranza clinica.
Are discussed some aspects of the patch test (PT), that are sometimes neglected even if particularly important: PT done with materials and products provided by the patients in relation with the Paradox phenomenon, the Compound allergy and the Quenching phenomenon; the late emergent positive reactions (know as ?Flare up? or ?Pseudo-fare up?), and late - in the strict sense of the word - persistent and contradictory positive reactions; the Angry back syndrome; the doubtful reac- tions; the relevance of positive reactions; the clinical tolerance.
Paolo Lisi, Leonardo Bianchi, Caterina Foti, Paolo Pigatto, Fabio Ayala, Massimo Gola, Antonio Cristaudo, Donatella Schena, Rossano Hermes Valsecchi, Luca Stingeni
Introduzione: l?eczema dei piedi, nel 3-11% dei casi, è causato da un?allergia da contatto da scarpe, per lo più dovuta a gomma, collanti, concianti chimici, coloranti, alcuni conservanti del cuoio e accessori metallici. I concianti vegetali sembrano avere minore rilevanza rispetto a quelli chimici nell?eziologia della dermatite allergica da contatto da calzature. Il loro potenziale sensibilizzante, tuttavia, è stato poco indagato. Obiettivi: precisare a) la concentrazione ottimale per saggiare mediante patch test i quattro concianti vegetali più largamente utilizzati e/o più ricchi di tannini (castagno, mimosa, quebracho e tara) e b) la prevalenza delle reazioni positive (irritanti e allergiche) agli stessi e a due pelli conciate al vegetale (cuoio da suola, vacchetta). Materiali e metodi: durante la fase 1 è stata valutata la concentrazione ottimale dei 4 concianti vegetali, mediante patch test, veicolandoli in vaselina e a concentrazioni scalari (5, 2 e 1%), in 100 soggetti con patologie dermatologiche di natura varia. Durante la fase 2 è stato valutato il potenziale sensibilizzante e irritante dei 4 concianti vegetali al 2% in vaselina e delle due pelli conciate al vegetale saggiate come tali in 563 pazienti consecutivi sottoposti a patch test per sospetta dermatite da contatto o per malattie cutanee a presunta patogenesi allergica. Risultati e discussione: lo studio ha documentato che la concentrazione ottimale per testare i concianti vegetali è il 2% in vaselina e che le reazioni positive ritardate ai concianti sono molto rare (0,4%) e clinicamente non rilevanti, mentre quelle alle pelli conciate sono più frequenti (1,2%), anche se solamente in 3 dei 7 pazienti erano verosimilmente rilevanti. Queste ultime, non associate a patch test positivo ai singoli concianti, potrebbero essere dovute a prodotti chimici utilizzati (ad esempio, conservanti) o accidentalmente introdotti durante il ciclo produttivo, o a nuovi composti di reazione tra le sostanze chimiche presenti.
Background: foot eczema is caused by shoe contact allergy in 3-11% of the cases. The most common sensitizers are represented by rubber, adhesives, chemical tans, dyes, several biocides and, the last but not the least, metal accessories. Vegetable tans would be less important than chromium salts in the etiology of footwear allergic contact dermatitis. However, few studies have been made on their sensitization potential. Objectives: the two goals for this study were to determine a) the optimal patch testing concentration for the four most widely used and rich of tannins vegetable tans (chestnut, mimosa, quebracho and tara) and b) the prevalence of irritant and allergic reactions to the four vegetable tans and two vegetable-tanned skins (sole leather, vacchetta). Materials and Methods: in phase 1 fnd the optimal patch testing concentration of the four vegetable tans diluted in petrolatum; this was evalu- ated by a serial dilution test (5, 2 and 1%) in 100 subjects with various skin diseases. In phase 2, sensitization and irritation potential of the four vegetable tans in petrolatum 2% and the two vegetable-tanned skins were investigated in 563 patients patch tested for eczematous dermatitis or any suspected allergic skin disorder. Results and discussion: the study demonstrates that optimal concentration to test vegetable tans in petrolatum is 2% and that delayed positive reactions to tans are very rare (0.4%) and not clinically relevant, while those to vegetable-tanned skins (1.2%) are more frequent but probably relevant only in 3 of the 7 patients. These last three cases were not associated to positive patch tests to single tan; therefore, they could be due to preserva- tives, chemical contaminants or reaction compounds introduced accidentally during the production cycle.