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INTRODUCTION: Decompression sickness (DCS) is a medical condition caused by outgassing of dissolved nitrogen following rapid ascent by divers and aviators. Cutaneous DCS, historically termed cutis marmorata (CM), presents as a predominantly truncal reticular violaceous-to-dusky eruption. The prevailing theories for its pathogenesis include: localized cutaneous outgassing, paradoxical embolism across a right-to-left shunt (RLS), and brainstem emboli disrupting autonomic control of cutaneous microcirculation. METHODS: We conducted a systematic review of reports of cutaneous DCS to investigate relationships among CM, RLS, and neurological sequelae to better elucidate the mechanism of CM. A literature search examining reports of cutaneous DCS yielded 31 eligible studies, comprising a pooled total of 128 patients. RESULTS: Of the patients with documented workup, 84% showed evidence of RLS with CM. Subsequently 18 patients underwent percutaneous closure of intracardiac RLS with no recurrence of DCS. Of the patients with documented neurological evaluations, 57% experienced both CM and neurological DCS manifestations. The coexistence of RLS and neurological symptoms with CM was noted in numerous cases; exact percentages of overlap cannot be stated due to data unavailability. DISCUSSION: Our results indicating the striking coexistence of RLS and neurological sequelae in CM patients is supportive of the paradoxical embolism theory of pathogenesis. The frequent coincidence of CM with RLS and neurological symptoms raises concern that CM may signify vulnerability to devastating systemic gas emboli. CM has historically been considered trivial and self-limiting; however, our results support reappraisal of its clinical significance and potential reclassification to the more severe subtype. [ABSTRACT FROM AUTHOR]

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Summary: Background: Sneddon syndrome is an occlusive vasculopathy that presents clinically with generalized livedo racemosa on the skin and transient ischemic attacks, strokes, and cognitive or motor deficits in the central nervous system. Antiplatelet or anticoagulant therapy is recommended. Due to the limited therapeutic efficacy and the resulting serious complications, we propose combination therapy with additional infusion cycles of alprostadil and captopril and report initial long‐term results. Patients and methods: We performed a systematic retrospective analysis of all patients with primary Sneddon syndrome who received combination therapy in our clinic between 1995 and 2020. Therapeutic outcomes were evaluated using descriptive statistics compared to historical controls receiving monotherapy. We also analyzed the event rate of complications when combination therapy was discontinued. Results: During the 99.7 patient‐years of follow‐up, there were no transient ischemic attacks and the stroke rate dropped to 0.02 per patient‐year. In comparison, the rates of transient ischemic attacks and strokes in the historical controls ranged from 0.08 to 0.035 per patient‐year. After discontinuation of alprostadil therapy, eight events occurred in three patients. Conclusions: Combination therapy reduces the long‐term incidence of ischemic events in patients with primary Sneddon syndrome. [ABSTRACT FROM AUTHOR]

Sickle cell disease is a monogenic hemoglobinopathy that results in the abnormal production of hemoglobin S, which yields the characteristic sickle-shaped red blood cells. Sickle cell vaso-occlusive crisis is a painful complication of sickle cell disease caused by red blood cell entrapment within the microcirculation. The resulting tissue ischemia triggers a secondary inflammatory process involved in the pathogenesis of varying inflammatory skin conditions. Chronic leg ulcers are the most common skin presentation in sickle cell disease. A 58-year-old woman with sickle cell disease presented with systemic edematous plaques with the most notable involvement of her bilateral legs, which exhibited reticulated purpuric patches with central pallor. We report a case highlighting an unusual presentation of livedo racemosa as the presenting sign in a patient with sickle cell disease in vaso-occlusive crisis.

Autoinflammatory diseases (AIDs) characterized by recurrent episodes of localized or systemic inflammation are disorders of the innate immune system. Skin lesions are commonly found in AIDs and cutaneous vasculitis can coexist with AIDs and even present as the most striking feature. This review aims to focus on the frequent cutaneous vasculitis association in three monogenic AIDs including familial Mediterranean fever (FMF), deficiency of adenosine deaminase type 2 (DADA2), and the recently identified adult‐onset VEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic) syndrome. Cutaneous vasculitis in FMF is characterized by: (1) small‐vessel vasculitis similar to IgA vasculitis with palpable purpura but increased intussusception complication and less vascular IgA deposit, and (2) cutaneous arteritis–like vasculitis presenting as subcutaneous nodules most often with higher glomerular involvement. DADA2 has a wide spectrum of clinical presentations ranging from fatal systemic vasculitis with multiple strokes, especially in pediatric patients, to limited cutaneous disease in middle‐aged patients. DADA2 shares similar clinical and histopathological features with polyarteritis nodosa (PAN). As a result, DADA2 is commonly initially misdiagnosed as childhood PAN. Livedo racemosa reveals the most common cutaneous manifestation of cutaneous vasculitis in patients with DADA2. VEXAS syndrome is a life‐threatening disease. A diagnosis of VEXAS syndrome should be strongly considered or could be made in patients with skin lesions characterized by Sweet syndrome–like eruption, livedo racemosa, concomitant relapsing polychondritis, deep venous thrombosis, pulmonary involvement, and progressive hematologic abnormalities such as myelodysplastic syndrome with a unique finding of cytoplasmic vacuoles in myeloid and erythroid precursor cells from bone marrow aspirate smear. As skin involvement is common in AIDs and may present as the most frequent manifestation, especially in DADA2 (70% to 90%) and VEXAS syndrome (83% to 91%), dermatologists play a crucial role in contributing to the early diagnosis of these AIDs with early initiation of the appropriate therapy to avoid progressing fatal outcomes. [ABSTRACT FROM AUTHOR]

Obliterative vasculopathies in dermatology represent a heterogeneous group of diseases with different pathogenesis. These are conditions of non-inflammatory occlusion of the vascular lumen with subsequently induced ischemia of the tissue (skin). In the current nomenclature, we also encounter the term cutaneous microvascular occlusive syndromes, which better characterize the involvement of skin vessels. Diseases that are responsible for occlusive syndromes include platelet pathology, the presence of cryoglobulins, infections affecting the vessel wall, embolisation (e.g. cholesterol), coagulopathy (antiphospholipid syndrome), or diseases accompanying chronic kidney failure (calciphylaxis). Possible skin manifestations include ulceration, necrotic lesions, livedo racemosa, and retiform purpura. The work provides a comprehensive view of the complex issue of these conditions and points to skin manifestations that are considered as manifestations of vasculitis in routine practice. [ABSTRACT FROM AUTHOR]

Objective: We sought to characterise the clinical picture of Martorell hypertensive ischaemic leg ulcer (HYTILU) by describing the ulcer borders with three clinical features: 'the red lipstick sign'; purple border; and livedo racemosa. We also aimed to characterise comorbidities and determinants of healing time. Method: A single-centre, retrospective cohort study was conducted between 2015–2020. We scrutinised ulcer photographs for relevant clinical signs. Data on comorbidities, medication and ulcer treatments, as well as method of diagnosis and healing time, were collected from patients' electronic medical records. Results: In total, 38 female patients and 31 male patients (mean age 73 years) were assessed, with a mean follow-up time of 174 days. The 'red lipstick-like' margin covered 0–50% of the ulcer margin in 56.5% of the ulcers, and 51–100% of the ulcer margin in 43.5% of the ulcers. Purple border or livedo racemosa was observed in 70.5% of the ulcers. All patients had hypertension and 52.2% of patients had type 2 diabetes. A heavy cardiovascular disease burden and frequent concomitant vascular pathologies were found. Infections requiring systemic antibiotics, ulcer size and duration of symptoms before diagnosis were strongly associated with healing time. We also found that use of systemic corticosteroids and severity of hypertension (measured by the number of antihypertensive medications used) delayed healing. Conclusion: Our data suggest that 'the red lipstick sign' could be a novel diagnostic feature in HYTILUs alongside purple border, livedo racemosa and necrotic/fibrinous ulcer bed. The results also elucidated HYTILU comorbidities, and showed that infections and delay in diagnosis impeded healing. [ABSTRACT FROM AUTHOR]

Hydrophilic polymer embolism (HPE) is a rare iatrogenic complication of the use of polymer-coated intravascular devices, which may affect several organ systems including the skin. Herein, we present a patient who developed a cutaneous eruption with associated neurologic manifestations secondary to localized HPE. This is a potentially underdiagnosed, life-threatening complication and physicians should consider HPE when evaluating skin eruptions in patients who have undergone endovascular procedures.

Abstract Background Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease caused by mutations in the ADA2 gene. DADA2 has a broad spectrum of clinical presentations. Apart from systemic manifestations, we can categorize most of the signs and symptoms of DADA2 into the three groups of vasculitis, hematologic abnormalities, and immunologic dysregulations. The most dominant vasculitis features are skin manifestations, mostly in the form of livedo racemosa/reticularis, and early onset ischemic or hemorrhagic strokes. Hypogammaglobulinemia that is found in many cases of DADA2 brings immunodeficiencies into the differential diagnosis. Cytopenia, pure red cell aplasia (PRCA), and bone marrow failure (BMF) are the hematologic abnormalities commonly found in DADA. Case presentation We introduce eleven patients with DADA2 diagnosis, including two brothers and sisters, one set of twin sisters, and one father and his daughter and son. Ten patients (91%) had consanguineous parents. All the patients manifested livedo racemose/reticularis. Ten patients (91%) reported febrile episodes, and seven (64%) had experienced strokes. Only one patient had hypertension. Two of the patients (11%) presented decreased immunoglobulin levels. One of the patients presented with PRCA. Except for the PRCA patient with G321E mutation, all of our patients delivered G47R mutation, the most common mutation in DADA2 patients. Except for one patient who unfortunately passed away before the diagnosis was made and proper treatment was initiated, the other patients’ symptoms are currently controlled; two of the patients presented with mild symptoms and are now being treated with colchicine, and the eight others responded well to anti-TNFs. The PRCA patient still suffers from hematologic abnormalities and is a candidate for a bone marrow transplant. Conclusions Considering the manifestations and the differential diagnoses, DADA2 is not merely a rheumatologic disease, and introducing this disease to hematologists, neurologists, and immunologists is mandatory to initiate prompt and proper treatment. The efficacy of anti-TNFs in resolving the symptoms of DADA2 patients have been proven, but not for those with hematologic manifestations. Similarly, they were effective in controlling the symptoms of our cohort of patients, except for the one patient with cytopenia.

Deficiency of adenosine deaminase 2 (DADA2) is a childhood-onset disease known with pleiotropic clinical manifestations due to a monogenic form of systemic vasculopathy. Although the clinical spectrum of DADA2, linked to biallelic mutations in the ADA2 gene, has significantly expanded since 2014, approximately 200 cases have been reported thus far. In this report, two siblings are presented to draw attention to an unreported mutation of DADA2 and different phenotypic features of the same missense type homozygous mutation, p.Ser50Leu (c.149C>T). Next-generation sequencing demonstrated an autosomal recessive inherited missense type p.Ser50Leu (c.149C>T) variant homozygous mutation in the ADA-2 gene. The index patient is a 10-year-old Iraqi citizen boy who was referred to us with a complaint of anemia. The patient still needed blood transfusions after 2 hematopoietic stem cell transplantations. His older brother was an 11-year-old boy who presented to the emergency with a history of recurrent lung infections since 7 years of age. Considering the genotype-phenotype relationship from literature data, although vasculitis and low ADA2 activity are defined in cases with missense mutations, immuno-hematological manifestations are remarkable in our patients rather than vasculitic manifestations. While bone marrow failure findings e.g., anemia, neutropenia, etc. are reported to be seen in the 5th and 6th decades of life, those were predominant clinical features in our patients despite their younger age. DADA2 should also be kept in mind in cases of otherwise unexplained cytopenia, especially when associated with panhypogammaglobulinaemia and bone marrow hypocellularity, irrespective of the age of the patient at presentation. [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]

In this Part 2 of a 2-part continuing medical education series, we review the epidemiology of peripheral vascular disease, its association with cutaneous symptoms, and the diagnosis and evaluation of cutaneous features of vascular disorders. As peripheral vascular disease becomes more prevalent globally, it is essential for dermatologists to become competent at accurately recognizing and diagnosing cutaneous manifestations and directing individuals to receive appropriate care and treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study is to evaluate the clinical, laboratory, and radiological findings and prognosis of patients with adenosine deaminase 2 deficiency (DADA2) and to highlight the conditions that DADA2 should be considered in the differential diagnosis in patients with neurological findings. METHODS: A case series of six DADA2 patients was presented in this retrospective, descriptive study. Clinical and laboratory data, treatment protocols, and prognosis of the patients were recorded. A diagnosis of DADA2 was established by ADA2 enzyme activity assay and/or ADA2 gene sequencing. RESULTS: Six patients with DADA2 were included in the study. The median age at symptom onset was 6.5 years (range 3.5-13.5 years). The median time to diagnosis from the initial presentation was 9 (3-72) months. Consanguinity was present in the families of 4 cases. The skin, nervous system, and musculoskeletal system were the most commonly involved systems. Vasculitis mimicking polyarteritis nodosa (PAN) was the predominant phenotype (n=4) in our case series. Four patients with PAN-like features had neurological involvement. Ischemic strokes were found in 3 patients, cranial nerve palsy in 2 patients, and seizures in 2 patients. The CECR1 gene was analyzed in all patients. We analyzed plasma ADA2 enzyme activity only in one patient. Anti-tumor necrosis factor (TNF)-α therapy was initiated. Inflammation was suppressed and remission was achieved in all patients. CONCLUSION: DADA2 should be considered in patients with PAN-like disease, a history of familial PAN/vasculitis, early-onset strokes/neurological involvement with systemic inflammation. Furthermore, anti-TNF-α therapy appears to be beneficial for the treatment of DADA2. [ABSTRACT FROM AUTHOR]

Background: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease caused by mutations in the ADA2 gene. DADA2 has a broad spectrum of clinical presentations. Apart from systemic manifestations, we can categorize most of the signs and symptoms of DADA2 into the three groups of vasculitis, hematologic abnormalities, and immunologic dysregulations. The most dominant vasculitis features are skin manifestations, mostly in the form of livedo racemosa/reticularis, and early onset ischemic or hemorrhagic strokes. Hypogammaglobulinemia that is found in many cases of DADA2 brings immunodeficiencies into the differential diagnosis. Cytopenia, pure red cell aplasia (PRCA), and bone marrow failure (BMF) are the hematologic abnormalities commonly found in DADA. Case presentation: We introduce eleven patients with DADA2 diagnosis, including two brothers and sisters, one set of twin sisters, and one father and his daughter and son. Ten patients (91%) had consanguineous parents. All the patients manifested livedo racemose/reticularis. Ten patients (91%) reported febrile episodes, and seven (64%) had experienced strokes. Only one patient had hypertension. Two of the patients (11%) presented decreased immunoglobulin levels. One of the patients presented with PRCA. Except for the PRCA patient with G321E mutation, all of our patients delivered G47R mutation, the most common mutation in DADA2 patients. Except for one patient who unfortunately passed away before the diagnosis was made and proper treatment was initiated, the other patients' symptoms are currently controlled; two of the patients presented with mild symptoms and are now being treated with colchicine, and the eight others responded well to anti-TNFs. The PRCA patient still suffers from hematologic abnormalities and is a candidate for a bone marrow transplant. Conclusions: Considering the manifestations and the differential diagnoses, DADA2 is not merely a rheumatologic disease, and introducing this disease to hematologists, neurologists, and immunologists is mandatory to initiate prompt and proper treatment. The efficacy of anti-TNFs in resolving the symptoms of DADA2 patients have been proven, but not for those with hematologic manifestations. Similarly, they were effective in controlling the symptoms of our cohort of patients, except for the one patient with cytopenia. [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]

Livedoid vasculopathy (LV) is a thrombo-occlusive vasculopathy that involves the dermal vessels. Clinically, it is characterized by the presence of painful purpuric ulcers on the lower extremities. Histopathologically, it shows intraluminal fibrin deposition and thrombosis, segmental hyalinization, and endothelial proliferation. It is important to notice that the term “atrophie blanche” is descriptive and it includes not only patients with LV but also patients with a combination of vasculitis and vasculopathy, that is, LV and medium-sized vasculitis such as cutaneous polyarteritis nodosa (PANc). Diagnosis is based on a proper clinicopathological correlation, excluding the main differential diagnosis and considering vasculitis as a mimicker or concomitant diagnosis. Coagulation disorders must also be studied although they are not found in all LV. Its frequency is reviewed as well. Treatment of LV is challenging, and different therapies have been attempted. Among them, pain management, wound care, control of cardiovascular risk factors, and both antiplatelets and anticoagulants, mostly rivaroxaban, are the main therapies used. These different therapies as well as their degree of evidence are reviewed.

Cutaneous polyarteritis nodosa (cPAN) was first reported by Lindberg in 1931. It has been recognized as a skin-limited vasculitis whose cutaneous histopathological features are indistinguishable from those of PAN. Cutaneous arteritis (CA) was defined as a form of single-organ vasculitis in the revised Chapel Hill Classification and was recognized as the same disease as cPAN. It became known that deficiency of adenosine deaminase 2 (DADA2) cases were included in cases that had been diagnosed with CA. Because of their similarity and differences in the treatment methods, DADA2 should be considered in CA cases, especially if they are diagnosed or developed in early childhood. Cutaneous arteritis may be classified as an immune complex-mediated vasculitis. It was reported that the pathogenesis of anti-lysosomal-associated membrane protein-2 (LAMP-2) antibodies and anti-phosphatidylserine-prothrombin complex (PS/PT) antibodies as good parameters in CA. The main skin manifestations include livedo racemosa, subcutaneous nodules, and ulcers. Although CA is recognized to have a benign clinical course, it has become known that it is easy to relapse. The existence of skin ulcers upon diagnosis or sensory neuropathies was suggested to be a predictor of poor prognosis. Cutaneous arteritis with them may need to be treated with more intensive therapies.

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.

Livedo racemosa (LRac) refers to violaceous, red, or blue netlike mottling of the skin in an irregular pattern caused by circulatory abnormalities. Central venous catheters (CVC) are widely used in neonates who require intensive care to offer steady intravenous access. CVCs are covered with a hydrophilic polymer gel that reduces friction between the sheath and the vessel wall, thereby minimizing vascular spasm, irritation, and aneurysm formation. However, the introduction of foreign material into the vein carries a risk of embolization. Recently, LRac was reported as a cutaneous manifestation of hydrophilic polymer gel embolization (HPE) in adults. We present a case of LRac in a newborn that developed following CVC insertion and resolved spontaneously after the catheter was removed. [ABSTRACT FROM AUTHOR]

Coronavirus disease (COVID-19) skin manifestations have been increasingly reported in medical literature. Recent discussions have identified a lack of images of skin of color (SOC) patients with COVID-19 related skin findings despite people with skin of color being disproportionately affected with the disease. There have been calls to prioritize the identification of COVID-19 skin manifestations in patients with SOC and disseminate these findings. The objective of this article is to review the existing literature on COVID-19 skin manifestations and, where possible, discuss how they may present differently in patients with SOC. Further research is needed to allow primary care physicians and dermatologists to be aware of and easily identify patients with cutaneous findings that may be secondary to COVID-19. Patients presenting with idiopathic dermatologic manifestations should be considered for COVID-19 testing and follow public health guidelines for self-isolation. [ABSTRACT FROM AUTHOR]

Background: The abundance of publications of COVID‐19‐induced chilblains has resulted in a confusing situation. Methods: This is a prospective single‐institution study from 15 March to 13 May 2020. Thirty‐two patients received PCR nasopharyngeal swabs. Of these, 28 patients had a thoracic CT‐scan, 31 patients had blood and urine examinations, 24 patients had skin biopsies including immunohistochemical and direct immunofluorescence studies, and four patients had electron microscopy. Results: COVID‐19‐induced chilblains are clinically and histopathologically identical to chilblains from other causes. Although intravascular thrombi are sometimes observed, no patient had a systemic coagulopathy or severe clinical course. The exhaustive clinical, radiological, and laboratory work‐up in this study ruled‐out other primary and secondary causes. Electron microscopy revealed rare, probable viral particles whose core and spikes measured from 120 to 133 nm within endothelium and eccrine glands in two cases. Conclusion: This study provides further clinicopathologic evidence of COVID‐19‐related chilblains. Negative PCR and antibody tests do not rule‐out infection. Chilblains represent a good prognosis, occurring later in the disease course. No systemic coagulopathy was identified in any patient. Patients presenting with acral lesions should be isolated, and chilblains should be distinguished from thrombotic lesions (livedo racemosa, retiform purpura, or ischemic acral necrosis). [ABSTRACT FROM AUTHOR]

Sneddon syndrome (SS) is a rare medium-vessel vasculopathy which characteristically presents with livedo racemosa (LR) and complications such as strokes. This case report describes a female presenting acutely with a stroke and, initially, no evidence of LR. Her antiphospholipid antibodies were negative, and her neuroimaging revealed multiple territory strokes with extensive vasculopathy and fragile neo-formed vessel collateralisation. She had progressive memory loss and multiple transient ischaemic attacks on a background of established infarctions. SS should be considered in any idiopathic medium-vessel vasculopathy despite the absence of LR. Medical therapy can be challenging and the importance of antiphospholipid status in risk stratifying anticoagulation against antiplatelet therapy is discussed with a proposed rheumatology management strategy. The medical option of hydroxychloroquine should be considered in all patients in view of its anti-thrombotic properties and efficacy in diseases such as systemic lupus erythematosus and antiphospholipid syndrome with the suggestion that SS may be a forme fruste of these diseases. Neurosurgical options should be considered for recurrent transient neurological symptoms. For our patient, this included an extracranial to intracranial bypass via a radial artery graft for haemodynamic stroke management confirmed on SPECT imaging. The traditional hallmark of SS has previously been LR. This case highlights an atypical presentation stressing the importance of diagnostic vigilance in a patient with an idiopathic medium-vessel vasculopathy, together with balancing the medical risk of antiplatelet therapy, anticoagulation and thrombolysis whilst revealing possible neurosurgical options in select SS patients.

Herein, we report a case-based review of the Sneddon Syndrome (SS), a rare chronic condition which affects small to medium blood vessels. It is known by its skin presentation, livedo racemosa (LRC), and the relapsing cerebrovascular events. However, neither LRC nor cerebrovascular events are exclusive to SS. A 36-year-old female with history of mitral valve prolapse, hypothyroidism, Raynaud phenomenon, hypertension, migraines, and four episodes of transient ischemic attacks (TIA), presented to our clinic with new skin findings, suggestive of LRC. Based on her previous history, current presentation and skin biopsy results, she was diagnosed with SS secondary to antiphospholipid syndrome. The present report illustrates the difficulty in recognizing SS and how the heterogeneity of the disease may be contributing to the difficulty making a distinct diagnosis. [ABSTRACT FROM AUTHOR]

Lymphocytic thrombophilic arteritis and Sneddon syndrome can have very similar clinical presentations with chronic persistent widespread blanchable livedo racemosa. Lymphocytic thrombophilic arteritis has only recently been described and generally is associated with a benign prognosis. Sneddon syndrome is associated with the development of multiple cerebrovascular accidents and progressive neurological impairment. We present three cases of Sneddon syndrome and compare them with lymphocytic thrombophilic arteritis to identify patients at risk of neurological events. [ABSTRACT FROM AUTHOR]

Livedo racemosa is a cutaneous finding characterized by a persistent, erythematous, or violaceous discoloration of the skin, in a broken, branched, discontinuous, and irregular pattern. A retrospective review of 33 cases with clinical diagnosis of livedo racemosa over the past 6 years was evaluated in the dermatology department of a tertiary care hospital. We found predominance in Caucasian women (78.8%); age ranged from 8 to 81 years, with a mean age of 36 years. Livedo racemosa was described as generalized in 12 patients (36.4%), although the main localization was on lower limbs (42%). After laboratory testing and histopathological examinations, 12 patients (36.4%) were classified with idiopathic livedo racemosa; secondary diseases were diagnosis in 21 patients (63.6%), including Sneddon's syndrome, cutaneous polyarteritis nodosa, systemic lupus erythematosus, and others. Medical history of thrombotic events was described in 8 (24.2%) patients, and also 8 (24.2%) patients had abnormal results for 2 or more thrombophilia laboratory tests. Skin biopsy showed no histological abnormalities in 11 cases (33.3%), thrombosis of dermal blood vessels in 10 (30.3%), intimal/subintimal thickening in 7 (21.2%), and vasculitis in 5 (15.2%). In conclusion, livedo racemosa is a clinical feature that might be correlated to vascular disorders, such as thrombotic and/or hypercoagulable states, autoimmune diseases, and neoplastic diseases, or it can be secondary to specific medications. It is essential to establish a correct approach in cases of livedo racemosa, which includes anamnesis, physical examination, laboratory test, histological examination, and complementary examination according to clinical findings, in order to diagnosis underlying causes. [ABSTRACT FROM AUTHOR]

Livedo is a net‐like violaceous skin pattern. It can be classified as physiological or pathological. The physiological livedo reticularis usually appears in cold conditions, whereas the pathological and irregular livedo, which persists in warm temperatures, is often labeled as 'livedo racemosa'. Some neurological pathologies are associated with livedo, most commonly those with an inflammatory component or those derived from systemic disorders. The present review summarizes the most important central and peripheral neurological diseases in pediatric and adult age groups associated with livedo, providing physicians with an overview of the clinical presentation, etiology, diagnosis and management of these conditions. [ABSTRACT FROM AUTHOR]

Decompression sickness and arterial gas embolism, collectively known as decompression illness (DCI), are serious medical conditions that can result from compressed gas diving. DCI can present with a wide range of physiologic and neurologic symptoms. In diving medicine, skin manifestations are usually described in general as cutis marmorata (CM). Mainly in the Anglo-American literature the terms cutis marmorata, livedo reticularis (LR), and livedo racemosa (LRC) are used interchangeably but actually describe pathophysiologically different phenomena. CM is a synonym for LR, which is a physiological and benign, livid circular discoloration with a net-like, symmetric, reversible, and uniform pattern. The decompression-associated skin discolorations, however, correspond to the pathological, irregular, broken netlike pattern of LRC. Unlike in diving medicine, in clinical medicine/dermatology the pathology of livedo racemosa is well described as a thrombotic/embolic occlusion of arteries. This concept of arterial occlusion suggests that the decompression-associated livedo racemosa may be also caused by arterial gas embolism. Recent studies have shown a high correlation of cardiac right/left (R/L) shunts with arterial gas embolism and skin bends in divers with unexplained DCI. To further investigate this hypothesis, a retrospective analysis was undertaken in a population of Austrian, Swiss, and German divers. The R/L shunt screening results of 18 divers who suffered from an unexplained decompression illness (DCI) and presented with livedo racemosa were retrospectively analyzed. All of the divers were diagnosed with a R/L shunt, 83% with a cardiac shunt [patent foramen ovale (PFO)/atrium septum defect (ASD)], and 17% with a non-cardiac shunt. We therefore not only confirm this hypothesis but when using appropriate echocardiographic techniques even found a 100% match between skin lesions and R/L shunt. In conclusion, in diving medicine the term cutis marmorata/livedo reticularis is used incorrectly for describing the actual pathology of livedo racemosa. Moreover, this pathology could be a good explanation for the high correlation of livedo racemosa with cardiac and non-cardiac right/left shunts in divers without omission of decompression procedures.

Background: Lymphocytic thrombophilic arteritis (LTA), or macular lymphocytic arteritis, is defined by a primary lymphocytic vasculitis. However, the nosology of LTA has been controversial, with speculation that it may represent an indolent non-nodule-forming variant of cutaneous polyarteritis nodosa (cPAN).Objective: This study compares the clinicopathologic features of patients with LTA or cPAN to assess if these conditions should be considered distinct entities.Methods: This is a cross-sectional study of all LTA and cPAN cases at a single tertiary center using prospectively collected clinical data and blinded histologic assessment.Results: The study included 17 patients with LTA and 13 patients with cPAN. Clinically, cases of LTA were distinguished by a more widespread pattern of livedo racemosa, which was noninfiltrated and asymptomatic. In contrast, cPAN was associated with localized starburst livedo, purpura, and episodic features including nodules, pain, and large inflammatory ulcers. When patients were separated according to the presence (>5%) or paucity (≤5%) of neutrophils on blinded histology review, they had distinct clinical features and differences in disease course.Limitations: This was a single-center study.Conclusion: Our data support the classification of LTA and cPAN as separate entities rather than a spectrum of the same disorder and highlight the importance of clinicopathologic correlation in distinguishing these conditions. [ABSTRACT FROM AUTHOR]

Sneddon syndrome is a rare, non-inflammatory vasculopathy that generally occurs in the third to fourth decade of life but may rarely present in the pediatric population. It is characterized by the skin finding of livedo racemosa and recurrent ischemic strokes. Other common neurologic manifestations include migraine and early cognitive decline. It may be associated with systemic lupus erythematosus (SLE) and antiphospholipid antibodies, or as in our case, thrombophilia and autoimmune workup may be negative. Optimal treatment for Sneddon syndrome is unknown. Here we report the case of an 18-year-old female, with a 3-year history of livedo racemosa and migraines, who presented with acute expressive aphasia and was found to have an ischemic stroke and an evidence of prior strokes on magnetic resonance imaging (MRI). Autoimmune and cardioembolic causes of stroke were ruled out. Given the findings of livedo racemosa and evidence of recurrent strokes, she was diagnosed with Sneddon Syndrome. Five years earlier, she had been diagnosed with Freiberg disease, which is the avascular necrosis of the second metatarsal head and was likely her first symptom of Sneddon syndrome. This is the first report of Freiberg disease associated with Sneddon syndrome. This paper highlights a rare cause of stroke in the pediatric population as well as the first report of avascular necrosis associated with Sneddon syndrome. Several manifestations of Sneddon syndrome can precede strokes by years. An awareness of those features may allow for the adoption of primary stroke prevention. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical features, genotype, and treatment approaches of patients with confirmed adenosine deaminase 2 (ADA2) deficiency with dissimilar phenotypes. Methods: A case series of five DADA2 patients from three families was presented. The clinical and laboratory data, treatment protocols, and outcome of the patients were recorded from the patients' medical charts. ADA2 gene was screened by next generation sequencing first and then verified by Sanger sequencing. Serum ADA2 enzyme activity was measured by modified spectrophotometric method. Results: The median (min–max) age at onset of symptoms and age at diagnosis were 11 (9–13.8) years and 15 (9–19) years, respectively. The median (min–max) follow-up period was 8 (6–45) months. There was consanguinity in two families (2/3). The main clinical manifestations are musculoskeletal (5/5), dermatological (4/5), and neurological (2/5). Homozygosity for the p.G47R mutation in ADA2 gene was detected in three patients. A homozygous mutation in ADA2 gene (c.650 T > A; p.Val217Asp) was detected in two siblings. Plasma ADA2 enzymatic activity was absent in all patients. Anti-tumor necrosis factor (TNF) therapy was commenced, and all patients became clinically inactive with normal acute-phase reactants. Conclusion: ADA2 mutations should be checked in patients with presence of inflammation and livedoid vasculitis when they have neurological findings, especially in the form of stroke; and a history suggesting for an inherited disease; or presence of resistance to conventional treatment. Besides, anti-TNF seems to be useful for treatment of DADA2. [ABSTRACT FROM AUTHOR]

Sneddon syndrome (SS) is a rare medium-vessel vasculopathy which characteristically presents with livedo racemosa (LR) and complications such as strokes. This case report describes a female presenting acutely with a stroke and, initially, no evidence of LR. Her antiphospholipid antibodies were negative, and her neuroimaging revealed multiple territory strokes with extensive vasculopathy and fragile neo-formed vessel collateralisation. She had progressive memory loss and multiple transient ischaemic attacks on a background of established infarctions. SS should be considered in any idiopathic medium-vessel vasculopathy despite the absence of LR. Medical therapy can be challenging and the importance of antiphospholipid status in risk stratifying anticoagulation against antiplatelet therapy is discussed with a proposed rheumatology management strategy. The medical option of hydroxychloroquine should be considered in all patients in view of its anti-thrombotic properties and efficacy in diseases such as systemic lupus erythematosus and antiphospholipid syndrome with the suggestion that SS may be a forme fruste of these diseases. Neurosurgical options should be considered for recurrent transient neurological symptoms. For our patient, this included an extracranial to intracranial bypass via a radial artery graft for haemodynamic stroke management confirmed on SPECT imaging. The traditional hallmark of SS has previously been LR. This case highlights an atypical presentation stressing the importance of diagnostic vigilance in a patient with an idiopathic medium-vessel vasculopathy, together with balancing the medical risk of antiplatelet therapy, anticoagulation and thrombolysis whilst revealing possible neurosurgical options in select SS patients. [ABSTRACT FROM AUTHOR]

Sneddon syndrome (SS) is an episodic or chronic, slowly progressive disorder and characterized by generalized livedo racemosa (patchy, violaceous, skin discoloration) and recurrent cerebrovascular events. The histopathology of skin and brain is remarkable for a noninflammatory thrombotic vasculopathy involving medium- and small-sized dermal and cerebral arteries, respectively. Approximately 80% of the SS patients are women with a median age of diagnosis at 40 years. However, the onset of the disease during childhood have been reported. Etiopathogenesis of SS is unknown with 2 primary mechanisms proposed - autoimmune/inflammatory versus thrombophilia. SS is primarily classified as antiphospholipid positive or negative type. Neurological manifestations usually occur in 3 phases: (1) prodromal symptoms such as headaches, dizziness, and vertigo, (2) recurrent strokes, and (3) early onset dementia. Livedo racemosa precedes the onset of recurrent strokes by more than 10 years, but in many instances, the significance of the skin lesion is recognized only after the appearance of the stroke. The involvement of the heart valves, systolic labile hypertension, and retinal changes are also commonly associated with this syndrome. Treatment of SS is primarily based on anecdotal reports. Antiplatelet and antithrombotic agents are used for secondary stroke prophylaxis, and a recent study showed a relatively lower stroke recurrence rate with the universal use of antiplatelet/antithrombotic agents. Routine use of anti-inflammatory or immunosuppressive therapies is controversial. Neuropsychiatric prognosis of SS is relatively poor with predominant deficits in the concentration, attention, visual perception, and visuospatial skills. [ABSTRACT FROM AUTHOR]

Livedo reticularis (LR) is a cutaneous physical sign characterized by transient or persistent, blotchy, reddish-blue to purple, net-like cyanotic pattern. LR is a benign disorder affecting mainly middle-aged females, whereas livedo racemosa (LRC) is pathologic, commonly associated with antiphospholipid antibody syndrome. This article aims to review the causes of LR and LRC along with the evaluation and management.

Abstract: We describe three patients who presented with a striking erythematous non‐blanching annular eruption and features of lymphocytic thrombophilic arteritis (LTA), with a prominent lymphocytic vasculitis involving deep dermal vessels. Lymphocytic inflammation was also evident in the superficial vessels and one patient had small superficial ulcers over the ankle area resembling livedoid vasculopathy (LV). Multiple biopsies demonstrated a persistent absence of neutrophils in the infiltrate consistent with a lymphocytic process. In addition to highlighting the annular morphology as a novel presentation of LTA, these cases suggest a possible relationship between LV and LTA and support the notion that they are distinct from neutrophilic vasculitides such as cutaneous polyarteritis nodosa. [ABSTRACT FROM AUTHOR]

A 55-year-old woman presented with a 5-year history of livedo racemosa on her limbs. Histology showed vasculitis of medium-sized arteries with a circumferential, hyalinised, intraluminal fibrin ring. Her laboratory investigations did not indicate any underlying systemic disease. The findings were consistent with lymphocytic thrombophilic arteritis (LTA), alias macular arteritis, which is a recently described entity. The importance of LTA lies in the fact that it is a close clinical and microscopic mimic of polyarteritis nodosa (PAN). LTA is believed to be a distinct entity by some and as a form of PAN by others. We have discussed this case in our report.

Independent of the size of the dog and the type of injury, serious infections may follow a dog bite and these may result in the abrupt onset of multiorgan failure. Early recognition of the warning signs with regard to the underlying severity of the infection is of the utmost importance. Reticulate skin eruptions constitute a precursory phenomenon.