Coagulation and skin autoimmunity

Several lines of evidence indicate that the immune system, inflammation, and coagulation are simultaneously activated in autoimmune and immune-mediated skin diseases. Pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha induce the expression of the main initiator of coagulation, i.e., tissue factor. The proteases of coagulation in turn act on protease-activated receptors inducing the expression of various pro-inflammatory cytokines triggering inflammation. The cross-talk among immune system, inflammation, and coagulation amplifies and maintains the activation of all three pathways. This review focuses on three skin disorders as chronic spontaneous urticaria (CSU), angioedema, and bullous pemphigoid (BP), in which the relationships among the three systems have been investigated or their clinical consequences are relevant. Markers of thrombin generation, fibrinolysis, and inflammation have been reported to be increased in the plasma during flares of CSU and angioedema, as well as in the active phase of BP, with the marker levels reverting to normal during remission. The coagulation activation seems to be important only at local level in CSU and angioedema while both at local and systemic levels in BP which is the only condition associated with an increased thrombotic risk. The prothrombotic state in autoimmune skin diseases raises the question of the indication of anticoagulant treatment, particularly in the presence of other cardiovascular risk factors

Il pioderma gangrenoso: nuovi aspetti clinici e patogenetici

Il pioderma gangrenoso (PG) \ue8 una rara dermatosi neutrofilica ad evoluzione cronica. Esordisce tipicamente con una o pi\uf9 pustole sterili che, nella presentazione classica della malattia, evolvono rapidamente in ulcere dolenti, di ampiezza e profondit\ue0 variabile, caratterizzate da bordi netti e rilevati di colorito eritemato-violaceo. Varianti di PG meno comuni sono la vegetante e la bollosa. Il PG \ue8 frequentemente associato a patologie sistemiche, in particolare malattie infiammatorie croniche intestinali, affezioni reumatologiche ed ematologiche e neoplasie, ma pu\uf2 presentarsi anche in forma idiopatica. La diagnosi di PG si basa sull\u2019aspetto clinico delle lesioni e sul quadro istopatologico, il quale, seppure non tipico, \ue8 suggestivo. Le terapie pi\uf9 accreditate per il trattamento del PG sono rappresentate dai corticosteroidi sistemici e dalla ciclosporina; tuttavia non sono al momento disponibili linee guida clinico-terapeutiche basate su studi controllati. Negli ultimi quattro anni abbiamo valutato in modo prospettico 20 pazienti (10 donne e 10 uomini) portatori di diverse varianti di PG, con l\u2019obiettivo di proporre una classificazione che metta in relazione il numero delle lesioni cutanee e la percentuale di superficie corporea coinvolta (BSA) con l\u2019approccio terapeutico. Sono stati individuati tre sottogruppi di PG: localizzato (numero di lesioni \uf0b3 1, \uf0a3 3; BSA \uf0a3 5), multilesionale (numero di lesioni > 3, \uf0a3 10; BSA > 5) e disseminato (numero di lesioni > 10; BSA > 25). La ciclosporina sistemica, in monoterapia o in associazione ai corticosteroidi sistemici, si \ue8 dimostrata la terapia pi\uf9 efficace sia nel PG multilesionale che in quello disseminato, mentre il tacrolimus ha dato ottimi risultati nelle forme localizzate. Gli antagonisti del TNF-\u3b1 vanno considerati in casi selezionati di PG resistente alla terapia immunosoppressiva convenzionale. Riteniamo pertanto che tale algoritmo terapeutico possa rivelarsi utile nella pratica clinica, anche se studi controllati dovranno confermarne la validit\ue0. Valutando i risultati di uno studio immunoistochimico da noi condotto, presentiamo infine alcuni aspetti nuovi nella patogenesi del PG

Cutaneous manifestations in patients with COVID-19 : a preliminary review of an emerging issue

Background: The infection caused by the recently identified SARS-CoV-2, called COronaVIrus Disease-19 (COVID-19), has rapidly spread throughout the world. With the exponential increase of patients worldwide, the clinical spectrum of COVID-19 is being better defined and new symptoms are emerging. Numerous reports are documenting the occurrence of different cutaneous manifestations in COVID-19 patients. Objectives: To provide a brief overview of the COVID-19-associated cutaneous lesions. Methods: Literature search was performed in the PubMed, Scopus and Web of Science databases up to 30 April 2020. This narrative review summarizes the available data regarding clinical and histological features of COVID-19-associated skin manifestations. Results: Literature reports showed a great heterogeneity in COVID-19-associated cutaneous manifestations, as well as in their latency periods and associated extracutaneous symptoms. Pathogenic mechanisms are unknown, although the role of hyperactive immune response, complement activation and microvascular injury has been hypothesized. Based on our experience and the literature data, we subdivided the reported cutaneous lesions into six main clinical patterns: i) urticarial rash, ii) confluent erythematous/maculo-papular/morbilliform rash, iii) papulovesicular exanthem, iv) chilblain-like acral pattern, v) livedo reticularis/racemosa-like pattern, vi) purpuric "vasculitic" pattern. These six patterns can be merged into two main settings: the first one - inflammatory/exanthematous - including the first three groups cited above and the second one including the vasculopathic/vasculitic lesions of the last three aforementioned groups. Conclusions: The possible presence of cutaneous findings leading to suspect COVID-19 puts dermatologists in a relevant position. Further studies are needed to delineate the diagnostic and prognostic value of such cutaneous manifestations

Main Oral Manifestations in Immune-Mediated and Inflammatory Rheumatic Diseases

Oral manifestations are frequent in patients with rheumatic diseases. The aim of this review is to offer readers practical advice concerning the onset, diagnosis and treatment of the main oral manifestations encountered in rheumatological and dental clinics. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, periodontal disease, and dysphagia may be the first expression of a number of rheumatic diseases. Some of these manifestations are aspecific and very frequent, such as oral aphthosis, which can be the first manifestation in patients with systemic lupus erythematosus; some are potentially dangerous, such as jaw claudication during the course of giant cell arteritis; and some are very rare but peculiar, such as strawberry-like gingivitis in patients with granulomatosis with polyangiitis. Other oral manifestations are due to adverse reactions to disease-modifying anti-rheumatic drugs. Oral alterations in rheumatic diseases are frequently overlooked in clinical practice, but their prompt recognition not only allows the local lesions to be appropriately treated, but also makes it possible to identify an underlying systemic disease