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Livedoid vasculopathy is a painful thrombo-occlusive vascular disorder characterized by spontaneous thrombosis in medium-size arterioles, which causes localized hypoxia and skin ulceration. As livedoid vasculopathy is rare, case reports are the primary means of expanding collective knowledge about its presentation and response to various therapies.

The breasts are a common location for diffuse dermal angiomatosis (DDA) in a context of obesity and macromastia. The typical clinical presentation includes erythematous or purplish plaques, reticulated telangiectasias, and sometimes livedo reticularis, often complicated by painful ulcerations of the breasts. Biopsy usually confirms a dermal proliferation of endothelial cells staining positively for CD31, CD34 and SMAa and negatively for HHV8. We report herein a woman with DDA of the breasts presenting as diffuse livedo reticularis and acrocyanosis, both long-standing and considered idiopathic following extensive investigations. Since a biopsy of the livedo did not document DDA features in our case, we suggest that our patient's livedo reticularis and telangiectasias could constitute a vascular predisposition for DDA, as its pathogenesis frequently involves an underlying disease involving ischemia, hypoxia, or hypercoagulability.

Many skin manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection reflect activation of cutaneous and systemic immune responses involving effector pathways of both the innate and adaptive arms of the immune system. This article reviews evidence from the recent clinical and scientific literature that informs the current understanding of the consequences of coronavirus disease 2019 (COVID-19)-induced immune cell activation, as relevant to dermatology. Topics include the clinical consequences of autoantibody production in patients with COVID-19, immunologic evidence for chilblains as a manifestation of SARS-CoV-2 infection, and the relationship between type I interferons and COVID-19 disease severity.

Key Clinical Message: The diagnosis of Sneddon Syndrome should be considered in adults with young‐onset dementia accompanied by neuropsychiatric signs and livedo racemosa. Magnetic resonance imaging and cerebral angiography are essential. A cutaneous biopsy may help in the diagnosis. Sneddon syndrome (SS) is a clinical entity corresponding to a noninflammatory thrombotic vasculopathy that typically includes livedo racemosa and cerebrovascular ischemia. Psychiatric symptoms with cognitive impairment often occur but are rarely the inaugural symptoms. We present a case of secondary SS in a 45‐year‐old man in whom dementia and psychosis revealed the disease. [ABSTRACT FROM AUTHOR]

Lymphocytic thrombophilic arteritis and livedoid vasculopathy may both present with livedo racemosa and ulceration. We present 6 cases with features of both conditions, raising the possibility that they are either closely linked or are part of a spectrum of the same condition. [ABSTRACT FROM AUTHOR]

Key Clinical Message The diagnosis of Sneddon Syndrome should be considered in adults with young‐onset dementia accompanied by neuropsychiatric signs and livedo racemosa. Magnetic resonance imaging and cerebral angiography are essential. A cutaneous biopsy may help in the diagnosis. Abstract Sneddon syndrome (SS) is a clinical entity corresponding to a noninflammatory thrombotic vasculopathy that typically includes livedo racemosa and cerebrovascular ischemia. Psychiatric symptoms with cognitive impairment often occur but are rarely the inaugural symptoms. We present a case of secondary SS in a 45‐year‐old man in whom dementia and psychosis revealed the disease.

Introduction. Sneddon syndrome is defined by the association of two cardinal disorders: one is the presence of livedo racemosa, and the other is the occurrence of strokes, often multiple and progressive. This syndrome is closely related to the anti-phospholipid syndrome (APS), with which the nosological limits are not yet clear. Autoimmunity and/or thrombophilia may accompany this syndrome, explaining in part its pathophysiology. Observation. We report the case of a 46-year-old female patient, without any notable pathological history, who presented with a long history of neurological symptoms such as headaches and dizziness. She complained of progressive memory problems, which appeared more recently, as well as paresthesia. She also described a Raynaud's phenomenon. The clinical examination showed livedo racemosa and arterial hypertension. The biological workup, notably immunological (anti-nuclear and anti-phospholipid antibodies), was negative. Cerebral MRI, performed twice, five years apart, revealed progressive cerebral ischemic lesions involving the frontal, parietal and occipital territories bilaterally. Sneddon syndrome was retained on the basis of clinical, biological and radiological presumptions. Anti-platelet aggregation and anti-hypertensive treatment was instituted. The evolution is marked by a stability of the disease. Conclusion. Since its first description in 1965, Sneddon syndrome still raises etio-pathogenic and nosological questions. Further studies are needed to better understand this disease. [ABSTRACT FROM AUTHOR]

Background: Livedo is a well-known skin condition in patients with systemic lupus erythematosus (SLE) which correspond to small vessels involvement. The influence of antiphospholipid antibodies (aPL) on the occurrence of livedo is controversial. The aim of our study was to estimate the risk of livedo associated with aPL in patients with SLE. Methods: We conducted a systematic review and meta-analysis of the literature from 1977 to 2021 to estimate the risk of livedo in SLE patients according to different aPL profiles. Data sources were PubMed, Embase, Cochrane Library, hand search, and reference lists of studies. Studies were selected if they included SLE patients with descriptions of the exposure to aPL and the outcome (livedo). Two independent investigators assessed study eligibility, quality, and extracted patient characteristics from each study as well as exposure (aPL) and outcome (livedo). Risk estimates were pooled using random effects models and sensitivity analyses. For all stages of the meta-analysis, we followed the PRISMA guidelines. PROSPERO registration number: CRD42015027377. Results: Of the 2,355 articles identified, 27 were included with a total of 4,810 SLE patients. The frequency of livedo was 25.5% in aPL-positive patients and 13.3% in aPL-negative patients. The overall Odds Ratio (OR) for livedo in aPL-positive patients compared to aPL-negative patients was 2.91 (95% CI; 2.17–3.90). The risk of livedo was significantly increased for most of aPL subtypes, including lupus anticoagulant (LA) (OR = 4.45 [95% CI; 2.21–8.94]), IgG anticardiolipin (OR = 3.95 [95% CI; 2.34–6.65]), and IgG anti-β2-glycoprotein 1 (OR = 3.49 [95% CI; 1.68–7.27]). Conclusions: We demonstrated in this meta-analysis an excess risk of livedo in aPL-positive SLE patients compared to aPL-negative patients. For daily practice, in patients with SLE, livedo associated with aPL could correspond to a peculiar group of patients with small vessel disease. Livedo could be a good candidate for inclusion in future classification criteria for antiphospholipid syndrome. [ABSTRACT FROM AUTHOR]

The infection caused by the recently identified SARS-CoV-2, dubbed coronavirus disease-19 (COVID-19), has become a pandemic. With exponential growth of morbidity among the people around the world, the clinical characteristics of COVID-19 are becoming clearer and description of new disease symptoms descriptions is emerging. The sufficient amount of descriptions of various skin manifestations in patients with COVID-19 has appeared, however they are characterized by great heterogeneity. The pathogenetic mechanisms of the development of skin rashes in patients with COVID-19 are currently unknown, however, hypotheses have been put forward that they have an overactive immune response, activation of the complement system and microvascular damage. Based on the published literature data and our own experience, the following characteristic types of skin rashes can be distinguished among the skin manifestations of this viral disease: urticaria, confluent, papulovesicular exanthema, acral rashes similar to frostbite, livedo reticularis and purpura. Possible development of skin lesions against the background of the development of COVID-19 provides the need to inform dermatologists about the features of the skin manifestations of this disease, as well as to study further these symptoms of COVID-19 to determine their diagnostic and prognostic value.

POLE is a pleiotropic gene with phenotypic expression of pathogenic variants depending on the type of variant, impact on the protein, and mode of inheritance. Heterozygous missense variants located within the exonuclease domain have been shown to result in polymerase proofreading‐associated polyposis (PPAP) which is characterized by an increased risk for colon polyps and colorectal cancer. Biallelic variants resulting in markedly reduced amounts of normal protein have been reported in two separate recessive pediatric syndromes: facial dysmorphism, immunodeficiency, livedo, and short stature as well as intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenital, and genital anomalies. Here we report two siblings identified to have POLE c.1686 + 32C > G in trans with POLE p.(Glu709*) via exome sequencing. A detailed review of the reported phenotypes in these two siblings and from available literature revealed that individuals with biallelic POLE pathogenic variants resulting in partial loss‐of‐function present with a similar phenotype: short stature and facial dysmorphism with or without immunodeficiency. These data suggest a phenotypic continuum between the previously reported POLE‐related recessive disorders. [ABSTRACT FROM AUTHOR]

Livedoid vasculopathy is a rare, chronic-recurrent occlusive disorder in the microcirculation of dermal vessels. The clinical appearance is characterized by Livedo racemosa, painful ulceration, located in the distal parts of the lower extremities, followed by healing as porcelain-white, atrophic scars, the so-called Atrophie blanche. Different conditions that can promote a hypercoagulable state, such as inherited and acquired thrombophilias, autoimmune connective-tissue diseases and neoplasms, can be associated with livedoid vasculopathy. Therefore, livedoid vasculopathy is currently considered to be a coagulation disorder, clearly distinguished from inflammatory vasculitis. Although there are hints to hypercoaguability and secondary inflammation, pathophysiology is not completely understood. Diagnosis is made by synopsis of history, clinical and histopathological findings. Early and adequate therapy is essential to maintain life quality and avoid irreversible complications. Better understanding of molecular mechanisms is required to establish appropriate therapy regimens. This article presents the current state of knowledge about livedoid vasculopathy and proposes an algorithmic approach for diagnosis and therapy.

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COVID‐19 is a systemic disease characterized by vascular damage, increased inflammation, and hypercoagulability. Acral ischemic lesions occur as a result of increased inflammation and cutaneous thrombosis. Skin lesions can sometimes be the only symptom of COVID‐19. In this respect, recognizing acro‐ischemic lesions, which are skin lesions, may help in the early diagnosis of the disease and in predicting the prognosis. In patients with skin lesions without typical symptoms, the diagnosis of COVID‐19 should be kept in mind. Herein, we describe five patients affected by COVID‐19 which developed acro‐ischemic lesions. [ABSTRACT FROM AUTHOR]

Cutaneous vasculitis is an inflammatory disease affecting the dermal blood vessel walls. The skin is a privileged organ in the setting of vasculitis since it is easily accessible for physical examination and safe biopsy, allowing an accurate characterization of inflammatory lesions. The skin is often involved. Also, cutaneous vasculitis can reflect a cutaneous component of a systemic vasculitis, a skin-limited or skin-dominant expression or variant of a systemic vasculitis, or be a single-organ vasculitis per se. Vasculitis lesions are multiple and polymorphic. They may induce a wide spectrum of clinical manifestations depending on the location and the size of the vessels involved. The depth of affected vessels is correlated with the type of cutaneous lesions. Involvement of small superficial vessels results mostly in urticarial, but relatively persistent plaques, papules, and palpable purpura. Involvement of vessels in the dermohypodermic junction or hypodermis results in ulcers, nodules, or livedo. The type of inflammatory infiltrate is also a key finding for the diagnosis of cutaneous vasculitis. Leukocytoclastic vasculitis is not a disease per se but the result of a pathophysiological process common to different causes. A better knowledge of the vascular anatomy of the skin, elementary lesions, and histological characteristics of dermatologic manifestations would allow a more relevant and more efficient diagnostic approach. We also propose a list of additional exams to be performed in front of skin lesions suggestive of vasculitis. The aim of our article is to provide an overview of elementary skin lesions and clinicopathologic correlations in cutaneous and systemic vasculitis. [ABSTRACT FROM AUTHOR]

A 21-year-old man had a long-standing history of leg ulcers and hyperpigmention over the feet. Over a span of 8 months, he had an acute ischemic stroke followed by a basal ganglia hemorrhage. He was finally diagnosed with DADA2 syndrome after genetic sequencing. The implications of this new syndrome and its links to stroke in the young are presented in this article.

Introduction: Distinct skin lesions associated with coronavirus disease 2019 (COVID-19) have been described, but data regarding their time of onset during the COVID-19 course are scant. Our objective was to systematically review the studies reporting the time of onset of selected skin lesions with respect to the reported onset of the COVID-19 core symptoms. Methods: A comprehensive search of studies published before 21 January 2021 was performed on MEDLINE via PubMed database using a predefined strategy to identify relevant articles. Results: Out of 354 references, 87 were selected, reporting a total of 895 patients with skin lesions associated with COVID-19. The most frequent pattern was exanthema (n = 430, 48%), followed by vascular (n = 299, 33%), urticarial (n = 105, 12%) and others (n = 66, 7%). Skin lesions occurred more frequently in the first 4 weeks from the COVID-19 onset (n = 831, 92%), whereas prodromal or late lesions were rarer (n = 69, 8%). The urticarial and exanthema patterns were more frequent in the first 2 weeks. About the vascular pattern some differences were noted among its subtypes. Livedoid lesions occurred mainly in the first 2 weeks, while chilblain-like lesions between weeks 2 and 4. Purpuric/petechial lesions were equally distributed during the first 4 weeks. Several skin manifestations did not fall into the pattern classification, including erythema multiforme, generalized pruritus, Kawasaki disease and others. Conclusion: The diversity in the time of onset of skin lesions as well as their polymorphic nature likely reflects the diversity of the pathogenetic underlying mechanisms. PROSPERO database registration number: CRD42021236331. [ABSTRACT FROM AUTHOR]

Background and purpose: Moyamoya angiopathy (MA) is a progressive cerebrovascular disease with a poorly understood pathophysiology. It is mainly characterized by progressive bilateral stenosis of the terminal intracranial part of the supraclinoid internal carotid arteries and the proximal parts of the middle and anterior cerebral arteries. This results in early‐onset ischemic or hemorrhagic strokes. The disease may be idiopathic (known as Moyamoya disease) or associated with other heritable or acquired conditions, including type 1 neurofibromatosis or other RASopathies, sickle cell disease, Down syndrome, or autoimmune disorders (known as Moyamoya syndrome). Apart from the brain, other organ manifestations including cutaneous ones have also been described in MA patients. Materials and methods: A literature research on PubMed was performed for articles mentioning the cutaneous association in MA and published between 1994 and October 2020. Conclusion: The present review summarizes the cutaneous associations as well as the coincidental dermatological findings seen in MA patients. Those include changes in the epidermis, dermis, or skin appendages for example café‐au‐lait spots, hypomelanosis of Ito, livedo racemosa, hemangiomas, premature graying of hair, chilblains etc. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is an acquired thrombophilic disorder in which autoantibodies are produced against a variety of phospholipids and phospholipid-binding proteins. The purpose of this article is to review cutaneous findings in patients with APS diagnosis. An overview regarding prevalence, description, pathogenesis and histopathology, are described for cutaneous manifestations of APS. [ABSTRACT FROM AUTHOR]

We report the case of an 82‐year old male patient admitted in our medical intensive care unit for diffuse skin lesions, 3 days after the onset of ceftriaxone for bilateral pneumonia without microbiological documentation. The patient concomitantly exhibited diffuse skin lesions compatible with livedo and neurological and haemodynamic failure. Biological analysis revealed acute haemolytic anaemia. Warming of patient, red blood‐cells transfusion and high‐doses corticosteroids were initiated and ceftriaxone was stopped. Despite these therapeutics, the patient exhibited multiple organ failure and died. The main suspected triggering factor of this acute and fatal haemolytic anaemia was ceftriaxone administration considering: (i) the delay between cephalosporin administration and symptoms; (ii) the worsening of livedo and acrocyanosis a few hours after meningeal ceftriaxone doses; and (iii) fatal evolution. Cephalosporin‐induced autoimmune haemolytic anaemia is a rare and serious cause of livedo that should be suspected in patients exhibiting livedo and acute haemolytic anaemia within hours/days following cephalosporin administration. [ABSTRACT FROM AUTHOR]

Livedoid vasculopathy (LV) is a rare, disabling disease characterized by painful ulcers, livedo reticularis and atrophy blanche. Hypercoagulation, endothelial, and microcirculatory dysfunction are believed to be responsible for the pathogenesis of this difficult-to-treat disease. This study sought to investigate the frequency of endothelial dysfunction, hypercoagulability, and nailfold capillaroscopic features in LV patients to shed light on its etiology. This case-control study included 16 patients with LV, 24 with systemic sclerosis (SSc), and 23 control subjects. Serum markers of endothelial dysfunction soluble endoglin, endocan, endothelin-1, lipoprotein a, plasminogen activator inhibitor-1 (PAI-1), soluble thrombomodulin, and von Willebrand factor were measured using enzyme-linked immunosorbent assays. Flow-mediated dilation and carotid intima-media thickness were examined as markers of endothelial dysfunction, and microcirculation was assessed with nailfold capillaroscopy. Thrombophilia-related parameters, including gene polymorphisms of factor V Leiden, prothrombin, PAI-1 genes, methylenetetrahydrofolate reductase (MTHFR) and factor XIII mutation and serum levels of protein C, protein S, antithrombin, homocysteine, D-dimer and antiphospholipid antibodies were investigated in LV patients. Plasminogen activator inhibitor-1 and soluble thrombomodulin levels were significantly higher in LV patients compared to control subjects (2.3 [2.05–2.79] ng/ml vs. 1.89 [1.43–2.33] ng/ml, p = 0.007; 1.15 [0.88–1.4] ng/ml vs. 0.76 [0.56–0.9] ng/ml, p = 0.004, respectively). Flow-mediated dilation was 25.4 % lower in the LV patients compared to the control group (14.77 % [11.26–18.26] vs. 19.80 % [16.47–24.88], p = 0.034). Capillaroscopic features, including ramifications (75 % vs. 8.7 %, p < 0.001), avascular areas (25 % vs. 0 %, p = 0.011) and dilatations (33.2 % vs. 0 %, p = 0.016), were significantly higher in LV patients than in controls. LV patients had multiple biochemical or genetic abnormalities related to thrombophilia, including heterozygous factor V Leiden mutations (6.3 %), MTHFR (C677T) mutations (heterozygous 43.8 %, homozygous 18.8 %), MTHFR (A1298C) mutations (heterozygous 37.5 %, homozygous 12.5 %), factor XIII heterozygous mutation (12.5 %), antithrombin deficiency (31.3 %), protein S deficiency (12.5 %), hyperhomocysteinemia (31.3 %), D-dimer elevation (25 %), anti-β2-glycoprotein I (12.5 %), lupus anticoagulant antibodies (6.3 %), and anticardiolipin antibodies (6.3 %). In conclusion, LV patients were characterized by an increased presence of thrombophilia-related parameters, and also exhibited vascular endothelial and microcirculatory dysfunction, resembling SSc. These findings support the complex interaction of thrombophilia, endothelial dysfunction, and microcirculation dysregulation in the pathogenesis of LV. Thus, the treatment of LV patients should be individualized, based on the identification of the predominant pathological pathways. • Thrombophilia parameters are often high in livedoid vasculopathy. • Endothelial dysfunction-associated parameters are impaired in livedoid vasculopathy. • Livedoid vasculopathy is characterized by endothelial dysfunction. • Scleroderma-like capillaroscopic features are seen in livedoid vasculopathy. • Livedoid vasculopathy is associated with microcirculatory dysfunction. [ABSTRACT FROM AUTHOR]

A 21-year-old man had a long-standing history of leg ulcers and hyperpigmention over the feet. Over a span of 8 months, he had an acute ischemic stroke followed by a basal ganglia hemorrhage. He was finally diagnosed with DADA2 syndrome after genetic sequencing. The implications of this new syndrome and its links to stroke in the young are presented in this article. [ABSTRACT FROM AUTHOR]

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

L'athérosclérose est une fréquente et redoutable complication du sujet âgé multitaré et ayant un ou plusieurs facteurs de risque cardiovasculaires. Elle peut toucher tous les troncs artériels, au niveau des membres inférieurs (A) elle est pourvoyeuse de l'artériopathie oblitérante des membres inférieurs. Nous présentons un cas de livédo ecchymotique de la cuisse droite (B) chez un sujet âgé ayant révélé un artériopathie oblitérante du membre inférieur homolatéral(C) avec un descellement septique d'une prothèse totale de la hanche.

Objectives Extra-criteria manifestations of antiphospholipid syndrome (APS) might impact on prognosis and morbidity of the disease. In this study, we aimed to evaluate a population of patients with primary APS (PAPS) whether the extra-criteria manifestations were more frequently found in subjects with higher adjusted Global APS Score (aGAPSS) values when compared to patients with thrombotic and/or obstetric APS (“criteria” manifestations) only. Methods Clinical records were analyzed to retrieve extra-criteria manifestation of APS, cardiovascular risk factors and antiphospholipid antibodies profile. The aGAPSS was calculated by adding the points, as follows: 3 for hyperlipidaemia, 1 for arterial hypertension, 5 for anticardiolipin antibodies IgG/IgM, 4 for anti-β2 glycoprotein I IgG/IgM, and 4 for lupus anticoagulant. Results This retrospective multicenter study included 89 consecutive PAPS [mean age 43.1 (S.D. ± 12.9), female 67%, 52% arterial and 65% venous]. Twenty-seven patients (30.3%) had a history of livedo, 19 (21.3%) had a history of confirmed thrombocytopenia, 3 (3.4%) had biopsy-proven antiphospholipid antibodies (aPL)-related nephropathy and 3 (3.4%) had a history of valvulopathy. Patients with extra-criteria manifestations presented a mean aGAPSS significantly higher [mean 10.30 (S.D. ± 3.57, range: 4–17) vs mean 8.16 (S.D. ± 3.52;range: 4–16, p = 0.005). When comparing patients with and without extra-criteria manifestations, the first group had significantly higher incidence of anti-β2GPI antibodies positivity (59% and 33%, respectively, p = 0.015), double aPL positivities (53% and 31%, respectively, p = 0.034), cerebrovascular events history (52% and 24%, respectively, p = 0.007) and arterial hypertension (52% and 24%, respectively, p = 0.007). Conclusions Our results suggest that patients with higher aGAPSS, might be at higher risk for developing extra-criteria manifestations of APS and should therefore undergo a thorough laboratory and instrumental evaluation. [ABSTRACT FROM AUTHOR]

Résumé Le déficit en adénosine déaminase 2 (DADA2) est une maladie auto-inflammatoire rare de description récente. Elle est de transmission génétique autosomique récessive, liée des mutations du gène ADA2 (ou CECR1 ) codant pour l’enzyme ADA2. Outre son rôle dans le métabolisme des purines, ADA2 agirait comme facteur de croissance pour les cellules endothéliales et dans la différenciation des monocytes ; ainsi ce serait la déviation en macrophages M1 pro-inflammatoire et la survenue de lésions endothéliales secondaires à l’absence d’ADA2 qui seraient à l’origine des manifestations du DADA2. Ses manifestations se regroupent en trois grands types : vasculaire inflammatoire, hématologique et immunologique pouvant remplir les critères diagnostiques d’une périartérite noueuse, d’une aplasie médullaire ou d’un déficit immunitaire commun, variable respectivement. Cliniquement, il existe des manifestations vasculaires cutanées, telles qu’un livedo, et une atteinte du système nerveux central à type d’accidents vasculaires cérébraux ischémiques et hémorragiques, ainsi que des arthralgies et des atteintes digestives. Les corticoïdes et les immunosuppresseurs sont peu efficaces et le traitement repose sur les anti-TNF pour les formes inflammatoires, sans que le mécanisme expliquant leur efficacité ne soit parfaitement élucidé. Ces derniers doivent être introduits en première intention. La place des antithrombotiques est débattue en raison du sur-risque d’hémorragie cérébrale. Deficiency of adenosine deaminase 2 (DADA2) is a recently described auto-inflammatory disorder. It is an autosomal recessive inherited disease, caused by mutations in the ADA2 gene (formerly known as CECR1 ) encoding ADA2 enzyme. Besides its role in the purine metabolism, it has been postulated that ADA2 may act as a growth factor for endothelial cells and in the differenciation of monocytes. Thus, deficiency of ADA2 would lead to endothelial damage and a skewing of monocytes into M1 pro-inflammatory macrophage, causing DADA2 manifestations. Three core clinical features have been described: inflammatory-vascular signs, hematologic abnormalities and immunodeficiency. Clinically, patients display intermittent fever, cutaneous vascular manifestations, such as livedo, ischemic strokes, arthralgia and abdominal pain crisis. Corticosteroids and immunosuppressive agents (i.e. cyclophosphamide, azathioprine, ciclosporin, methotrexate) appear to be poorly effective. Although the mechanism has not been elucidated, anti-TNF agents have been proven efficient in DADA2 and should therefore be used as first line therapy for vasculitis. Role of anti-platelet and anticoagulant therapies in stroke-prophylaxis remains to be discussed, as those patients display a high risk of intracranial bleeding. [ABSTRACT FROM AUTHOR]

Essential thrombocythemia ( ET) is a rare clonal myeloproliferative disorder with a prevalence rate of approximately 1-3 cases per 100 000 individuals per year. ET is characterized by a persistent increase in the platelet count with hyperplasia of bone marrow megakaryocytes. It is difficult to make a diagnosis of ET, because most thrombocythemia are reactive to certain disease conditions including iron deficiency anemia, infection, collagen diseases and malignant tumors. Mutation in the Janus kinase ( JAK)2 gene is present in approximately 50-70% of ET patients, and somatic mutations in the calreticulin ( CALR) gene were recently discovered in approximately 20-25% of sporadic patients with ET or primary myelofibrosis. Various cutaneous manifestations of ET often occur by microvascular thrombosis and precede severe arterial and venous thromboembolic events in other organs. Therefore, in order to prevent such severe events, it is important to make an early diagnosis of ET based on a number of cutaneous manifestations. Here, we report two cases of ET diagnosed based on livedo racemosa on feet with gene mutations in JAK2 and CALR, respectively, and show the pathological and immunohistological findings of the livedo resulting from platelet thrombosis rather than vasculitis. We also review the cutaneous manifestations in current published reports of Japanese ET patients. Our patients were successfully treated with low-dose aspirin, a vasodepressor and hydroxyurea, following regressed livedo and reduced platelet counts. [ABSTRACT FROM AUTHOR]

The patient was a 47-year-old woman with a painful ulcer that had appeared on the right 5th toe two weeks before she visited our hospital. Histopathological examination showed that thrombi were present in small blood vessels in the dermis and pancytosis was detected in a blood test, suggesting polycythemia-associated ulceration of the toe. Essential thrombocythemia was diagnosed based on bone marrow puncture and chromosomal test findings. Platelet count and the ulcer were improved by oral hydroxyurea.

KEY TEACHING POINTS. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is the association of thrombosis and/or pregnancy morbidity with antiphospholipid antibodies (aPL). Thirty to forty percent of systemic lupus erythematosus (SLE) patients are tested positive for aPL, which may have an impact on the SLE presentation, management, and prognosis. Compared with SLE patients without aPL, those with aPL have a higher prevalence of thrombosis, pregnancy morbidity, valve disease, pulmonary hypertension, livedo reticularis, thrombocytopenia, hemolytic anemia, acute/ chronic renal vascular lesions, and moderate/severe cognitive impairment; worse quality of life; and higher risk of organ damage. The use of low-dose aspirin (LDA) is controversial for primary thrombosis and pregnancy morbidity prevention because of the lack of strong prospective controlled data. Similarly, the use of anticoagulation is controversial for patients with an aPL-related nephropathy. Until further studies are available, physicians should discuss the risk/benefits of LDA or anticoagulation as well as the available literature with patients. [ABSTRACT FROM AUTHOR]