Pioderma gangrenoso: review della letteratura e nuove prospettive terapeutiche

Il Pioderma Gangrenoso(PG) è una rara dermatosi infiammatoria neutrofila ad eziologia sconosciuta, che è stata descritta per la prima volta nel 1930 da Brunsting.Sebbene una percentuale variabile dal 25 al 50% dei casi di PG sia idiopatico, in quasi la metà dei casi si associa ad altre malattie, in particolare le associazioni più comuni sono con le malattie infiammatorie croniche intestinali(IBD), con malattie reumatologiche, ematologiche e con disordini immunologici. Attualmente il PG viene considerato una patologia idiopatica, ad andamento cronico, infiammatoria, neutrofilia e ulcerativa, in cui il processo che ne è alla base è una chemiotassi neutrofila anormale.. Si tratta di una patologia che richiede un approccio multidisciplinare del paziente e che coinvolge diversi specialisti: dermatologi, gastroenterologi, immunologi, chirurghi plastici ed altri specialisti a seconda delle sedi in cui il PG va a localizzarsi.L’incidenza globale del PG non è certa, ma è stata stimata approssimativamente tra 3-10 pazienti per milione per anno6. Il picco di incidenza è compreso tra i 20 e i 50 anni e con una lieve prevalenza nel sesso femminile, il rapporto femmine/maschi è variabile da 1:1 a 3:1. E’ una patologia rara in età pediatrica con un’incidenza di circa il 4% . Si suppone che nell’eziopatogenesi della malattia siano interessati fattori immunologici e una disfunzione dei neutrofili, ciò sarebbe validato da una serie di considerazioni: • Frequente associazione con malattie autoimmuni • Fenomeno della patergia (comparsa di nuovi lesioni su un sito di trauma) • Deficit della risposta immune cellulo-mediata • Deposito di immunoglobuline nei vasi ematici del derma e l’associazione del PG con l’iperglobulinemia mono o policlonale. . Si distinguono 4 varianti cliniche di PG: ulcerativa, pustolosa,bollosa e vegetante.La diagnosi di PG è esclusivamente clinica, non esistono markers sierologici, ematologici o istopatologici che possano essere considerati caratteristici di questa malattia. Sebbene esistano delle linee guida generale per la gestione del PG, il clinico dovrà avere un approccio personalizzato ad ogni singolo caso, tenendo in considerazioni diverse variabili: numero, sede e profondità delle lesioni, le malattie associate, le condizioni generali del paziente, e i rischi correlati al ricorso ad una determinata terapia. L’obiettivo del trattamento terapeutico è quello di ridurre il processo infiammatorio dell’ulcera, in maniera tale da promuovere la guarigione, la riduzione del dolore, controllare le malattie associate. La nostra esperienza è che il paziente con associate IBD, artrite erosiva o disordini mielodisplastici rispondono meglio se le malattie associate sono trattate in maniera aggressiva. Nel PG idiopatico si può ottenere una remissione indotta da brevi cicli( 6-9 mesi) di farmaci immunosoppressori.La terapia locale ha come scopo quello di ridurre il potenziale infiammatorio delle lesioni, prevenire infezioni secondarie, gestire l’essudato, proteggere da eventuali traumi, gestire la sintomatologia dolorosa. Molti casi di PG richiedono una terapia sistemica per ottenere una guarigione completa. Numerosi farmaci sono stati utilizzati ma non esistono in letteratura trials randomizzati e controllati che ne dimostrino l’efficacia terapeutica. Il trattamento delle malattie associate è una condizione importante in quanto ha un impatto favorevole sulle lesioni cutanee. I corticosteroidi sistemici rappresentano i farmaci di prima scelta nella terapia del PG: corticosteroidi orali vengono somministrati al dosaggio di 1-2 mg/kg/die e consentono di ottenere una riduzione del dolore e promuovere la guarigione.La ciclosporina rappresenta una valida opzione terapeutica nel trattamento di quei casi di PG resistenti alla terapia cortisonica o in cui i cortisonici determinano importanti effetti collaterali. Altri farmaci che possono essere utilizzati in alternativa ai cortisonici sono immunosoppressori quali: ciclofosfamide,dapsone, azatioprina,micofenolato mofetile,etc.La patogenesi del PG rimane sconosciuta, ma l’associazioni con malattie quali le IBD e l’artrite reumatoide in cui il TNF-α svolge un ruolo chiave nello sviluppo, indica come tale molecola abbia sicuramente importanza nella determinazione del PG. Il TNF- α è una citochina proinfiammatoria prodotta da macrofagi, linfociti e polimorfonucleati neutrofili. Svolge numerose attività biologiche, tra cui: apoptosi, necrosi tumorale, attivazione e metabolismo dei granulociti, linfociti, eosinofili, fibroblasti, condrociti e cellule endoteliali. Inoltre induce edema, prende parte alla formazione del granuloma, attiva la cascata coagulativa, ed è implicato nel richiamo di cellule infiammatorie. I farmaci biologici anti TNF-α rappresentato pertanto un nuovo approccio terapeutico al Pioderma gangrenoso e vari case report ne hanno dimostrato l'efficacia

Clinical evaluation of the efficacy and safety of a medical device in various forms containing Triticum vulgare for the treatment of venous leg ulcers – A randomized pilot study

This study was carried out to assess the efficacy and tolerability of the topical application of an aqueous extract of Triticum vulgare (TV) in different vehicles (cream, impregnated gauzes, foam, hydrogel, and dressing gel) for the treatment of venous lower leg ulcers. Fifty patients were randomized to receive one of the five investigational vehicles. Treatment was performed up to complete healing or to a maximum of 29 days. The wound size reduction from baseline was the primary efficacy variable, which was measured by means of a noninvasive laser scanner instrument for wound assessment. In all groups, apart from the foam group, a similar trend toward the reduction of the surface area was observed. The cream showed the greatest effect on the mean reduction of the lesion size. At last visit, six ulcers were healed: two in the cream group, three in the gauze group, and one in the dressing gel group. In the patients treated with the cream, the gauzes, the hydrogel, and the dressing gel, the reduction of lesion size was 40%–50%; the reduction was smaller in the foam group. No impact in terms of age on the healing process was found. The Total Symptoms Score decreased in all groups during the study; a greater efficacy in terms of signs/symptoms was observed in the patients treated with the gauzes. In the dressing gel group, one patient had an infection of the wound after 3 weeks of treatment and 2 of colonization, leading to a systemic antibiotic treatment. The events were judged as nonrelated to the device used. On the basis of the results, it could be argued that the medical device may be useful in the treatment of chronic venous ulcer

Awareness of obesity among patients with psoriasis

Dear Editor, Chronic plaque psoriasis is frequently associated with metabolic comorbidities, including obesity that have an important impact on the disease

Secukinumab demonstrates improvements in absolute and relative psoriasis area severity indices in moderate-to-severe plaque psoriasis: results from a European, multicentric, retrospective, real-world study

AbstractObjective: This European, multicentric, retrospective study aimed to collect data on secukinumab effectiveness in a real-world setting.Research design and methods: All psoriatic patients st..

Acne fulminans associated with lymecycline intake: A case report

Acne fulminans (AF) is a rare acne variant characterized by sudden onset of painful nodules on the face, chest, and back in the presence of systemic symptoms. Pharmacologic agents such as steroid hormones and isotretinoin are well-known triggers, and several cases have been described. We report a case of AF occurring a few days after lymecycline therapy initiation

A new class of biologic agents facing the therapeutic paradigm in psoriasis: anti-IL-23 agents

Psoriasis is a chronic inflammatory skin disease whose pathogenesis is driven by multiple cytokine-mediated pathways. In this immunologic setting, the centrality of the IL-23/IL-17 axis and its therapeutic relevance has emerged. Areas covered: This review is aimed at collecting preliminary data on IL23p19 blockers developed for the treatment of plaque psoriasis. Three agents, guselkumab, risankizumab, and tildrakizumab, are currently being tested in phase III trials, while LY2525623 is currently being tested in phase II trials. Treatment with these agents resulted in a marked improvement in disease severity, confirming the pathogenic relevance of IL-23 in psoriasis. Expert opinion: Selective neutralization of IL-23 is an advantageous strategy for treating psoriasis. Preliminary data from phase II and III trials have shown the capability of this therapeutic class in inducing complete clearance or almost complete clearance in many patients: the highest PASI 90 rates were achieved by guselkumab, tildrakizumab, and risankizumab in 73.3%, 74% and 77% of cases, respectively. Moreover, the highest PASI 100 rates were achieved in 33%, 14%, and 48% of patients treated with guselkumab, tildrakizumab, and risankizumab, respectively. Further studies are needed to confirm this remarkable efficacy over long-term treatment periods

Risankizumab for the treatment of moderate to severe psoriasis

Introduction: Psoriasis is a chronic inflammatory skin disorder pathogenically mediated by multiple cytokines, including interleukin (IL)-23, IL-17, and TNF. An emerging class of therapeutics that selectively blocks IL-23 has been developed. Among these new agents, risankizumab is now being investigated in phase III clinical trials, and the preliminary data are promising in inducing an excellent clinical response. Areas covered: This review aims to describe the pathogenic role of IL-23 in psoriasis and to collect clinical data related to the efficacy and safety of risankizumab, an anti-IL-23p19 agent, in the treatment of psoriasis. Expert opinion: Risankizumab showed high response rates in reaching complete or almost complete clearance of psoriasis. When compared to other similarly effective drugs, it may show some advantages related to its mechanism of action (direct blockade of the main pathogenic pathway), safety (no impact on the immune surveillance against Candida infection), therapeutic regimen (every-12-week injections), and effectiveness in the treatment of immune-mediated psoriasis comorbid conditions, such as psoriatic arthritis and Crohn’s disease

Epidermal skin grafting in vitiligo: a pilot study

Vitiligo is a multifactorial acquired dermatosis characterised by achromic or hypochromic macules and by the absence of functioning melanocytes. Treatment depends on the extent of the affected areas and on disease activity. Surgical techniques have proven to be effective in stable cases but can be time-consuming and, in some cases, aesthetically unsatisfying or painful for the patients. The aim of the study was to assess the clinical safety and effectiveness of a new automatic epidermal skin harvesting device in patients with stable localised vitiligo over a minimum 12-month period. This new system (CELLUTOME™ Epidermal Harvesting System, KCI, an ACELITY Company, San Antonio, TX) is a commercially available epidermal skin harvesting system that can be used without local anaesthesia or other pre-treatments and has been shown to have low rates of donor site morbidity. Epidermal skin grafts can used in patients with acute and hard to heal chronic wounds, burns and stable vitiligo. The use of advanced therapies may improve the quality of life, have cost benefits and accelerate re-pigmentation of patients with vitiligo. In our preliminary study, this system was seen to be a safe and efficacious means of harvesting epidermal micrografts containing melanocytes for use in patients with stable vitiligo unresponsive to standard therapies