Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.

Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and leonine facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor ß and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.

Effectiveness and Safety of Anti-interleukin-17 Therapies in Elderly Patients with Psoriasis.

Anti-interleukin-17 agents have recently been developed for the treatment of psoriasis. This study evaluated the tolerance and effectiveness of anti-interleukin-17 agents for psoriasis in elderly patients in daily practice. A multicentre, retrospective study was performed, involving psoriatic patients aged ≥65 years who had received an anti-interleukin-17 agent, including secukinumab, ixekizumab or brodalumab. A total of 114 patients were included: 72 received secukinumab, 35 ixekizumab, and 7 brodalumab. Treatment was stopped in 32 patients (28.9%), because of relapses in 14 patients (41.2%), primary failures in 11 patients (32.4%), or adverse events in 7 patients (20.6%). The 3 most frequently reported adverse events were injection site reactions (n = 4), oral candidiasis (n = 3), and influenza-like illness (n = 3). Regarding effectiveness, 80 patients (70%) reached a Physician Global Assessment score of 0/1, 6 months after treatment initiation. In conclusion, anti-interleukin-17 therapy appears to be an effective and safe therapeutic option for psoriasis treatment in patients aged ≥ 65 years.

Real-World Effectiveness and Safety of Apremilast in Older Patients with Psoriasis.

INTRODUCTION: Apremilast is a drug recently developed for psoriasis. Few data are available on its use in the elderly. We evaluated the tolerance and effectiveness of apremilast used in daily practice for psoriasis treatment in older patients. METHODS: We performed a multicenter, retrospective study involving patients aged ≥ 65 years who had received apremilast as a psoriasis treatment. Demographic data and details regarding psoriasis and adverse events (AEs) were collected from patient medical records. RESULTS: 135 patients were included (mean age: 73.5 years). Treatment was stopped in 74 patients (54.8%) for AEs (n = 43, 56.6%), primary failures (n = 18, 23.4%), and relapses (n = 7, 9.2%). When patients were stratified by age at treatment initiation, the main cause of discontinuation in patients ≥ 75 years was AEs, whereas in patients aged 65-74 years it was primary failures (28.3%). Sixty-one patients reported AEs, mainly digestive (n = 49). Regarding effectiveness, 45.2% of patients reached PGA 0/1 between 3 and 6 months after treatment initiation. One-year apremilast continuation rates were better in the 65-74 and 75-84 years subgroups than in the > 85 years subgroup (p = 0.01). CONCLUSION: Apremilast seems to be an effective and safe therapeutic option for psoriasis in the elderly. The main AEs reported by patients did not seem to differ from those reported previously in younger populations. However, AEs were more frequent in patients > 75 years old leading to more frequent discontinuation of apremilast compared with younger patients, suggesting a higher level of vigilance is needed in the elderly.

Higher Frequency of Dipeptidyl Peptidase-4 Inhibitor Intake in Bullous Pemphigoid Patients than in the French General Population.

Dipeptidyl peptidase-4 inhibitors have been suspected to induce bullous pemphigoid (BP). The objective of this study was to compare the observed frequency of gliptin intake in a large sample of 1,787 BP patients diagnosed between 2012 and 2015 in France, with the expected frequency after indirect age standardization on 225,412 individuals extracted from the database of the National Healthcare Insurance Agency. The secondary objective was to assess the clinical characteristics and the course of gliptin-associated BP, depending on whether gliptin was continued or stopped. The observed frequencies of intake of the whole gliptin class and that of vildagliptin in the BP population were higher than those in the general population after age standardization (whole gliptin class: 6.0%; 95% confidence interval = 4.9-7.1% vs. 3.6%, observed-to-expected drug intake ratio = 1.7; 95% confidence interval = 1.4-2.0; P < 0.0001; vildagliptin = 3.3%; 95% confidence interval = 2.5-4.1% vs. 0.7%, ratio = 4.4; 95% confidence interval = 3.5-5.7; P < 0.0001). The association of any gliptin+metformin was also higher than in the general population, ratio = 1.8 (95% confidence interval = 1.3-2.4; P < 0.0001). Gliptin-associated BP had no specific clinical characteristics. Gliptin was stopped in 48 (45.3%) cases. Median duration to achieve disease control, rate, and delay of relapse were not different whether gliptin was stopped or continued. This study strongly supports the association between gliptin intake, particularly vildagliptin, and the onset of BP.

Severe androgenetic alopecia as a proxy of metabolic syndrome in male psoriatic patients older than 59 years.

BACKGROUND: Whereas several studies have underlined the association between severe psoriasis and metabolic syndrome (MetS), the association of androgenetic alopecia (AGA) and MetS have yielded inconsistent results. OBJECTIVE: To investigate the relationship between AGA and the components of MetS in a population of psoriatic male patients. METHODS: A non-interventional, cross-sectional, multicenter study was conducted in France. A standardized questionnaire was completed, including information on components of MetS and other possible risk factors. MetS was defined in this study as a combination of three or more of the four components of MetS: waist circumference, hyperlipidemia, diabetes mellitus and hypertension. In addition, a standardized simplified Norwood classification limited into 5 grades (0-4) was used. RESULTS: In a total of 1073 male patients, hypertension, high waist circumference, diabetes mellitus and hyperlipidemia were observed in 28%, 59%, 11%, and 31%, respectively. In age-adjusted multivariate analysis, severe AGA (grade 3-4 versus grade 0) was associated with the presence of at least one component of MetS. By groups of age, a statistically significant association of severe AGA and MetS was demonstrated in patients over 59 years. Severe AGA was also associated with a first degree familial history of major cardiovascular event in patients older than 59 years. CONCLUSIONS: Our study, based on a simplified but stringent definition of MetS, confirmed the link between severe AGA and individual components of MetS in psoriatic patients. This argues for careful follow-up with regular screening in male psoriatic patients with severe AGA in order to early detect determinants of MetS.