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.

Bone Metabolism in Patients with Hidradenitis Suppurativa: A Case-control Study.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicles. The aim of this case-control study was to assess whether HS is associated with disturbances in trabecular bone score, bone mineral density, bone remodelling markers, and calciotropic hormones. A total of 81 patients and 79 controls of similar age and sex were included. Demographic, anthropometric, laboratory data, trabecular bone score, bone mineral density, serum 25-hydroxyvitamin D (25OHD), serum amino-terminal pro-peptide of type 1 collagen (PINP), and C-terminal telopeptide of type 1 collagen (CTX) concentrations were assessed in both groups. Patients with HS had lower serum 25OHD levels than controls, and approximately 62% of them had vitamin D deficiency. Serum PINP was increased and CTX was decreased in patients with HS. Fully adjusted trabecular bone score values were lower in patients with HS compared with controls. Adjusted lumbar bone mineral density was similar in HS and controls, whilst total hip bone mineral density was lower in patients with HS. There were no statistical differences regarding disease severity in terms of 25OHD, serum turnover markers, bone mineral density, or trabecular bone score values. This study shows that patients with HS have lower trabecular bone score and total hip bone mineral density values than population-based controls. In addition, the prevalence of vitamin D deficiency is high in subjects with HS.

Successful treatment of idiopathic Harlequin Syndrome with oxybutynin and propranolol.

Harlequin syndrome (HS) is a rare entity derived from the dysfunction of the sympathetic nervous system. It is characterised by unilateral facial flushing and sweating induced by exercise, heat and emotion. Most cases are primary with an unknown pathogenic mechanism. In these cases, the prognosis is favourable. Medical or surgical treatments are not usually required for idiopathic HS. However, symptomatic treatment may be indicated when symptoms affect the quality of life of patients. We present the case of a patient with idiopathic HS successfully treated with oxybutynin and propranolol. In this patient, a marked improvement in both hyperhidrosis and facial erythema was noted with this combined therapy. We consider it of interest to highlight the response of our patient to the treatment employed, which may be advantageous in future cases of this rare disorder.

Secondary hypereosinophilic syndrome: an unusual manifestation in a patient with syringotropic mycosis fungoides and human immunodeficiency virus infection.

Syringotropic mycosis fungoides is a very rare variant of cutaneous T-cell lymphomas characterised by prominent involvement of the eccrine glands. Hypereosinophilic syndrome refers to a rare group of conditions that are associated with persistent eosinophilia with organ involvement. It is classified into idiopathic, primary and secondary (reactive). We report herein an unusual case of hypereosinophilic syndrome with great impact on morbidity, which developed in a patient with human immunodeficiency virus infection and long-time misdiagnosed syringotropic mycosis fungoides.

Evaluation of serum omentin-1 and apelin concentrations in patients with hidradenitis suppurativa.

INTRODUCTION: Recent studies suggest a role of adipokines in the pathogenesis of hidradenitis suppurativa (HS). Omentin-1 and apelin are two recently identified adipokines that have been involved in the regulation of metabolic and inflammatory responses. AIM: To investigate serum omentin-1 and apelin levels in patients with HS and to assess their associations with metabolic parameters, disease severity and HS risk. MATERIAL AND METHODS: This case-control study included 139 non-diabetic individuals (78 HS patients and 61 ageand sex-matched controls). Serum concentrations of omentin-1 and apelin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured in all participants. RESULTS: Serum omentin-1 concentrations were significantly higher in HS patients compared to controls, whereas apelin serum levels did not significantly differ between both groups. These differences in omentin-1 concentrations remained significant even after adjusting for age, sex, and body mass index (BMI). The results of logistic regression analysis showed that increased omentin-1 plasma levels were an independent risk factor for HS. However, we found no association between serum levels of both omentin-1 and apelin with HS severity. CONCLUSIONS: Our results show that patients with HS have raised omentin-1 serum levels, which are associated with HS risk.

Association of retinol binding protein4 (RBP4) and ghrelin plasma levels with insulin resistance and disease severity in non-diabetic patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with insulin resistance (IR). Retinol binding protein 4 (RBP4) and ghrelin are two bioactive proteins that have been involved in glucose metabolism and IR, but also in the regulation of immune and inflammatory processes. The aim of this study was to determine the serum levels of RBP4 and ghrelin in patients with HS, and to assess the possible relationship between these levels and IR, disease severity and HS risk. A total of 137 subjects (77 HS patients and 60 controls) without diabetes mellitus were enrolled in this cross-sectional study. Patients with HS had significantly higher RBP4 but lower ghrelin plasma levels than controls, independently of body mass index (BMI). Serum RBP4 levels were positively correlated to disease severity and IR in HS patients. However, we found no association between ghrelin levels and any clinical or laboratory parameters. Moreover, high serum RBP4 and low ghrelin levels were associated with an increased risk for HS. Our results suggest that high RBP4 levels may be a surrogate biomarker for IR in patients with HS. Moreover, increased RBP4 and decreased ghrelin levels could also be independent risk factors for the development of HS.

What causes hidradenitis suppurativa ?-15 years after.

The 14 authors of the first review article on hidradenitis suppurativa (HS) pathogenesis published 2008 in EXPERIMENTAL DERMATOLOGY cumulating from the 1st International Hidradenitis Suppurativa Research Symposium held March 30-April 2, 2006 in Dessau, Germany with 33 participants were prophetic when they wrote "Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy." (Kurzen et al. What causes hidradenitis suppurativa? Exp Dermatol 2008;17:455). Fifteen years later, there is no doubt that the desired renaissance of solid basic HS research is progressing with rapid steps and that HS has developed deep roots among inflammatory diseases in Dermatology and beyond, recognized as "the only inflammatory skin disease than can be healed". This anniversary article of 43 research-performing authors from all around the globe in the official journal of the European Hidradenitis Suppurativa Foundation e.V. (EHSF e.V.) and the Hidradenitis Suppurativa Foundation, Inc (HSF USA) summarizes the evidence of the intense HS clinical and experimental research during the last 15 years in all aspects of the disease and provides information of the developments to come in the near future.

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.

Histopathologic differences between cutaneous vasculitis associated with severe bacterial infection and cutaneous vasculitis secondary to other causes: study of 52 patients.

OBJECTIVES: To determine if cutaneous vasculitis (CV) associated with severe infection has some histopathologic findings that may help us to differentiate patients with this condition from other patients with CV. METHODS: We reviewed the skin biopsy specimens of patients with leukocytoclastic CV associated with a severe bacterial infection. Histopathologic findings of these patients were compared with those observed in leukocytoclastic CV secondary to other causes. Biopsy-proven leukocytoclastic CV were stratified as follows: group a): CV associated with severe underlying bacterial infection; group b): CV without severe bacterial infection but with systemic involvement; group c): CV without systemic involvement. Slides were reviewed by expert pathologists that were blind to the clinical information. The severity of vascular lesions was measured according to a semiquantitative scale (Hodge index). A comparative study between group a) and the other groups was conducted. RESULTS: group a) included 12 patients (2 women/10 men), mean age± SD 56±15 years; group b) 21 patients (10 women/11 men), 52±18 years; and group c) 19 patients (12 women/7 men), 59±24 years. Presence of neutrophilia was significantly increased in biopsies from group a) when compared with the other two groups. Also, a trend to higher frequency of pustular dermatosis was found in patients from group a). Hodge index, degree of inflammatory infiltrate and deep arterioles involvement were similar in all groups. CONCLUSIONS: Neutrophilia is common in skin biopsies of patients with CV associated with severe bacterial infection. No other histopathological findings help us to establish the presence of a severe underlying infection.

Increased prevalence of subclinical atherosclerosis in patients with hidradenitis suppurativa (HS).

BACKGROUND: Chronic inflammatory diseases have been associated with increased prevalence of subclinical atherosclerosis. Hidradenitis suppurativa (HS) is a chronic inflammatory disease involving intertriginous skin. OBJECTIVE: We sought to investigate the potential association between HS and subclinical atherosclerosis. METHODS: This study included 68 patients with HS and 136 age- and sex-matched healthy control subjects. Patients with history of cardiovascular events, diabetes mellitus, chronic kidney disease, or another concomitant inflammatory condition were excluded. Carotid intima-media thickness and carotid plaques were measured by carotid ultrasonography. Adjustments were made for age, sex, and traditional cardiovascular risk factors. RESULTS: Patients had greater carotid intima-media thickness values than control subjects (0.615 ± 0.097 vs 0.578 ± 0.098 mm; P = .012). Carotid plaques were also more frequent in patients than in control subjects (30.9% vs 22.1%). In the multivariable regression model adjusted for age, sex, and traditional cardiovascular risk factors, HS was significantly related to the presence of carotid plaques (odds ratio 2.99, 95% confidence interval 1.26-7.13; P = .013). LIMITATIONS: Causality could not be assessed. CONCLUSIONS: These results indicate an increased frequency of subclinical atherosclerosis in patients with HS. Accordingly, HS should be considered a disease associated with potentially increased cardiovascular risk.

Coexistence of Hidradenitis Suppurativa with Autoimmune Thyroiditis: Report of Three Cases.

Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory skin disease affecting terminal hair follicles in apocrine-gland-bearing skin. The pathogenesis of HS is still unknown, although increasing evidence suggests that the immune system plays an important role. Herein we describe 3 patients with HS coexisting with autoimmune (Hashimoto's) thyroiditis (AT). To our knowledge, the co-occurrence of these two diseases has not previously been described. The coexistence of HS with autoimmune disorders, such as AT, may support the hypothesis on dysregulation of the immune system's function as implicated in the pathogenesis of HS. Based on our findings, we feel that an assessment of thyroid function and antithyroid antibodies should be performed in patients with HS.

Single-organ cutaneous small-vessel vasculitis according to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides: a study of 60 patients from a series of 766 cutaneous vasculitis cases.

OBJECTIVE: Cutaneous vasculitis (CV) encompasses a wide group of entities characterized by inflammation of skin blood vessels. The term single-organ vasculitis was recently coined by the 2012 Chapel Hill Consensus Conference (CHCC) to define vasculitis affecting a single organ. To our knowledge there are no published reports on single-organ cutaneous small vessel vasculitis (SoCSVV). Our aim was to characterize this entity from a wide series of patients with CV. METHODS: We analysed cases of SoCSVV from a series of 766 patients with CV from a single university referral centre. According to 2012 CHCC, the following conditions were required to define SoCSVV: (i) skin biopsy showing characteristic leucocytoclastic vasculitis and (ii) vasculitis limited to skin. RESULTS: We included 60 patients (26 women and 34 men) with a mean age of 56 years. The main precipitating factors for SoCSVV were drugs [26 patients (52%)] and previous infection [17 patients (34%)]. The main clinical manifestations were palpable purpura (81.7%) and fever (18.3%). The most frequent laboratory findings were leucocytosis and elevated ESR. Nearly one-quarter of patients with SoCSVV required pharmacological therapy. Corticosteroids (15%) and NSAIDs (13.3%) were the main agents prescribed. After a median follow-up of 4 months, complete recovery was observed in all the patients, although relapses occurred in 8% of patients. CONCLUSION: SoCSVV defined according to the 2012 CHCC may be considered a benign disease usually associated with drugs and/or a previous infection.