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Em 1907 EHRMANN descreveu dois tipos diferentes de livedo: um patológico, o livedo racemoso, e um “fisiológico”, o livedo reticular. Ambos são causados pela redução do fluxo sanguíneo e pela redução da tensão de oxigênio no segmento da pele. É importante diferenciar clinicamente os dois tipos de livedo. O livedo racemoso associa-se com doenças sistémicas como esclerodermia sistémica. É a manifestação dermatológica mais comum da síndrome do anticorpo antifosfolipídeo. Relatamos o caso de uma paciente com livedo racemoso associado à esclerodermia cutânea.

SummaryIndependent of the size of the dog and the type of injury, serious infections may follow a dog bite and these may result in the abrupt onset of multiorgan failure. Early recognition of the warning signs with regard to the underlying severity of the infection is of the utmost importance. Reticulate skin eruptions constitute a precursory phenomenon.

Microscopic polyangiitis is a pauci-immune necrotizing small- and medium-vessel vasculitis mainly involving the lung and kidneys but also the peripheral nerves and skin. A variety of skin lesions are observed in about half of patients. The most common cutaneous manifestations are palpable purpura, livedo racemosa, and skin nodules. Histology of skin lesions typically shows leukocytoclasia with fibrinoid degeneration, neutrophil infiltration, and sometimes erythrocyte extravasation around the affected capillaries and small vessels in the dermis. Direct immunofluorescence shows absence of immunoglobulin deposits. A detailed clinical history and physical examination complemented by histological studies can aid in discriminating microscopic polyangiitis from other vasculitides affecting the skin.

Wir beschreiben den Fall einer 43-jahrigen Patientin mit einer seit Kindheit bestehenden intermittierend schmerzhaften Livedo racemosa am Rucken, die im Krankheitsverlauf zu Ulzerationen fuhrte. Die umfangreichen Untersuchungen konnten keinen Hinweis auf eine zugrunde liegende Erkrankung erbringen, wobei initial und im Verlauf insbesondere kein Anhalt fur ein Sneddon-Syndrom bestand. Mittels konserativer und chirurgischer Masnahmen konnte zunachst eine Abheilung der Ulzerationen erreicht werden, diese rezidivierten jedoch in der Folgezeit. Eine zyklische Therapie mit Iloprost-Infusionen fuhrte im vorliegenden Fall zu einer langfristigen Abheilung der Ulzerationen und zum Sistieren der Schmerzsymptomatik. Eine derartige Behandlung ist bisher fur diese Erkrankung in der wissenschaftlichen Literatur noch nicht beschrieben.

Background Sneddon's syndrome is defined as a combination of idiopathic livedo racemosa generalisata and symptoms of cerebrovascular defect. The disease usually starts with vascular symptoms in the epidermis, with neurological deficits becoming evident later. For this reason, histological examination of skin biopsies and determination of arteriolar occlusion is of particular importance for reliable categorization and early diagnosis. To date, these methods have been considered to be too insensitive. Objectives To evaluate the sensitivity of skin biopsies in Sneddon's syndrome. Methods We took a total of five deep punch biopsies (4 mm) from different areas of the livedo (three from white and two from red areas) in 15 patients. Present knowledge of the pathogenic relationships and the particular anatomical features of the skin were taken into account. Results The method had a sensitivity of 27% with one biopsy, 53% with two biopsies and 80% with three biopsies taken from white areas in all cases. Conclusions Skin biopsies using the method presented achieved a high sensitivity, suggesting that the diagnosis in clinically suspected cases could be confirmed in the majority of cases with this technique.

Classic variants of cutaneous borreliosis are erythema chronicum migrans (ECM), lymphadenosis benigna cutis (LBC) and acrodermatitis chronica atrophicans (ACA). Other dermatoses have been reported in the literature as possibly linked to borreliosis. A 59-year old female patient was seen in the late phases of cutaneous borreliosis with histologically confirmed ACA. In addition, prominent livedo racemosa was seen on the legs, also showing tissue changes similar to those of ACA. Borrelia burgdorferi infection was serologically confirmed by the presence of anti-IgM and anti-IgG antibodies. The clinical spectrum of late cutaneous borreliosis should be enlarged to include livedo racemosa.

We report on a case of intracerebral hemorrhage associated with livedo racemosa in a 13-year-old girl. A skin biopsy specimen showed endothelitis and mixed inflammatory cellular infiltrate around the small arteries. We believe that the cerebral hemorrhage might have been caused by fragility of the intracranial small arteries and that this case could be an example of an early stage of Sneddon's syndrome.

The prevalence and clinical and laboratory associations of IgM, IgG and IgA rheumatoid factors (RF) were determined in 352 patients with systemic lupus erythematosus (SLE). IgM, IgG, and IgA class RF were detected in 17.9%, 20.5%, and 20.5% of the sera, respectively. RF were associated with sicca syndrome, hypergammaglobulinemia, high titer of antinuclear antibodies, anemia, SSA- and SSB-antibodies, and with the presence of HLA-DR3. RF correlated negatively with nephritis and livedo racemosa. Moreover, we observed an association of RF and parameters of inflammatory activity such as elevated erythrocyte sedimentation rate (ESR) and leukopenia. Analysis of immunoglobulin classes revealed that laboratory parameters of inflammatory activity, SSA- and SSB-antibodies and HLA-DR3 correlated with IgA RF only. IgA RF define a subgroup of SLE patients characterized by distinct autoimmune phenomena and high disease activity in the absence of nephritis.

Hintergrund: Livedo racemosa mit Beteiligung des Zentralnervensystems ist als Sneddon-Syndrom bekannt. Neuere Ergebnisse sprechen fur das Vorliegen eines generalisierten und progredienten arteriellen Verschlusprozesses kleinerer und mittlerer Gefase, dessen Atiologie letztlich noch nicht bekannt ist. Ein Zusammenhang mit dem Antiphospholipidantikorpersyndrom, den Kollagenosen und Koagulopathien wird diskutiert, hereditare und toxische Faktoren scheinen im Einzelfall eine Rolle zu spielen. Fallbeschreibung: Diagnostik und Verlauf eines Sneddon-Syndroms werden anhand einer Falldarstellung bei einer 56jahrigen Patientin mit dementieller Entwicklung und Hemiparese nach langjahrig vorbestehender Livedo racemosa beschrieben. MRT-, SPECT- und TCD-Befunde deuteten auf diffuse fleckformige zerebrale Ischamien im Bereich kleinerer und mittelgroser Gefase hin. Weder histopathologische Untersuchungen von Haut, Hirngewebe noch Hirnhauten zeigten richtungweisende Befunde. Allein laborchemische Parameter wiesen in die Richtung einer Vaskulitis. Die Livedo racemosa erfuhr eine positive Beeinflussung unter immunsuppressiver Therapie. Schlusfolgerung: Das Sneddon-Syndrom ist wahrscheinlich keine Krankheitsentitat. Die Phanomenologie wird bei differenter Genese durch den Topos der pathologisch-anatomischen Veranderungen in der Dermis und dem Zentralnervensystem bestimmt. Eine Differenzierung in symptomatische und idiopathische Formen ist im Hinblick auf therapeutische Entscheidungsprozesse relevant.

Es wird uber einen Fall von Kalziphylaxie bei einer 40jahrigen Patientin mit terminaler Niereninsuffizienz berichtet. Nach 22 Jahren Hamodialyse entwickelte die Patientin multiple Herde von Livedo racemosa sowie schmerzhafte Nekrosen und Ulzera an der Hufte und den unteren Extremitaten. Als Ursache lies sich radiologisch eine Kalzinose peripherer Arterien, insbesondere der Becken- und Oberschenkelarterien und der Interdigitalarterien der Hande, sowie histologisch eine Fibrose und Kalzinose kleiner subkutaner Arterien aufzeigen. Mittels transkutaner Sauerstoffpartialdruckmessungen konnte eine generalisierte kutane Mikroangiopathie nachgewiesen werden. Laborchemisch bestand ein moderat ausgepragter sekundarer Hyperparathyreoidismus mit masiger Erhohung des Kalzium-Phosphat-Produkts. Neben der Hamodialysetherapie wurde der Versuch einer medikamentosen Verbesserung der Mikrozirkulation unternommen. Der Verlauf war durch ein protrahiertes Abheilen der Ulzera und das Auftreten neuer kutaner Nekrosen gekennzeichnet. Die Kalziphylaxie ist eine seltene Spatkomplikation bei Patienten mit fortgeschrittener, meist terminaler Niereninsuffizienz, die durch die Histologie gesichert wird und oft, aber nicht notwendigerweise, mit einem gestorten Kalzium- und Phosphatstoffwechsel sowie mit leicht erhohten Parathormonspiegeln assoziiert ist. Die Kalziphylaxie wird als Sonderform der metastatischen Kalzinose eingestuft.

We report a case of systemic cholesterol embolisms (CE) with rare localization to the level of the face from a tight carotid stenosis. The case history is that of a 75 year old patient who presented with cholesterol embolisms in the territory of the external carotid artery. The patient underwent successful carotid endarterectomy with no postoperative neurological event.

Livedo racemosa with cerebrovascular lesions has been described as Ehrmann-Sneddon syndrome. The etiopathogenetic factors provoking the vascular lesions, however, are of high diversity reaching from mechanical to autoimmune causes. We present a male patient with typical livedo racemosa, muscle pain and feeling of coldness of the forearms. By dermatohistopathology and magnetic resonance tomography of the brain, Ehrmann-Sneddon syndrome could be confirmed. At this time a chronic streptococcal infection could be diagnosed. Antibiotics, anticoagulants and vascularity-supplying therapy improved the clinical and subjective symptoms. Six months later, the patient developed dizziness, vision disorder, hypesthesia of the right forehead, malaise and weight loss. A further diagnostic workup including echocardiography revealed a myxoma of the left atrium. This report illustrates the association of Ehrmann-Sneddon syndrome with cardiac myxoma and points out that cardiac diagnostic examination should be included when dealing with small-vessel involvement of the brain.

Objectives Livedo racemosa is a reticulate eruption that presents with branched and partially blanchable incomplete rings. Livedo racemosa is distinct from livedo reticularis, a similar condition that presents with a diffuse and symmetrical blanchable eruption. In contrast to livedo reticularis which may be physiological, livedo racemosa is always associated with an underlying pathology. To our knowledge, this is the first report of panniculitis ossificans and heterotopic ossification of small saphenous vein (SSV) presenting with livedo racemosa. Methods We present a 70-year-old male referred for investigation and management of progressive pigmentation and ‘lipodermatosclerosis’ of lower limbs. There was no history of deep venous thrombosis but an earlier ultrasound had detected a non-occlusive thrombus in the left SSV. Examination and investigations revealed the skin eruption to be livedo racemosa and the associated subcutaneous induration and nodularity to be due to panniculitis ossificans. Biopsy of the SSV demonstrated segmental heterotopic ossification. Duplex ultrasound demonstrated bilateral superficial and deep venous incompetence but no evidence of an acute or chronic venous thrombosis. The patient was diagnosed with heterotopic ossification secondary to venous insufficiency and managed conservatively. Conclusion Livedo racemosa may be an early sign of panniculitis ossificans and its presence should trigger further diagnostic investigations.

A 64-year-old male patient presented with painful ulcerations and livedo racemosa of both lower limbs. He had a history of cerebral and myocardial infarctions. Dermatohistologic findings and laboratory tests of the patient's coagulation system revealed the diagnosis of livedoid vasculopathy with heterozygous factor V Leiden mutation and sticky platelet syndrome type II. Systemic treatment with acetylsalicylic acid and heparin as well as topical therapy with disinfectant and granulation-inducing agents resulted in improvement of the skin lesions.

A 59-year-old woman with retinal vein thrombosis and livedo racemosa had hematuria (4+) and proteinuria (1.7 g/day). Skin biopsy showed swollen blood vessel walls with infiltration of mononuclear cells, which were compatible with livedo racemosa (vasculitis). Magnetic resonance imaging (MRI) of the brain demonstrated multiple lacunar infarctions in the basal ganglia and white matter. Renal biopsy showed that small round cells had infiltrated into the interstitium, and a reticular structure was observed in the glomerular hilus. An amorphous substance composed of a single cell was present in the glomerular capillary lumen. Immunofluorescent study demonstrated the deposition of only IgA, in a segmental pattern differing from the diffuse global mesangial pattern seen in IgA nephropathy. After combined therapy including 40 mg/day prednisolone, 50 mg/day cyclophosphamide, antiplatelet drug, and anticoagulant was started, proteinuria and hematuria improved to 0.5 g/day and 2+, respectively, at the time of discharge. Sneddon's syndrome is a rare entity characterized by livedo racemosa and cerebrovascular lesions. In our patient with livedo racemosa, occlusion of cerebral blood vessels, and nephropathy with segmental immunoglobulin A (IgA) deposition, no antiphospholipid antibodies were detected on routine examination. Dermatologists, neurologists, psychiatrists, and nephrologists should be aware of the existence of Sneddon's syndrome with nephropathy (LI-O-N).

A case report is presented to illustrate the cutaneous manifestations in essential thrombocythaemia. Knowledge of the related skin lesions may lead to earlier detection of this myeloproliferative disorder. Treatment may prevent severe haemorrhagic or thrombotic complications. Erythromelalgia is causally related to thrombocythaemia; prompt relief of painful symptoms after treatment with aspirin is typical.

A 61-year-old patient with life-threatening angioneurotic oedema was found to have an acquired C1-inhibitor (C1-INH) deficiency. In addition to lowered serum levels of C1-INH (both protein concentration and enzymatic activity), C2, C4 and CH50, which are characteristic for the hereditary form of angioneurotic oedema, markedly lowered C1q was found, which is typical for the acquired form. There were no antibodies against C1-INH. Repeated thorough examinations disclosed no neoplasm, though the presence of neoplasm has often been reported to be associated with the acquired C1-INH deficiency. However, the patient showed persistent paraproteinaemia and paraproteinuria and developed livedo reticularis. Treatment with danazol resulted in a rise in the complement fraction levels and cessation of angioneurotic oedema. Paraproteinaemia and livedo reticularis persisted unchanged.

Sneddon syndrome (SS) is increasingly recognised as a cause of ischaemic stroke in young adults. As the natural course of SS is not well defined, the authors performed a prospective six year clinical and neuroradiological follow up study. Thirteen patients with definite diagnosis of SS (livedo racemosa, characteristic skin biopsy, and history of stroke) entered a follow up programme that consisted of clinical examinations, two magnetic resonance imaging (MRI) investigations, and a comprehensive laboratory follow up protocol. The most frequent clinical findings during follow up had been headache (62%) and vertigo (54%). Seven patients (54%) suffered from transient ischaemic attacks, however, completed stroke has not been obtained during follow up. Progression of white matter lesions detected in MRI were present in 10 of 13 patients. Laboratory follow up protocol revealed transient antiphospholipid antibodies in two subjects. This prospective six year follow up study suggests a low incidence of territorial stroke but outlines progressive leucencephalopathy in patients with SS.

Systemic polyarteritis nodosa (PAN) is a vasculitis characterized and defined by necrotizing inflammatory changes in medium and/or small arteries. Children and adults with vasculitis differ in the relative frequency of some clinical manifestations and concomitant diseases. The European League against Rheumatism (EULAR)/Pediatric Rheumatology European Society (PRES) working group has proposed a classification of childhood vasculitis. With support from EULAR, the Pediatric Rheumatology International Trials Organization (PRINTO), and PRES, a formal statistical validation process, which included large-scale, web-based data collection, was undertaken. I now propose a set of criteria for systemic juvenile PAN that combines a modified mix of the EULAR/PRES criteria and the EULAR/PRINTO/PRES criteria. Cutaneous juvenile PAN is characterized by the presence of cutaneous features with no systemic involvement. The common cutaneous manifestations include cutaneous nodules and livedo racemosa. Our research group previously established an algorithm for the differential diagnosis of primary cutaneous vasculitis. We have recently developed a new version of that algorithm to diagnose vasculitis with cutaneous manifestations from a dermatologic point of view. Treatment of systemic juvenile PAN is based on a combination of cortico-steroids and immunosuppressant agents. The clinical course of cutaneous juvenile PAN is generally benign.

In anticardiolin syndrome (ACS) a typical antibody constellation is associated with thrombotic and hematologic disorders. Furthermore, recurrent abortion, cerebral ischemia and different skin disorders occur. We report the case of a 29-year-old female suffering for the first time from painful, necrotic deep ulcers on the upper and lower legs and livedo racemosa on the arms as a rare example of a merely cutaneous manifestation of ACS with no demonstrable underlying disease. After systemic treatment with high-dose methylprednisolone, azathioprin and hydrocolloid dressings, healing of the scar tissue occurred. Simultaneously, a maintenance dose of acetylsalicylic acid (100 mg/day) was administered. So far, neither cutaneous relapse nor other signs of ACS have occurred.

We present 5 patients in whom the diagnosis of livedo racemosa gave rise to clinical and laboratory investigations revealing arterial disease of different etiologies. This presentation emphasizes the importance of not missing the clinical diagnosis of livedo racemosa.

The Chapel Hill Consensus Conference criteria define cryoglobulinemic vasculitis (CV) as “vasculitis, with cryoglobulin immune deposits, affecting small vessels (i.e. capillaries, venules, or arterioles), and associated with cryoglobulins in the serum.” Hepatitis C virus (HCV) infection is the underlying etiologic factor in the majority of cases of CV, but it also occurs secondary to other infections (e.g., hepatitis B), connective tissue diseases (e.g., Sjogren’s syndrome), and hematolymphoid proliferations (e.g., Waldenstrom’s macroglobulinemia). Purpura, arthralgia, and weakness are the most common presenting signs and symptoms but any organ can be affected (skin, kidney, and nerves most frequently). The extent of involvement and disease severity progress with time in the absence of treatment. Recurrent palpable purpura associated with post-inflammatory hyperpigmenation is the most frequent cutaneous manifestation of CV but others include nodules, leg ulcers, livedo racemosa, and digital gangrene, i.e., signs of muscular-vessel vasculitis. Skin biopsy shows a small-vessel neutrophilic vasculitis equally affecting superficial and deep dermal and subcutis vessels, with neutrophilic muscular-vessel vasculitis in a minority of cases. Thrombosis, in some instances by hyaline/ type I cryoglobulin thrombi, contributes to the ischemic damage. By direct immunofluorescence, abundant IgM, and complement deposits are found in the affected vessels, highlighting the immune-complex mediated pathogenesis. Adverse prognostic factors for HCV-related CV include the presence of ulcers and renal insufficiency. Anti-HCV therapy (interferon-α and ribavirin) with or without rituximab is associated with a favorable clinical response, but relapse is common. In some patients, the persistent CV necessitates the administration of immunosuppressive agents.

Sneddon's syndrome is a systemic disease characterized by generalized livedo racemosa and cerebrovascular disease. We present a case of Sneddon's syndrome which has typical dermatological lesions and occipital infarct demonstrated by both CT and MRI.

Susac's syndrome (SS) is a rare microangiopathy affecting the precapillary arterioles of the brain, retina and inner ear, presumably resulting from an autoimmune endotheliopathy. We report the first case of SS with histologically proven skin involvement, in a 24-year-old male who presented a subacute encephalopathy, branch retinal artery occlusions and bilateral hearing loss, two weeks after the onset of a livedo racemosa of the flanks and feet. Skin biopsies revealed a thrombus in several dermal arterioles, endothelial cells swelling and a mild perivascular lymphocytic infiltrate, which correspond to the same histological findings as previously observed in brain but also in muscle biopsies of patients with SS. A complete recovery was achieved in 4 months with corticosteroids. Follow-up MRI showed centro-callosal "holes". Skin involvement in SS has pathological plausibility since serum antibodies directly binding to central nervous system but also to generic endothelium cells have been reported. Our report supports that SS is a systemic disease that could affect other organs in addition to the brain, retina and inner ear. We suggest careful skin examination should be considered in patients with a suspicion of SS.

We present a 40-year-old man with erythematous-to-violaceous, broken, reticulated patches on the upper chest, back, and extremities, which is consistent with livedo racemosa. The cutaneous findings appeared after an increase in dilantin dose and subsequently improved after a reduction in dilantin dose. Furthermore, antinuclear antibodies and antihistone antibodies were detected. We therefore believe that the livedo racemosa is a cutaneous manifestation of a drug-induced systemic lupus erythematosus. We review the distinctive features of livedo racemosa as well as its associations with several disorders. Although there are no effective treatments for livedo racemosa, patients often are placed on low-dose aspirin and counseled to avoid smoking in an effort to protect against their increased risk of stroke and arterial thrombosis.

Sneddon's syndrome is a potentially fatal arterio-occlusive disorder characterized by generalized livedo racemosa and cerebrovascular lesions. Skin biopsies often fail to yield diagnostic arterial lesions. In the present series, affected vessels were found in skin biopsies from 12 of 15 patients with Sneddon's syndrome. Selection of the correct biopsy site (seemingly uninvolved skin at the center of a livedo racemosa area), adequate biopsy size (1 to 2 cm), and serial sections are essential for the detection of relevant vascular pathology. Only small to medium-sized arteries of the dermis-subcutis boundary were found to be involved. Lesions follow a distinct course. The initial stage displays partial detachment of endothelial cells, adhesion of mononuclear cells interspersed with fibrin ("endothelitis"), a marked edema of the surrounding connective tissue with numerous dilated capillaries, and a predominantly lymphohistiocytic infiltrate with polymorphonuclear leukocytes. In the early phase a sponge-like plug is formed from mononuclear cells, fibrin, and red blood cells, leading to partial to complete obstruction. A perivascular inflammatory infiltrate, devoid of polymorphonuclear leukocytes, is located around affected arteries; in the adventitia of the occluded vessel, a very regular corona of dilated capillaries appears that is continuous with more peripheral dilated and branching vessels. Organization of the occluding plug ensues in the intermediate stage by "subendothelial cell proliferation," most likely due to immigrating smooth muscle cells. In the final stage, the occluding artery undergoes fibrosis, shrinkage, and atrophy.

Sneddon's syndrome is a rare disease with strong gender prevalence of females. This syndrome is characterized by livedo racemosa and cerebrovascular lesions. Since no specific test is available, the clinical differentiation from other disorders with similar symptomatology may raise difficulties. The cerebral involvement includes strokes with cases of more than one ischaemic event having been reported. Associations with convulsions, heart valve disease, systemic hypertension, and renal impairment have been described. We report the case of a 5-year-old boy who was anaesthesized for dental surgery. Due to the fact that 50% of Sneddon's syndrome patients develop mental retardation, even minor procedures require general anaesthesia. A review of the literature is added and specific anaesthesiological aspects of the perioperative care of Sneddon's syndrome are discussed.

Sneddon syndrome (SS) is characterized by livedo racemosa, recurrent ischemic strokes, and often progressive vascular dementia. Treatment options for SS center on either anticoagulation or immunosuppression to prevent strokes and to dissipate the skin findings, with these modalities based historically on the presence or absence of antiphospholipid antibodies (APA) respectively. However, few effective treatments have been reported to reverse the cognitive decline in SS. We report a case of a woman with seronegative SS (absence of APA) with cognitive decline who demonstrated objective and subjective improvements in her memory and emotional functioning after treatment with cyclophosphamide.

The antiphospholipid syndrome (APS) is a multi-system autoimmune disorder characterized by recurrent arterial and venous thromboses and pregnancy morbidity (Hughes 1983). The most common clinical manifestations of the APS are shown in Table 16.1. Cutaneous manifestations of the APS include livedo reticularis (livedo racemosa), leg ulcers, skin necrosis, superficial thrombophlebitis, splinter hemorrhages, digital ischemia, and gangrene. Many of these features must be distinguished from vasculitis, which can also be associated with these findings. The APS is linked to multiple central nervous system manifestations. These are listed in Table 16.2. The APS can occur in a primary form which is not associated with another underlying condition. In addition, it can develop concurrently with disorders such as systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL) are a heterogeneous group of immunoglobulins directed at phospholipid binding proteins. Three antibodies are central to the diagnosis of APS: the lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and β-2-glycoprotein 1. aCL and β-2-glycoprotein 1 are detected by enzyme-linked immunosorbent assays. The LA is commonly detected by the dilute Russell viper venom time, but other assays are also available (Brandt et al. 1995). aPL are found in less than 1% of healthy populations of all ages. However, the figure is substantially higher among healthy older populations — as high as 5%. The prevalence in SLE is substantially higher, on the order of 24% for IgG aCL, 13% for IgM aCL, and 15% for LA (Cervera et al. 1993). APS has a significant impact on morbidity and mortality (Shah et al. 1998; Jouhikainen et al. 1993; Schulman et al. 1998; Ruiz-Irastorza et al. 2004). In one longitudinal study of SLE patients, aPL-related thromboses accounted for 27% of all deaths in the cohort (Cervera et al. 1993). The term “catastrophic APS” refers to a rare but potentially lethal disorder characterized by accelerated thrombosis, multiple organ involvement that includes renal thrombotic microangiopathy and death in a high percentage of patients (Bucciarelli et al. 2006). The combination of anticoagulation, glucocorticoids, and plasma exchange is a useful treatment approach to the catastrophic APS (Bucciarelli et al. 2006). Immuno-suppression, particularly with cyclophosphamide, should be avoided. Arterial and venous events associated with the APS are treated initially with unfractionated or low molecular weight heparins, followed by oral anticoagulation with warfarin. Women with APS are at high risk of complications during pregnancy and in the postpartum period. In the postnatal period, women with Thrombotic APS should be given thromboprophylaxis with subcutaneous hepa-rin followed by the resumption of oral anticoagulation as soon as possible. Controversies in the management of patients during pregnancy are discussed.

The term livedo reticularis refers to a reddish-violet reticular discoloration of the skin that mainly affects the limbs. It is caused by an interruption of blood flow in the dermal arteries, either due to spasm, inflammation, or vascular obstruction, and is associated with diseases of varying etiology and severity. To establish the cause of livedo reticularis, it is essential to determine its course (chronic, acute, or fulminant), the presence of other cutaneous signs such as nodules, retiform purpura or necrosis, and the possible association of general symptoms or laboratory findings that suggest a particular systemic process. The aim of this review is to describe the diagnosis and treatment of the disease.

O escopo deste artigo é revisar os estados de hipercoagulabilidade sangüínea (trombofilias) mais provavelmente encontrados por dermatologista. Seus sinais cutâneos incluem o livedo reticular, necrose cutânea, ulcerações e isquemia digital, púrpura retiforme, além de úlceras nas pernas. Revisamos seu tratamento adequado, bem como ressaltamos as manifestações cutâneas que impõem pesquisa laboratorial de trombofilias e os exames indicados nessas situações.

Background We encountered a distinct arteriolar histopathologic finding of lymphocytic vasculitis associated with a hyalinized fibrin ring in vessel lumina. Identical histologic findings have previously been described as macular arteritis. Observations We describe 5 women (mean age, 25 years; age range, 20-34 years) with persistent, slowly progressive, patchy and reticular hyperpigmentation associated with livedo racemosa affecting predominantly the lower limbs. In the biopsy samples, infiltration of muscular vessel wall by inflammatory cells, affecting small arteries of the dermosubcutaneous junction or superficial subcutis, was present. Of the infiltrate, 90% or more consisted of mononuclear cells, mainly lymphocytes with an admixture of histiocytes. Neutrophils and eosinophils were absent or scant. Inflammation was confined to the vicinity of the vessel and the immediate surrounding panniculus. A concentric fibrin ring involving the entire periphery of the lumina of affected vessels was present in all the patients. Laboratory investigation results revealed that 4 patients had antiphospholipid antibodies in their serum. One of these patients had a heterozygous mutation of the factor V Leiden gene. Conclusion We term this arteritis lymphocytic thrombophilic arteritis to reflect the histologic features that combine lymphocytic vascular inflammation with changes representing a thrombophilic endovasculitis.

Background and objective Livedo reticularis racemosa and cerebrovascular lesions characterize Sneddon's syndrome. We report 23 patients with livedo racemosa and describe the association with thrombotic events. Our objective was to determine whether livedo racemosa may be an independent clinical marker for the development of thrombotic events in patients who test negative for anti-phospholipid antibodies. Methods Twenty-three patients with widespread livedo racemosa were studied. None of the patients were positive for anti-phospholipid antibodies. The clinical protocol included a register of thrombotic events, fetal death or miscarriages, hypertension, and valvular heart disease. Cerebral MRI and echocardiography were systematically performed in all patients. Results Nineteen patients (82.60%) had thrombotic events. Fifteen (65.21%) had arterial thrombosis and eleven (47.82%) presented venous occlusions. Seven patients (30.43%) had both arterial and venous thrombosis. Fetal losses were recorded in seven cases (30.43%), with a total number of 33; five patients had 3 or more fetal losses. Eleven out of 23 patients (47.82%) had valvular heart disease. Arterial hypertension was detected in 16 (69.56%) patients. Four patients did not have thrombotic events but had other clinical manifestations. After anti-coagulation therapy was withdrawn, a new thrombotic event was observed in 9 out of the 14 treated patients (64.28%). Conclusions Livedo racemosa seems to be a good clinical marker for the detection of hypercoagulable states even in the absence of anti-phospholipid antibodies or other known biologic markers of thrombosis. Long-term anti-coagulation is probably warranted in patients with livedo racemosa and a previous thrombotic event.

We report a 51-year-old woman who presented with dementia, livedo racemosa, polyarthralgia, mild renal insufficiency, proteinuria, and thrombocytopenia. Cutaneous and renal biopsy specimens both showed an identical specific occlusive arteriolopathy consistent with Sneddon syndrome and antiphospholipid syndrome. However, no antiphospholipid antibodies were detected and we, therefore, diagnosed seronegative antiphospholipid-like syndrome. We discuss the nosology of this entity and its association with non-antiphospholipid antibody–related Sneddon syndrome. The common denominator of Sneddon syndrome and antiphospholipid syndrome with or without antiphospholipid antibodies seems to be the endothelial damage and occlusive arteriolopathy. Skin biopsy is useful to confirm the diagnosis of seronegative antiphospholipid-like syndrome.

Sneddon syndrome is a rare disorder characterised by generalised livedo racemosa of the skin with extracutaneous neurological symptoms like headache, vertigo, transient ischaemic attacks (TIA), stroke, and seizures. Diagnosis of Sneddon syndrome is based on these clinical features and positive findings in skin biopsies, namely the histological proof of occlusion of arterioles by intimal proliferation. We describe three cases of young patients with clinical characteristics of Sneddon syndrome, but in only two cases could this diagnosis be confirmed by skin biopsies. These cases stress the difficulty of diagnosing Sneddon syndrome and show the additive value of skin biopsies in this process.

The results of investigations in 34 patients (28 women, 6 men) with livedo racemosa generalisata are presented. Neurologic or psychiatric symptoms were present in 28 patients. Nineteen patients had had one or more cerebral infarctions, and epilepsy (Sneddon's syndrome) developed in six. In most cases livedo preceded the neurologic disorder. In addition, many patients with livedo racemosa generalisata had Raynaud's phenomenon, cardiac abnormalities, or vascular changes in the ocular fundus.

Objective In 1931 Lindberg described a limited and benign subcutaneous form of panarteritis nodosa, which, in contrast to systemic panarteritis, only affects the skin. The terms panarteritis nodosa cutanea benigna, cutaneous polyarteritis nodosa, apoplexia cutanea Freund as well as livedo with nodules are used synonymously for this vasculitis which predominantly affects women in the fifth decade of life. Cutaneous lesions characteristically comprise painful subcutaneous nodules or vasculitis racemosa at the lower extremities. The cutaneous panarteritis may be regarded as its own entity or an isolated skin manifestation within systemic panarteritis nodosa. Methods Seven patients (M = 3, F = 4) presented with subcutaneous, painful nodules (n = 2), erythema and edema (n = 2) or livedo racemosa (n = 3) on the lower extremities. Histological examination revealed perivascular lymphocyte inflammatory infiltrates with fibrinoid necrosis and bulging of endothelial cells. In a direct immunofluorescence examination neither immunoglobulin nor complement deposits could be found. Serological autoimmune parameters, abdominal ultrasound examination, and chest X-rays showed no systemic manifestation. Erythrocyte sedimentation rate was slightly raised, and hepatitis B/C serology was negative. Results Topical corticosteroids under occlusion (n = 3), oral methyl-prednisolone (n = 4) in combination with either azathioprine (n = 4) or mycophenolate mofetil (n = 2) showed no relapses [follow up 28.43 (6–82) months]. Conclusion The etiology of panarteritis nodosa cutanea is unknown in detail. Both focal infections and hypersensitivity reactions are discussed. Differential diagnosis includes systemic panarteritis, livedo reticularis, Sneddon's syndrome or erythema nodosum. Despite the prognostically favorable but prolonged chronic course of the disease over decades, patients should be regularly examined to exclude possible transition to systemic disease.

Background Deficiency of adenosine deaminase 2 (DADA2) associated with mutations in the CECR1 gene causes a vasculopathy with systemic inflammation. The full clinical spectrum and management of these patients are yet to be defined. Objectives We aimed to assess the characteristics and course of our DADA2 patients and compare them to the cases in the literature. Methods This is a descriptive case series of Turkish patients diagnosed with DADA2 at the Hacettepe University. For mutation analysis we performed Sanger sequencing of 10 protein-coding exons of CECR1 . Results We report five Turkish patients with DADA2. All were initially diagnosed as polyarteritis nodosa (PAN) due to the systemic nature of their disease fulfilling the classification criteria for the disease and all but one having necrotizing arteritis lesions based on skin biopsy. Two had arterial aneurysms. All had skin lesions varying from livedo racemosa to necrotic ulcers on fingers. Four had varying features and degrees of central nervous system involvement. Mutation analysis showed homozygosity for the p.G47R (c. 139G>A) mutation in the CECR1 gene in all five patients. All were initially treated with corticosteroids; however none responded. One adult patient with extensive systemic amyloidosis was resistant to immunosuppressive and plasma treatments and died due to necrotizing pneumonia. The second adult patient partially improved with etanercept and plasmapheresis. The pediatric patients had better prognosis; one is on monthly plasma replacement and the other one on etanercept treatment with a good control of disease. The patient with a previous diagnosis of cutaneous PAN has responded to mycophenolate mofetil treatment. At literature review there are 44 DADA2 patients reported, including five ours. Patients who are homozygous for the p.G47R mutation have fewer strokes and predominantly a PAN-like phenotype compared to patients with other mutations. Conclusions DADA2 may be classified as a secondary vasculitis due to a probable cause. The response to immunosuppressive treatment and the B cell defects in these patients places the disease in between the spectrum of innate and adaptive immune dysregulation. A genotype-phenotype correlation may exist for DADA2, with the G47R mutation causing a predominantly PAN-like phenotype while other mutations causing predominantly a vasculopathy with central nervous system disease (especially strokes). References Navon Elkan P, Pierce SB, Segel R, et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med 2014;370(10):921-931 Zhou Q, Yang D, Ombrello AK, et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med 2014;370(10):911-920 Garg N, Kasapcopur O, Foster J, 2nd, et al. Novel adenosine deaminase 2 mutations in a child with a fatal vasculopathy. Eur J Pediatr 2014;173(6):827-830 Disclosure of Interest None declared

We report the case of a 37-year-old woman presenting with progressive livedo racemosa (panel A), limited physical capabilities and behavioural disorders. Cerebral magnetic resonance imaging (MRI) showed …

Livedo is a cutaneous sign of striking violaceous netlike patterned erythema of the skin. This dermatological phenomenon is of special interest in the differential diagnosis in neurological patients. In 1907 Ehrmann distinguished two different patterns of livedo: the pathological livedo racemosa and the physiological livedo reticularis. Despite important clinical differences, in the English language literature the heading livedo reticularis is still used for all types of livedo. A literature review about the spectrum of differential diagnosis in patients with livedo reticularis (especially cutis marmorata and amantadine-induced livedo reticularis) and livedo racemosa (especially Sneddon's syndrome, Divry-van Bogaert syndrome, systemic lupus erythematosus, antiphospholipid antibody syndrome, polyarteritis nodosa, cholesterol embolization syndrome, livedoid vasculopathy and haematological diseases) is provided.

Background— Sneddon’s syndrome is characterized by the association of ischemic cerebrovascular events and widespread livedo racemosa. The pathophysiology of Sneddon’s syndrome remains elusive, but various prothrombotic abnormalities have been previously reported in this setting. Low levels of protein Z, a downregulator of coagulation, have been recently linked to an increased risk of arterial thrombosis. The purpose of this study was to investigate the levels of protein Z in a series of Sneddon’s syndrome patients without circulating antiphospholipid antibodies in comparison with an age- and sex-matched control population. Methods— Twenty-six patients and 78 healthy controls had determination of their protein Z blood levels by an enzyme-linked immunoassay test. Patients’ thrombotic and vascular risk factors, including tobacco smoking, arterial hypertension, oral contraceptive agents, dyslipidemia, factor V Leiden, and factor II mutation were recorded. Results— Protein Z plasma levels were significantly lower in patients (mean 1.47 mg/L) than in controls (mean 1.93 mg/L) ( P =0.02). Prevalence of protein Z deficiency (level P =0.001) among patients (31%) than among controls (3.8%). Factor V Leiden and heavy smoking were observed in 4 and 7 patients, respectively. Conclusions— Sneddon’s syndrome could be viewed as the peculiar clinical expression of various and sometimes associated coagulation abnormalities. Low levels of protein Z may account, at least partly, for the thrombotic events observed in Sneddon’s syndrome and shed a new light on its pathophysiology. Clinical implications for protein Z deficiency in this setting deserve further investigations.

Vasculopathy is a not well–described presentation of neurofibromatosis type 1 in the dermatologic literature. We report a fatal case of neurofibromatosis vasculopathy in a 28-year-old woman who presented with skin ulcers and livedo racemosa; extensive gastrointestinal ulcers; and infarction of the bowel, liver, and spleen. Being alert to this manifestation may avoid unnecessary delay in diagnosis and enable, whenever possible, appropriate therapy.