Medium-sized Vessels Research Articles

TNF-α blockers for the treatment of Kawasaki disease in children

Kawasaki disease (KD) is an acute inflammatory vasculitis (inflammation of the blood vessels) that mainly affects children between six months and five years of age. The vasculitis primarily impacts medium-sized blood vessels, especially in the coronary arteries. In most children, intravenous immunoglobulin (IVIG) and aspirin therapy rapidly reduce inflammatory markers, fever, and other clinical symptoms. However, approximately 15% to 20% of children receiving the initial IVIG infusion show persistent or recurrent fever and are classified as IVIG-resistant. Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine that plays an important role in host defence against infections and in immune responses. Several studies have established that blocking TNF-α is critical for obtaining anti-inflammatory effects in children with KD, thus, there is a need to identify benefits and risks of TNF-α blockers for the treatment of KD. To evaluate the efficacy and safety of using TNF-α blockers (i.e. infliximab and etanercept) to treat children with Kawasaki disease. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 19 September 2018. We also undertook reference checking of grey literature. We included randomised controlled trials (RCTs) that compared TNF-α blockers (i.e. infliximab and etanercept) to placebo or other drugs (including retreatment with IVIG) in children with KD, reported in abstract or full-text. Two review authors independently applied the study selection criteria, assessed risk of bias and extracted data. When necessary, we contacted study authors for additional information. We used GRADE to assess the certainty of the evidence. We included five trials from 14 reports, with a total of 494 participants. All included trials were individual RCTs that examined the effect of TNF-α blockers for KD.Five trials (with 494 participants) reported the incidence of treatment resistance. TNF-α blockers reduced the incidence of treatment resistance (TNF-α blocker intervention group 30/237, control group 58/257; risk ratio (RR) 0.57, 95% confidence interval (CI) 0.38 to 0.86; low-certainty evidence).Four trials reported the incidence of coronary artery abnormalities (CAAs). Three trials (with 270 participants) contributed data to the meta-analysis, since we could not get the data needed for the analysis from the fourth trial. There was no clear difference between groups in the incidence of CAAs (TNF-α blocker intervention group 8/125, control group 9/145; RR 1.18, 95% CI 0.45 to 3.12; low-certainty evidence).Three trials with 250 participants reported the adverse effect 'infusion reactions' after treatment initiation. The TNF-α blocker intervention decreased infusion reactions (TNF-α blocker intervention group 0/126, control group 15/124; RR 0.06, 95% CI 0.01 to 0.45; low-certainty evidence).Two trials with 227 participants reported the adverse effect 'infections' after treatment initiation. There was no clear difference between groups (TNF-α blocker intervention group 7/114, control group 10/113; RR 0.68, 95% CI 0.33 to 1.37; low-certainty evidence).One trial (with 31 participants) reported the adverse effect 'cutaneous reactions' (rash and contact dermatitis). There was no clear difference between the groups for incidence of rash (TNF-α blocker intervention group 2/16, control group 0/15; RR 4.71, 95% CI 0.24 to 90.69; very low-certainty evidence) or for incidence of contact dermatitis (TNF-α blocker intervention group 1/16, control group 3/15; RR 0.31, 95% CI 0.04 to 2.68; very low-certainty evidence).No trials reported other adverse effects such as injection site reactions, neutropenia, infections, demyelinating disease, heart failure, malignancy, and induction of autoimmunity. We found a limited number of RCTs examining the effect of TNF-α blockers for KD. In summary, low-certainty evidence indicates that TNF-α blockers have beneficial effects on treatment resistance and the adverse effect 'infusion reaction' after treatment initiation for KD when compared with no treatment or additional treatment with IVIG. Further research will add to the evidence base. Due to the small number of underpowered trials contributing to the analyses, the results presented should be treated with caution. Further large high quality trials with timing and type of TNF-α blockers used are needed to determine the effects of TNF-α blockers for KD.

Very painful acute frontal sinusitis revealing granulomatosis with polyangiitis

IntroductionGranulomatosis with polyangiitis (GPA) is a necrotizing vasculitis of small and medium-sized vessels comprising inflammation of the vessel wall and perivascular and extravascular granulomas, frequently presenting in the form of chronic sinusitis. ObservationWe report the case of a 27-year-old man who presented with very painful acute frontal sinusitis that was managed medically and surgically. The symptoms rapidly recurred despite treatment and CT scan demonstrated diffuse thickening of the sinus mucosa. Anti-proteinase 3 ANCA were positive. Biopsy of a pulmonary nodule confirmed the diagnosis of GPA. The patient was treated with corticosteroids in combination with rituximab, resulting in improvement of the clinical, laboratory and CT signs. DiscussionIn the presence of persistent, acute, localized sinusitis despite appropriate treatment, associated systemic signs and/or the presence of other signs suggestive of GPA, the ENT surgeon must request a targeted work-up. In the absence of treatment, GPA can be fatal within a few months. However, with currently available treatment, remission is obtained in 80% of cases with a 75% 10-year survival rate.

Case report of a 28-year-old man with aortic dissection and pulmonary shadow due to granulomatosis with polyangiitis

BackgroundGranulomatosis with polyangiitis (GPA) is characterised by the main violation of the upper and lower respiratory tract and kidney. GPA is considered a systemic vasculitis of medium-sized and small blood vessels where aortic involvement is extremely rare.Case presentationA 28-year-old male was admitted to the hospital due to 4 h of chest pain. Computed tomography scan of the aorta showed a thickened aortic wall, pulmonary lesions, bilateral pleural effusion and pericardial effusion. The aortic dissection should be considered. An emergency operation was performed on the patient. Surgical biopsies obtained from the aortic wall showed destructive changes, visible necrosis, granulation tissue hyperplasia and a large number of acute and chronic inflammatory cells. Nearly a year later, the patient was re-examined for significant pulmonary lesions. His laboratory studies were significantly positive for anti-neutrophilic antibody directed against proteinase 3. Finally, the diagnosis of GPA was obviously established.ConclusionsAlthough GPA rarely involves the aorta, we did not ignore the fact that GPA may involve large blood vessels. In addition, GPA should be included in the systemic vasculitis that can give rise to aortitis and even aortic dissection.

Hyaline vascular variant of unicentric Castleman disease of the tonsil: a case report

BackgroundCastleman disease (CD) is a lymphoproliferative disorder with an unknown etiology. The disease may be unicentric (UCD) or multicentric (MCD), and three histopathologic variants have been described: hyaline vascular (HV), plasma cell (PC), and mixed type. Extranodal CD is rare. Herein, we report a case of CD presenting as a tonsillar mass, which has not been documented in the literature.Case presentationThe patient was a 32-year-old man. Laryngoscopy revealed tonsillar hypertrophy, and the patient underwent a low-temperature plasma tonsillectomy. Microscopic examination of permanent sections showed lymphoid follicular hyperplasia, a portion of which appeared to be a fusion of nodular hyperplasia (composed of lymphoid follicles of variable size and shape). These distinctive follicles with atrophic hyalinized germinal centers and a broad mantle zone of small lymphocytes formed concentric rings (so-called onion-skin arrangement). Medium-sized vessels and a plethora of capillaries were present in the center of the lymphatic follicles, mantle zones, and interfollicular areas. A characteristic lollipop appearance was also observed due to the onion-skin arrangement of the expanded mantle zone lymphocytes with a vessel penetrating the germinal center. No aberrant lymphoid population was present based on CD3, CD5, CD20, CD79α, CD21, CD23, bcl-2, cyclin D1, and ki-67 immunostaining. Tests for human herpesvirus (HHV)-8 and Epstein Barr virus (EBV)-encoded small RNA (EBER) were negative. Therefore, a diagnosis of an HV variant UCD was rendered. The patient was treated by local excision without any other therapy based on the diagnosis. At the 7-month follow up, the patient had no recurrent symptoms or masses.ConclusionWe present an unusual case of a tonsil presenting hyaline vascular Castleman disease (HVCD). This study aims to highlight CD as a differential diagnosis that should be considered by otolaryngologists and pathologists for lymphoproliferative disorders of the tonsil.

Exclusively ocular and cardiac manifestation of granulomatosis with polyangiitis \u2013 a case report

BackgroundGranulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibodies (ANCA)-associated necrotizing granulomatous vasculitis that affects small to medium size vessels. While the classical form with renal and respiratory tract involvement is mainly seen, a limited form (i.e., with no renal disease) may also occur. We present an unusual case of GPA manifesting merely as a bilateral ocular involvement and complete heart block.Case presentationWe report a case of a 60-year-old male patient with a limited form of GPA who initially presented with bilateral chronic conjunctivitis and complete atrioventricular block. His visual acuity subsequently declined due to progression to bilateral panuveitis with exudative retinal detachment. The laboratory investigation revealed the elevation of acute phase reactants and strongly positive cytoplasmic ANCA (c-ANCA). Despite negative conjunctival and musculocutaneous biopsy results, the positive c-ANCA, and the clinical manifestation, i.e., heart and ocular involvement, led to the diagnosis of GPA. The remission was achieved with cyclophosphamide and methylprednisolone systemic therapy.ConclusionsA limited form of GPA may be a diagnostic chameleon. Though rare, it is essential to consider even extremely uncommon findings. Our patient is the first case of such a unique demonstration of the limited GPA manifesting as a bilateral ocular involvement and complete heart block.

A methodology based on data filtering to identify reference fleets to account for the abundance of fish species: Application to the Striped red mullet (Mullus surmulletus) in the Bay of Biscay

For data-limited stocks (DLS), professional fishing data can be used as a potential source of information, especially in the absence of appropriate scientific survey, to understand abundance evolution under realistic hypothesis on resource catchability. This work focuses on a data-filtering approach, the selected fishing effort must reflect vessel activity that is least dependent on their technical characteristics and as stable as possible over time. The variable of interest is landing by fishing sequence (landing for a given gear, gear mesh, day and ICES statistical rectangle) called LPUE. In order to account for the abundance of the species, it was necessary to consider the discards. The method thus proceeds in 4 steps: (i) focus on LPUE variability and causes' prioritization; (ii) cluster definition to obtain a typology of vessels; (iii) average LPUE per cluster analysis; (iv) consideration of gear mesh classes and seasonal variations (quarters). This approach is outlined for the Striped red mullet of the Bay of Biscay that is currently in DLS category 5. Two reference fleets are thereby proposed: firstly the otter trawlers composed of small vessels (7.9–15.8 m) with a gauge of 2–43.9 grt, an engine power between 44 and 256 kW and a gear mesh of 70–79 mm; secondly the set gillnetters, which are defined by medium-sized vessels (8.2–14.8 m, 2–30.2 grt, 70–331 kW) whose gear mesh is either 50–59 mm (2nd and 3rd quarters), 60–69 mm (2nd quarter) or greater than 90 mm (2nd quarter). LPUEs of these fleets show a downward trend, significant in two out of four cases which may reflect a deterioration of the status of the Striped red mullet stock.

Differentiation of Vascular Characteristics Using Contrast-Enhanced Ultrasound Imaging

Ultrasound contrast imaging has been used to assess tumour growth and regression by assessing the flow through the macro- and micro-vasculature. Our aim was to differentiate the blood kinetics of vessels such as veins, arteries and microvasculature within the limits of the spatial resolution of contrast-enhanced ultrasound imaging. The highly vascularised ovine ovary was used as a biological model. Perfusion of the ovary with SonoVue was recorded with a Philips iU22 scanner in contrast imaging mode. One ewe was treated with prostaglandin to induce vascular regression. Time-intensity curves (TIC) for different regions of interest were obtained, a lognormal model was fitted and flow parameters calculated. Parametric maps of the whole imaging plane were generated for 2 × 2 pixel regions of interest. Further analysis of TICs from selected locations helped specify parameters associated with differentiation into four categories of vessels (arteries, veins, medium-sized vessels and micro-vessels). Time-dependent parameters were associated with large veins, whereas intensity-dependent parameters were associated with large arteries. Further development may enable automation of the technique as an efficient way of monitoring vessel distributions in a clinical setting using currently available scanners.

A delayed diagnosis of eosinophilic granulomatosis with polyangiitis complicated with extensive artery occlusion of lower extremities in children: case report and literature review

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis in children. A delayed or missed diagnosis of pediatric EGPA is common, owing to the atypical clinical manifestation and limited recognition of this disorder. The vasculitis in EGPA typically involves small to medium size vessels. Extensive occlusion of arteries in the extremities was being extremely rare and has never been reported in children.Case presentationA 10-year and 10-month-old girl with recurrent wheezing and breathlessness during exercise, was initially diagnosed with asthma at the age of five years. Despite unexplained manifestations, including intermittent remarkably increased eosinophilia, uncontrolled allergic rhinitis, and recurrent petechia, from the onset of asthma through to its remission, the consideration of EGPA was completely ignored until the patient presented with aggravated petechia and severe ulceration of the lower extremities, associated with extensive stenosis and/or occlusion of the arteries of the shank and foot. Given her history of asthma, eosinophilia, allergic rhinitis, mononeuropathy, pulmonary infiltrates, and vasculitis confirmed by the skin biopsy, the diagnosis of EGPA was ultimately confirmed. Regrettably, the initial inappropriate and irrational use of corticosteroid failed to relieve the symptoms until more aggressive treatment with intravenous methylprednisolone was started. This was followed by methotrexate treatment, with tapering of prednisone, without relapse over a six-month follow-up.ConclusionsPediatric rheumatologists should be alert to the possibility of EGPA in children with refractory asthma associated with unexplained manifestations, and should be aware of the thromboembolic complications as vascular sequelae of EGPA.

Localization, Morphologic Features, and Chemical Composition of Calciphylaxis-Related Skin Deposits in Patients With Calcific Uremic Arteriolopathy

Calcific uremic arteriolopathy (CUA), a rare, potentially fatal, disease with calcium deposits in skin, mostly affects patients with end-stage renal disease who are receiving dialysis. Chemical composition and structure of CUA calcifications have been poorly described. To describe the localization and morphologic features and determine the precise chemical composition of CUA-related calcium deposits in skin, and identify any mortality-associated factors. A retrospective, multicenter cohort study was conducted at 7 French hospitals including consecutive adults diagnosed with CUA between January 1, 2006, and January 1, 2017, confirmed according to Hayashi clinical and histologic criteria. Patients with normal renal function were excluded. For comparison, 5 skin samples from patients with arteriolosclerosis and 5 others from the negative margins of skin-carcinoma resection specimens were also analyzed. Localization and morphologic features of the CUA-related cutaneous calcium deposits were assessed with optical microscopy and field-emission-scanning electron microscopy, and the chemical compositions of those deposits were evaluated with μ Fourier transform infrared spectroscopy, Raman spectroscopy, and energy dispersive radiographs. Thirty-six patients (median [range] age, 64 [33-89] years; 26 [72%] female) were included, and 29 cutaneous biopsies were analyzed. Calcific uremic arteriolopathy and arteriolosclerosis skin calcifications were composed of pure calcium-phosphate apatite. Calcific uremic arteriolopathy vascular calcifications were always circumferential, found in small to medium-sized vessels, with interstitial deposits in 22 (76%) of the samples. A thrombosis, most often in noncalcified capillary lumens in the superficial dermis, was seen in 5 samples from patients with CUA. Except for calcium deposits, the vessel structure of patients with CUA appeared normal, unlike thickened arteriolosclerotic vessel walls. Twelve (33%) patients died of CUA. Calcific uremic arteriolopathy-related skin calcifications were exclusively composed of pure calcium-phosphate apatite, localized circumferentially in small to medium-sized vessels and often associated with interstitial deposits, suggesting its pathogenesis differs from that of arteriolosclerosis. Although the chemical compositions of CUA and arteriolosclerosis calcifications were similar, the vessels' appearances and deposit localizations differed, suggesting different pathogenetic mechanisms.

Clinical characteristics of Polish patients with ANCA-associated vasculitides\u2014retrospective analysis of POLVAS registry

ObjectiveAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers—members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS).MethodsWe conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population).ResultsParticipating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3–12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06–9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05–6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3–25.5), skin involvement (OR = 4.4; 95% CI = 1.02–19.6), and age > 65 (OR = 6.3; 95% CI = 1.18–33.7).ConclusionsIn this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease.

The Gut Microbiota-Host Partnership as a Potential Driver of Kawasaki Syndrome.

Kawasaki syndrome (KS) is a necrotizing vasculitis of small- and medium-sized vessels mostly affecting children under 5 years of age; a host of clinical and epidemiological data supports the notion that KS might result from an infectious disease. However, many efforts have failed to identify a potentially universal trigger of KS. The contribution of the intestinal microbial community—called the “microbiota”—to KS has been evaluated by an increasing number of studies, though limited to small cohorts of patients. Differences in the microbiota composition were found in children with KS, both its acute and non-acute phase, with abnormal colonization by Streptococcus species in the intestinal tract and a wider presence of Gram-positive cocci in jejunal biopsies. In particular, a higher number of Gram-positive cocci (of the genera Streptococcus and Staphylococcus), Eubacterium, Peptostreptococcus, and HSP60-producing Gram-negative microbes have been found in the stools of KS children, and their effects on the antigenic repertoire of specific T cells and Vβ2 T cell expansion have been assessed. Conversely, Lactobacilli were lacking in most children with KS compared with other febrile illnesses and healthy controls. All studies available to date have confirmed that an imbalance in the gut microbiota might indirectly interfere with the normal function of innate and adaptive immunity, and that variable microbiota interactions with environmental factors, mainly infectious agents, might selectively drive the development of KS in genetically susceptible children. Further investigations of the intestinal microflora in larger cohorts of KS patients will provide clues to disentangle the pathogenesis of this disease and probably indicate disease-modifying agents or more rational KS-specific therapies.

Autoimmune Aspects of Kawasaki Disease.

Kawasaki disease (KD) is a vasculitis that is part of systemic vasculitis syndrome. It affects medium-sized vessels and is characterized by hypercytokinemia. Although the etiology of KD remains unidentified, epidemiological features point to the role of infection and genetic predisposition. Recent studies on KD revealed endothelial damage and resultant thrombin generation, as well as B-cell activation during the acute phase. Several antiendothelial cell autoantibodies (AECAs) have been identified in KD patients. Analysis of this phenomenon together with the recently developed concept of immunothrombosis reveals a potential pathogenic mechanism for KD. First, polyclonal antibodies generated against invading microorganisms would exhibit cross-reactivity toward endothelial cell components and become dominant during affinity maturation. Binding of AECAs to endothelial cells would cause endothelial activation or damage, with proinflammatory cytokine release, thus fostering a hypercoagulable state resulting from leukocyte activation by proinflammatory cytokines. This, in turn, would lead to coronary artery lesions. KD vasculitis might be initiated upon binding of AECAs to the vasa vasorum and progress to panvasculitis and a vulnerable vessel wall, resulting in an aneurysm. The aneurysm would cause flow recirculation and alteration of wall shear stress. Consequently, platelets activated by shear stress, along with ultralarge von Willebrand factor (VWF) released by endothelial cells, would cause platelet-driven arterial thrombosis. Autoimmunity-associated thrombosis initiated by binding of AECAs to endothelial cells might play a major role in the pathogenesis of certain subtypes of KD. The notion of KD consisting of subtypes, the major one of which is AECA-associated vasculitis, will help improve our understanding of KD and further promote early and accurate diagnosis, which remains challenging.

Feline Hypertrophic Cardiomyopathy: The Consequence of Cardiomyocyte-Initiated and Macrophage-Driven Remodeling Processes?

vHypertrophic cardiomyopathy (HCM) is the most commonly diagnosed cardiac disease in cats. The complex pathophysiology of HCM is still far from clear, but myocardial remodeling is a key process, and cardiomyocyte disarray, interstitial fibrosis, leukocyte infiltration, and vascular dysplasia are described histopathologic features. The present study systematically investigated the pathological processes in HCM, with the aim to shed more light on its pathogenesis. Hearts from 18 HCM cases and 18 cats without cardiac disease (controls) were examined, using light and transmission electron microscopy, immunohistochemistry, and morphometric approaches to identify and quantify the morphological changes. Reverse transcription-quantitative polymerase chain reaction was applied to provide additional mechanistic data on remodeling processes. In HCM, the left and right ventricular free wall and septal myocardium exhibited a significantly reduced overall cellularity, accompanied by a significant increase in interstitial Iba1-positive cells with macrophage morphology. In addition, the myocardium of almost half of the diseased hearts exhibited areas where cardiomyocytes were replaced by cell-rich fibrous tissue with abundant small and medium-sized vessels. HCM hearts also showed significantly higher transcription levels for several inflammatory and profibrotic mediators. Our findings suggest that HCM is the consequence of cardiac remodeling processes that are the result of cardiomyocyte damage and to which macrophages contribute by maintaining an inflammatory and profibrotic environment.

Ocular Manifestations of Granulomatosis with Polyangiitis: A Review of the Literature.

Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease of unknown etiology that is characterized by granulomatous inflammation, tissue necrosis, and vasculitis in small- and medium-sized vessels. Ocular and orbital manifestations are common in almost half of patients with GPA, affecting every structure of the eye, from the eyelid and orbit to the retina, the choroid, and the optic nerve, with a wide range of severity. Since imaging findings are not always specific for the diagnosis of GPA, biopsy is useful to confirm the diagnosis. Regarding treatment, a localized pharmaceutical and surgical approach may be helpful to achieve remission, while immunosuppressive therapy, corticosteroids, and cyclosporine are also useful. In any case, multidisciplinary intervention is required to reduce the rates of relapse and morbidity in patients with GPA.

Evolution of sinonasal radiological findings in a case of granulomatosis with polyangiitis

Abstract Wegener’s granulomatosis (Granulomatosis with Polyangiitis) is an autoimmune granulomatous disorder of unknown etiology. The basic pathology is necrotizing granulomatous inflammation with necrotizing vasculitis involving medium-sized blood vessels. The typical triad of involvement of the upper and lower respiratory tracts and the kidneys is observed in varying proportions in individual patients. The sinonasal involvement is observed in the majority of patients and it can be involved in isolation in up to a quarter of affected individuals. The sinonasal changes involve both the soft tissue and bony architecture, with refractory chronic sinusitis associated with erosion of the cartilaginous and bony skeleton and may lead to saddle nose and other facial deformities in advanced cases. The radiology has a contributory role as diagnostic and diseases monitoring aid. The various radiological findings associated with the disease (bone erosion with osteoneogenesis) have been mentioned in the literature. We present the progression of a radiological abnormality in a patient with a localized form of Wegener’s Granulomatosis and highlight some peculiar appearances observed on radiology in the patient.

Vasculitis and peripheral neuropathy.

Vasculitis of medium-sized and small vessels commonly affects peripheral nerves and can occur in context of a systemic vasculitis with multiorgan involvement or a nonsystemic vasculitis limited to the peripheral nervous system. This review summarizes the clinical and pathological features of systemic and nonsystemic vasculitis of the peripheral nervous system. Vasculitis of peripheral nerves is a diffuse process that affects the vasa nervorum along the entire length of affected nerves but appears to cause injury primarily in a zone in the proximal-middle of the nerve that is particularly susceptible to ischemic injury. Nerve biopsy can help establish the diagnosis of a systemic vasculitis, particularly when other organ involvement is not clinically apparent, and is required for diagnosis of nonsystemic vasculitic neuropathy. Observational studies suggest that nonsystemic vasculitic neuropathy responds to immunosuppressive therapy but conclusive data are lacking. The current review summarizes the clinical and pathological features of both systemic and nonsystemic vasculitis of the peripheral nervous system so that clinicians can better recognize, make a more timely diagnosis, and thus treat this condition more effectively in their patients.

Microscopic polyangiitis associated with subarachnoid hemorrhage.

Microscopic polyangiitis (MPA), an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, is a systemic disease that damages all organs through predominantly affecting small vessels. However, few cases of MPA are related to aneurysms on medium-sized muscular vessels, and whether subarachnoid hemorrhage (SAH) is associated with MPA is still unclear. An 85-year-old woman with rapid progressive glomerular nephritis caused by MPA complained of sudden severe headache due to SAH 2 days after admission and subsequently underwent surgery. Cerebrovascular disease occurring simultaneously with MPA might result in poor prognosis, and the complications exacerbate the condition and lead to high mortality; thus, physicians should pay more attention to cerebral aneurysms concurrent with MPA. Among patients with MPA, it is important to identify priority cases and investigate the intracranial vessel environment. To the best of our knowledge, this is a rare report about SAH associated with MPA. We recommend that the presence of cerebrovascular disease should be considered in patients with MPA to improve their prognosis.

Explosive Granulomatosis with Polyangiitis Mimicking Infective Endocarditis

Background: Granulomatosis with polyangiitis (GPA) is a rare systemic disease that causes necrotizing granulomatous inflammation of small- and medium-sized blood vessels. Infective endocarditis (IE), which is a disease due to infection of the innermost surface of the heart, is pathophysiologically distinct from GPA and yet these two entities can manifest in strikingly similar ways. Case presentation: We report a case of a 46-year-old male whose presentation and history were strikingly suggestive of IE but was ultimately diagnosed with GPA. Originally, he presented with fever, oral ulcers, and purpuric lesions on the extremities. The patient had a history of illicit drug use and had recently undergone a dental procedure one week prior to presentation, which were classic risk factors for IE. His fever and respiratory difficulty were unresponsive to antibiotic therapy. His respiratory and renal status declined explosively during his hospitalization, requiring intubation and intensive level care. His clinical progression, negative blood cultures, and a positive c-ANCA screen prompted a workup that was more consistent with GPA. Administration of anti-inflammatory medications and plasmapheresis eventually lead to the resolution of his symptoms. Because of his precipitous pulmonary decline, his outcome would have been poor if the correct diagnosis of GPA were to have been overlooked. Conclusions: ANCA-associated vasculitis and infective endocarditis can demonstrate similar clinical findings, including in the skin. Overlap in serologic markers and other organ involvement can lead to difficulty in distinguishing these two diseases, which require contrasting treatment methods. We highlight and compare the similarities and differences between GPA and IE in discussion of this interesting case to emphasize the importance of being clinically vigilant in differentiating these two separate disease processes.

Vasculo-Behçet disease complicated by conversion disorder diagnosed with <sup>18</sup>F-fluoro-deoxy-glucose positron emission tomography combined with computed tomography (PET/CT)

Vasculitis in Behçet's disease, termed "vasculo-Behçet's disease," is a major cause of mortality and morbidity. We report a case of vasculo-Behçet's disease complicated by conversion disorder, in which 18F-fluoro-deoxy-glucose positron emission tomography combined with computed tomography (FDG PET/CT) was useful for the diagnosis. A twenty-two-year-old woman recently diagnosed with tonsillitis presented with fever, right foot pain, left equinovarus foot, and numbness in both hands and feet. Laboratory data showed elevated levels of c-reactive protein (CRP). The patient was positive for HLA B51; pathergy testing was also positive. Nerve conduction velocity and electromyography were normal. MRI showed swelling of the left crural muscle group. PET/CT showed intense FDG uptake in the left popliteal artery, demonstrating active vasculitis. The patient was diagnosed with vasculo-Behçet's disease and treated with corticosteroids, colchicine, and infliximab, which led to obvious improvement of the MRI findings and reduction in CRP. However, left equinovarus foot and numbness in the extremities persisted. She also developed aphonia. They were attributed to psychogenic dystonia and conversion disorder, and psychiatric treatment was effective in relieving those symptoms. We suggest that PET/CT may be useful for the early diagnosis of medium-sized vessel vasculitis in patients with Behçet's disease.

Spontaneous Bilateral Carotid Artery Dissection Revealing Multifocal Fibromuscular Dysplasia

Background: Fibromuscular dysplasia (FMD) is a rare idiopathic segmental non-arteriosclerotic and non-inflammatory arterial disease of small to medium-sized vessels. Although it is considered a benign entity, FMD can lead to potentially severe cerebrovascular complications. We present an atypical clinical case of ischemic stroke (IS) caused by bilateral carotid dissection revealing multifocal FMD. Case Report: A 43-year-old right-handed female with no medical history suddenly developed somnolence with left-sided weakness. Clinical examination revealed left hemiplegia and left central facial paralysis with an NIHSS score: 22. Cerebral tomography (CT) with arterial angiogram revealed abilateralis of the middle cerebral arteries (MCA), a double dissection of the internal carotids (IC), aneurysmal ectasia of the left IC, and aneurysm of the M2 segment of the MCA. Brain magnetic resonance imaging (MRI) with arterial angiography confirmed the bilateral dissection. A cerebral angiography (CA) revealed a radiological pattern of multifocal FMD. The angiography of the aorta and its branches showed adiffuse dysplasia of the renal arteries. The patient was put under antiaggregants. The modified Rankin score (mRS) after three months was three. Conclusion: Cerebrovascular FMD has typical angiographic features, the “string of beads” appearance being the most common. Although the risk of a stroke in patients with cervical FMD is low, it can lead to a severe stroke and the long-term risks are unknown. Patient registries should be encouraged to better understand the mechanisms and evolutionary profile of FMD and alert clinicians to this potentially disabling condition.