Painful, Tender, Localized, Idiopathic Livedo Reticularis.

Livedo reticularis (LR) is a unique cutaneous condition characterized by a reddish-blue to purple, net-like cyanosis of the skin, often associated with disturbances in cutaneous blood flow. This case report discusses a 30-year-old woman with a history of Hashimoto thyroiditis, vitamin D deficiency, migraines, and goiter who presents with painful, localized LR on her right flank. Despite her extensive medical history, there were no significant findings in her laboratory and imaging studies, including a normal epidermis in skin biopsies. The LR in this case is distinguished by its persistence and the presence of pain, a symptom not commonly associated with LR. Various treatments, including 5% lidocaine ointment, oral analgesics, and gabapentin, were considered, but her symptoms remained stable over 13 months. This case exemplifies the complexity of LR, particularly when presenting with atypical symptoms like pain. It highlights the need for further research into the pathophysiology and treatment of LR, especially in cases deviating from the typical symptomatology, and suggests the potential value of a multi-disciplinary approach to management.

Adenosine deaminase 2 deficiency in a Chinese patient: Report of one novel mutation and literature review.

OBJECTIVE: Through a case of deficiency of adenosine deaminase 2 (DADA2) to improve domestic clinicians' understanding of the disease, and to review the literature, promote dermatologists for clinical secondary primary lesion diagnosis. METHOD: Analysis of a case diagnosed with DADA2 deficiency of clinical manifestations, laboratory, imaging examination and treatment methods, and discussion through literature analysis. RESULTS: The child with recurrent fever, limbs nodular erythema, gradually in the limbs. CT of lower limb skin showed mild edema of the spinous layer, intact basal layer, dilated vascular congestion in the superficial dermis, visible RBC extravasation, and changes of telangiectasia ring purpura were considered. Cranial magnetic resonance imaging (MRI) showed a left choroidal cleft cyst. Genetic test was the CECR1 mutation. The treatment with adalimumab was effective. CONCLUSION: In this case, DADA2 is the seventh case in China, and the CECR1 mutation site (c.254A> T p.N85I,c.851G>T p. G284V) was a compound heterozygous mutation. Mastering the clinical characteristics is helpful for clinicians to diagnose this disease.

Sneddon's syndrome concurrent with cerebral venous sinus thrombosis: A case report.

BACKGROUND: This report delves into the diagnostic and therapeutic journey undertaken by a patient with Sneddon's syndrome (SS) and cerebral venous sinus thrombosis (CVST). Particular emphasis is placed on the comprehensive elucidation of SS's clinical manifestations, the intricate path to diagnosis, and the exploration of potential underlying mechanisms. CASE SUMMARY: A 26-year-old woman presented with recurrent episodes of paroxysmal unilateral limb weakness accompanied by skin mottling, seizures, and cognitive impairment. Digital subtraction angiography revealed CVST. Despite negative antiphospholipid antibody results, skin biopsy indicated chronic inflammatory cell infiltration. The patient was treated using anticoagulation, antiepileptic therapy, and supportive care, which resulted in symptom improvement. The coexistence of SS and CVST is rare and the underlying pathophysiology remains uncertain. This case underscores the challenge in diagnosis and highlights the need for early clinical differentiation to facilitate accurate assessment and prompt intervention. CONCLUSION: This article has reported and analyzed the clinical data, diagnosis, treatment, and prognosis of a case of SS with CVST and reviewed the relevant literature to improve the clinical understanding of this rare condition.

Livedo reticularis y dengue

Se presenta a un varón de 40 años, residente en la ciudad de Lima, sin viajes recientes, con fiebre, malestar general, cefalea y diarrea. Acudió al Servicio de Emergencia y los exámenes auxilares mostraron leucopenia y trombocitopenia leve. Los estudios para Epstein-Barr, hepatitis B, toxoplasma, rubéola, citomegalovirus, herpes 1 y 2 y COVID-19 fueron negativos. Los anticuerpos IgM y IgG para dengue fueron negativos, y la proteína NS1 fue positiva. El paciente fue diagnosticado con dengue y solo recibió paracetamol. En el seguimiento, en el séptimo día de enfermedad, se le halló afebril y con lesiones dérmicas tipo livedo reticularis en los miembros, principalmente. Se resalta este inusual patrón cutáneo en dengue.

We present the case of a 40-year-old male, resident of Lima city, with no recent travels, with fever, general malaise, headache and diarrhea. He went to the Emergency Department and auxiliary tests showed leukopenia and mild thrombocytopenia. Studies for Epstein-Barr, hepatitis B, toxoplasma, rubella, CMV, herpes 1-2 and COVID-19 were negative. IgM and IgG antibodies for dengue were negative and NS1 protein was positive. He was diagnosed with dengue. He only received paracetamol. On follow-up, on the seventh day of illness, he was found afebrile and with livedo reticularis type dermal lesions on the limbs, mainly. This unusual cutaneous pattern in dengue is highlighted.

An Eight-Year-Old Child With Sneddon Syndrome: A Rare Case Report.

We present a rare case of slow-progressing neurocutaneous vasculopathy described as Sneddon syndrome. A child presented with global developmental delay, congenital livedo racemosa, unilateral vision loss, and a past history of focal neurological deficit. Our main objective is to make physicians aware of this nature of presentation in children.

Tofacitinib as monotherapy in cutaneous polyarteritis nodosa: a case series.

Objective: Cutaneous polyarteritis nodosa (CPAN) is a distinct clinical entity represented by a chronic, relapsing, benign course, with rare systemic involvement. Treatment is with CSs, CYC or other conventional synthetic DMARDs (csDMARDs). In this case series, we aimed to share our varied clinical experience of successfully treating patients with CPAN, with tofacitinib in a refractory/relapsing course or as upfront monotherapy without CSs/csDMARDs. Methods: We report this retrospective case series managed at our rheumatology centre in Bangalore from 2019 to 2022. Four patients identified as CPAN on biopsy were able to achieve disease-free remission with tofacitinib as part of their treatment, with no relapse on further follow-up. Our patients presented with subcutaneous nodules and cutaneous ulcers. After systemic evaluation, all the patients underwent skin biopsy, which showed fibrinoid necrosis in the vessel walls of the dermis, with a histopathological impression of CPAN. They were initially treated with a conventional approach of CSs with/without csDMARDs. On experiencing a refractory/relapsing course, tofacitinib was tried in all the patients as either CS sparing or upfront monotherapy without concomitant csDMARDs. Results: Use of tofacitinib resulted in improvement of ulcers and paraesthesia and in gradual healing of skin lesions, albeit with scarring, with no further recurrence or relapse over a follow-up period of 6 months for all the patients. The therapeutic effect of tofacitinib was consistent when used either as CS sparing or as upfront monotherapy, thereby proving the drug to be a promising option that warrants larger trials in future to treat the subset of patients with established CPAN. Conclusion: Tofacitinib could be used for disease-free remission as monotherapy for CPAN either upfront or as CS sparing, even without concomitant csDMARDs, in those patients who are dependent on CSs or multiple DMARDs.

Manifestaciones dermatológicas en pacientes con lupus eritematoso sistémico, estudio de 5 años

Introducción: Las manifestaciones dermatológicas constituyen un grupo fundamental dentro de la morbilidad extraarticular en pacientes con lupus eritematoso sistémico. Su importancia radica en la elevada frecuencia de presentación y en el papel diagnóstico de la enfermedad. Objetivo: Describir las manifestaciones dermatológicas identificadas en pacientes con diagnóstico de lupus eritematoso sistémico. Métodos: Investigación básica, descriptiva, transversal, que tuvo como universo a 87 pacientes con diagnóstico de lupus eritematoso sistémico, según criterios del Colegio Americano de Reumatología, atendidos durante el periodo junio 2017 - junio 2022 en la consulta externa de reumatología de la Clínica Metropolitana de la ciudad de Riobamba. La muestra quedó conformada por 72 pacientes a los cuales se les aplicó una encuesta para obtener información relacionada con las características generales de los pacientes y de la enfermedad. Resultados: Promedio de edad de 40,59 años, predominio de pacientes entre 40 y 49 años (30,56 %), del sexo femenino (95,83 %) y con tiempo de evolución entre 1 y 5 años (62,50 %). El 86,11 % de los pacientes refirió manifestaciones dermatológicas, el rash malar (74,19 %) y el livedo reticular (33,87 %) fueron las de mayor frecuencia de presentación. El 65,30 % de los casos usan protección solar, el bloqueador solar fue el más utilizado (61,70 %). Conclusiones: Las manifestaciones dermatológicas más frecuentes en el curso evolutivo del lupus fueron el rash malar, livedo reticular y la alopecia.

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.

Hepatitis C Virus-associated Cryoglobulinemic Livedo Reticularis Improved with Direct-acting Antivirals.

We herein report a case of hepatitis C virus (HCV)-associated cryoglobulinemic livedo reticularis in a woman in her 60s that improved with direct-acting antivirals (DAAs). Hyperpigmentation was observed in both lower legs, and a skin biopsy confirmed livedo reticularis, suggesting a relationship with cryoglobulinemia and HCV infection. DAAs with an NS5A inhibitor+NS3/4A protease inhibitor (glecaprevir/pibrentasvir) were administered for eight weeks, and a sustained virological response (SVR) was obtained. The disappearance of serum cryoglobulin was confirmed approximately two years after an SVR was obtained and livedo reticularis was improved. DAA therapy can be an effective therapeutic option for extrahepatic complications associated with HCV infection.

Part II: Cutaneous manifestations of peripheral vascular disease.

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.

Clinical analysis of skin lesions in livedoid vasculopathy: a study of 46 Chinese patients.

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.

A comprehensive narrative review of the cutaneous manifestations associated with COVID-19.

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.

Livedo reticularis following administration of ChAdOx1 nCoV-19 vaccine (AZD1222): a report of two cases.

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.

Livedoid vasculopathy - A diagnostic and therapeutic challenge.

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.

Risk of livedo with antiphospholipid antibodies in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

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-ß2-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.

Mystery(n) Phenotypic Presentation in Europeans: Report of Three Further Novel Missense RNF213 Variants Leading to Severe Syndromic Forms of Moyamoya Angiopathy and Literature Review.

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.

Skin manifestations of pancreatic diseases.

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.

Mammalian Target of Rapamycin Pathway Assessment in Antiphospholipid Antibody-Positive Patients with Livedo.

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.

Transient breast livedo reticularis-like exanthem in an adolescent with COVID-19.

Livedo reticularis-like eruptions have been described in different viral infections. In patients with COVID-19, livedo reticularis-like rashes are usually mild, typically present in a symmetric distribution and mostly involve the lower limbs. A case of livedo reticularis located exclusively on the breasts of a girl with mild systemic symptoms of COVID-19 is presented. Coagulation studies were normal and findings disappeared within 1 week.