Livedoid vasculopathy: A review with focus on terminology and pathogenesis.

Livedoid vasculopathy (LV) is a rare thrombotic vasculopathy of the dermis characterized by painful, relapsing ulcers over the lower extremities. Diagnosis is challenging due to the overlap in clinical appearance and nomenclature with other skin disorders. Treatment selection is complicated by poor understanding of the pathogenesis of LV and lack of robust clinical trials evaluating therapy efficacy. The terminology and pathophysiology of LV are reviewed here, along with its epidemiology, clinical and histologic features, and treatment options. A diagnostic pathway is suggested to guide providers in evaluating for comorbidities, referring to appropriate specialists, and choosing from the available classes of therapy.

In vitro diagnostics for the medical dermatologist. Part II: Hypercoagulability tests.

The skin often provides initial clues of hypercoagulability with features such as livedo reticularis, livedo racemosa, retiform purpura, necrosis, and ulcerations. Because these cutaneous manifestations are nonspecific, laboratory testing is often needed to evaluate for underlying causes of hypercoagulability. Importantly, these disorders are reported to be the most common mimicker, resulting in an erroneous diagnosis of pyoderma gangrenosum. Understanding inherent properties of, and indications for, available tests is necessary for appropriate ordering and interpretation of results. Additionally, ordering of these tests in an indiscriminate manner may lead to inaccurate results, complicating the interpretation and approach to management. This second article in this continuing medical education series summarizes information on methodology, test characteristics, and limitations of several in vitro laboratory tests used for the work up of hypercoagulability and vasculopathic disease as it pertains to dermatologic disease.

Development of sacral/buttock retiform purpura as an ominous presenting sign of COVID-19 and clinical and histopathologic evolution during severe disease course.

Retiform purpura has been described as a relatively frequent cutaneous finding in patients with coronavirus disease 2019 (COVID-19). The etiology is hypothesized to be related to thrombotic vasculopathy based on lesional biopsy specimen findings, but the pathogenesis of the vasculopathy is not completely understood. Here, we present a case of a retiform purpuric patch on the sacrum/buttocks in a hospitalized patient prior to subsequent diagnosis of COVID-19 and an eventual fatal disease course. Two lesional biopsy specimens at different time points in the disease course revealed thrombotic vasculopathy, despite therapeutic anticoagulation. Detailed histopathologic evaluation using immunohistochemical markers suggest the etiology of the vasculopathy involves both persistent complement activation and platelet aggregation, which possibly promote ongoing thrombus formation. This case highlights that sacral/buttock retiform purpuric patches may be a presenting sign of infection with SARS-CoV-2 virus and may represent an ominous sign supporting a future severe disease course. In addition, biopsy specimen findings at separate time points demonstrate that cutaneous vasculopathy may persist despite adequate systemic anticoagulation, possibly due to the combination of persistent complement and platelet activation. Finally, occlusive thrombi in sacral/buttock retiform purpuric patches may contribute to future ulceration and significant cutaneous morbidity in patients who survive COVID-19.

Investigating the spectrum of dermatologic manifestations in COVID-19 infection in severely ill patients: A series of four cases.

COVID-19, an infectious disease caused by the novel coronavirus, was initially identified in Wuhan, China, in December 2019. By March 2020, it was declared a pandemic by the World Health Organization. Although most findings have been reported in the lungs, primarily due to catastrophic respiratory decline, other organs, including the skin, are affected. Recent reports have been published describing the clinical spectrum of COVID-19-related lesions. In addition, recent case series have described a subset of these lesions having underlying thrombotic microangiopathy with increased complement activation characterized by increased C4d deposition within the blood vessel walls. Herein, we describe a series of COVID-19-related cutaneous manifestations found at autopsy examination and their underlying histopathologic findings. Although the clinical manifestations seen in these lesions vary widely, the underlying etiology of thrombotic microangiopathy remains consistent and reproducible.

Lupus erythematosus: Significance of dermatologic findings.

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.

Do Doppler Changes Reflect Pathology of Placental Vascular Lesions in IUGR Pregnancies?

OBJECTIVES: Doppler assessment of uteroplacental (UP) and fetoplacental (FP) circulation detects abnormal waveforms in intrauterine growth-restricted (IUGR) pregnancies. Similarly, histopathology also reveals lesions of vascular compromise in IUGR placenta. We evaluated an association between Doppler and histopathological (HP) assessment of the maternal and fetal circulation in IUGR. METHODS: IUGR cases with both Doppler and histopathology assessment were selected from our database. Doppler patterns recorded UP and FP insufficiency. The HP vascular lesions were classified as maternal vascular underperfusion and fetal thrombotic vasculopathy (FTV). IUGRs were grouped based on (i) presence of preeclampsia (PE), (ii) clinical onset (early vs late) of IUGR (early onset [EO]/late onset), and (iii) gestational age (term, T/preterm, PT). RESULTS: Abnormal Doppler waveforms were present in 69 of the total 88 IUGR cases (78.4%). The most frequent pattern was fetoplacental insufficiency (FPI) (66%) which was combined with uteroplacental insufficiency (UPI) in 49%. HP showed vascular lesions in 52.3% and most frequent was FTV (38%). PE-associated IUGR (n = 49) had higher UPI pattern (75.5% vs 43.6%, P = .004), while normotensive IUGR had higher FPI pattern (28.2% vs 8.2%, P = .01). EO-IUGR (n = 55) and PT-IUGR (n = 52) had significant abnormal Doppler waveforms (P < .05) with higher combined patterns and brain sparing. Doppler was more sensitive for fetal vascular lesions than maternal (75.8% vs 66.7%). However, 42% of cases with normal Doppler findings showed HP vascular lesions. CONCLUSION: IUGR pregnancies harbor significant vascular compromise. Fetal circulatory lesions were more common in IUGR pregnancies. In a significant number of cases with normal Doppler report, vascular lesions were identified on histopathology, emphasizing placental examination in all cases of IUGR.

The Placenta in Neonatal Encephalopathy: A Case-Control Study.

OBJECTIVE: We assessed whether specific histologic placental lesions were associated with risk for neonatal encephalopathy, a strong predictor of death or cerebral palsy. STUDY DESIGN: Case-control study of singletons with gestational ages ≥35 weeks. Data were abstracted from a prospectively collected database of consecutive births at a hospital in which placental samples from specified sites are collected and stored for all inborn infants. Placentas of infants with neonatal encephalopathy were compared with randomly selected control infants (ratio of 1:3). Placental histologic slides were read by a single experienced perinatal pathologist unaware of case status, using internationally recommended definitions and terminology. Findings were grouped into inflammatory, maternal, or fetal vascular malperfusion (FVM) and other lesions. RESULTS: Placental samples were available for 73 of 87 (84%) cases and 253 of 261 (97%) controls. Delivery complications and gross placental abnormalities were more common in cases, of whom 4 died. Inflammation and maternal vascular malperfusion did not differ, and findings consistent with global FVM were more frequent in case (20%) than control (7%) placentas (P = .001). There was a trend toward more segmental FVM and high-grade FVM (fetal thrombotic vasculopathy) among cases. Some type of FVM was observed in 24% of placentas with neonatal encephalopathy. In infants with both neonatal encephalopathy and placental FVM, more often than in infants with neonatal encephalopathy without FVM, electronic fetal monitoring tracings were considered possibly or definitely abnormal (P = .028). CONCLUSIONS: Vascular malperfusion of subacute or chronic origin on the fetal side of the placenta was associated with increased risk of neonatal encephalopathy.

Placental hypoxic overlap lesions: a clinicoplacental correlation.

AIM: This retrospective analysis is aimed to study clinical and placental associations of placental acute, chronic, and acute-on-chronic (overlap) hypoxic lesions. MATERIAL AND METHODS: Frequencies of 32 clinical (maternal and fetal) and 47 placental (gross and microscopic) phenotypes were compared by the Yates χ(2) with the Holm-Bonferroni correction among consecutive placentas from 2831 ≥ 16-week gestations: 778 placentas with chronic hypoxic lesion(s) (diffuse patterns of hypoxic placental injury, chorangiosis, excessive extravillous trophoblasts, microscopic chorionic pseudocysts, clusters of decidual multinucleate trophoblasts), 481 placentas with acute hypoxic lesion(s) (infarction, intravillous hemorrhage, deep meconium penetration, membrane laminar necrosis), 585 placentas with hypoxic overlap lesion(s) (coexisting at least one lesion from each of the above groups), and 987 placentas without placental hypoxic lesions, adjusted for gestational age. RESULTS: The control group was dominated by premature rupture of membranes, inflammatory pattern of placental injury, and poor prenatal care. The fetal and placental hypoxic patterns were associated not only with increased frequency of clinical hypoxia-associated conditions, but also abnormal umbilical cord coiling, intervillous thrombi, retroplacental hematomas, and placental features of fetal thrombotic vasculopathy, particularly in association with hypoxic overlap lesions. CONCLUSION: Placental hypoxic overlap lesions are associated with clinical complications of pregnancy and predispose to thrombotic lesions, some most likely stasis-induced.

Efficacy of intravenous immunoglobulins in livedoid vasculopathy: long-term follow-up of 11 patients.

BACKGROUND: Evidence for the efficacy of various therapies of livedoid vasculopathy (LV) is limited. OBJECTIVE: We sought to determine efficacy and tolerability of 2 g/kg of intravenous immunoglobulins (IVIG) every 4 weeks in patients with LV. METHODS: This was a long-term follow-up study of 11 patients with LV treated with 2 g/kg of IVIG assessing the clinical characteristics, disease course, and quality of life. RESULTS: The treatment regimen led to complete remission of ulcerations and pain in 17 of 29 disease episodes (59%) after 3 cycles and in 25 of 29 episodes (86%) after 6 cycles. Two disease episodes showed remission after 7 and 8 cycles, resulting in a total number of remissions of 27 (93%). Subscore analysis showed resolution of pain in 80% after 2 IVIG cycles. Disease severity and quality of life were significantly improved after 6 cycles. Median duration of remissions was 26.7 months after initial and 7.5 months after subsequent disease episodes. LIMITATIONS: This was a retrospective study that did not include the comparison of IVIG efficacy and its impact on quality of life with treatment options. CONCLUSIONS: In our patients with LV, high-dose IVIG led to fast and complete resolution of pain and ulcerations and to substantial improvement in quality of life.

Umbilical artery thrombosis and maternal positive autoimmune antibodies: two case reports and a literature review.

Background: Previous studies have shown that abnormal increases in autoimmune antibodies in pregnant women may increase the risk of maternal thrombosis. However, at our hospital, two pregnant women presented with umbilical artery thrombosis and positive maternal autoantibodies were detected in both, which led us to consider whether maternal autoantibodies also played a role in umbilical artery thrombosis. Case presentation: Case 1: Fetal ultrasound of a 34-year-old pregnant woman at 30+4 weeks gestation showed two umbilical arteries, with an inner diameter of approximately 0.15 cm for the smaller was artery. However, only a single umbilical artery blood flow signal was detected. Due to fetal distress, which was noted on abnormal cardiotocography and Doppler ultrasound, an emergency cesarean section was performed at 31+1 weeks gestation. The Apgar score of the newborn was 3-8-8. Umbilical cord examination detected thrombosis in the two umbilical arteries. Moreover, blood test results during pregnancy showed nRNP/Sm antibody (+) and SS antibody (+++). Case 2: The first systematic ultrasound of a 33-year-old twin pregnancy at 24+3 weeks gestation was normal, but routine fetal ultrasound at 27+1 weeks gestation showed only one umbilical artery between fetus A and the placenta. Blood test results showed that the patient was anti-nRNP/Sm antibody (+) in the rheumatoid immune activity test at 27+3 weeks gestation. An emergency cesarean section was performed at 34+6 weeks gestation because of the single umbilical artery and abnormal maternal coagulation. Both umbilical cords of fetus A and B blood test results showed anti-nRNP/Sm antibody (++). The pathological examination of the umbilical cord and placenta showed the presence of old thrombosis in one of the umbilical arteries of fetus A. Conclusions: Abnormal maternal autoantibodies may be a risk factor for umbilical artery thrombosis. For these pregnant women, conducting more detailed ultrasound monitoring might get early detection of UAT formation and avoid the occurrence of adverse pregnancy outcomes.

A Diagnostic Dilemma of a Case of Granulomatosis With Polyangiitis (GPA) Presenting With Thrombotic Vasculopathy.

Granulomatosis with polyangiitis (GPA) is a rare disease with a prevalence of about three in 100,000 persons in the United States. GPA is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis affecting predominantly small-sized vessels. It can present with localized or systemic symptoms with multiple organ involvement, thus making diagnosis challenging. Common skin lesions in GPA are palpable purpura, petechiae, ulcers, and livedo reticularis. These lesions usually have underlying vasculitis with or without granuloma on histology findings. To date, there have been no previous reports about thrombotic vasculopathy in GPA before. We present a case of a 25-year-old female who presented with intermittent joint pain for weeks, purpuric rash, and mild hemoptysis for a few days. A review of systems was notable for a 15-pound weight loss in one year. Physical examination was significant for a purpuric rash on the left elbow and toe, and left knee swelling and erythema. Presenting laboratory results were notable for anemia, indirect hyperbilirubinemia, mildly elevated D-dimers, and microscopic hematuria. Chest radiograph revealed confluent airspace disease. Extensive infectious workup was negative. A skin biopsy of her left toe revealed dermal intravascular thrombi without evidence of vasculitis. The thrombotic vasculopathy did not favor vasculitis but raised concern for a hypercoagulable state. However, extensive hematologic workup was negative. Bronchoscopy findings were consistent with diffuse alveolar hemorrhage. Later, cytoplasmic ANCA (c-ANCA) and anti-proteinase 3 (PR3) antibody titers were positive. Her diagnosis was unclear since both skin biopsy and bronchoscopy were nonspecific and inconsistent with her positive antibody results. The patient eventually underwent a kidney biopsy, which showed pauci-immune necrotizing and crescentic glomerulonephritis. Finally, a diagnosis of granulomatosis with polyangiitis was made based on the kidney biopsy and positive c-ANCA. The patient was treated with steroids and IV rituximab and discharged home with outpatient rheumatology follow-up. Due to multiple signs and symptoms including thrombotic vasculopathy, there was a diagnostic dilemma requiring a multidisciplinary approach. This case highlights the importance of pattern recognition for the diagnostic framework of rare disease entities and the multidisciplinary collaborative efforts required to reach the final diagnosis.

Case report: A case of fetal umbilical vein varix presenting disseminated intravascular coagulation, polycythemia, and neonatal hepatitis in an extremely low birth weight infant.

Reports on the clinical course of fetal umbilical vein varix in premature infants are limited. We report a case of an extremely low body weight infant with intra-abdominal umbilical vein varix who developed disseminated intravascular coagulation, polycythemia, and hyperbilirubinemia after birth; late-onset neonatal hepatitis; and fetal thrombotic vasculopathy confirmed by placental histopathology. Ultrasonography after birth showed a dilated portion of the umbilical vein at the hepatic hilum with thrombi inside. We speculate that the umbilical vein varix caused the fetal thrombotic vasculopathy, and the presence of umbilical vein varix and fetal thrombotic vasculopathy in combination with prematurity caused coagulopathy, polycythemia, hyperbilirubinemia, and hepatitis. Despite the favorable outcomes reported in the literature, premature infants with umbilical vein varix may require careful observation and management for coagulopathy and late-onset hepatitis. Furthermore, placental histopathology could aid in the understanding of various clinical outcomes in infants with umbilical vein varices.

Abnormal thrombosis and neutrophil activation increase hospital-acquired sacral pressure injuries and morbidity in COVID-19 patients.

Hospitalized patients have an increased risk of developing hospital-acquired sacral pressure injury (HASPI). However, it is unknown whether SARS-CoV-2 infection affects HASPI development. To explore the role of SARS-CoV-2 infection in HASPI development, we conducted a single institution, multi-hospital, retrospective study of all patients hospitalized for ≥5 days from March 1, 2020 to December 31, 2020. Patient demographics, hospitalization information, ulcer characteristics, and 30-day-related morbidity were collected for all patients with HASPIs, and intact skin was collected from HASPI borders in a patient subset. We determined the incidence, disease course, and short-term morbidity of HASPIs in COVID-19(+) patients, and characterized the skin histopathology and tissue gene signatures associated with HASPIs in COVID-19 disease. COVID-19(+) patients had a 63% increased HASPI incidence rate, HASPIs of more severe ulcer stage (OR 2.0, p<0.001), and HASPIs more likely to require debridement (OR 3.1, p=0.04) compared to COVID-19(-) patients. Furthermore, COVID-19(+) patients with HASPIs had 2.2x increased odds of a more severe hospitalization course compared to COVID-19(+) patients without HASPIs. HASPI skin histology from COVID-19(+) patients predominantly showed thrombotic vasculopathy, with the number of thrombosed vessels being significantly greater than HASPIs from COVID-19(-) patients. Transcriptional signatures of a COVID-19(+) sample subset were enriched for innate immune responses, thrombosis, and neutrophil activation genes. Overall, our results suggest that immunologic dysregulation secondary to SARS-CoV-2 infection, including neutrophil dysfunction and abnormal thrombosis, may play a pathogenic role in development of HASPIs in patients with severe COVID-19.

Levamisole-Adulterated Cocaine-Induced Thrombotic Vasculopathy With Negative Serology.

Substance abuse is an important public health issue in the United States. The prevalence of cocaine use is wide, and it is noted to be adulterated with a substance called levamisole, which can increase the bulk and possibly potentiate cocaine's euphoric effect. Literature shows that levamisole-induced vasculopathy has a strong association with antineutrophil cytoplasmic antibodies (ANCA) antibodies. However, we report a case of biopsy-confirmed levamisole-related thrombotic vasculopathy with negative perinuclear antineutrophil cytoplasmic antibody (p-ANCA) and cytoplasmic antineutrophil cytoplasmic autoantibody (c-ANCA) antibodies. Our case highlights the serious consequences of substance abuse. Here, we provide educational value and encourage physicians to keep the differentials broad when encountering a dermatological case in patients with cocaine use and highlight the importance of skin biopsy for the diagnosis and appropriate management.

Neonatal thrombosis.

Neonatal thromboembolism in pediatric patients is a rare but life-threatening condition mainly caused by combinations of at least 2 prothrombotic triggering risk factors such as the central venous lines, septic condition, and prematurity. Other risk factors include asphyxia, dehydration, liver dysfunction, inflammation, and maternal condition. Neonatal hemostatic system is different from one of the older children and adults. Coagulation proteins do not cross the placenta but are synthesized in the fetus from an early stage. In the term neonate, concentrations of several procoagulant proteins, particularly the vitamin K dependent and contact factors are reduced when compared with adults. Conversely, levels of antithrombin, heparin cofactor II and protein C and S are low at birth and fibrinolysis system is characterized by the decreased level of plasminogen and alpha-1-antiplasmin, increased tissue plasminogen activator. These features all tend to be gestational dependent and are more present in the preterm infant. Primarily in this context neonates appear to be at a higher risk of thrombosis than older children. Thrombotic complications reach their peak in the group of children born at 22-27 weeks. The role of inherited thrombophilic risk factors in neonatal VTE development is poorly defined. The presence of inherited and acquired thrombophilia in mother and newborn is also responsible for the development of thrombosis in neonates and should be considered. Thrombophilia in the mother can lead to increased coagulation potential and prethrombotic conditions during pregnancy, causing thrombotic vasculopathy at the placental level. The benefit of identifying thrombophilia in the sick preterm newborns who are in the group of risk for development of thrombotic complications may facilitate the thromboprophylaxis. Further research regarding assessment of risk factors, diagnostics and treatment strategy is required.

Histopathologic evaluation of placentas after diagnosis of maternal severe acute respiratory syndrome coronavirus 2 infection.

Background: The impact of maternal severe acute respiratory syndrome coronavirus 2 infection on placental histopathology is not well known. Objective: To determine if any significant placental histopathologic changes occur after the diagnosis of severe acute respiratory syndrome coronavirus 2 infection during pregnancy and whether these changes are correlated with the presence or absence of symptoms associated with the infection. Study Design: A retrospective cohort study of women diagnosed as having severe acute respiratory syndrome coronavirus 2 infection who delivered at a single center from April 9, 2020 to April 27, 2020, and had placental specimens reviewed by the Department of Pathology. Women with singleton gestations and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection were eligible for inclusion. Historical controls selected from a cohort of women who delivered 6 months before the study period were matched in a 1:1 fashion by weeks of gestation at delivery. Histopathologic characteristics were evaluated in each placenta, and the incidence of these findings was compared between placentas of those who received a diagnosis of maternal severe acute respiratory syndrome coronavirus 2 infection and historical controls, and between placentas from patients with or without typical symptoms related to the infection. Statistical analyses included the use of Wilcoxon rank-sum test and Fisher's exact test for the comparison of categorical and continuous variables. Statistical significance was defined as a P value of <.05. Results: A total of 50 placentas after the diagnosis of maternal severe acute respiratory syndrome coronavirus 2 infection and 50 historical controls were analyzed. Among the placentas from patients diagnosed with severe acute respiratory syndrome coronavirus 2 infection, 3 (6%) were preterm (33 3/7, 34 6/7, and 36 6/7 weeks of gestation), 16 (32%) were from patients with typical symptoms related to the infection, and 34 (68%) were from patients without typical symptoms related to the infection. All patients had received a diagnosis of severe acute respiratory syndrome coronavirus 2 infection in the third trimester. Decidual vasculopathy was not visualized in any of the placentas from patients diagnosed as having severe acute respiratory syndrome coronavirus 2 infection. There was no statistically significant difference in placental histopathologic characteristics between the groups. Severe acute respiratory syndrome coronavirus 2 test results for all neonates at 24 hours of life were negative. Conclusion: Based on the results of this study, there are no significant placental histopathologic changes that occur after the diagnosis of severe acute respiratory syndrome coronavirus 2 infection in women during the third trimester of pregnancy compared with a gestational age-matched historical control group. Similar incidences of histopathologic findings were also discovered when comparing placentas from patients with severe acute respiratory syndrome coronavirus 2 infection with or without the presence of symptoms typically related to the infection.

Levamisole-induced vasculopathy: A systematic review.

OBJECTIVE: To characterize levamisole-induced vasculopathy. METHODS: We performed a systematic review searching MEDLINE for articles published from 1972 to 2016. RESULTS: We retrieved 357 references and abstracts and selected 111 articles. Levamisole-induced vasculopathy was reported in 192 patients, with a female predominance (n = 122, 63.5%). Median [interquartile range] age was 44 [38-50]. Skin was the most frequently involved organ (n = 182, 94.8%). Cutaneous lesions were mostly on the face (n = 136, 70.8%), especially the ears. Purpura (n = 131, 68.2%) was the most reported cutaneous lesion. Organ involvement included acute renal failure (n = 24, 12.5%), and pulmonary involvement (n = 20, 10.4%). Anti-neutrophil cytoplasmic antibodies (ANCAs) were found in 167/178 patients (93.8%), with both anti-myeloperoxydase and anti-proteinase 3 specificity reported in 51/118 patients (43.2%). Anti-phospholipid (APL) antibodies were found in 93/137 patients (67.9%). Leukopenia was detected in 69/138 patients (50%). Skin biopsies identified vasculitis and thrombotic vasculopathy in 73/148 (49.3%) and 62/148 (41.9%) patients, respectively. The outcome was favourable in 116/134 patients (86.6%), but relapses were reported in 33 (28.4%), mainly on levamisole re-exposure. CONCLUSION: Levamisole-induced vasculopathy is characterized by a female predominance, skin involvement, ANCA and/or APL antibody positivity, leukopenia, vasculitis or vascular thrombotic histological lesions, and despite possible systemic involvement, a favourable outcome with levamisole interruption.

Fetal vascular malperfusion, an update.

Fetal vascular malperfusion is the most recent term applied to a group of placental lesions indicating reduced or absent perfusion of the villous parenchyma by the fetus. The most common etiology of malperfusion is umbilical cord obstruction leading to stasis, ischemia, and in some cases thrombosis. Other contributing factors may include maternal diabetes, fetal cardiac insufficiency or hyperviscosity, and inherited or acquired thrombophilias. Severe or high grade fetal vascular malperfusion is an important risk factor for adverse pregnancy outcomes including fetal growth restriction, fetal CNS injury, and stillbirth. Overall recurrence risk for subsequent pregnancies is low.

Neonatal renal and inferior vena cava thrombosis associated with fetal thrombotic vasculopathy: a case report.

BACKGROUND: Fetal thrombotic vasculopathy is a described placental diagnosis associated with adverse perinatal outcomes. It may also predispose children to somatic thromboembolic events. As far as we know, this is the first case of inferior vena cava thrombosis associated with fetal thrombotic vasculopathy in a completely asymptomatic newborn. CASE PRESENTATION: We report the case of an asymptomatic, full-term Turkish male neonate delivered at 39 weeks of gestation diagnosed as having thrombosis of the renal vein and inferior vena cava. Diagnosis was guided only by the presence of edematous umbilical cord with macroscopic signs of clotting and, subsequently, microscopic features of the placenta, suggesting fetal thrombotic vasculopathy. CONCLUSIONS: Thrombosis of the renal and inferior vena cava in our healthy, asymptomatic full-term neonate is clearly associated with fetal thrombotic vasculopathy. The diagnosis of thrombosis in this neonate was incidental. This suggests that fetal thrombotic vasculopathy may cause unrecognized neonatal thrombosis. Untreated neonatal thrombosis may later compromise growth and function of the involved organs; therefore, maintaining a high index of suspicion based on thrombotic vasculopathy is paramount.