Search

Background: Chronic spontaneous urticaria (CSU) is defined as spontaneous occurrence of wheals and/or angioedema for ≥6 weeks. Omalizumab is a monoclonal anti-IgE antibody effective in refractory CSU, but its mechanism of action and markers predictive of response remain not completely defined., Objectives: To correlate baseline levels of two proposed biomarkers, total IgE (bIgE) and d-dimer (bd-dimer), and clinical parameters to omalizumab response and to relapses after drug withdrawal., Methods: In this retrospective Italian multicentre study, clinical data were collected in 470 CSU patients, and bIgE and bd-dimer were measured in 340 and 342 patients, respectively. Disease activity was determined by Urticaria Activity Score 7 (UAS7) at week 1 and 12 after omalizumab starting. Relapses were evaluated during a 2- and 3-month interval after a first and a second course of treatment, respectively., Results: bIgE correlated to a good response to omalizumab since levels were significantly higher in responders than non-responders (P = 0.0002). Conversely, bd-dimer did not correlate to response. There was no correlation between both bIgE and d-dimer and either first or second relapse. Disease duration was significantly longer in patients who experienced either first or second relapse (P < 0.0001 and P = 0.0105, respectively), while baseline UAS7 correlated only to first relapse (P = 0.0023)., Conclusions: Our study confirms bIgE as a reliable biomarker predicting response to omalizumab in CSU, while it does not support the usefulness of bd-dimer unlike previous findings. CSU duration before omalizumab and baseline UAS7 may be clinical markers of relapse risk., (© 2018 European Academy of Dermatology and Venereology.)

Background: The number of elderly patients with psoriasis is steadily increasing in the Western world; nevertheless, they are frequently excluded from biological clinical trials and described as a high-risk group for adverse events. Thus, there is lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biological systemic drugs., Objective: Our aim was to describe our experience with all biological therapies currently used in the elderly (>65 years) psoriatic patients., Methods: A retrospective multicentric review of clinical records of all psoriatic patient aged 65 years or older actually receiving biological drugs (etanercept, adalimumab, infliximab, golimumab, certolizumab pegol, ustekinumab or secukinumab) was undertaken., Results: Our study population included 266 elderly psoriatic patients actually receiving any biological therapy (adalimumab 31.2%, ustekinumab 28.9%, etanercept 20.3%, secukinumab 15%, infliximab 3%, golimumab 1% and certolizumab pegol 0.6%). The PASI score at the baseline (week 0) ranged from 4 to 54; mean ± SD, 16.5 ± 7.1, which changed after biological administration to 3.7 ± 8 at week 16, 1.6 ± 2.1 at week 28 and 1.2 ± 2.1 at week 52. Among 266 elderly psoriatic patients, 25 adverse events were reported during the observation period. The most frequent events were infections with 12 (48%) reports, followed by malignancies with four (16%) reports., Conclusions: To date, our study represents the widest experience on the use of biological drugs in elderly psoriatic patients. We found that all biologics for psoriasis showed a great efficacy also in elderly people, and the rate and the type of adverse effects were similar to the younger patients. In conclusion, the age alone should not limit our therapeutic options. Further observational study using multiple data sources is needed to evaluate long-term effectiveness and safety for elderly psoriatic patients., (© 2018 European Academy of Dermatology and Venereology.)

Background: Few studies have compared the use of different biologics in a real-life setting in plaque psoriasis patients., Objective: To compare the efficacy of biologics in psoriasis/psoriatic arthritis patients., Methods: Patients treated with adalimumab, etanercept and ustekinumab for at least 16 weeks were included. Achievement of Psoriasis Area Severity Index (PASI), PASI 90/100 response and time taken to achieve PASI 90/100 response were measured. Logistic regression was used to evaluate the effect of psoriasis localization on achievement of PASI 100 response., Results: Two hundred and fifty five patients were included. No difference was observed in PASI 90 response between etanercept and ustekinumab (65.5 vs. 55.4%), while adalimumab-treated patients had a higher response versusustekinumab (71.6 vs. 55.4%, p = .02). More patients achieved complete remission (PASI 100 response) with adalimumab versus etanercept (65.7 vs. 23%, p < .001) or ustekinumab (65.7 vs. 44.6%, p = .003). Adalimumab-treated patients achieving PASI 90 responded more quickly (by three and six months) versus ustekinumab or etanercept. PASI100 response was achieved in ∼43% of adalimumab and ustekinumab treated-patients by three months versus etanercept (14.3%), increasing to 92.5, 85.4 and 35.7%, respectively by six months. PASI100 response was associated with psoriasis nail involvement or genital psoriasis., Conclusion: In the real-life setting, adalimumab was the most effective biological agent for the treatment of plaque psoriasis.

Background: Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with psoriasis (PsO). Early diagnosis and prompt therapeutic intervention are crucial for limiting PsA progression and prevention of disability. Dermatologists are in a privileged position to detect early PsA. The management of patients with PsA in the dermatology setting is widely variable., Objective: To provide practical recommendations for the management of patients with PsA in the dermatology setting including early diagnosis and treatment., Methods: A consensus document was written by an expert panel composed by dermatologists (n = 12) and rheumatologists (n = 6). Eleven highly relevant questions were selected and elaborated with answers/statements based on a narrative literature review. The resulting document was discussed in a face-to-face meeting adopting a nominal group technique to reach consensus (i.e. 100% agreement) using the Delphi method., Results: A consensus was achieved in defining the following: the clinical characteristics differentiating inflammatory and non-inflammatory signs and symptoms of joint disease; the most important differential diagnoses of PsA in clinical practice; the most useful screening questionnaires, serum laboratory tests and imaging techniques for the detection of early PsA; the criteria for dermatologist to refer patients with PsO to rheumatologist; the criteria for the diagnosis of PsA; the selection of the indices that the dermatologist could use for measuring the activity and severity of PsA in clinical practice; when systemic steroids and/or intra-articular steroid injections are indicated in the treatment of PsA. Finally, systemic treatments including synthetic and biologic disease-modifying antirheumatic drugs to be considered for the treatment of PsA have been reported., Conclusions: The implementations of these practical recommendations could be very helpful for the management of patients with PsA in the dermatology setting including early diagnosis and treatment., (© 2017 European Academy of Dermatology and Venereology.)

Background: Little data are available about the safety of TNF-α inhibitors in patients with HCV and HBV infection. In particular, data concerning the use of adalimumab in patients with psoriasis and concomitant viral hepatitis are lacking and little is known about the drug's real safety in this context., Objective: To assess the long-term safety of adalimumab in a group of 17 consecutive psoriatic patients affected by chronic HBV infection and 20 consecutive psoriatic patients affected by chronic HCV infection., Methods: Thirty-seven consecutive patients with psoriasis and concomitant HBV or HCV infection being treated with adalimumab at four Italian referral centres (Modena, Padova, Verona and Turin) were assessed before the treatment and at the end of follow-up. Viral load and radiological studies (echography, Fibroscan) were also carried out in some of the patients., Results: The patients responded well to treatment and did not show any HBV or HCV reactivation in a mean follow-up period of 27 and 40 months, respectively. The fibrosis score in eight HCV patients showed a slight reduction: pretreatment mean value 5.83 and post-treatment mean value 5.65., Conclusion: The use of adalimumab seems to be safe in patients with severe psoriasis and HBV or HCV infection. Nevertheless, large-scale prospective studies will be able to provide vital information on the impact of anti-TNF treatment on hepatic function in patients with psoriasis and concomitant chronic HCV or HBV infection and appropriate monitoring scheduling., (© 2017 European Academy of Dermatology and Venereology.)

Background: Interleukin (IL) inhibitors are increasingly used in the management of moderate-to-severe plaque psoriasis. However, their use in patients with a history of cancer is debated., Objective: We conducted a multicenter retrospective study across nine Italian Dermatology Units to assess the real-world effectiveness and safety of IL inhibitors (IL-23, IL-17, IL-12/23) in 136 oncological patients with moderate-to-severe plaque psoriasis. In particular, we evaluated 116 patients who developed the neoplasm before starting the biologic with a mean time from diagnosis of neoplasia to the first biologic dose of 8.31 years. We also assessed 20 patients who received a diagnosis of neoplasm during treatment with IL inhibitors after a mean time of 2.41 years from the start of the biologic with a cumulative incidence of 3.06 per 1000 individuals., Results: Three patients experienced neoplasm recurrence during treatment with IL inhibitors, which led to the discontinuation of these drugs. In our study, biologics have demonstrated safety and effectiveness as treatment options for patients with both a history of neoplasm and those with concurrent tumors. However, further investigation is needed, particularly through larger and longer multicenter studies.

Aim: The aim of this study was to provide practical recommendations for optimizing the use of conventional and biological systemic treatments for moderate-severe chronic plaque psoriasis, particularly in case of transitioning and switching., Methods: A total number of 147 dermatologists from 33 different countries including Italy achieved consensus in providing practical recommendations for the use of conventional and biological treatments for moderate to severe psoriasis based on systematic literature review and/or expert opinion., Results: In general, the continuous treatment regimen should be preferred in order to achieve a complete and long-term control of psoriasis. However, the treatment could be stopped or the dose reduced in case of complete disease clearance. A conventional drug could be associated to biological treatment in selected cases. Transitioning and/or switching could be considered in case of inefficacy or intolerance. A period of wash up is required if transitioning or switching is due to safety issues., Conclusion: This study provides practical suggestions for the optimal use of conventional and biological treatments for chronic plaque psoriasis.

Psoriasis is a chronic inflammatory skin disease triggered by interplay between immune mediators from both innate and adaptive immune systems and skin tissue, in which the IL-23/IL-17 axis is critical. PI3Kδ and PI3Kγ play important roles in various immune cell functions. We found that mice lacking functional PI3Kδ or PI3Kγ are largely protected from imiquimod (IMQ)-induced psoriasis-like dermatitis, correlating with reduced IL-17 levels in the lesions, serum, and the draining lymph nodes. TCRγδ T cells were the major IL-17-producing population in the draining lymph nodes and were significantly diminished in IMQ-treated PI3Kδ knockin and PI3Kγ knockout mice. We also show that PI3Kδ and PI3Kγ inhibitors reduced IFN-γ production by human TCRγδ T cells and IL-17 and IFN-γ production by PBMCs from psoriatic or healthy donors. In addition, inhibition of PI3Kγ, but not PI3Kδ, blocked chemotaxis of CCR6(+)IL-17-producing cells from IMQ-treated mice or healthy human donors. Taken together, these data indicate that PI3Kδ and/or PI3Kγ inhibitors should be considered for treating IL-17-driven diseases, such as psoriasis.

Erythema elevatum diutinum (EED) is a localized, low-grade form of leukocytoclastic vasculitis mainly affecting adults, with only a few pediatric cases reported in the literature. The pathogenesis of this dermatosis is unknown, although an Arthus-type reaction to bacterial and viral antigens seems involved. We describe a case of EED in a 9 year-old child suffering from recurrent pharyngotonsillitis induced by Streptococcus pyogenes. Clinical presentation of the dermatosis was atypical, with vesicles and bullae intermingled with red-purple papules and plaques distributed mainly over the extensor aspects of the extremities. Histopathological examination of a vesiculo-bullous lesion revealed a subepidermal bulla containing neutrophils and nuclear dust suggesting dermatitis herpetiformis. Fibrin in vessel walls was observed throughout the dermis. Direct immunofluorescence was negative. A prompt and complete response to sulphone therapy was obtained in conjunction with tonsillectomy. Clinicians should be aware of atypical presentations of EED in children with vesicles and bullae mimicking During's disease.

Sweet syndrome (SS) associated with myeloproliferative disorders has been considered an inflammatory process mediated by neutrophils in which immunologic mechanisms are operative. The authors report the case of a 68-year-old man suffering from a myelodysplastic syndrome, who presented with a relapsing skin eruption resembling SS. Histopathologically, the skin infiltrates showed prominent neutrophilic features masking the underlying malignant process. Extensive immunophenotypic studies of skin revealed the presence of a few immature myeloid cells intermingled with an overwhelming infiltrate of neutrophils. The atypical cells in the skin had a phenotype identical to that of leukemic cells in the peripheral blood and bone marrow. Whether or not immature myeloid cell precursors constitute a specific infiltrate of leukemia cutis or are a result of recruitment of circulating leukemic cells to this area of inflammation is discussed.