Erdheim-Chester Disease Due to a Novel Internal Duplication of NRAS: Response to Targeted Therapy with Cobimetinib.

Histiocytoses encompass a group of exceptionally rare disorders characterized by the abnormal infiltration of tissues by histocytes. Among these, Erdheim-Chester disease (ECD) stands out as a multisystem histiocytosis that typically affects bones and various other tissues. Historically, the treatment of ECD has been challenging. However, recent breakthroughs in our understanding, particularly the discovery of somatic mutations in the RAS-MAPK pathway, have opened new opportunities for targeted therapy in a significant subset of patients with ECD and other histiocytoses. In this report, we present the case of a patient with ECD harboring a previously unidentified microduplication in the NRAS gene in a small fraction of skin cells. This discovery played a pivotal role in tailoring an effective therapeutic approach involving kinase inhibitors downstream of NRAS. This case underscores the crucial role of deep sequencing of tissue samples in ECD, enabling the delivery of personalized targeted therapy to patients.

Biomarkers of endothelial dysfunction and atherosclerosis in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased prevalence of subclinical atherosclerosis and cardiovascular risk. Angiopoietin-2 (Ang-2), asymmetric dimethylarginine (ADMA), and osteoprotegerin (OPG) are molecules related to endothelial dysfunction (ED) and atherosclerosis, but also to disease severity in patients with chronic inflammatory disorders. In this case-control study, we aimed to investigate serum Ang-2, ADMA, and OPG levels in patients with HS, and to assess the potential relationship between these levels and disease severity. Seventy-five patients with HS and 60 controls were assessed. Serum Ang-2, ADMA, and OPG concentrations were determined in all participants. HS patients had significantly higher Ang-2 and ADMA levels than controls after adjusting for confounders. Besides, Ang-2 concentrations positively correlated with disease severity in the adjusted multivariable analysis. Nevertheless, serum OPG levels did not significantly differ between HS patients and controls. Our results indicate that serum Ang-2 and ADMA levels are significantly increased in patients with HS. Furthermore, Ang-2 might be a suitable marker of HS severity.

High prevalence of cryofibrinogenemia in patients with chilblains during the COVID-19 outbreak.

BACKGROUND: Many cutaneous manifestations have been described in possible association with the COVID-19 pandemic, including acral lesions resembling chilblains. The underlying pathomechanisms of COVID-19 chilblains are not fully understood. The aim of this study was to describe the clinical, pathological, and laboratory findings of a series of patients who developed chilblains during the COVID-19 outbreak and to investigate the possible factors that could be involved in the pathogenesis of these lesions. METHODS: We conducted a prospective cohort study that included 54 patients who presented with chilblains during the highest peak in the incidence of COVID-19 in Cantabria (northern Spain). Skin biopsies were performed on 10 of these patients who presented with recent lesions. Laboratory investigations, including immunological analysis, serological studies, and the assessment of cryoproteins, were also performed. RESULTS: Most patients presented erythematous plaques located on the toes and/or purpuric macules located on the feet. Histopathological findings were compatible with those of idiopathic chilblains. Immunohistochemical evaluation showed C3d and C4d deposits in the vessel walls in seven cases. The autoimmunity panel was negative in most of our series. Cryoprotein testing showed positive cryofibrinogen in two-thirds (66.7%) of the patients assessed. On follow-up, most patients presented almost complete resolution, although six patients required prednisone and antiaggregant drug treatment. CONCLUSIONS: This study shows, for the first time to our knowledge, a high prevalence of cryofibrinogenemia in patients with chilblains during the COVID-19 pandemic. Cryofibrinogenemia could be implicated in the pathogenesis of chilblains related to COVID-19.

Atherogenic index of plasma is associated with the severity of Hidradenitis Suppurativa: a case-control study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with several comorbidities and vascular risk factors, such as dyslipidemia. The present study aimed to assess the possible associations between the lipid profile and atherogenic indexes and the severity of HS. METHODS: This case-control study enrolled 78 HS patients and 62 healthy controls. Classic lipid profile and lipoprotein ratios, including the atherogenic index of plasma (AIP), were evaluated. The severity of HS was measured by the HS Physician Global Assessment (PGA). RESULTS: HS-patients had lower serum total cholesterol and HDL-C levels and higher AIP than the control group. AIP was positively correlated to BMI, waist circumference, systolic and diastolic blood pressure, LDL-C, triglycerides, non-HDL-C, ApoB, HOMA, and hs-CRP and negatively to HDL-C and ApoA1. For the overall lipid profile, only AIP was related to a more severe HS (PGA ≥ 3) after controlling for age, sex, BMI, insulin resistance (IR), active smoking, and statin use (r = 0.268; p = 0.023). Multiple logistic regression adjusted for age, sex, BMI, IR, smoking status and statin use, showed that AIP ≥ 0.11 was significantly associated with the severity of HS (OR, 4.38; CI 95%, 1.09-17.50; p = 0.037). CONCLUSIONS: In conclusion, these results showed that AIP is significantly and independently associated with HS severity.