Cutaneous Manifestations of COVID-19.

Patients with coronavirus disease 2019 (COVID-19) present with multisystem signs and symptoms, including dermatologic manifestations. The recent literature has revealed that dermatologic manifestations of COVID-19 often are early onset and provide helpful cues to a timely diagnosis. We compiled the relevant emerging literature regarding the dermatologic manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) so that physicians can be aware of the various clinical cutaneous presentations in this time of high incidence of COVID-19.

Synergistic Impact of Systolic Blood Pressure and Perfusion Status on Mortality in Acute Heart Failure.

BACKGROUND: Physical examination remains the cornerstone in the assessment of acute heart failure. There is a lack of adequately powered studies assessing the combined impact of both systolic blood pressure (SBP) and hypoperfusion on short-term mortality. METHODS: Patients with acute heart failure from 41 Spanish emergency departments were recruited consecutively in 3 time periods between 2011 and 2016. Logistic regression models were used to assess the association of 30-day mortality with SBP (<90, 90-109, 110-129, and ≥130 mm Hg) and with manifestations of hypoperfusion (cold skin, cutaneous pallor, delayed capillary refill, livedo reticularis, and mental confusion) at admission. RESULTS: Among 10 979 patients, 1143 died within the first 30 days (10.2%). There was an inverse association between 30-day mortality and initial SBP (35.4%, 18.9%, 12.4%, and 7.5% for SBP<90, SBP 90-109, SBP 110-129, and SBP≥130 mm Hg, respectively; P<0.001) and a positive association with hypoperfusion (8.0%, 14.8%, and 27.6% for those with none, 1, ≥2 signs/symptoms of hypoperfusion, respectively; P<0.001). After adjustment for 11 risk factors, the prognostic impact of hypoperfusion on 30-day mortality varied across SBP categories: SBP≥130 mm Hg (odds ratio [OR]=1.03 [95% CI, 0.77-1.36] and OR=1.18 [95% CI, 0.86-1.62] for 1 and ≥2 compared with 0 manifestations of hypoperfusion), SBP 110 to 129 mm Hg (OR=1.23 [95% CI, 0.86-1.77] and OR=2.18 [95% CI, 1.44-3.31], respectively), SBP 90 to 109 mm Hg (OR=1.29 [95% CI, 0.79-2.10] and OR=2.24 [95% CI, 1.36-3.66], respectively), and SBP<90 mm Hg (OR=1.34 [95% CI, 0.45-4.01] and OR=3.22 [95% CI, 1.30-7.97], respectively); P-for-interaction =0.043. CONCLUSIONS: Hypoperfusion confers an incremental risk of 30-day all-cause mortality not only in patients with low SBP but also in normotensive patients. On admission, physical examination plays a major role in determining prognosis in patients with acute heart failure.

Sneddon Syndrome: A Comprehensive Overview.

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.

A systematic review and meta-analysis of cutaneous manifestations in late- versus early-onset systemic lupus erythematosus.

OBJECTIVES: Although systemic lupus erythematosus (SLE) most commonly occurs in reproductive-age women, some are diagnosed after the age of 50. Recognizing that greater than one-third of SLE criteria are cutaneous, we undertook a systematic review and meta-analysis to evaluate differences in cutaneous manifestations in early- and late-onset SLE patients. METHODS: We searched the literature using PubMed, CINAHL, Web of Science, and Cochrane Library. We excluded studies that did not include ACR SLE classification criteria, early-onset controls, that defined late-onset SLE as <50 years of age, or were not written in English. Two authors rated study quality using the Newcastle Ottawa Quality Scale. We used Forest plots to compare odds ratios (95% CI) of cutaneous manifestations by age. Study heterogeneity was assessed using I(2). RESULTS: Overall, 35 studies, representing 11,189 early-onset and 1727 late-onset patients with SLE, met eligibility criteria. The female:male ratio was lower in the late-onset group (5:1 versus 8:1). Most cutaneous manifestations were less prevalent in the late-onset group. In particular, malar rash [OR = 0.43 (0.35, 0.52)], photosensitivity [OR = 0.72 (0.59, 0.88)], and livedo reticularis [OR = 0.33 (0.17, 0.64)] were less common in late-onset patients. In contrast, sicca symptoms were more common [OR = 2.45 (1.91, 3.14)]. The mean Newcastle Ottawa Quality Scale score was 6.3 ± 0.5 (scale: 0-9) with high inter-rater reliability for the score (0.96). CONCLUSIONS: Overall, cutaneous manifestations are less common in late-onset SLE patients, except sicca symptoms. Future studies should investigate etiologies for this phenomenon including roles of immune senescence, environment, gender, and immunogenetics.

Unilateral livedoid vasculopathy associated with involutional phase of cutaneous infantile hemangioma: the connection to coagulation disorders.

Livedoid vasculopathy is a bilateral painful and recurrent cutaneous ulcerative disorder of the legs that leads to atrophie blanche, atrophic white-porcelain scars, and is associated with disorders of fibrinolysis and/or coagulation. We present a young boy with an association between livedoid vasculopathy in the area of a previous involuted cutaneous hemangioma. We found 4 uncommon abnormalities associated with thrombo-occlusive events: heterozygous 20210 A→G genotype of prothrombin, reduced activity of anticoagulation proteins C and S, and elevated lipoprotein (a).

Livedoid vasculopathy - a thrombotic disease.

Livedoid vasculopathy is a rare, chronic occlusive disease of vessels supporting the upper layers of the skin. It is characterized by purpuric maculae and recurrent painful ulcerations mostly affecting the lower leg. These ulcerations occur episodically especially in summer time and heal slowly, leaving characteristic porcelain-white scars called ’atrophie blanche’.This review is focused on the current knowledge on livedoid vasculopathy and modern therapy strategies resulting from its etiopathogenetic associations with prothrombotic states. Livedoid vasculopathy and its pathophysiology are clearly distinguished from inflammatory vasculitis and thus require a different therapeutic approach. The prevention of irreversible residual scarring and improving the quality of life of patients in this often misdiagnosed disease is one of the main treatment goals.

The prevalence of abnormal pulse wave velocity, pulse contour analysis and ankle-brachial index in patients with livedo reticularis: a controlled study.

OBJECTIVE: To evaluate the prevalence of abnormal pulse wave velocity (PWV), pulse contour analysis (PCA) and abnormal ankle-brachial pressure index (ABPI) in patients with livedo reticularis (livedo) and without livedo. METHODS: We recruited 74 patients, of whom 41 had livedo: 16 APS, 9 APS with SLE and 16 with livedo (negative for aPL or lupus). The other group of 33 patients without livedo consisted of 10 APS, 8 APS with SLE and 15 with SLE only. Livedo was diagnosed and confirmed by a dermatologist. PWV was assessed in fasting patients by the Micro Medical PulseTrace analyser using a 4 MHz continuous-wave directional Doppler probe and digital PCA was analysed by Micro Medical PulseTrace by the same operator. Chi-square with Yates's correction was used for comparing results. RESULTS: The median age of the livedo patients was 46 (29-71) years and of the non-livedo patients was 45 (25-68) years. Abnormal values of PWV in 10/41 (24.40%), ABPI in 4/41 (9.8%) and PCA in 10/41 (24.40%) patients were observed in the livedo group and in the non-livedo group abnormal values of PWV in 1/33 (P ≤ 0.025), ABPI in 0/33 (P = NS) and PCA in 5/33 (P = NS) were observed. CONCLUSION: Patients with livedo reticularis are more likely to have abnormal PWV, indicating arterial stiffness.

Livedo reticularis tras inyección subcutánea de interferón beta-1b / Livedo reticularis following subcutaneous injection of interferon beta-1b

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The catastrophic antiphospholipid syndrome in Serbia: diagnostic and management problems.

Antiphospholipid antibodies (aPL) are a common cause of acquired thrombophilia, termed antiphospholipid syndrome (APS, Huges syndrome). Catastrophic antiphospholipid syndrome (CAPS, Asherson's syndrome) is an unusual form of APS characterized with multi-organ failure and high mortality. Fortunately, CAPS accounts for less than 1% of APS cases. The recurrence rate is low with a stable clinical course if these patients are treated with adequate anticoagulation therapy. Due to the rarity of the condition, an international registry of CAPS patients was created in 2000 supported by the European Forum on Antiphospholipid Antibodies held in Taormina, Italy at the Tenth International Congress on aPL. The objective of our study is to describe characteristics of 12 Serbian patients with CAPS included in the international CAPS registry.

[Livedo: from pathophysiology to diagnosis]. / Livedo: de la physiopathologie au diagnostic.

PURPOSE: We propose a diagnostic approach when facing a livedo. First, the pathophysiology of the livedo is reviewed using key articles barely quoted in the literature. Then the topic is handled in two ways. Figures and tables allow a rapid reading convenient "at the patient's bedside". The subject is also reviewed thoroughly, and we emphasize the intricacy of the various pathophysiological mechanisms involved for each livedo's related disease. Diseases associated with livedo are then briefly described with emphasis on the key diagnostic features and prevalence. Usefulness of the main diagnostic procedures is discussed. CURRENT KNOWLEDGE AND KEY POINTS: A livedo is a usually purplish-blue erythema, reticulated (small and complete meshes) or racemosa (large broken circular segments) which is related to a slowdown of the blood flow in the dermic venules. These venules form adjacent circles communicating with each other, parallel to the skin surface. The blood flow slowdown may be due to a local vasoconstriction (vasomotor livedo) or to an arteriolar occlusion. Arteriolar occlusion may be related to blood abnormalities (thrombosis, high viscosity, embolus) or to increased parietal thickness (vasculitis, calcic deposition, intimal hyperplasia). It is not always possible to clinically distinguish a vasomotor livedo from those associated with diseases. Diagnostic procedures should be oriented by the medical history, the features of the livedo, and associated symptoms. Usefulness of the skin biopsy is usually limited to the situations where the livedo is infiltrated or necrotic. FUTURE PROSPECTS AND PROJECTS: To raise controversy about their importance and implications, some pathophysiological data are presented: intimal pseudohyperplasia in Sneddon's syndrome and antiphospholipid syndrome, and white cell activation in essential thrombocythemia.

Livedo reticularis as a criterion for antiphospholipid syndrome.

Many consensus meetings were organized in an attempt to improve the present criteria for antiphospholipid syndrome (APS) classification. In this regard, a high prevalence of antiphospholipid antibodies in systemic lupus erythematosus patients was reported in association with the presence of livedo reticularis (LR). In these studies, the association between LR, migraine, and the development of thrombosis (strokes, valvular dysfunctions) was evident. During the last decade, it was strongly suggested that many clinical symptoms (LR, valvular dysfunctions) or laboratory features (thrombocytopenia) should be considered as "minor criteria" for APS. The inclusion of these clinical symptoms in the criteria for APS classification could become of additive value especially when they exist together in one patient. This review summarizes the data that question or support this idea.