Hair Shaft Abnormalities as a Dermoscopic Feature of Mycosis Fungoides: Pilot Results.

INTRODUCTION: Diagnosis of persistent erythematous, scaly patches, or plaques can be complex since psoriasis (Ps), eczematous dermatitis (ED), and mycosis fungoides (MF) can be considered. Dermoscopy, which is a noninvasive diagnostic tool, is commonly used to examine blood vessels, scales, and background color; however, research on hair shaft evaluation in inflammatory dermatoses remains scarce. The aim of the study was dermoscopic evaluation of hair shafts in skin lesions localized on the non-scalp skin areas in patients diagnosed with MF, Ps, and ED. METHODS: This was a retrospective evaluation of 55 patients diagnosed with MF, Ps, and ED. Photographic and dermoscopic documentation of these patients and detailed medical history were evaluated. RESULTS: A total of 21 patients with MF, 21 patients with Ps, and 13 patients with ED were evaluated. The examination revealed the presence of various abnormalities of hair shafts (e.g., numerous pili torti, single pili torti, 8-shaped hairs, pigtail hairs, broken hairs, hair shafts rapidly tapered over long sections, hair shafts irregular in thickness, angulated hairs, branched hairs, the presence of trichorrhexis nodosa, and monilethrix-like hairs), yellow dots, and black dots. The presence of pili torti was found in 80% of patients with MF, compared with 16% of patients with Ps and 8% of patients with ED (p < 0.005), with multiple pili torti found only in MF patients (67%) (p < 0.005). Statistically significant differences also applied to hair shafts rapidly tapering over long sections and 8-shaped hairs, which occurred only in MF patients (p < 0.005 and p = 0.035, respectively). CONCLUSIONS: The presence of hair shaft abnormalities such as numerous pili torti, 8-shaped hairs, and hair shafts rapidly tapering over long sections is an important criterion that should be considered in the dermoscopic differentiation of the patchy/plaque mycosis fungoides and inflammatory dermatoses, such as psoriasis and eczematous dermatitis localized on the non-scalp skin areas.

Trichoscopy of Androgenetic Alopecia: A Systematic Review.

Background: Androgenetic alopecia, the most common cause of non-scarring hair loss, is a consequence of the gradual miniaturization of the hair follicles. In the majority of male androgenetic alopecia cases, a patient's history and clinical evaluation may be sufficient to establish the diagnosis, while for women, they should be supplemented with trichoscopy. Methods: The PubMed and Scopus databases were used to collate published studies and to analyze the most typical trichoscopic findings in patients diagnosed with androgenetic alopecia. A total of 34 articles were retrieved after exclusion. Results: The most common features identified using trichoscopy included hair diameter variability (94.07% of patients), vellus hairs (66.45%) and the peripilar sign (43.27%). Others, such as the honeycomb pattern, yellow and white dots, were less relevant. Conclusions: We concluded that hair diameter variability, vellus hairs and the peripilar sign represented valuable indicators for the diagnosis of androgenetic alopecia.

Targeting SRSF2 mutations in leukemia with RKI-1447: A strategy to impair cellular division and nuclear structure.

Spliceosome machinery mutations are common early mutations in myeloid malignancies; however, effective targeted therapies against them are still lacking. In the current study, we used an in vitro high-throughput drug screen among four different isogenic cell lines and identified RKI-1447, a Rho-associated protein kinase inhibitor, as selective cytotoxic effector of SRSF2 mutant cells. RKI-1447 targeted SRSF2 mutated primary human samples in xenografts models. RKI-1447 induced mitotic catastrophe and induced major reorganization of the microtubule system and severe nuclear deformation. Transmission electron microscopy and 3D light microscopy revealed that SRSF2 mutations induce deep nuclear indentation and segmentation that are apparently driven by microtubule-rich cytoplasmic intrusions, which are exacerbated by RKI-1447. The severe nuclear deformation in RKI-1447-treated SRSF2 mutant cells prevents cells from completing mitosis. These findings shed new light on the interplay between microtubules and the nucleus and offers new ways for targeting pre-leukemic SRSF2 mutant cells.

Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxoedema and scleroedema.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this consensus provides clinicians with an overview of the diagnosis and treatment of scleromyxoedema and scleroedema (of Buschke).

Hematopoietic and eosinophil-specific LNK(SH2B3) deficiency promote eosinophilia and arterial thrombosis.

Increased eosinophil counts are associated with cardiovascular disease and may be an independent predictor of major cardiovascular events. However, the causality and underlying mechanisms are poorly understood. GWAS have shown an association of a common LNK variant (R262W, T allele) with eosinophilia and atherothrombotic disorders. LNK(TT) reduces LNK function and Lnk-deficient mice display accelerated atherosclerosis and thrombosis. This study was undertaken to assess the role of eosinophils in arterial thrombosis in mice with hematopoietic Lnk deficiency. Hematopoietic Lnk deficiency increased circulating and activated eosinophils, JAK/STAT signaling in eosinophils and carotid arterial thrombosis with increased eosinophil abundance and extracellular trap formation (EETosis) in thrombi. Depletion of eosinophils by anti-Siglec-F antibody or by the ∆dbIGata1 mutation eliminated eosinophils in thrombi and markedly reduced thrombosis in mice with hematopoietic Lnk deficiency but not in control mice. Eosinophil depletion reduced neutrophil abundance and NETosis in thrombi without altering circulating neutrophil counts. To assess the role of Lnk specifically in eosinophils, we crossed Lnkf/f mice with eoCre mice. Lnk∆eos mice displayed isolated eosinophilia, increased eosinophil activation and accelerated arterial thrombosis associated with increased EETosis and NETosis in thrombi. DNase I infusion abolished EETs and NETs in thrombi and reversed the accelerated thrombosis. Human iPSC-derived LNK(TT) eosinophils showed increased activation and EETosis relative to isogenic LNK(CC) eosinophils, demonstrating human relevance. These studies show a direct link between eosinophilia, EETosis and atherothrombosis in hematopoietic Lnk deficiency and an essential role of eosinophil LNK in suppression of arterial thrombosis.

Differential diagnosis of red scalp. The importance of trichoscopy.

Red scalp is a common complaint which may constitute a diagnostic and therapeutic challenge in daily clinical practice. Among the numerous diseases which cause diffuse scalp erythema are psoriasis, seborrheic dermatitis, contact dermatitis, diffuse lichen planopilaris, dermatomyositis and scalp rosacea. Accurate diagnosis is crucial for optimal treatment outcomes. Histology most frequently discriminates the underlying condition, but it requires scalp biopsy. In many cases the combination of clinical examination and trichoscopy is sufficient for establishing the correct diagnosis. The main trichoscopic features of psoriasis are silver-white scaling, regular distributed dotted (glomerular) vessels or twisted red loops and punctate hemorrhages. Yellowish-white scaling and thin arborizing vessels are typical features of seborrheic dermatitis. Contact dermatitis is characterized by the presence of yellow exudate and polymorphic vessels, while perifollicular scaling and erythema with the lack of follicular openings are typical findings in lichen planopilaris. In scalp dermatomyositis, tortuous and arborizing vessels with interfollicular and perifollicular pigmentation may be detected. The most characteristic features of scalp rosacea are perifollicular scaling and arborizing vessels. This review also summarizes histologic features and therapeutic options for these conditions.

BRCC3-Mediated NLRP3 Deubiquitylation Promotes Inflammasome Activation and Atherosclerosis in Tet2 Clonal Hematopoiesis.

BACKGROUND: Clonal hematopoiesis (CH) has emerged as an independent risk factor for atherosclerotic cardiovascular disease, with activation of macrophage inflammasomes as a potential underlying mechanism. The NLRP3 (NLR family pyrin domain containing 3) inflammasome has a key role in promoting atherosclerosis in mouse models of Tet2 CH, whereas inhibition of the inflammasome product interleukin-1ß appeared to particularly benefit patients with TET2 CH in CANTOS (Cardiovascular Risk Reduction Study [Reduction in Recurrent Major CV Disease Events]). TET2 is an epigenetic modifier that decreases promoter methylation. However, the mechanisms underlying macrophage NLRP3 inflammasome activation in TET2 (Tet methylcytosine dioxygenase 2) deficiency and potential links with epigenetic modifications are poorly understood. METHODS: We used cholesterol-loaded TET2-deficient murine and embryonic stem cell-derived isogenic human macrophages to evaluate mechanisms of NLRP3 inflammasome activation in vitro and hypercholesterolemic Ldlr-/- mice modeling TET2 CH to assess the role of NLRP3 inflammasome activation in atherosclerosis. RESULTS: Tet2 deficiency in murine macrophages acted synergistically with cholesterol loading in cell culture and with hypercholesterolemia in vivo to increase JNK1 (c-Jun N-terminal kinase 1) phosphorylation and NLRP3 inflammasome activation. The mechanism of JNK (c-Jun N-terminal kinase) activation in TET2 deficiency was increased promoter methylation and decreased expression of the JNK-inactivating dual-specificity phosphatase Dusp10. Active Tet1-deadCas9-targeted editing of Dusp10 promoter methylation abolished cholesterol-induced inflammasome activation in Tet2-deficient macrophages. Increased JNK1 signaling led to NLRP3 deubiquitylation and activation by the deubiquitinase BRCC3 (BRCA1/BRCA2-containing complex subunit 3). Accelerated atherosclerosis and neutrophil extracellular trap formation (NETosis) in Tet2 CH mice were reversed by holomycin, a BRCC3 deubiquitinase inhibitor, and also by hematopoietic deficiency of Abro1, an essential scaffolding protein in the BRCC3-containing cytosolic complex. Human TET2-/- macrophages displayed increased JNK1 and NLRP3 inflammasome activation, especially after cholesterol loading, with reversal by holomycin treatment, indicating human relevance. CONCLUSIONS: Hypercholesterolemia and TET2 deficiency converge on a common pathway of NLRP3 inflammasome activation mediated by JNK1 activation and BRCC3-mediated NLRP3 deubiquitylation, with potential therapeutic implications for the prevention of cardiovascular disease in TET2 CH.

Dermoscopy as a Noninvasive Diagnostic Tool for Hailey-Hailey Disease and Darier Disease.

INTRODUCTION: Hailey-Hailey disease (HHD) and Darier disease (DD) are rare genetic disorders for which differential diagnosis, especially in less obvious cases, can be difficult. The diagnosis is based on the clinical picture and family history, and is confirmed by histopathologic examination. Dermoscopy is a noninvasive technique that is primarily used at the present time to diagnose skin cancers. However, in the past few years this technique has also been increasingly used as a noninvasive diagnostic tool of inflammatory skin diseases. The aim of the study was to evaluate whether dermoscopy is a useful noninvasive diagnostic tool for HHD and DD. METHODS: We performed an observational retrospective case series study involving 13 patients with HHD (n = 8) and DD (n = 5). The presence or absence of standardized dermoscopic features of inflammatory diseases (according to International Dermoscopy Society [IDS] guidelines) was assessed in these patients. RESULTS: The most distinctive feature of HHD was white clouds separated by pink furrows, visible in all cases (8/8; 100.0%). Another distinctive clue of HHD was the crumbled fabric pattern seen in six patients with HHD (6/8; 75.0%). These dermoscopic findings were not present in patients with DD. The most typical features of DD in the dermoscopic examination was star-like or oval-shaped yellow areas surrounded by whitish halo, visible in all patients (5/5; 100.0%). Another distinctive dermoscopic clue of DD was pinkish homogeneous structureless background, which was present in all patients (5/5, 100.0%). These latter two features were not observed in patients with HHD. CONCLUSION: Dermoscopy reveals distinctive features of HHD and DD, respectively. Therefore, we conclude that dermoscopy can be an excellent complementary noninvasive tool in the diagnostic process of patients with HHD and DD.

Hailey-Hailey disease and Darier disease are rare genetic disorders, which are diagnosed based on the clinical picture and confirmed with skin biopsy. Dermoscopy is noninvasive diagnostic tool, which enables skin visualization at a 10-fold magnification. Currently, dermoscopy is mainly used to diagnose skin cancers. In the recent years, dermoscopy has been also increasingly used as a noninvasive diagnostic tool of inflammatory skin diseases. The aim of the study was to assess whether demoscopy may be a useful tool in diagnosing Hailey-Hailey disease and Darier disease. The study included thirteen patients: eight with Hailey-Hailey disease and five with Darier disease. The most typical dermoscopic feature of Hailey-Hailey disease was white clouds separated by pink furrows, which were visible in all cases. Another distinctive clue was crumbled fabric pattern seen in 75.0% of patients with Hailey-Hailey disease. These dermoscopic findings were not present in patients with Darier disease. In dermoscopic examination the most typical feature of Darier disease was star-like or oval-shaped yellow areas surrounded by whitish halo, visible in all patients. Also, pinkish homogeneous structureless background was present in all patients with Darier disease. These features were not observed in patients with Hailey-Hailey disease. Dermoscopy reveals characteristic features of Hailey-Hailey disease and Darier disease. Therefore, it can be an excellent complementary tool in the diagnostic process of patients with those diseases.

Blockade of IL-6 signaling alleviates atherosclerosis in Tet2-deficient clonal hematopoiesis.

Clonal hematopoiesis (CH) increases the risk of atherosclerotic cardiovascular disease possibly due to increased plaque inflammation. Human studies suggest that limitation of interleukin-6 (IL-6) signaling could be beneficial in people with large CH clones, particularly in TET2 CH. Here we show that IL-6 receptor antibody treatment reverses the atherosclerosis promoted by Tet2 CH, with reduction of monocytosis, lesional macrophage burden and macrophage colony-stimulating factor 1 receptor (CSF1R) expression. IL-6 induces expression of Csf1r in Tet2-deficient macrophages through enhanced STAT3 binding to its promoter. In mouse and human Tet2-deficient macrophages, IL-6 increases CSF1R expression and enhances macrophage survival. Treatment with the CSF1R inhibitor PLX3397 reversed accelerated atherosclerosis in Tet2 CH mice. Our study demonstrates the causality of IL-6 signaling in Tet2 CH accelerated atherosclerosis, identifies IL-6-induced CSF1R expression as a critical mechanism and supports blockade of IL-6 signaling as a potential therapy for CH-driven cardiovascular disease.

Ocular involvement in autoimmune bullous diseases.

Autoimmune bullous diseases represent a heterogenous group of disorders caused by autoantibodies against adhesion molecules; the location of the target protein determines the level of cleft formation. The spectrum of ocular lesions in autoimmune bullous diseases can range from mild symptoms to severe involvement with sight impairment and even, in some cases, blindness. In pemphigus vulgaris, the prevalence of ocular involvement has been reported to be between 7% and 26%. The most common clinical sign of ocular pemphigus vulgaris is bilateral conjunctivitis with hyperemia. Ocular involvement also occurs in 41% to 70% of patients with paraneoplastic pemphigus. The main ocular manifestations are bilateral cicatrizing conjunctivitis with symblepharon formation, and shortening of the fornices. In mucous membrane pemphigoid, ocular involvement is seen in 61% to 70% of patients; the most frequent ocular finding is cicatricial conjunctivitis. Patients with autoimmune bullous diseases having common ocular involvement should be assessed by an ophthalmologist to avoid serious complications. Diagnostic procedures and treatment require multidisciplinary care based on the close cooperation between dermatologists and ophthalmologists.

Markers of Venous Thromboembolism Risk in Patients with Alopecia Areata: Is There Anything to Worry about?

BACKGROUND: Numerous studies have indicated that alopecia areata is associated with a chronic systemic inflammation, which is considered as a risk factor for venous thromboembolism. The aim of the study was to evaluate the following markers of venous thromboembolism risk: soluble fibrin monomer complex (SFMC), thrombin-antithrombin complex (TATC), and prothrombin fragment 1 + 2 (F1 + 2) in patients with alopecia areata and compare them with healthy controls. METHODS: In total, 51 patients with alopecia areata [35 women and 16 men; mean age: 38 (19-54) years] and 26 controls [18 women and 8 men; mean age: 37 (29-51) years] were enrolled in the study. The serum concentrations of thromboembolism markers were measured using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: An increased level of SFMC was detected in patients with alopecia areata compared with the controls [25.66 (20-34.86) versus 21.46 (15.38-29.48) µg/ml; p < 0.05)]. In addition, a higher level of F1 + 2 was observed in patients with alopecia areata in comparison with the control group [70150 (43720-86070) versus 38620 (31550-58840) pg/ml; p < 0.001]. No significant correlation was detected among SFMC or F1 + 2 and the Severity of Alopecia Tool (SALT) score, disease duration, or the number of the hair loss episodes. CONCLUSION: Alopecia areata may be associated with an increased risk of venous thromboembolism. Regular screening and preventive management of venous thromboembolism may be beneficial in patients with alopecia areata, especially before and during systemic Janus kinase (JAK) inhibitors or glucocorticoid therapy.

Patient-Derived iPSCs Faithfully Represent the Genetic Diversity and Cellular Architecture of Human Acute Myeloid Leukemia.

The reprogramming of human acute myeloid leukemia (AML) cells into induced pluripotent stem cell (iPSC) lines could provide new faithful genetic models of AML, but is currently hindered by low success rates and uncertainty about whether iPSC-derived cells resemble their primary counterparts. Here we developed a reprogramming method tailored to cancer cells, with which we generated iPSCs from 15 patients representing all major genetic groups of AML. These AML-iPSCs retain genetic fidelity and produce transplantable hematopoietic cells with hallmark phenotypic leukemic features. Critically, single-cell transcriptomics reveal that, upon xenotransplantation, iPSC-derived leukemias faithfully mimic the primary patient-matched xenografts. Transplantation of iPSC-derived leukemias capturing a clone and subclone from the same patient allowed us to isolate the contribution of a FLT3-ITD mutation to the AML phenotype. The results and resources reported here can transform basic and preclinical cancer research of AML and other human cancers. SIGNIFICANCE: We report the generation of patient-derived iPSC models of all major genetic groups of human AML. These exhibit phenotypic hallmarks of AML in vitro and in vivo, inform the clonal hierarchy and clonal dynamics of human AML, and exhibit striking similarity to patient-matched primary leukemias upon xenotransplantation. See related commentary by Doulatov, p. 252. This article is highlighted in the In This Issue feature, p. 247.

The role of trichoscopy beyond hair and scalp diseases. A review.

Trichoscopy is a diagnostic tool for hair and scalp diseases. It was recently shown that it also allows the identification of features associated with disorders that typically do not affect the scalp. The aim of this article was to analyse and outline the usefulness of trichoscopy in suspecting such diseases. Connective tissue diseases were the most investigated systemic disorders in regard to trichoscopy. The most common features of systemic lupus erythematosus, systemic sclerosis and dermatomyositis are thick arborizing and tortuous vessels. Avascular areas are present in systemic sclerosis. Spermatozoa-like vessels may be observed in cutaneous T-cell lymphomas, while salmon-coloured areas with arborizing and linear vessels may be seen in patients with cutaneous B-cell lymphomas. In patients with advanced multiple myeloma, follicular spicules may be observed. Trichoscopic features of angiosarcomas include pink areas, red, polymorphic areas and dark red to purple areas. Polymorphous vessels and whitish areas on a pink background are the predominating trichoscopic features of metastases of malignant tumours to the scalp. Cutaneous sarcoidosis is characterized by orange-coloured areas and telangiectasias. Systemic amyloidosis may manifest with salmon-coloured perifollicular halos, while the most common trichoscopic features of syphilitic alopecia are as follows: decreased number of hairs per follicular unit, vellus hairs, background erythema, focal atrichia and yellow dots. In conclusion, dermatologists may suspect some systemic diseases on the basis of trichoscopic findings.

Immunopathogenesis of Atopic Dermatitis: Focus on Interleukins as Disease Drivers and Therapeutic Targets for Novel Treatments.

Atopic dermatitis is a chronic, recurrent inflammatory skin disorder manifesting by eczematous lesions and intense pruritus. Atopic dermatitis develops primarily as a result of an epidermal barrier defect and immunological imbalance. Advances in understanding these pathogenetic hallmarks, and particularly the complex role of interleukins as atopic dermatitis drivers, resulted in achieving significant therapeutic breakthroughs. Novel medications involve monoclonal antibodies specifically blocking the function of selected interleukins and small molecules such as Janus kinase inhibitors limiting downstream signaling to reduce the expression of a wider array of proinflammatory factors. Nevertheless, a subset of patients remains refractory to those treatments, highlighting the complexity of atopic dermatitis immunopathogenesis in different populations. In this review, we address the immunological heterogeneity of atopic dermatitis endotypes and phenotypes and present novel interleukin-oriented therapies for this disease.

Enterotoxin Gene Cluster and selX Are Associated with Atopic Dermatitis Severity-A Cross-Sectional Molecular Study of Staphylococcus aureus Superantigens.

Staphylococcus aureus superantigens (SAgs) have been reported to aggravate atopic dermatitis. However, comprehensive analyses of these molecules in multiple microniches are lacking. The present study involved 50 adult patients with active atopic dermatitis. S. aureus was isolated from the lesional skin, nonlesional skin, and anterior nares. Multiplex-PCR was performed to identify genes encoding (1) selX (core genome); (2) seg, selI, selM, selN, selO, selU (enterotoxin gene cluster, EGC); and (3) sea, seb, sec, sed, see, tstH (classic SAgs encoded on other mobile genetic elements). The results were correlated to clinical parameters of the study group. selx and EGC were the most prevalent in all microniches. The number of SAg-encoding genes correlated between the anterior nares and nonlesional skin, and between the nonlesional and lesional skin. On lesional skin, the total number of SAg genes correlated with disease severity (total and objective SCORAD, intensity, erythema, edema/papulation, lichenification and dryness). Linear regression revealed that AD severity was predicted only by selx and EGC. This study revealed that selX and EGC are associated with atopic dermatitis severity. Anterior nares and nonlesional skin could be reservoirs of SAg-positive S. aureus. Restoring the physiological microbiome could reduce the SAg burden and alleviate syndromes of atopic dermatitis.

Lipocalin-2 and insulin as new biomarkers of alopecia areata.

Lipocalin-2 and visfatin are proinflammatory adipokines involved in the regulation of glucose homeostasis. Their role has been described in numerous inflammatory skin diseases such as atopic dermatitis and psoriasis. Recently, an increased prevalence of metabolic abnormalities has been reported in patients with alopecia areata. The aim of the study is to determine the serum levels of lipocalin-2 and visfatin in patients with alopecia areata in comparison with healthy controls. Moreover, the serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol), high-density lipoprotein cholesterol (HDL-cholesterol), triglycerides, fasting glucose, insulin, c-peptide, and homeostasis model assessment for insulin resistance (HOMA-IR) were evaluated. Fifty-two patients with alopecia areata and 17 control subjects were enrolled in the study. The serum levels of lipocalin-2 [mean ± standard deviation, SD: 224.55 ± 53.58 ng/ml vs. 188.64 ± 44.75, p = 0.01], insulin [median (interquartile range, IQR): 6.85 (4.7-9.8) µIU/ml vs. 4.5 (3.5-6.6), p<0.05], c-peptide [median (IQR): 1.63 (1.23-2.36) ng/ml vs. 1.37 (1.1-1.58), p<0.05)], and HOMA-IR [median (IQR): 1.44 (0.98-2.15) vs. 0.92 (0.79-1.44), p<0.05) were significantly higher in patients with alopecia areata compared to the controls. The serum concentration of insulin and HOMA-IR correlated with the number of hair loss episodes (r = 0.300, p<0.05 and r = 0.322, p<0.05, respectively). Moreover, a positive correlation occurred between insulin, HOMA-IR, c-peptide and BMI (r = 0.436, p <0.05; r = 0.384, p<0.05 and r = 0.450, p<0.05, respectively). In conclusion, lipocalin-2 and insulin may serve as biomarkers for alopecia areata. Further studies are needed to evaluate the role of insulin as a prognostic factor in alopecia areata.

Patients with alopecia areata are at risk of endothelial dysfunction: results of a case-control study.

BACKGROUND: Alopecia areata (AA) is an autoimmune form of hair loss, which may affect any hair-bearing area. It has been suggested that AA is associated with an increased risk of metabolic and cardiovascular comorbidities. AIM: To evaluate the early predictors of cardiovascular disease [endothelial function (EF) and arterial stiffness (AS)] in patients with AA without prior cardiovascular disease, and compare with healthy controls (HCs). METHODS: In total, 52 patients with AA (38 women and 14 men; mean age 41 years, range 30-52 years) and 34 HCs, matched for age, sex and body mass index, were enrolled in the study. EF, expressed as reactive hyperaemia index (RHI), and AS, identified by augmentation index at 75 beats/min (AI@75) were assessed with the use of the Endo-PAT 2000 device. Endothelial dysfunction (ED) was defined as RHI value ≤1.67. RESULTS: ED was observed in 22 of 52 patients with AA (42%) and in 4 of 34 HCs (12%) (P < 0.01). Moreover, mean RHI was lower in patients with AA compared with HCs (1.90 ± 0.31 vs. 2.11 ± 0.45; P = 0.03). There was no significant difference in AI@75 between patients with AA and HCs. CONCLUSIONS: Patients with AA show abnormalities in early predictors of cardiovascular diseases. Regular cardiovascular screening might be appropriate for patients with AA.