Update on subcutaneous methotrexate for inflammatory arthritis and psoriasis

Methotrexate (MTX) is one of the mainstays of treatment for several immune-mediated inflammatory joint and skin diseases, especially rheumatoid arthritis (RA) and moderate-to-severe psoriasis. Oral MTX has been used for the treatment of such diseases for decades for many reasons. There is, however, a relevant interpatient variability of clinical and safety outcomes that can also be related to differences in patients’ individual pharmacogenomic profile. Orally administered MTX has been found to have a saturable intestinal absorption and nonlinear pharmacokinetics, with significant consequences on drug bioavailability and clinical efficacy. The current evidence shows that parenterally administered MTX results in rapid and complete absorption, higher serum levels, and less variable exposure than oral dosing. The use of parenteral MTX, particularly when administered as a subcutaneous (SC) injection, has recently raised great interest in order to overcome the limitations of oral MTX. The effectiveness and safety of SC MTX have mostly been assessed in rheumatological settings, especially in patients with RA. There are only a limited number of data on SC MTX in juvenile idiopathic arthritis and even fewer in psoriatic disease. Various clinical experiences have suggested that SC MTX is more effective than oral MTX and may provide significant benefit even in patients in whom oral MTX proved to be inadequate. The increased efficacy of SC MTX resulting from higher drug exposure compared with oral MTX has been associated with a similar safety profile and in various reports even with a lower frequency of gastrointestinal complaints. The aim of this article was to review the available literature data on SC MTX treatment of inflammatory arthritis, with special emphasis on RA and psoriasis, examining differences with oral MTX treatment. A brief mention of pharmacokinetics, pharmacodynamic features and pharmacoeconomic considerations is also given

Epidemiology of pediatric psoriasis: a population-based study using two Italian data sources

: Background: Psoriasis can be associated with certain comorbidities. This information is important for family pediatricians (FPs) and general practitioners (GPs) who have a key role in the identification and management of skin diseases. This study aimed to assess the incidence and prevalence rates of pediatrics psoriasis and its association with specific comorbidities.Methods: A retrospective cohort study was performed in patients aged less than 18 years registered in two Italian primary care databases (Pedianet and HSD) between 2015 and 2019. Prevalence and incidence of psoriasis were estimated, and a case-control design was adopted to assess specific comorbidities in psoriasis patients.Results: The annual prevalence rate of psoriasis was 0.2% in Pedianet and between 0.5% and 0.7% in HSD. The incidence rate ranged from 0.47 to 0.58 and from 1.3 to 1.77 per 1,000 person-years in Pedianet and HSD, respectively. Allergic rhinitis, asthma, celiac disease, other malabsorption disease and non-infective cutaneous diseases showed a statistically significant association with psoriasis in Pedianet, while no statistically significant difference was found in HSD.Conclusion: Given the FP-GP transition of patients, there is a need for an accurate registration of clinical correlates, enabling GPs to implement strategies to minimize the lifetime risk of psoriatic progression

Pustular Psoriasis: From Pathophysiology to Treatment

Pustular psoriasis (PP) is a clinicopathological entity encompassing different variants, i.e., acute generalized PP (GPP), PP of pregnancy (impetigo herpetiformis), annular (and circinate) PP, infantile/juvenile PP, palmoplantar PP/palmoplantar pustulosis, and acrodermatitis continua of Hallopeau (ACH), which have in common an eruption of superficial sterile pustules on an erythematous base. Unlike psoriasis vulgaris, in which a key role is played by the adaptive immune system and interleukin (IL)-17/IL-23 axis, PP seems to be characterized by an intense inflammatory response resulting from innate immunity hyperactivation, with prominent involvement of the IL-36 axis. Some nosological aspects of PP are still controversial and debated. Moreover, owing to the rarity and heterogeneity of PP forms, data on prognosis and therapeutic management are limited. Recent progresses in the identification of genetic mutations and immunological mechanisms have promoted a better understanding of PP pathogenesis and might have important consequences on diagnostic refinement and treatment. In this narrative review, current findings in the pathogenesis, classification, clinical features, and therapeutic management of PP are briefly discussed

Randomized, controlled, double-blind clinical study evaluating the safety and efficacy of MD2011001 cream in mild-to-moderate atopic dermatitis of the face and neck in children, adolescents and adults

This mono-center randomized, controlled, double-blind study evaluates the safety and efficacy of MD2011001 cream versus placebo, in mild-to-moderate atopic dermatitis (AD). MD2011001 is a nonsteroidal topical cream containing vitamin E, epigallocatechin gallate and grape seed procyanidins

The Intriguing Links between Psoriasis and Bullous Pemphigoid

The coexistence of psoriasis with autoimmune bullous diseases (AIBDs), particularly bullous pemphigoid (BP), has been documented in case reports and series, as well as in epidemiological studies. The onset of psoriasis precedes that of BP in the majority of cases. Patients with concomitant BP and psoriasis are generally younger at the onset of BP and present with fewer erosions and blisters as compared with patients suffering from isolated BP. Intriguingly, it has been speculated that some BP cases with comorbid psoriasis can actually correspond to anti-laminin gamma-1 pemphigoid, a rare form that was recently recognized as a distinct entity and which can mimic BP and/or other subepidermal AIBDs. The pathomechanisms underlying the BP–psoriasis association have not yet been identified, although several hypotheses have been proposed. The most credited among such hypotheses involves the so-called “epitope spreading” phenomenon, with tissue injury secondary to a primary inflammatory process (i.e., psoriasis) leading to the exposure of sequestered antigens evoking a secondary autoimmune disease (i.e., bullous pemphigoid). This narrative review aims to give a brief overview of the association between psoriasis and BP, examining epidemiological, clinical, and immunopathological features, the pathomechanisms underlying this association, the treatments for psoriasis incriminated as potential triggers of BP, and the therapeutic management of patients with psoriasis and BP

Hydradenitis suppurativa and inflammatory bowel disease: An unusual, but existing association

Inflammatory bowel disease (IBD) could be associated with several extra-intestinal manifestations (EIMs) involving musculoskeletal, hepatopancreatobiliary, ocular, renal, and pulmonary systems, as well as the skin. In the last years, hidradenitis suppurativa (HS) is acquiring an increasing interest. IBD, especially Crohn's disease (CD), is among the most reported associated diseases in HS patients. The aim of this paper is to give a brief overview of data showing a possible epidemiologic and pathogenetic association between IBD and HS. We performed a pooled-data analysis of four studies and pooled prevalence of HS in IBD patients was 12.8%, with a 95%CI of 11.7%-13.9%. HS was present in 17.3% of subjects with CD (95%CI: 15.5%-19.1%) and in 8.5% of UC patients (95%CI: 7.0%-9.9%). Some items, especially altered immune imbalance, are generally involved in IBD pathogenesis as well as invoked by HS. Smoking is one of the most relevant risk factors for both disorders, representing a predictor of their severity, despite, actually, there being a lack of studies analyzing a possible shared pathway. A role for inheritance in HS and CD pathogenesis has been supposed. Despite a genetic susceptibility having been demonstrated for both diseases, further studies are needed to investigate a genetic mutual route. Although the pathogenesis of IBD and HS is generally linked to alterations of the immune response, recent findings suggest a role for intestinal and skin microbiota, respectively. In detail, the frequent finding of Staphylococcus aureus and coagulase-negative staphylococci on HS cutaneous lesions suggests a bacterial involvement in disease pathogenesis. Moreover, microflora varies in the different cutaneous regions of the body and, consequently, two different profiles of HS patients have been identified on these bases. On the other hand, it is well-known that intestinal microbiota may be considered as "the explosive mixture" at the origin of IBD despite the exact relationship having not been completely clarified yet. A better comprehension of the role that some bacterial species play in the IBD pathogenesis may be essential to develop appropriate management strategies in the near future. A final point is represented by some similarities in the therapeutic management of HS and IBD, since they may be controlled by immunomodulatory drugs. In conclusion, an unregulated inflammation may cause the lesions typical of both HS and IBD, particularly when they coexist. However, this is still a largely unexplored field