Search

Background: Retinal artery occlusions are rare amongst young adults, and relevant risk factors and etiology remain unclear. In this report, we present a case of central retinal artery occlusion (CRAO) as the initial manifestation of mixed connective tissue disease (MCTD) in a young woman. Case presentation: A 22-year-old female presented to the emergency department with a sudden decrease in visual acuity in her right eye for 1 hour. She reported a similar episode in her left eye five years prior, which resolved spontaneously after 2 hours. Initially misdiagnosed with optic neuritis in the right eye at another hospital, she was referred to our institution the following day. Clinical examination revealed a CRAO in her right eye. A detailed medical history revealed that she had developed livedo reticularis (LR) on both lower limbs five years ago, which had been overlooked and untreated. Further rheumatologic history, hematologic tests, and an autoimmune work-up confirmed a diagnosis of mixed connective tissue disease (MCTD). Conclusion: In young patients presenting with CRAO, further examinations should be conducted to investigate systemic disease or an embolic source to prevent future sequelae. [ABSTRACT FROM AUTHOR]

Sneddon syndrome is a rare neurocutaneous syndrome that mainly involves the small and medium arteries. It is clinically characterized by widespread livedo reticularis with recurrent ischemic strokes. This case described a young woman who has suffered multiple minor strokes over the past decade, accompanied by spinal subarachnoid hemorrhage and multiple intracranial aneurysms. Genetic testing revealed a heterozygous mutation in the adenosine deaminase 2 (ADA2) (c.1240G>A). The patient had been treated with clopidogrel for antiplatelet aggregation but later discontinued the therapy. For young patients with a history of recurrent strokes, physicians should closely observe and inquire about the skin lesions in detail and recommend cerebral angiography and genetic testing to more comprehensively assess and manage such cases. [ABSTRACT FROM AUTHOR]

Abstract Background Retinal artery occlusions are rare amongst young adults, and relevant risk factors and etiology remain unclear. In this report, we present a case of central retinal artery occlusion (CRAO) as the initial manifestation of mixed connective tissue disease (MCTD) in a young woman. Case presentation A 22-year-old female presented to the emergency department with a sudden decrease in visual acuity in her right eye for 1 hour. She reported a similar episode in her left eye five years prior, which resolved spontaneously after 2 hours. Initially misdiagnosed with optic neuritis in the right eye at another hospital, she was referred to our institution the following day. Clinical examination revealed a CRAO in her right eye. A detailed medical history revealed that she had developed livedo reticularis (LR) on both lower limbs five years ago, which had been overlooked and untreated. Further rheumatologic history, hematologic tests, and an autoimmune work-up confirmed a diagnosis of mixed connective tissue disease (MCTD). Conclusion In young patients presenting with CRAO, further examinations should be conducted to investigate systemic disease or an embolic source to prevent future sequelae.

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.

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]

Background. Polyarteritis nodosa is an acute, subacute or chronic immune complex disease associated with peripheral and visceral artery involvement, predominantly of middle and small sizes, development of destructive-proliferative arteritis and subsequent peripheral and visceral ischaemia.Cases description. The present paper describes two clinical cases of polyarteritis nodosa in patient R., aged 12, and patient A., aged 9, and demonstrates the difficulties of diagnosing the disease in its early stages. Patient R., aged 12, was admitted to the Rheumatology Unit of the Krasnodar Krai Children’s Clinical Hospital with complaints of red, patchy, dense rash on the palms and plantar surface of the feet. The child has been ill since September 2017, and after a history of tonsillitis suffered a fever of 37 °C, pain in the right heel area, nodular thickening on the feet, livedo reticularis, swelling of both hands. The disease had a recurrent course. The boy was treated with prednisolone, mycophenolate mofetil, hydroxychloroquine and three courses of rituximab (April 2018, January 2019, September 2020). Repeated courses of human normal immunoglobulin and alprostadil therapy were carried out. The treatment showed positive dynamics, fever was eliminated, general well-being improved, and acute inflammatory markers in blood became normal. The skin retained minimal manifestation of livedo, nodularities on the feet did not progress in dynamics. Patient A. was admitted to the Rheumatology Unit of the Krasnodar Krai Children’s Clinical Hospital in April 2022 with complaints of weakness, myalgia of the lower extremities and necrosis foci in the left lumbar region. The medical history indicates that in March 2022, the boy, being in good health before, developed a bluish, painful rash on his lower legs after a workout. Skin changes and soreness resolved on their own without treatment. After examination, a diagnosis was made as follows: juvenile polyarteritis nodosa, activity score — 3.Conclusion. The diagnosis of polyarteritis nodosa can be often problematic due to the very character of the disease featured by absence of specific symptoms, by polymorphism of clinical manifestations, and by lack of clear diagnostic and laboratory markers.

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: Unusual clinical course. Background: The profound ability of viral infections to convincingly mimic vasculitis, thereby pathologically influencing vessels of any caliber, is undeniably significant. Notably, adult patients with B19V infection frequently experience joint pain and cutaneous eruptions, which are ostensibly immune responses to the infection and necessitate careful differentiation from autoimmunity. Conversely, vasculitis syndromes represent an amalgamation of diseases characterized by vascular inflammation, predominantly classified based on the impacted vessels' size and location. Although the expedited diagnosis and therapeutic management of vasculitis are paramount, many conditions, including infectious diseases, can potentially masquerade as vasculitis, necessitating rigorous differential diagnosis. Case Report: A 78-year-old male patient presented with fever, bilateral leg edema, skin rash, and foot numbness to the outpatient department. Blood investigations showed elevated inflammatory parameters, and urinalysis showed proteinuria and occult blood presence. We considered SVV, particularly microscopic polyangiitis, which causes acute renal injury, as the provisional diagnosis. Blood investigations, including auto-antibodies and a skin biopsy, were performed. However, his clinical symptoms resolved spontaneously before these investigation results were reported. Subsequently, the patient was diagnosed with B19V infection based on B19V immunoglobulin M antibody positivity. Conclusions: B19V infection mimics vasculitis. Even in geriatric patients, particularly during B19V infection outbreaks, clinicians should conduct thorough interviews and examinations while contemplating the likelihood of B19V infection as a potential vasculitis mimic. [ABSTRACT FROM AUTHOR]

The study objective is to demonstrate a rare cause of recurrent acute cerebrovascular diseases in a young patient – Sneddon syndrome. The patient revealed gene polymorphism: homozygous 4G/5G in the plasminogen activator inhibitor-1 (PAI-1) gene, C807T in the glycoprotein I gene (GPIa), T1565C in the glycoprotein III gene (GPIIIa), G1639A in the vitamin K epoxide reductase gene (VKORC1), increased homocysteine, which were risk factors for thrombosis.

Sneddon syndrome is a rare, progressive disease that affects relatively young people, mainly female, and manifests itself in two main symptoms: livedo reticularis and recurrent cerebral infarctions. First described in 1965 by the English dermatologist Ian Bruce Sneddon, the syndrome named in his honor unites a heterogeneous group of diseases with different pathogenesis and similar clinical manifestations. Skin manifestations of the disease in the form of reticular livedo are benign, cerebrovascular manifestations are reduced to repeated cerebral infarctions, progressive dementia and can lead to the death of patients. The literature review describes the basic concepts of the etiology, pathogenesis of primary and secondary forms of Sneddon syndrome, and proposes the concept of Sneddon’s disease to describe the primary forms of the syndrome. The article contains photographs of patients from the clinical practice of the authors of the article. The review also describes methods of diagnosis and differential diagnosis of the disease and recommended methods of treatment, which is based on the elimination of additional risk factors for vascular damage and thrombosis, blood pressure control, lipid and carbohydrate metabolism, as well as the appointment of anticoagulant and disaggregant therapy. The use of anti-inflammatory or immunosuppressive therapy remains controversial. The main goal of treatment is the prevention of organic brain damage and neuropsychiatric complications. Unfortunately, the neuropsychiatric prognosis of Sneddon syndrome is relatively poor with the development of impaired memory, concentration, and visual-spatial skills. In exceptional cases, the progression of the disease can lead to death.

Although symptoms of pancreatic diseases such as pancreatitis, acute and chronic and, carcinoma of the pancreas are mainly gastrointestinal in nature, the extra-pancreatic symptoms are also important. These include skin symptoms, such as pancreatic panniculitis, acanthosis nigricans, livedo reticularis, necrolytic migratory erythema, cutaneous signs of hemorrhage, as in persons with severe acute pancreatitis, or the finding of cutaneous metastases of pancreatic carcinoma, which may be a sign of advanced disease. The pancreas is therefore one of those organs for which diagnosis and therapy are often multidisciplinary. In this review article, we summarize current knowledge of the possible skin manifestations of pancreatic disorders.

The systemic and respiratory clinical manifestations of coronavirus disease 2019 (COVID‐19) include fever, coughing, sneezing, sore throat, rhinitis, dyspnea, chest pain, malaise, fatigue, anorexia and headache. Moreover, cutaneous manifestations have been reported in 0.2% to 20.4% of cases. Early diagnosis of COVID‐19 leads to a better prognosis; knowledge of its cutaneous manifestations is one way that may help fulfil this goal. In this review, PubMed and Medline were searched with the terms "dermatology", "skin" and "cutaneous", each in combination with "SARS‐CoV‐2" or "COVID‐19". All articles, including original articles, case reports, case series and review articles published from the emergence of the disease to the time of submission, were included. In this comprehensive narrative review, we tried to provide an analysis of the cutaneous manifestations associated with COVID‐19, including maculopapular rash, urticaria, Chilblain‐like, vesicular lesions, livedo reticularis and petechiae in asymptomatic/symptomatic COVID‐19 patients that might be the first complication of infection after respiratory symptoms. Immune dysregulation, cytokine storms, side effects of antiviral drugs, environmental conditions and high‐dose intravenous immunoglobulin (IVIG) therapy might be involved in the pathogenesis of the cutaneous manifestations in COVID‐19 patients. Therefore, knowledge of cutaneous COVID‐19 manifestations might be vital in achieving a quick diagnosis in some COVID‐19 patients, which would help control the pandemic. Further research is very much warranted to clarify this issue. [ABSTRACT FROM AUTHOR]

Introduction: Dermatological manifestations constitute a fundamental group within extra-articular morbidity in patients with systemic lupus erythematosus. Its importance lies in the high frequency of presentation and in the diagnostic role of the disease. Objective: To describe the dermatological manifestations identified in patients diagnosed with systemic lupus erythematosus. Methods: Basic, descriptive, cross-sectional research, whose universe was 87 patients diagnosed with systemic lupus erythematosus, according to the criteria of the American College of Rheumatology, treated during the period June 2017 - June 2022 in the rheumatology outpatient clinic of the Metropolitan Clinic. from the city of Riobamba. The sample was made up of 72 patients to whom a survey was applied to obtain information related to the general characteristics of the patients and the disease. Results: Average age of 40.59 years, predominance of patients between 40 and 49 years (30.56%), female (95.83%) and with evolution time between 1 and 5 years (62.50%). 86.11% of the patients reported dermatological manifestations, malar rash (74.19%) and livedo reticularis (33.87%) were the most frequently present. 65.30% of the cases used sun protection, being sunscreen the most used (61.70%). Conclusions: Dermatological manifestations are frequent in the evolutionary course of lupus, predominantly malar rash, livedo reticularis and alopecia.

Background: Clinical data regarding cutaneous manifestations in Chinese patients with livedoid vasculopathy (LV) are limited. Objectives: To assess clinical features of skin lesions in LV, especially the characteristics of extensive livedo reticularis and pigmented purpuric dermatosis‐like lesions in these patients. Methods: This was a single‐center retrospective study of 46 Chinese patients with LV between March 2021 and July 2021. The characteristics of skin lesions in LV were described in detail. Results: A total of 29 females and 17 males were included in this study, with a mean age of 27.7 years (ranging from 13 to 51 years). Twenty (43.5%) patients developed their first skin lesions before age 18. Among 46 patients, 33 presented livedo reticularis with 78.8% (n = 26) of these patients whose livedo reticularis was extensive. Seven patients had lesions simulating pigmented purpuric dermatosis, including four cases of pigmented purpura and three cases of telangiectatic purpura. Numbness was found in 16 patients, mainly in the lower limbs (62.5%), ankles (31.3%), and dorsum of the feet (18.8%). Conclusions: For patients with symptoms of extensive livedo reticularis, retiform purpura, or numbness, it is necessary to make a differential diagnosis. [ABSTRACT FROM AUTHOR]

Although symptoms of pancreatic diseases such as pancreatitis, acute and chronic and, carcinoma of the pancreas are mainly gastrointestinal in nature, the extra-pancreatic symptoms are also important. These include skin symptoms, such as pancreatic panniculitis, acanthosis nigricans, livedo reticularis, necrolytic migratory erythema, cutaneous signs of hemorrhage, as in persons with severe acute pancreatitis, or the finding of cutaneous metastases of pancreatic carcinoma, which may be a sign of advanced disease. The pancreas is therefore one of those organs for which diagnosis and therapy are often multidisciplinary. In this review article, we summarize current knowledge of the possible skin manifestations of pancreatic disorders. [ABSTRACT FROM AUTHOR]

Background: Childhood vasculitis is a heterogeneous disorder, characterized by inflammation of the blood vessel walls. Multiple organs and/or tissues are affected, either simultaneously or successively. Vascular neuropathy occurs when the vasa nervorum is affected. Presentation includes mononeuritis multiplex, acute motor/motor-sensory axonal neuropathy, pure sensory neuropathy, and chronic inflammatory demyelinating polyneuropathy. Making a diagnosis is a challenge when neurological manifestations appear for the first time or are isolated. Clinical Description: A 12-year-old girl presented with acute pain and progressive weakness of both lower limbs for 12 days, followed by diffuse abdominal pain and low-grade fever. Salient neurological findings were diminished power and hyporeflexia in all limbs. Guillain–Barre syndrome was suspected in view of symmetric ascending paralysis and a suggestive nerve conduction study. The child had neutrophilic leukocytosis but sterile cultures. The successive development of inflammatory demyelinating polyneuropathy, persistent fever, vasculitic phenomena (hypertension, severe myalgia, rashes, multiple infarcts, acute renal cortical necrosis, and gangrene of the digit), and elevated acute-phase reactants was suggestive of a multisystemic small-vessel and medium-sized vasculitis syndrome, such as polyarteritis nodosa (PAN). A diagnosis of PAN was established based on the satisfaction of clinical criteria. Management: The patient was administered pulse methylprednisolone and oral steroids, with which there was a dramatic recovery. Monthly cyclophosphamide was continued in view of major systemic involvement. Conclusion: Early recognition and management of childhood vasculitis syndrome is associated with good outcomes.

Livedoid vasculopathy (LV) is a rare, chronic, and occlusive disease of the veins supplying the upper parts of the skin. The pathogenesis of the disease is not precisely understood, and its attacks are often unpredictable but tend to worsen during the summer. LV affects women more often. This increased risk for LV in women might be related to sex-specific physiological conditions, such as pregnancy, or a higher incidence of LV-associated conditions, such as connective tissue diseases, hypercoagulable states, and venous stasis in women. The typical clinical appearance of LV consists of three main findings: livedo racemose, atrophie blanche, and skin ulcers. The purpose of this comprehensive review was to analyze LV in all aspects and mainly focus on early diagnosis for successful clinical management with a holistic and multidisciplinary approach. A detailed history, dermatological examination, and laboratory testing are essential for a diagnosis of LV. When LV is clinically suspected, a skin biopsy should be taken to confirm the diagnosis. Another critical step is to investigate the underlying associated conditions, such as connective tissue diseases, hypercoagulable states, thrombophilia, and malignancy. Unfortunately, no associated conditions can be detected in approximately 20% of all cases (idiopathic LV) despite all efforts. The diagnosis of the disease is delayed in most patients. Thus, irreversible, permanent scars appear. Early and appropriate treatment reduces pain and prevents the development of scars and other complications. Antiplatelet drugs and anticoagulants can be preferred as the first-line treatments along with general supportive measures. Other therapeutic options might be considered in unresponsive cases. Preference for refractory cases is based on availability, clinical experience, and patient-related factors (comorbidities, age, sex, and compliance). These include anabolic steroids, intravenous immunoglobulin, hyperbaric oxygen therapy, psoralen-ultraviolet A, vasodilators, fibrinolytics, immunomodulators, and immunosuppressives.

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 cutaneous appearance of transient or persistent livedo reticularis is characterized by violaceous, mottled, ring-shaped interconnecting lesions that form a reticular or net-like pattern. It can occur physiologically in response to cold exposure, such as in cutis marmorata, but can also be induced by pathological conditions such as vascular obliterans or venodilation. We report two cases of livedo reticularis that occurred on the lower limbs of two patients post ChAdOx1 nCoV-19 vaccination. As the patients had no other likely causes of livedo reticularis, the reticular skin lesions were suspected to occur in association with the ChAdOx1 nCoV-19 vaccination. Livedo reticularis is an uncommon adverse reaction, with few cases being reported post ChAdOx1 nCoV-19 vaccination. [ABSTRACT FROM AUTHOR]

Objective: In antiphospholipid antibody (aPL) nephropathy, activation of the mammalian target of rapamycin (mTOR) contributes to endothelial cell proliferation, a key finding of aPL microvascular disease. Here, we examined mTOR activation in the skin of aPL-positive patients with livedo.Methods: Three patient groups with livedo were studied: (1) persistently aPL-positive with systemic lupus erythematosus (SLE); (2) persistently aPL-positive without SLE; and (3) aPL-negative SLE (control). After collecting aPL-related medical history, two 5-mm skin biopsies of livedo were performed on each patient: (1) peripheral (erythematous-violaceous lesion); and (2) central (nonviolaceous area). We stained specimens for phosphorylated protein kinase B (p-AKT) and phosphorylated S6 ribosomal protein (p-S6RP) as mTOR activity markers, CD31 to identify endothelial cells, and Ki-67 to show cellular proliferation. We counted cells in the epidermis and compared mTOR-positive cell counts between peripheral and central samples, and between patient groups, using Freidman test and Wilcoxon signed-rank test.Results: Ten patients with livedo reticularis were enrolled: 4 aPL-positive without SLE (antiphospholipid syndrome [APS] classification met, n = 3), 4 aPL-positive SLE (APS classification met, n = 3), and 2 aPL-negative SLE (control). In all aPL-positive patients, epidermal p-AKT and p-S6RP staining were significantly increased in both peripheral and central skin samples when compared to aPL-negative SLE controls; both were more pronounced in the lower basal layers of epidermis.Conclusion: Our study demonstrates increased mTOR activity in livedoid lesions of aPL-positive patients with or without SLE compared to aPL-negative patients with SLE, with more prominent activity in the lower basal layers of the epidermis. These findings may serve as a basis for further investigating the mTOR pathway in aPL-positive patients. [ABSTRACT FROM AUTHOR]

The emergence of severe acute respiratory syndrome coronavirus 2 has made it crucial to develop safe vaccines. Three main types of vaccines are currently available. Although they have proven to be very secure, they have caused various adverse effects. We here report a rare case of livedo reticularis following the administration of COVID-19 vaccine in a 54-year-old woman. It occurred 24 hours after vaccination, accompanied by respiratory, digestive, and neurological disorders and deterioration in general condition. Examinations revealed skin lesions compatible with livedo reticularis, mild inflammatory syndrome and hypercholesterolemia. Imaging showed no abnormalities. Immunological tests were positive for lupus anticoagulant. The patient received symptomatic treatment, with improvement in neurological and joint symptoms and a slight regression of skin rashes. After three months, the lupus anticoagulant test remained positive, confirming post-vaccination antiphospholipid syndrome (APS). The association of livedo reticularis with COVID-19 vaccine should not be underestimated and its degree of severity remains to be determined. More data and cases need to be collected for a more in-depth and detailed analysis., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts., (Copyright: Meryem Ouhaddach et al.)

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.

Moyamoya angiopathy (MMA) is a rare cerebral vasculopathy in some cases occurring in children. Incidence is higher in East Asia, where the heterozygous p.Arg4810Lys variant in RNF213 (Mysterin) represents the major susceptibility factor. Rare variants in RNF213 have also been found in European MMA patients with incomplete penetrance and are today a recognized susceptibility factor for other cardiovascular disorders, from extracerebral artery stenosis to hypertension. By whole exome sequencing, we identified three rare and previously unreported missense variants of RNF213 in three children with early onset of bilateral MMA, and subsequently extended clinical and radiological investigations to their carrier relatives. Substitutions all involved highly conserved residues clustered in the C-terminal region of RNF213, mainly in the E3 ligase domain. Probands showed a de novo occurring variant, p.Phe4120Leu (family A), a maternally inherited heterozygous variant, p.Ser4118Cys (family B), and a novel heterozygous variant, p.Glu4867Lys, inherited from the mother, in whom it occurred de novo (family C). Patients from families A and C experienced transient hypertransaminasemia and stenosis of extracerebral arteries. Bilateral MMA was present in the proband's carrier grandfather from family B. The proband from family C and her carrier mother both exhibited annular figurate erythema. Our data confirm that rare heterozygous variants in RNF213 cause MMA in Europeans as well as in East Asian populations, suggesting that substitutions close to positions 4118–4122 and 4867 of RNF213 could lead to a syndromic form of MMA showing elevated aminotransferases and extracerebral vascular involvement, with the possible association of peculiar skin manifestations. [ABSTRACT FROM AUTHOR]

Coronavirus disease (COVID-19) presents multisystemic involvement and up to 20% of the cases can show dermatological signs. A narrative review of the literature on the main mucocutaneous manifestations associated with COVID-19 infection was conducted to describe the pathophysiological mechanisms and to classify the lesions into maculopapular, urticarial, vesicular bullous, pernio-like, necrotic livedo, vasculitic, with involvement of the hair follicle, ungular or oral. Additionally, the main clinical manifestations, histopathological characteristics and treatments were introduced. [ABSTRACT FROM AUTHOR]

IMPORTANCE: Classic calciphylaxis associated with renal failure is a life-threatening disease. Warfarin-associated calciphylaxis without renal injury has been described, but whether it is a subset of classic calciphylaxis or a different entity remains unknown. We describe 1 case of warfarin-associated calciphylaxis, present data from 2 others from our institution, and review all cases of warfarin-associated calciphylaxis available in the literature. Our review indicates that warfarin-associated calciphylaxis is clinically and pathophysiologically distinct from classic calciphylaxis. OBJECTIVE: To review warfarin-associated calciphylaxis and determine its relationship to classic calciphylaxis. DESIGN, SETTING, AND PARTICIPANTS: We searched MEDLINE and Ovid without language or date restrictions for case reports of calciphylaxis from the inpatient setting using the terms calciphylaxis and warfarin, non-uremic calciphylaxis, and nonuremic calciphylaxis. We defined nonuremic calciphylaxis as a histopathologic diagnosis of calciphylaxis without severe kidney disease (serum creatinine level >3 mg/dL; glomerular filtration rate

ImportanceClassic calciphylaxis associated with renal failure is a life-threatening disease. Warfarin-associated calciphylaxis without renal injury has been described, but whether it is a subset of classic calciphylaxis or a different entity remains unknown. We describe 1 case of warfarin-associated calciphylaxis, present data from 2 others from our institution, and review all cases of warfarin-associated calciphylaxis available in the literature. Our review indicates that warfarin-associated calciphylaxis is clinically and pathophysiologically distinct from classic calciphylaxis.ObjectiveTo review warfarin-associated calciphylaxis and determine its relationship to classic calciphylaxis.Design, setting, and participantsWe searched MEDLINE and Ovid without language or date restrictions for case reports of calciphylaxis from the inpatient setting using the terms "calciphylaxis and warfarin," "non-uremic calciphylaxis," and "nonuremic calciphylaxis." We defined nonuremic calciphylaxis as a histopathologic diagnosis of calciphylaxis without severe kidney disease (serum creatinine level >3 mg/dL; glomerular filtration rate

A 37-year-old woman with well-controlled Graves' disease on carbimazole therapy presented with new-onset livedo reticularis (LR) on her legs which later regressed spontaneously. The history, examination, and investigations did not reveal any known cause for the lesion. Literature search has revealed only one report of LR in a patient of Graves' disease who had thyrotoxicosis and coexisting anticardiolipin antibodies. The patient in this report was euthyroid at the time of development of LR and did not have any antiphospholipid antibody. It is not clear whether this finding was incidental or there is a true association of LR with Graves' disease.

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]

Livedoid vasculopathies are a group of heterogeneous disorders featuring cutaneous ischemia. Common pathological features include perivascular fibrinoid deposition with absence of evident features of vasculitis. Livedo reticularis is a pattern of vascular reticular pigmentary changes that associate in some conditions and disorders, reflecting the underlying mechanism of predominantly arterial ischemic event. In this case report, we present a 43-year-old female patient who developed a bilateral multiple hyperpigmented nonpruritic lesions on both arms and thighs with spontaneous skin ulcerations of 3-month duration. The biopsy results revealed characteristics consistent with vasculopathy. The patient has showed a remarkable improvement on combination of cyclosporin and dapsone.

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is rare, but it can be triggered by chemicals, infections, and drugs. Patients who use anti-thyroid drugs are prone to involve with ANCA-associated vasculitis. Perinuclear ANCA (p-ANCA) is almost always positive in these patients. Patients have various presentations and symptoms such as (arthritis, edema) and this disorder usually resolves with discontinuation of the drug, however, some patients require high-dose steroids, immunosuppressive or plasmapheresis. A 38-yearold woman with a history of Graves' disease was on long-term treatment with propylthiouracil (PTU), presented with severe bone pain, arthritis and edema in both feet. The patient's manifestations were resolved with discontinuation of PTU, iodine therapy, and corticosteroid administration. [ABSTRACT FROM AUTHOR]

Se describe el caso clínico de un paciente de 51 años de edad con antecedente patológico personal de ser un fumador empedernido, el cual acudió al Cuerpo de Guardia del Hospital Provincial Docente Dr. Joaquín Castillo Duany de Santiago de Cuba por presentar disnea asociada a cifras elevadas de tensión arterial y livedo reticular en la cara anterior abdominal. Debido al cuadro clínico y a los resultados de los exámenes complementarios, fue trasladado a la Unidad de Cuidados Intensivos, donde posteriormente se le diagnosticó pancreatitis aguda grave, tras realizar una laparotomía exploratoria y hallar zonas isquémicas en las asas intestinales. El paciente mantuvo una evolución tórpida y falleció a causa de una disfunción múltiple de órganos.

Abstract Background: Macular lymphocytic arteritis most commonly presents as hyperpigmented macules on the lower limbs. The pathogenesis of this disease is still unclear and there is an ongoing debate regarding whether it represents a new form of cutaneous vasculitis or an indolent form of cutaneous polyarteritis nodosa. Objective: To describe clinical, histopathological, and laboratory findings of patients with the diagnosis of macular lymphocytic arteritis. Methods: A retrospective search was conducted by reviewing cases followed at the Vasculitis Clinic of the Dermatology Department, School of Medicine, University of São Paulo, between 2005 and 2017. Seven patients were included. Results: All cases were female, aged 9-46 years, and had hyperpigmented macules mainly on the legs. Three patients reported symptoms. Skin biopsies evidencing a predominantly lymphocytic infiltrate affecting arterioles at the dermal subcutaneous junction were found, as well as a typical luminal fibrin ring. None of the patients developed necrotic ulcers, neurological damage, or systemic manifestations. The follow-up ranged from 18 to 151 months, with a mean duration of 79 months. Study limitations: This study is subject to a number of limitations: small sample of patients, besides having a retrospective and uncontrolled study design. Conclusions: To the best of the authors’ knowledge, this series presents the longest duration of follow-up reported to date. During this period, none of the patients showed resolution of the lesions despite treatment, nor did any progress to systemic vasculitis. Similarities between clinical and skin biopsy findings support the hypothesis that macular lymphocytic arteritis is a benign, incomplete, and less aggressive form of cutaneous polyarteritis nodosa.

Rapidly progressive interstitial lung disease (RP-ILD) and its distinctive cutaneous features are highly associated with the presence of anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody in patients with dermatomyositis (DM), leading to a poor prognosis. We describe the case of a 25-year-old man who developed progressive proximal muscle weakness with RP-ILD and had unusual cutaneous findings (cutaneous ulcerations and livedo reticularis) accompanied by classical cutaneous features (heliotrope rash, Gottron’s papules, Gottron’s sign, and flagellate erythema). Blood test was positive for anti-MDA5 antibody. He was treated with intravenous corticosteroids and immunoglobulin, but passed away due to respiratory failure within 1 month after admission. Our case highlights that the presence of cutaneous ulcerations and livedo reticularis, in addition to RP-ILD, are useful clinical clues that may aid in the detection of anti-MDA5 antibody, early initiation of combined immunosuppressants, and prognosis prediction in patients with classical DM.

Background: The coronavirus disease 2019 (COVID-19) pandemic has affected the whole world for a short span of time. As it is a novel virus, its manifestations have been slowly revealed. Cutaneous manifestations of COVID-19 have gradually been reported from different regions of the world. However, their significance in diagnosis, as well as predicting prognosis, remains to be established. Objective: This review describes the cutaneous manifestations of COVID-19 patients from diverse regions with the aim of highlighting any important associations. Methods: A literature search was conducted using “PubMed” for original articles, case series, and case reports using the search terms “cutaneous manifestations” and “skin manifestations” in combination with “COVID-19” published up to 31 May. Results: Nine original research articles and 35 case series or case reports were identified, including 458 confirmed COVID-19 cases. The ratio of male to female patients was 0.94, and the patients' age ranged from 2 months to 84 years. In 10% of cases, skin lesions appeared before systemic manifestations. The most common cutaneous manifestation was macular/maculo-papular rash (42.5%), followed by acute urticaria (17.9%), vesicular rash (15.3%), pseudo-chilblain or acral purpuric lesions (15.1), and livedo-reticularis (4.4%). The majority of reported cases were located in Spain, Italy, and France. These manifestations do not seem to be sex-, age-, or country-specific. Conclusion: It is necessary to conduct worldwide registries and prospective studies to assess the true incidence of cutaneous manifestations of COVID-19 and to streamline their categorization based on their pathogenesis. There appears to be no specific manifestation at present, but a high index of suspicion can help in the diagnosis of patients presenting with cutaneous lesions as the first manifestation.

A wide range of side effects can occur during drug administration. Nicolau Syndrome (NS) is a rare iatrogenic side effect of medications injected Intramuscularly (i.m.). The clinical manifestations range from localised pain and erythema to total necrosis requiring amputation. The present report is about a five-year-old boy, who developed NS after receiving an i.m. injection of benzathine penicillin for treatment of pharyngitis. He developed symptoms minutes after the injection including intense pain at the site of injection followed by progressive discolouration and impairment of movement of the affected limb. The patient was treated with pentoxifylline, methylprednisolone, heparin and antibiotics in a hospital and after one month, complete improvement was noticed.

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.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Livedoid vasculopathy (LV) is a rare disease characterized by livedo racemosa, atrophie blanche, ulcerations, and severe pain. Low molecular weight heparins and rivaroxaban can be used in LV-patients. In addition, intravenous immunoglobulins (IVIG) have been described as treatment-option. Objectives: Objective was to investigate the therapeutic effect of IVIG on ulcer, pain and restrictions in daily life. Methods: Thirty-two LV-patients who received IVIG at the Department of Dermatology Tübingen between 01/2014 and 06/2019 were identified. Twenty-five of these patients were available for further follow up and were included in the study. Patients were interviewed using a questionnaire focusing on the course of the disease, symptoms, and subjective response to IVIG-treatment. Results: Twenty-five patients were included in the study (mean follow up: 28.9 months). Patients received an average of 6.8 cycles (range 1-45) of IVIG during the observed period. Significant improvements were seen regarding skin findings, pain, and limitation of daily activities. Complete remission of symptoms was observed in 68% of patients. Good tolerability of IVIG was shown in 92%. Conclusions: A good therapy response regarding ulceration, pain, and daily life restrictions with good tolerability was demonstrated for IVIG (2 g/kg bodyweight over 5 days). [ABSTRACT FROM AUTHOR]