38 research outputs found

    Phosphodiesterase 4 inhibition in the treatment of psoriasis, psoriatic arthritis and other chronic inflammatory diseases

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    Agents which increase intracellular cyclic adenosine monophosphate (cAMP) may have an antagonistic effect on pro-inflammatory molecule production so that inhibitors of the cAMP degrading phosphodiesterases have been identified as promising drugs in chronic inflammatory disorders. Although many such inhibitors have been developed, their introduction in the clinic has been hampered by their narrow therapeutic window with side effects such as nausea and emesis occurring at sub-therapeutic levels. The latest generation of inhibitors selective for phosphodiesterase 4 (PDE4), such as apremilast and roflumilast, seems to have an improved therapeutic index. While roflumilast has been approved for the treatment of exacerbated chronic obstructive pulmonary disease (COPD), apremilast shows promising activity in dermatological and rheumatological conditions. Studies in psoriasis and psoriatic arthritis have demonstrated clinical activity of apremilast. Efficacy in psoriasis is probably equivalent to methotrexate but less than that of monoclonal antibody inhibitors of tumour necrosis factor (TNFi). Similarly, in psoriatic arthritis efficacy is less than that of TNF inhibitors. PDE4 inhibitors hold the promise to broaden the portfolio of anti-inflammatory therapeutic approaches in a range of chronic inflammatory diseases which may include granulomatous skin diseases, some subtypes of chronic eczema and probably cutaneous lupus erythematosus. In this review, the authors highlight the mode of action of PDE4 inhibitors on skin and joint inflammatory responses and discuss their future role in clinical practice. Current developments in the field including the development of topical applications and the development of PDE4 inhibitors which specifically target the subform PDE4B will be discussed

    A randomized controlled trial of an emollient with ceramide and filaggrin-associated amino acids for the primary prevention of atopic dermatitis in high-risk infants

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    Background: Skin barrier dysfunction may precede infantile development of clinical atopic dermatitis (AD). Early-life emollient therapy to enhance barrier function may prevent or modify AD development in high-risk infants. Objectives: (a) To determine whether daily full-body application of an emollient with ceramide and amino acids (study emollient) can reduce the cumulative AD incidence compared to standard skin care at 1 year of age. (b) To evaluate the study emollient's effect on skin barrier function, natural moisturizing factor and the microbiome using non-invasive biophysical and biochemical techniques. Methods: We performed a single-centre, investigator-blinded, randomized controlled trial enrolling infants at high risk for AD development determined by family history. The intervention was full-body once-daily application of the study emollient. The control arm was asked to not apply full-body emollient regularly and only use an emollient of their choice for dry skin. The primary outcome was the cumulative incidence of AD diagnosed at 12 months by a blinded investigator. Results: Less than half the target sample size was enrolled (n = 100, goal sample was 208) with 28% lost to follow-up. Across all clinical end points, a numerical trend was observed in favour of the intervention, although not statistically significant likely due to lack of power from under-enrolment. AD was diagnosed in 13.2% vs. 25.0% at 12 months (P = 0.204) and 19.4% vs. 31.0% at 2 years (P = 0.296) in intervention vs. control groups, respectively. There were no significant differences between groups in skin barrier or microbiome assessments. While there were no serious adverse events, there were more cases of reported contact dermatitis in the intervention vs. control arms, 9.3% vs. 4.3%, respectively; however, these events were not related to the study emollient and most mild in severity. Conclusion: The observed trends suggest a protective effect of daily study emollient therapy compared to control

    How to Evaluate Treatment Response in Hair Diseases

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    When treating patients with scalp diseases, it is essential to be able to evaluate treatment response. Treatment response will allow further decision-making such as increasing or decreasing treatment dose, changing the treatment vehicle, changing therapy, or adding adjuvant treatments. Sometimes, hair disorders have multifactorial causes, so response to treatment may be affected not only by the prescribed therapy but also by other factors. Follow-up must include photographic and trichoscopic documentation, as well as inquiring about patient coping and expectations. Treatment goals must be clear to the patient. We should consider that a patient might have more than one disease or a new disease can appear such as contact dermatitis, impetigo, or tinea. If there is no response after 3–6 months of therapy with good patient compliance, a trichoscopy-guided biopsy might reveal valuable information. Another important challenge to be considered is cicatricial alopecia; even to the most trained eye, cicatricial diseases can mimic noncicatricial pathologies, and cicatricial alopecias tend to have an initial inflammatory phase in which no cicatricial findings are found. Dynamic trichoscopy is the best way to evaluate treatment response since it allows the assessment of trichoscopic signs of active disease. This assessment will benefit therapeutic decision and selection of a biopsy area. Knowledge of trichoscopic signs of active inflammation and signs of fibrosis in each disease will enable the clinician to understand that trichoscopy allows to identify the mechanisms of the disease rather than pathognomonic and unchanging signs. In this chapter, we will describe every step to be taken in all the possible presentations that a physician could face during treatment of hair disorders. The authors have tried to summarize and explain step by step what to expect, how to evaluate, and what to do when treatment is not working, trying to offer a guidance for all those who help patients with hair disorders
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