Comorbidity and Therapeutic Approaches in Patients with Necrobiosis Lipoidica

<b><i>Background:</i></b> Necrobiosis lipoidica (NL) is a rare granulomatous disorder of unknown aetiology. Randomized controlled studies are not available due to it being an orphan disease. <b><i>Objectives:</i></b> We evaluated patients in 2 dermatological centres to cluster data about epidemiology, the therapeutic approaches for NL, and their efficacy. <b><i>Materials and Methods:</i></b> Comorbidity and the efficacy of the applied treatment was assessed for 98 patients. <b><i>Results:</i></b> We identified 54% of patients with concomitant diabetes and 19% with thyroidal disorders. Topical steroids (85.7%) were predominantly used followed by calcineurin inhibitors (31%) and phototherapy (41.8%). Systemically, fumaric acid esters were more frequently applied (26.8%) than steroids (24.4%) and dapsone (24.4%). Steroids, compression therapy, calcineurin inhibitors, phototherapy, fumaric acid esters, and dapsone showed remarkable efficacy. <b><i>Conclusion:</i></b> Therapeutic options were chosen individually in accordance with the severity of NL and presence of ulceration. Topical calcineurin inhibitors, systemic application of fumaric acid esters, and dapsone represent effective alternatives to the use of steroids.

Translating the 2020 AAD-NPF Guidelines of Care for the Management of Psoriasis With Systemic Nonbiologics to Clinical Practice

In 2020, the American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF) released a set of guidelines for the management of psoriasis in adults with systemic nonbiologic therapies, including acitretin, apremilast, cyclosporine, fumaric acid esters, methotrexate, and tofacitinib. This review addresses dosing, efficacy, toxicity, drug-related interactions, and contraindications alongside evidence-based treatment recommendations for each systemic therapy. Important considerations for treatment such as drug selection, initiation of therapy, drug monitoring, and patient management also are discussed. Physicians are encouraged to use these recommendations to guide treatments based on individual patient needs and disease characteristics.

Different Fumaric Acid Esters Elicit Distinct Pharmacologic Responses

ObjectiveTo test the hypothesis that dimethyl fumarate (DMF, Tecfidera) elicits different biological changes from DMF combined with monoethyl fumarate (MEF) (Fumaderm, a psoriasis therapy), we investigated DMF and MEF in rodents and cynomolgus monkeys. Possible translatability of findings was explored with lymphocyte counts from a retrospective cohort of patients with MS.MethodsIn rodents, we evaluated pharmacokinetic and pharmacodynamic effects induced by DMF and MEF monotherapies or in combination (DMF/MEF). Clinical implications were investigated in a retrospective, observational analysis of patients with MS treated with DMF/MEF (n = 36).ResultsIn rodents and cynomolgus monkeys, monomethyl fumarate (MMF, the primary metabolite of DMF) exhibited higher brain penetration, whereas MEF was preferentially partitioned into the kidney. In mice, transcriptional profiling for DMF and MEF alone identified both common and distinct pharmacodynamic responses, with almost no overlap between DMF- and MEF-induced differentially expressed gene profiles in immune tissues. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated oxidative stress response pathway was exclusively regulated by DMF, whereas apoptosis pathways were activated by MEF. DMF/MEF treatment demonstrated that DMF and MEF functionally interact to modify DMF- and MEF-specific responses in unpredictable ways. In patients with MS, DMF/MEF treatment led to early and pronounced suppression of lymphocytes, predominantly CD8+ T cells. In a multivariate regression analysis, the absolute lymphocyte count (ALC) was associated with age at therapy start, baseline ALC, and DMF/MEF dosage but not with previous immunosuppressive medication and sex. Furthermore, the ALC increased in a small cohort of patients with MS (n = 6/7) after switching from DMF/MEF to DMF monotherapy.ConclusionsFumaric acid esters exhibit different biodistribution and may elicit different biological responses; furthermore, pharmacodynamic effects of combinations differ unpredictably from monotherapy. The strong potential to induce lymphopenia in patients with MS may be a result of activation of apoptosis pathways by MEF compared with DMF.