Analysis of Serbian Primary Antiphospholipid Syndrome Patients Confirmed a Strong Association Between Livedo Reticularis and Arterial Thrombosis: A National Cross-Sectional Cohort Study.

BACKGROUND: Antiphospholipid syndrome (APS) is characterized by antiphospholipid antibodies (aPLs) associated with thrombosis (arterial and/or venous) and/or obstetrical manifestations. However, various manifestations, which are considered to be noncriteria manifestations, are frequently found in APS. AIM: The purpose of this study was to evaluate whether noncriteria manifestations may be found more frequently in subjects with thrombotic and/or obstetrical APS ("criteria" manifestations) in a population of patients with primary APS (PAPS). This study presents the results from our national cohort. PATIENTS AND METHODS: This is a cross-sectional study of 360 PAPS patients. Data regarding the presence of thrombocytopenia, livedo reticularis, chorea, and valvulopathy were analyzed. The aPL analysis included the detection of anticardiolipin antibodies (aCLs: immunoglobulin G [IgG]/IgM), anti-ß 2 glycoprotein I (IgG/IgM), and lupus anticoagulant positivity. RESULTS: In our cohort, livedo reticularis was significantly related to arterial thromboses in the same way as valvular manifestations (valvular vegetations and valvular thickening and dysfunction not related to age) ( p = 0.0001, p = 0.013, respectively). Age was strongly related to all the noncriteria manifestations analyzed. Thrombocytopenia was significantly related to ß 2 glycoprotein I IgG and lupus anticoagulant positivity ( p = 0.043, p = 0.030, respectively), as well as to double and triple aPL positivity ( p = 0.041, p = 0.013 respectively). Moreover, in a multivariate model, livedo reticularis was strongly and independently related to arterial thrombosis in our cohort (odds ratio, 2.010; confidence interval, 1.229-3.288; p = 0.005). CONCLUSION: This cross-sectional analysis of a large cohort of Serbian PAPS patients confirmed a strong relationship between livedo reticularis and arterial thrombosis, suggesting a more cautious approach regarding the presence of noncriteria manifestations, especially livedo reticularis, in APS.

Antiphospholipid-negative Sneddon's syndrome: A comprehensive overview of a rare entity.

The term Sneddon's syndrome (SS) has been used since 1965 to describe a vasculopathy characterized by a combination of cerebrovascular disease with livedo racemosa. SS may be classified as antiphospholipid+ (aPL+) or antiphospholipid- (aPL-). Little is known about aPL- SS; in this review we describe the epidemiology and pathogenesis of aPL- SS, as well as the clinical and histologic features. We discuss recent findings in terms of neurologic and cardiac involvement. Moreover, differential diagnoses of conditions that may present with both livedo racemosa and stroke are discussed. Finally, we discuss real-life practical issues such as the initial investigations to be performed, long-term follow-up, and therapeutic management of aPL- SS patients.

Livedoid vasculopathy in 75 Brazilian patients in a single-center institution: Clinical, histopathological and therapy evaluation.

This study presents a single center experience with livedoid vasculopathy (LV). A rare disease that can lead to severe quality of life impairment. Characterize clinical data of LV patients at the Dermatology Division at the University of São Paulo. A retrospective and transversal study was conducted, from 1 January 2005 to 31 December 2019. About 75 patients diagnosed as LV and confirmed by skin biopsy were included. Epidemiology, clinical appearance, histopathology data, and treatment history were observed. There were 78.66% Caucasian women, with a mean age of 39.9 years. Frequent cutaneous manifestations were ulcers, atrophic blanche-like scars, hyperpigmentation, purpuras, telangiectasias, and livedo racemosa. Pain, pruritus, and hypoesthesia were the main symptoms. After treatment, almost 40% of cases relapsed during spring and summer months. About 66% of cases had thrombophilia factors associated, such as high levels of lipoprotein(a). Frequent treatments included acetylsalicylic acid, pentoxifylline, and diosmin with hesperidin. Not being a prospective study. This research provides useful data on Latin American LV patients, indicating multifactorial conditions involved in LV pathogenesis. An extensive work-up including autoimmune laboratory tests, thrombophilia factors, and other conditions associated with venous stasis should be part of LV investigation and controlled to improve treatment response.

Livedo Racemosa: Clinical, Laboratory, and Histopathological Findings in 33 Patients.

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.

Characteristics, risk factors and treatment reality in livedoid vasculopathy - a multicentre analysis.

BACKGROUND: Livedoid vasculopathy (LV) is a rare cutaneous thrombotic disease. It is characterized by occlusion of dermal vessels resulting in livedo racemosa, ulceration and atrophie blanche. Clear guidelines for diagnosis and treatment are missing. OBJECTIVE: The purpose of this study was to better characterize epidemiology, clinical appearance and treatment reality of LV in a well-defined patient cohort. METHODS: The cohort was allocated within a prospective, multicentre, phase IIa trial that investigated the effect of rivaroxaban in LV. RESULTS: Analysis of 27 patients revealed that LV patients had an increased Body Mass Index (BMI; 11/27), hypertension (19/27) and increased levels of lipoprotein (a) (5/12) and homocysteine (10/12) in the blood. The female-to-male ratio was 2.1 : 1, and the median age was 53.0 years [interquartile range (IQR) 40.5-68]. Investigation of the clinical appearance found that 82% of patients had livedo racemosa, and the ankle region was most likely to be affected by ulceration (56-70%). The analysis of patient treatment history showed that heparin was most effective (12/17), while anti-inflammatory regimens were, although often used (17/24), not effective (0/17). CONCLUSION: We add clinical clues for a data supported diagnosis of LV, and we provide evidence that anticoagulants should be administered in monotherapy first line (EudraCT number 2012-000108-13-DE).

Autoantibody profile and clinical patterns in 619 Italian patients with cutaneous lupus erythematosus.

BACKGROUND: Anti-nuclear antibodies (ANA), anti-extractable nuclear antigens (ENA) and anti-dsDNA antibodies are often associated with cutaneous lupus erythematosus (CLE), with variable frequency depending on skin subtype. However, specific data based on large case-series on the pathogenetic, diagnostic and prognostic meaning of such autoantibodies are still lacking. OBJECTIVE: To characterize the correlations between CLE subtypes as well as LE-non-specific skin lesions and their autoantibody pattern. METHODS: Epidemiological, clinical and immunopathological data of 619 Italian patients with CLE and LE-non-specific skin lesions were analysed. Differences in age, sex, clinical features and autoantibody profile were evaluated in each LE subgroup. RESULTS: Anti-nuclear antibodies (P < 0.0001), anti-dsDNA (P < 0.0001), ENA (P = 0.001), anti-Sm (P = 0.001), anti-RNP (P = 0.004) and anti-histone (P = 0.005) antibodies were associated with SLE. A strong association between ANA (P < 0.0001) and anti-dsDNA (P < 0.0001) and female gender was also found: positive ANA and positive anti-dsDNA had a higher prevalence among females. Chronic CLE resulted to be negatively associated with ENA (OR = 0.51, P < 0.0001), anti-Ro/SSA (OR = 0.49, P < 0.0001) and anti-dsDNA (OR = 0.37, P < 0.0001). Intermittent CLE resulted to be negatively associated with ENA (OR = 0.50, P = 0.007) and ANA (OR = 0.61, P = 0.025). Subacute CLE resulted to be associated with ENA (OR = 5.19, P < 0.0001), anti-Ro/SSA (OR = 3.83, P < 0.0001), anti-Smith (OR = 2.95, P = 0.004) and anti-RNP (OR = 3.18, P = 0.007). Acute CLE resulted to be strongly associated with anti-dsDNA (OR = 6.0, P < 0.0001) and ANA (OR = 18.1, P < 0.0001). LE-non-specific skin lesions resulted to be significantly associated with systemic involvement. Livedo reticularis was significantly associated with ENA (P = 0.007) and anti-Ro/SSA (P = 0.036). Palpable purpura and periungual telangiectasia were significantly associated with ANA. CONCLUSION: According to our findings, some well-known associations between CLE subtypes and autoantibody profile were confirmed; moreover, specific association between autoantibodies and LE-non-specific skin lesions was highlighted. A strict association between anti-ENA and anti-Ro/SSA antibodies and livedo reticularis, ANA and palpable purpura, and ANA and periungual telangiectasia was evidenced.

Livedoid Vasculopathy: A French Observational Study Including Therapeutic Options.

Livedoid vasculopathy is a rare thrombotic cutaneous disease. This observational study aimed to assess the clinical and biological features of livedoid vasculopathy and the efficacy of treatments. Patients enrolled had typical livedoid vasculopathy both clinically and histologically. Investigation of thrombophilia was performed. Electromyography was undertaken in the presence of symptoms suggesting peripheral neuropathy. Eighteen women and 8 men were included, with a mean age of 35.5 years at onset. Twenty patients had at least one thrombophilia factor. Ten patients had a peripheral neuropathy with 2 of these patients demonstrating a specific thrombo-occlusive vasculopathy on muscle biopsy. Anticoagulation with low molecular weight heparin was the most prescribed therapy and was associated with the best outcome (effective in 14 patients). Eight patients had severe disease refractory to anticoagulation and required intravenous immunoglobulins, producing a good response in 6 patients.

Epidemiological, clinical and laboratory profiles of cutaneous polyarteritis nodosa patients: Report of 22 cases and literature review.

UNLABELLED: Cutaneous polyarteritis nodosa (CPAN) is a rare disease that affects small and middle caliber vessels of the deep dermis and subcutaneous tissue and its etiopathology remains yet to be understood. METHODS: Retrospective review of twenty two cases diagnosed as CPAN and confirmed by skin biopsy over the last 11 years was evaluated in our department. RESULTS: We found predominance in white woman, mean age of 39.4 years, showing no comorbidities in most of our sample. Mean follow-up time was 58 months. The most frequent cutaneous manifestations were ulcers, livedo racemosa, subcutaneous nodules, atrophie blanche lesions and purpuras; with lower limb involvement in all cases, however other areas were also involved. The main regional symptoms were pain and paresthesia, while systemic complaints were absent in the majority of cases. Mononeuritis multiplex was identified in a quarter of our sample. Most of the laboratory findings were non-specific. There was evidence for previous contact with Mycobacterium tuberculosis in 46.1% of cases which were tested for purified protein derivative (PPD) test. In our patients the disease course was benign and without complications, and systemic polyarteritis nodosa did not develop in any patient. CONCLUSIONS: An extensive work-up including laboratory tests on autoimmunity and thrombophilic factors and investigation of infectious diseases, especially previous contact with tuberculosis agent, should be part of the CPAN investigation.

Calciphylaxis treated with sodium thiosulfate: report of two cases.

Although traditionally observed in patients with end-stage renal disease and secondary hyperparathyroidism, calciphylaxis has been reported in patients with normal renal and parathyroid function. There is no evidence-based therapy available. The use of sodium thiosulfate (STS) has been increasingly described. Herein we describe two patients who responded well to this treatment.

Association between systemic non-criteria APS manifestations and antibody type and level: results from the Serbian national cohort study.

OBJECTIVES: The aim of this study was to investigate the importance of aPL type and level for non-criteria-related events in APS patients. METHODS: Our study included 374 patients: 260 with PAPS and 114 with APS associated with systemic lupus erythematosus (SLE). RESULTS: We discovered significant connection between migraine and LA absence, livedo reticularis and aCL-IgG, skin ulcerations with aCL-IgG and anti-ß2GPI-IgM, pseudovasculitis lesions with aCL-IgG, aCL-IgM and anti-ß2GPI-IgM, and thrombocytopenia with aCL-IgM, aCL-IgG and anti-ß2GPI-IgG. Thrombocytopenia occurred more frequently in patients with more than one aPL. In PAPS, epilepsy correlated with ß2GPI-IgM, migraine with aCL-IgM, and thrombocytopenia with aCL-IgM, aCL-IgG, anti ß2GPI-IgG and LA. Skin ulcerations occurred more frequently in IIc category patients and in patients with high levels of aCL-IgG and anti ß2GPI-IgG. Livedo reticularis was more prominent in PAPS with high levels of aCL-IgG. Significantly higher prevalence of thrombocytopenia was observed in patients with high levels of aCL-IgG and anti ß2GPI-IgG. Epilepsy was related to high levels of anti ß2GPI-IgM and thrombocytopenia in the SAPS was correlated with aCL-IgG. Skin ulcerations were more prevalent in aCL-IgM positive SAPS patients and epilepsy more frequently in SAPS patients with high levels of anti ß2GPI-IgG. CONCLUSIONS: Our study showed that certain aPL type with certain level correlated with non-criteria manifestations, suggesting their predictive role.

A ten-year retrospective study on livedo vasculopathy in Asian patients.

INTRODUCTION: This study aims to analyse the clinico-epidemiological characteristics of Asian patients diagnosed with livedo vasculopathy (LV). MATERIALS AND METHODS: We performed a retrospective analysis of all patients diagnosed with LV from 1997 to 2007 at our centre. RESULTS: Seventy patients were diagnosed with LV with a mean age of 39 years, female: male ratio of 3:1 and no racial predilection. Most cases remained purely cutaneous, presenting with painful leg ulcers and atrophie blanche. Peripheral neuropathy was the only extra-cutaneous complication (9%). In patients who were screened, associations included hepatitis B (7%) and hepatitis C (4%), positive anti-nuclear antibody (14%), positive anti-myeloperoxidase antibody (5%), positive anti-cardiolipin antibodies (7%) and positive lupus anticoagulant (2%). In 49 patients who achieved remission, 55% required combination therapy, most commonly with colchicine, pentoxifylline and prednisolone. In those treated successfully with monotherapy, colchicine was effective in 59% followed by prednisolone (17.5%), pentoxifylline (17.5%) and aspirin (6%). Mean follow-up period was 50 months. CONCLUSION: LV in Asian patients is a high morbidity, chronic relapsing ulcerative skin condition. Most patients require induction combination therapy for remission. As further evidence emerges to support a procoagulant pathogenesis, a standardised protocol is needed to investigate for prothrombotic disorders during diagnosis.