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Cutaneous vasculities (CV) represents a diagnostic challenge, occurs as primary cutaneous disorder or as a manifestation of other entities.To search the cause of CV. Methods: Patients with CV were prospectively evaluated. In all patients, skin biopsies were drawn, and direct immunofluorescence was done in most of the patients. American College of Rheumatology (ACR) and Chapel Hill Consensus Conference Criteria (CHCC) were used for classification.32 patients were studied. There was female predominance (71.8%). Children presented drug-associated CV or Schönlein-Henoch púrpura (SHP). Adults presented more frequently SHP, systemic lupus erythematosus or paraneoplastic vasculitis, other diagnosis as polyarteritis nodosa, microscopic polyangiitis, thrombotic vasculitis (post-puerperal), antiphospholipid syndrome, Churg-Strauss syndrome, and drug-associated CV were presented. Using the ACR and CHCC criteria, 50% of cases were classified.In our institution, during this work the etiologic diagnostic of CV increased more than twice. However, in the case of HSV or LA and SHP none of the proposed criteria had high specificity; other parameters were used to discern between both. Six patients remained as not classified. In our view, cryoglobulins and hepatitis serology do not seem useful unless patient’s history supports they need to be done. Unclassified patients were followed-up closely for 2 years.Las vasculitis cutáneas (VC), primarias o como manifestación de enfermedades sistémicas, constituyen un reto diagnóstico.Determinar las causas de VC.Se incluyeron pacientes con diagnóstico de CV, a los cuales se les realizó valoración clínica, biopsia cutánea y exámenes de laboratorio. En la mayoría de los casos se realizó inmunofluorescencia directa. Los casos se clasificaron con los criterios del American College of Rheumatology (ACR) y la Chapel Hill Consensus Conference (CHCC).Se incluyeron 32 pacientes; la frecuencia fue mayor en mujeres (71.8%). Los niños presentaron VC asociadas a medicamentos o púrpura de Schönlein-Henoch (PSH). En adultos se reportó con más frecuencia PSH, vasculitis asociada a lupus eritematoso sistémico y vasculitis paraneoplásicas; otros diagnósticos etiológicos incluyeron poliarteritis nodosa (PAN), poliangeítis microscópica (PAM), vasculitis trombótica (pospuerperal), síndrome antifosfolípidos (SAF), síndrome de Churg-Strauss (SCS) y VC asociada a medicamentos. Utilizando los criterios del ACR y la CHCC para vasculitis se clasificó el 50% de los casos.En el Hospital Gea, durante este trabajo, el diagnóstico etiológico de las CV se incrementó más del doble. Sin embargo, en relación a los diagnósticos vasculitis por hipersensibilidad (VHS) y PSH ninguna de las clasificaciones utilizadas contaba con criterios específicos. Seis pacientes permanecieron sin clasificar. Observamos que los estudios de crioglobulinas y serología para hepatitis no son útiles como estudios iniciales, salvo que la historia clínica del paciente lo sugiera. Los pacientes sin clasificar se siguieron por dos años.

Somatic and germline PI3K-AKT-mTOR pathway pathogenic variants are involved in several segmental overgrowth phenotypes such as the PIK3CA-related overgrowth spectrum (PROS), Proteus syndrome, and PTEN hamartoma tumor syndrome. In this study, we describe five patients with PROS. We identified by high-throughput sequencing four different somatic PIK3CA pathogenic variants in five individuals. The Glu726Lys variant, which was previously reported in megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome, was identified in two patients with unclassified PROS. The Cys420Arg substitution, which was previously reported in CLOVES, was found in a patient with fibroadipose hyperplasia. Additionally, relatively rare pathogenic variants, His1047Tyr and Tyr1021Cys, were detected in two patients with MCAP. Therefore, we suggest performing deep sequencing of PIK3CA in all patients with suspected PROS, instead of targeted polymerase chain reaction for hotspot pathogenic variants.

PURPOSE OF REVIEW: The main purpose of this review is to present newly reported cutaneous manifestations of systemic vasculitis, updates in investigations to verify systemic involvement in cases with cutaneous vasculitis and new therapeutic guidelines. The spectrum of COVID-19-related vasculitis is also covered. RECENT FINDINGS: Only a few reports highlighted new cutaneous presentations or associations with some systemic vasculitic entities. For example, the association of inflammatory disorders with Takayasu arteritis, the importance of considering Kawasaki disease in febrile children with erythema nodosum, the development of necrotic ulcers on fingers and toes in Behcet's disease and the possible presence of polyarteritis nodosa-like pathological features in vulvar ulcers of Behcet's disease. New attempts to classify cutaneous manifestations of giant cell arteritis (GCA) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the diagnostic investigations for cutaneous vasculitis cases to verify systemic involvement are discussed. Treatment of systemic vasculitis with cutaneous vasculitis should be tailored according to disease status. A plethora of reports in the past 2 years focused on the broad spectrum of COVID-19 vasculitic manifestations. SUMMARY: Although newly reported cutaneous manifestations of systemic vasculitis are relatively uncommon, the plethora of reports in the past 2 years on COVID-19 vasculitis necessitates the expansion of the classification of vasculitis associated with probable cause to include severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) vasculitis.

Background Mucopolysaccharide polysulfate (MPS) is a heparinoid and MPS-containing formulations are widely used as moisturizers for dry skin and to treat peripheral vascular insufficiency. Although MPS has therapeutic effects in skin diseases with microvascular abnormalities, the effects of MPS on microvascular function remain incompletely understood. Objective The aim of this study was to evaluate the functional activities of MPS on human pericytes (HPC) and human dermal microvascular endothelial cells (HDMEC) in vitro, and on microvascular permeability of the skin. Methods The protein expression of angiopoietin (Ang)-1 in HPC, and platelet-derived growth factor-BB (PDGF-BB) and phosphorylated tyrosine-protein kinase receptor 2 (Tie2) in HDMEC were measured in the presence or absence of MPS. The vascular barrier was evaluated by the expressions of claudin-5 and vascular endothelial (VE)-cadherin, and transendothelial electrical resistance (TEER). Results In HPC, MPS dose-dependently enhanced Ang-1 secretion, which activated Tie2 in HDMEC. In HDMEC, MPS significantly increased the production of PDGF-BB, which is important for the recruitment of HPC to the vascular endothelium, and significantly increased the phosphorylation of Tie2, which results in the activation of the Ang-1/Tie2 signaling . MPS significantly increased the expression of tight junction protein claudin-5 and TEER in the HDMEC. Moreover, the intradermal injection of MPS prevented vascular endothelial growth factor-induced increase in vascular permeability in mouse skin. Conclusion We found that MPS promoted microvascular stabilization and barrier integrity in HDMEC via Ang-1/Tie2 activation. These results suggest that MPS might improve microvascular abnormalities in various diseases accompanied by disturbances in Ang-1/Tie2 signaling.

Frontiers in immunology 13, 1-14 (2022). doi:10.3389/fimmu.2022.1029423, Published by Frontiers Media, Lausanne

BACKGROUND Lasers have great importance in the management of vascular skin lesions. AIM To determine the efficacy of 577-nm pro-yellow laser in cure of certain vascular skin diseases. MATERIAL AND METHODS Seventy-four patients who are diagnosed as vascular skin diseases were involved in this study. All participants were treated with 577-nm pro-yellow laser with 4-week intervals. The photographs that were taken before and at every following visit were used to evaluate improvement. RESULTS A significant improvement occurred in port-wine stain, rosacea, facial telangiectasia, venous lake, scrotal angiokeratoma, and cherry angioma cases. CONCLUSION Vascular skin lesions can be treated with 577-nm pro-yellow laser with a minimal adverse effect and great success rate.

Background Purpura in inpatients commonly leads to dermatologic consultation. The differential diagnosis is broad and algorithms are intricate. Objective We evaluated inpatient consultations for complex purpura to document the most common diagnoses and to validate the true diagnostic utility of histopathology, clinical morphology, and distribution. Methods We reviewed a case series of 68 inpatients during a 4-year period with a dermatologic consultation for purpura and biopsy findings of vasculitis or microvascular occlusion. Results Key features of complex purpura are nonbranching (round) versus branching (retiform) morphology, dependent versus acral or generalized distribution, and leukocytoclastic vasculitis versus microvascular occlusion (with emphasis on depth of involvement). Dependent nonbranching purpura with only superficial vessels involved by leukocytoclastic vasculitis was most often due to IgA vasculitis or cutaneous single-organ small-vessel vasculitis. In contrast, deeper involvement by leukocytoclastic vasculitis was suggestive of systemic disease (eg, antineutrophil cytoplasmic antibody–associated vasculitis). Branching purpura was concerning, with greater than 90% sensitivity and specificity for microvascular occlusion and associated high mortality (≈50%). The majority of patients who died had acral branching lesions. Limitations Small sample size, inpatients at a tertiary care center, and retrospective nature are some limitations. Conclusion Nonbranching dependent purpura corresponded to leukocytoclastic vasculitis, with the most common diagnoses being IgA vasculitis or skin-limited small-vessel vasculitis; patients with deep involvement often had systemic diseases. In this series, branching purpura was due to microvascular occlusion rather than medium-vessel vasculitis, and had associated high mortality.

Herein, the different skin manifestations in patients with lupus erythematosus are reviewed, and their diagnostic, pathogenic and prognostic relevance are discussed, as well as their impact on therapeutic choices. The so-called specific lesions of LE result from an autoimmune pathomechanism and they allow diagnosis of LE by simple clinicopathological correlation since the findings are characteristic. They include the classic acute, subacute and chronic variants, characterised microscopically by interface dermatitis; the dermal variants of lupus, such as tumid lupus, displaying dermal perivascular lymphocytic infiltrate with mucin deposition under the microscope, and lupus profundus, in which lymphocytic lobular panniculitis progressing to hyaline fibrosis is found. Antimalarials are the treatment of choice for patients with specific LE lesions. The presence of some dermatological signs is the result of thrombotic vasculopathy. Their recognition allows the identification of lupus patients at increased cardiovascular risk and with a worse overall prognosis. Those signs include reticulated erythema on the tip of the toes, splinter hemorrhages, atrophie blanche, pseudo-Degos lesions, racemosa-type livedo, anetoderma, ulceration and necrosis. Those clinical manifestations, often subtle, must be recognised, and if present, patients should be treated with antiplatelet drugs. Finally, neutrophilic cutaneous lupus erythematosus includes a few entities that suggest that autoinflammatory mechanisms might play a key role in certain lupus manifestations. Among those entities, it is very important to diagnose neutrophilic urticarial dermatosis, which can mimic a classic lupus flare, because it is characterised by rash with joint pain, but immunosuppressants are not helpful. Dapsone is the treatment of choice.

Macular arteritis (MA) has a striking discordance between the clinical presentation of hyperpigmented macules and the histopathologic findings of a lymphocytic arteritis with intraluminal hyalinized fibrin ring and thrombosis. It has been proposed that MA represents the chronic, indolent, lymphocytic form of the neutrophil-predominant cutaneous polyarteritis nodosa. MA usually affects middle-aged women asymptomatically on the legs. There is also a slightly more severe variant with more infiltrated plaques and livedo racemosa, termed lymphocytic thrombophilic arteritis. MA and lymphocytic thrombophilic arteritis have similar histologic features, both with a largely intact vascular elastic lamina, despite the abundant fibrin and endarteritis obliterans. There is no evidence for progression from MA to lymphocytic thrombophilic arteritis to cutaneous polyarteritis nodosa, and aggressive therapy should be avoided in MA, given the indolent, benign disease course.

Glomus tumors are rare benign neoplasms arising from the neuromyoarterial structure called glomus body. They present as angiomatous papules, soft and painful, especially to cold and pressure. In general, they are solitary and affect the extremities, located mainly the subungual bed. Extradigital lesions are rare and can constitute a diagnostic challenge. This is the report of a patient with an extradigital lesion on the left arm, and its dermoscopic aspects, including angiomatous lagoons circumscribed by a pale halo, a structure not previously described in the two reports of extradigital glomus tumor with dermoscopic features, found in the literature.

Vascular occlusion has multiple, diverse clinical manifestations, some of which can have grave consequences for patients. It also has a wide variety of causes, including thrombi, which we recently addressed in partI of this review. In this second part, we look at additional causes of vascular occlusion.

Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy. Based on a French collaboration, we collected clinical features of 33 patients (21 females, 12 males, median age of 9.9 years) with MCAP carrying mosaic PIK3CA pathogenic variants. MRI images were reviewed for 21 patients. The main clinical features reported were macrocephaly at birth (20/31), postnatal macrocephaly (31/32), body/facial asymmetry (21/33), cutaneous capillary malformations (naevus flammeus 28/33, cutis marmorata 17/33). Intellectual disability was present in 15 patients. Among the MRI images reviewed, the neuroimaging findings were megalencephaly (20/21), thickening of corpus callosum (16/21), Chiari malformation (12/21), ventriculomegaly/hydrocephaly (10/21), cerebral asymmetry (6/21) and polymicrogyria (2/21). This study confirms the main known clinical features that defines MCAP syndrome. Taking into account the phenotypic heterogeneity in MCAP patients, in the context of emerging clinical trials, we suggest that patients should be evaluated based on the main neurocognitive expression on each patient.

Capillary malformations - arteriovenous malformation, hereditary hemorrhagic telangiectasia and Sturge-Weber syndrome - are rare diseases in which cutaneous capillary malformations (CM) may be associated with cerebral vascular malformations. The clinical presentation of each disease is described with focus on how to distinguish them in the clinic and differential diagnoses are listed. This review finds that upon thorough and careful examination of patients, cutaneous CM might be a diagnostic hallmark for underlying disease and therefore a significant clinical observation.

Cutaneous Vasculitides - Clinical Manifestations, Diagnosis, and Aetiology

The pathogenesis of livedoid vasculopathy (LV) remains unknown. Although platelet activation occurs in LV, little research has been conducted on LV platelet morphology parameters. The purpose of this study was to investigate whether platelet morphology changes in LV and its clinical significance.Twenty-seven LV patients and 21 cutaneous small vessel vasculitis (CSVV) patients, all at the active stage, were included. Platelet parameters in active- and stable-stage LV and CSVV patients were compared. Correlations between these platelet parameters and LV composite clinical scores were analysed.LV patients' mean age was 25.48 years (range: 9-62 years), and 81.48% (22/27) were women and 18.52% (5/27) were men. The platelet counts and plateletcrit (PCT) levels were significantly elevated in LV patients compared with CSVV patients and in active-stage LV patients compared with stable-stage LV patients after treatment. LV patient composite clinical scores that reflected disease severity and activity were positively correlated with the platelet count and PCT levels.Altered platelet morphology was detected in LV patients. Platelet count and PCT might be haematological biomarkers for early prediction of LV activity and relapses and for differential identification between LV and CSVV.

PIK3CA-related overgrowth spectrum (PROS) disorders are caused by somatic, gain-of-function mutations in PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) that result in hyperactivation of the phosphatidylinositol-3-kinase (PI3K) signaling pathway. PROS encompasses a broad spectrum of overlapping phenotypes that vary considerably in their severity and tissue distribution, leading to different and complex experiences for affected children and their families. The parent of a child with the PROS disorder megalencephaly-capillary malformation (MCAP) coauthored this article. MCAP is characterized by significant neurological involvement, and she describes personal experiences with this condition, including delays associated with obtaining a correct diagnosis, finding an experienced care team, challenges with schooling, medical complications, and the ongoing emotional and financial impacts on their lives. A physician perspective, which reinforces the challenges faced by the young child and his family, is provided by a clinician and researcher specializing in PROS disorders with central nervous system involvement. The physician reviews the mechanism of disease, some of the challenges in accurately diagnosing PROS conditions, disease-related complications, current treatment options and their limitations, and emerging therapeutic options including ongoing clinical trials. Our objective is to share these experiences and insights to benefit patients with PROS disorders, their families, and health care professionals involved with caring for patients with PROS.

A wide range of extrapulmonary manifestations in patients with COVID-19 has been reported during the ongoing pandemic, thus making the clinical spectrum of this new disease very heterogeneous. While COVID-19-associated vasculitis and vasculopathy have been described, cutaneous leukocytoclastic vasculitis (cLcV) due to SARS-CoV-2 has rarely been reported, and if it has, with relatively mild courses. We present the case of a 93-year-old man who, after having survived classic COVID-19 infection, developed a fulminant cLcV leading to extensive skin necrosis and tissue damage that resulted in his death. Considering the negative workup for other triggers of vasculitis, we find that cLcV is a secondary manifestation of COVID-19, even though SARS-CoV-2 polymerase chain reaction in the skin biopsy was not present in the tissue. We hypothesize this by providing a pathophysiologic rationale (eg, SARS-CoV-2-induced endotheliitis, complement activation, and interleukin 6 dominant intra- and perivascular inflammation).

Drug-induced vasculitis and anticoagulant-related skin reactions are commonly encountered in the inpatient and outpatient settings. The spectrum of clinical presentation is broad and ranges from focal, skin-limited disease, to more extensive cutaneous and soft tissue necrosis, to potentially fatal systemic involvement. The prompt recognition of these adverse events can have a significant impact on patient morbidity and mortality. We highlight the key features of the clinical presentation with an emphasis on primary lesion morphology, distribution, and epidemiology of purpuric drug reactions. The proposed pathophysiology, histologic findings, and therapeutic interventions of these potentially life-threatening diseases are discussed.