Probable Vasculitis Research Articles

Diagnostic Dilemma of a Complex Case of Cerebral Vasculitis: A Rare Probable Drug-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Large Vessel Involvement

Diagnostic Dilemma of a Complex Case of Cerebral Vasculitis: A Rare Probable Drug-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Large Vessel Involvement

Diversity of XMEN Disease: Description of 2 Novel Variants and Analysis of the Lymphocyte Phenotype.

Variants in MAGT1 have been identified as the cause of an immune deficiency termed X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection and neoplasia (XMEN) disease. Here, we describe 2 cases of XMEN disease due to novel mutations in MAGT1, one of whom presented with classical features of XMEN disease and another who presented with a novel phenotype including probable CNS vasculitis, HHV-8 negative multicentric Castelman disease and severe molluscum contagiosum, thus highlighting the clinical diversity that may be seen in this condition. Peripheral blood immunophenotyping of these 2 patients, together with an additional 4 XMEN patients, revealed reduced NKG2D expression, impaired CD28 expression on CD8+ T cells, CD4+ T cell lymphopenia, an inverted CD4:CD8 ratio and decreased memory B cells. In addition, we showed for the first time alterations to the CD8+ T cell memory compartment, reduced CD56hi NK cells, MAIT and iNKT cells, as well as compromised differentiation of naïve CD4+ T cells into IL-21-producing Tfh-type cells in vitro. Both patients were treated with supplemental magnesium with limited benefit. However, one patient has undergone allogeneic haematopoietic stem cell transplant, with full donor chimerism and immune reconstitution. These results expand our understanding of the clinical and immunological phenotype in XMEN disease, adding to the current literature, which we further discuss here.

Vasculitic neuropathy: Comparison of clinical predictors with histopathological outcome.

To improve diagnostic accuracy, in this study we compared prebiopsy clinical parameters with subsequent pathological confirmation of peripheral nerve vasculitis. Clinical, laboratory, and neurophysiological parameters were analyzed for consecutive patients referred for nerve biopsy with suspected vasculitis. Patients were assigned pathological categories of definite, probable, possible, or absent vasculitis using validated guidelines. Patients with definite or probable vasculitis were considered to have pathologically confirmed vasculitis. From a cohort of 78 patients, biopsy confirmed vasculitis in 29.5%. Parameters that best differentiated between pathologically confirmed and pathologically unlikely vasculitis were stepwise clinical progression (34.8% vs. 5.6%), the presence of serum anti-myeloperoxidase antibody (28.6% vs. 2.2%) and rheumatoid factor seropositivity (38.1% vs. 10.7%). Pathologically absent vasculitis was frequent in patients with normal (100%) or primarily demyelinating (87.5%) nerve conduction studies. Factoring the negative predictors of pathologically confirmed vasculitis into decision-making can reduce the frequency of diagnostically unhelpful nerve biopsies. Muscle Nerve 59:643-649, 2019.

Vasculitic Neuropathy: A Retrospective Analysis of Nerve Biopsies and Clinical Features from a Single Tertiary Care Center.

Objective:Vasculitic neuropathy can be either restricted to the peripheral nerves or associated with systemic involvement of other organs. The objective of this study was to analyze the nerve biopsies reported as “vasculitic neuropathy” with clinical features.Materials and Methods:All cases diagnosed with vasculitic neuropathy were retrospectively analyzed and categorized as systemic vasculitis and nonsystemic vasculitic neuropathy based on the clinical features. The histological features were further evaluated and classified according to the Peripheral Nerve Society Guidelines.Results:Of the 126 cases, there were 65 nonsystemic vasculitis, 45 secondary systemic vasculitis, and 16 primary systemic vasculitis. Definite vasculitis was more common in the systemic vasculitis group. The epineurial vessels were predominantly involved with chronic axonal changes.Conclusion:The sensitivity of definite vasculitis on nerve biopsy was 54.76%. The sensitivity increases when the diagnostic criteria of definite and probable vasculitis were applied taking into account perivascular inflammation accompanied by vascular changes and axonopathy.

Clinical, electrophysiological and laboratory parameters, and outcome in patients with biopsy proven systemic and nonsystemic vasculitic neuropathy.

To describe the clinical and laboratory findings of patients with biopsy proven vasculitic neuropathy. Peripheral neuropathies form one of the most common disorders of the nervous system. However, more than 50% of them are labelled as 'idiopathic' and, therefore, treatment options become less. In this study, we tried to evaluate the phenotypic as well as laboratory characteristics and outcome of patients with biopsy proven vasculitic neuropathy. Review of biopsy proven definite or probable vasculitic neuropathy was done. The cohort consisted of 67 subjects. There were 21 patients of systemic vasculitis (SVS) and 46 of non-systemic vasculitic neuropathy (NSVN). The nerve biopsy revealed definite vasculitis in 37 and probable vasculitis in 30 patients. The symptoms at onset were paraesthesia (68.7%), and paraesthesia and weakness (28.4%). Diffuse polyneuropathy occurred in 70.1% patients. The course was chronic in the majority (80.59%) of patients. Electrophysiology revealed mononeuritis multiplex in 32.84%, and polyneuropathy in 67.16% of patients. Pure sensory neuropathy was present in 16.42%. Among the patients who had undergone bilateral nerve conduction studies, the majority (71.05%) of patients had an asymmetric neuropathy. An elevated erythrocyte sedimentation rate (ESR) was observed in 80.59% (mean 71.57 ± 30.81 mm/1hr [in SVS] and 35.24 ± 21.62mm/1 hr in NSVN) of patients. The treatment included steroids, other immunomodulators, and symptomatic medications. The mean follow up was 10.98 ± 9.58 months. The outcome was good in 73.46% (43.8% with SVS and 87.88% with NSVN) patients, with those having a NSVN having a significantly better outcome. Vasculitis is a potentially treatable cause of peripheral neuropathy. The clinical features, electrophysiology, laboratory results and nerve biopsy may help in the diagnosis and categorization of patients into non-systemic and systemic vasculitic neuropathies. The long-term outcome is better in patients with NSVN compared to those with systemic vasculitis.

Subacute myopathy as the initial presentation of anca positive vasculitis associated with crohn’s disease

Objectives Myopathy as the presenting symptom from an ANCA positive vasculitis is uncommon. Vasculitis secondary to Crohn’s disease is an equally uncommon phenomenon. We report the first case of Crohn’s associated ANCA positive vasculitis causing a subacute proximal myopathy as the initial clinical manifestation. We also highlight the clinical improvement following institution of rituximab as rescue therapy. Case A 27 years old female with recently diagnosed active Crohn’s disease presented with a 9 months history of progressive proximal upper and lower limb weakness. She had been treated with a course of steroids 6 months prior. She denied any constitutional symptoms. Examination revealed proximal muscle wasting and weakness in both upper and lower limbs. Positive investigations included a positive ANCA with high PR3 titre and a muscle biopsy demonstrating probable vasculitis. She was diagnosed with myopathy secondary to Crohn’s associated ANCA-positive vasculitis. She was treated with adalumimab and then infliximab which was upgraded to rituximab as rescue therapy when there was no response. The rituximab led to significant improvement to her weakness clinically. Conclusions Vasculitis should be considered as a differential diagnosis for subacute myopathy in patients with an inflammatory or autoimmune phenotype. Muscle biopsy and ANCA immunofluorescence and titres are useful investigations. Whilst there is a lack of established evidence about the ideal agent for treating Crohn’s associated vasculitis, case reports suggest using TNF-alpha inhibitors or rituximab.

Asymptomatic vasculitic neuropathy.

We performed a retrospective analysis of the clinical, pathological, and electrophysiological features of 21 cases of Asymptomatic vasculitic neuropathy (AsVN). Among 270 patients with biopsy-proven vasculitic neuropathy, we identified 21 (7.8%) who had asymptomatic neuropathy. Of the 21 patients with AsVN, 11 were women and 10 were men. Their mean age was 62.5 years. Referring physicians suspected systemic vasculitis on the basis of clinical and laboratory features, but none of the patients had neuropathy by examination. Screening nerve conduction studies identified neuropathy in all patients, leading us to perform a sural nerve biopsy, which confirmed the diagnosis of vasculitis. Twelve patients had active (type I), 6 had inactive (type II), and 3 had probable (type III) vasculitis. Vasculitis was primary in 10 patients and secondary in 11. Nerve conduction study is an important tool for identifying AsVN, a subtype of vasculitic neuropathy.

THU0446 Pilot of an Ambulatory Care Unit in Rheumatology Department

BackgroundRheumatology Ambulatory Care Unit (RACU) pilot was carried out in James Cook University Hospital from January 2013 to March 2013 to provide systematic acute rheumatological care to patients soon after...

Usefulness of superficial peroneal nerve/peroneus brevis muscle biopsy in the diagnosis of vasculitic neuropathy

Sensitivity, specificity, and diagnostic yield of the superficial peroneal nerve (SPN)/peroneus brevis muscle (PBM) biopsy in 43 patients with clinically suspected vasculitic neuropathy was studied. Biopsies were classified as “definite”, “suspicious” or “possible” in accordance with established criteria. Vasculitis was detected in 27 patients (21 with non-systemic vasculitis, and six with systemic vasculitis). In patients with “definite” vasculitis (n=13), the sensitivity of SPN/PBM biopsy was 76.4% with 100% specificity. By including patients suspicious for vasculitis (n=10), sensitivity increased to 85.1% but the specificity dropped to 87.5%. The overall diagnostic yield of SPN biopsy in those patients with definite vasculitis was 76.9% (10/13), and 53.8% (7/13) for muscle biopsy. The addition of muscle biopsy increased the diagnostic yield by 23%. Asymmetric nerve fiber loss, Wallerian degeneration and presence of hemosiderin were statistically significant markers of probable vasculitis. Muscle tissue was more likely to show hemosiderin (85.7%) than a nerve biopsy (71%). A combined SPN/PBM biopsy offers excellent diagnostic yield in the diagnosis of vasculitic neuropathy.

Determining drug causation from geriatric clinical observations: The case study of a suspected hypersensitivity vasculitis with glomerular involvement associated with lansoprazole

Drug causation assessment is a systematic process, designed to estimate the probability of a drug's implication in the onset of an adverse event. Postmarketing surveillance is very useful for geriatric medicine, because it gives a better idea of a drug's efficiency and safety in special populations, such as older adults. Although the probabilistic reasoning used in drug causation assessment often leaves some degree of uncertainty, especially in a geriatric milieu where polymedication and multimorbidity are frequent, it is the international pooling of many individual observations that allows one to distinguish signals from noise. These difficulties are discussed on the occasion of a geriatric patient with a probable hypersensitivity vasculitis and glomerular involvement related to lansoprazole treatment. Our case's interest stems from three elements: (1) amongst the proton pump inhibitors (PPI), lansoprazole is rarely reported of having an immunoallergic effect, (2) our data yield evidence of a probable glomerular involvement whereas PPIs have been mainly incriminated of causing acute interstitial nephritis and (3) we assume that the hypersensitivity reaction to lansoprazole was maintained by subsequent administration of another PPI, omeprazole, speaking in favour of a class effect. However, our case report presents several typical confounding factors often encountered in geriatric postmarketing drug surveillance. We discuss how such problems are taken into account in the WHO pharmacovigilance methodology.

The use of nerve and muscle biopsy in the diagnosis of vasculitis: a 5 year retrospective study

Introduction: Peripheral nerve vasculitis is an important condition which can be diagnostically challenging and is one of the principal current indications for nerve and muscle biopsy. Previous studies have suggested...

La biopsie neuro-musculaire dans le diagnostic des vascularites

One characteristic histological lesion on biopsy specimens is mandatory to establish the diagnosis of vasculitis. Combined nerve and muscle biopsies, by the same cutaneous incision, improve significantly the percentage of positive results. Nerve fragments should be taken in every patient presenting sensory manifestations. Such vasculitic lesions are present in medium-sized arterioles and/or small vessels, and correspond mainly to 4 necrotizing vasculitis: panarteritis nodosa (PAN), microscopic polyangiitis (MPA), Churg and Strauss syndrome and Wegener granulomatosis. Microvasculitis should be added to these classical entities, because it corresponds to small vessel wall infiltration by inflammatory cells, as observed in PAN and MPA, but without any necrosis. Microvasculitis has to be differentiated from the inflammatory cell infiltrates surrounding small vessels. However, such perivascular inflammatory cell infiltrates enable the diagnosis of probable vasculitis when associated with clusters of neo-vessels, hemosiderin deposits, or a focal damage of nerve fibers. Grossly, one third of vasculitis diagnosis is confirmed on muscle fragments, a second third on nerve fragments, and the last third on both nerve and muscle fragments. Moreover, in the search for vasculitis, an unpredicted diagnosis of lymphoma or amyloidosis is occasionally established on the neuro-muscular biopsy.

Combined nerve and muscle biopsy in the diagnosis of vasculitic neuropathy. A 16‐year retrospective study of 202 cases

We reviewed 202 biopsies performed on patients with suspected vasculitic neuropathy, of which 24 Churg-Strauss cases are studied separately. Specimens from the superficial peroneal nerve and peroneus brevis muscle were taken simultaneously by one incision. Without taking into account constitutional signs, systemic involvement was present in 131 patients, whereas the remaining 47 corresponded to non-systemic patients with lesions limited to peripheral nervous system and adjoining muscles. Diagnosis of panarteritis nodosa or microscopic polyangiitis, according to the size of involved vessels, was attested by an infiltration of vessel walls by inflammatory cells associated with fibrinoid necrosis or sclerosis. Microvasculitis was diagnosed when inflammatory infiltration concerned small vessels with few or no smooth-muscle fibers and without any necrosis. Microvasculitis was present in 11 of 46 non-systemic cases, and this predominance is statistically significant. Isolated perivascular cell infiltrates in the epineurium were considered not significant but allowed the diagnosis of 'probable vasculitis' if associated with at least one of the following features: regenerating small vessels, endoneurial purpura, asymmetric nerve fiber loss, and/or asymmetric acute axonal degeneration. Necrotizing vasculitis was visible in 60 cases: in nerve (16 cases), in muscle (19 cases), and both (25 cases). Microvasculitis was present in 25 cases: in nerve (19 cases), muscle (four cases), or both (two cases). Moreover, granulomatous vasculitis was found in the nerve of one non-systemic patient presenting also sarcoid granulomas in muscle. There were 24 'probable vasculitis' and 68 negative cases. Muscle biopsy improved the yield of definite vasculitis by 27%.

Encephalopathy and severe neuropathy due to probable systemic vasculitis as an initial manifestation of mixed connective tissue disease

We described a 69-year-old woman with neurological manifestations due to mixed connective tissue disease (MCTD). The patient demonstrated subacute cognitive decline, seizure and gait disturbance with no connective tissue manifestation. She had been diagnosed with dementia at another hospital, later in our hospital, serological examinations disclosed high titers of anti-RNP antibody. Cognitive dysfunction in this patient was dramatically ameliorated by steroid therapy. Three months later, she developed edema of the hands, synovitis and acrosclerosis. The patient was finally diagnosed as having MCTD. We emphasized MCTD as a rare cause of "treatable dementia".

Nonsystemic vasculitic neuropathy: insights from a clinical cohort.

Nonsystemic vasculitic neuropathy (NSVN) is an uncommon disorder. Few series with small numbers of patients have been reported. The prognosis and treatment of patients presenting with NSVN remain uninvestigated. The authors sought to address these issues by assembling a large retrospective cohort with extended follow-up. All nerve biopsies performed over 20 years were reviewed; cases with definite, probable, or possible vasculitis were segregated for clinical correlation. Patients satisfying clinical criteria for NSVN at presentation were selected. Clinicopathologic, treatment, and outcome measures were analyzed in patients followed for > or = 6 months. A total of 48 patients (30 women, 18 men) with a median of 63 months of follow-up were identified. Most patients (85%) had extensive, overlapping involvement of multiple nerves. Only one had a symmetric polyneuropathy. Most neuropathies (96%) were painful. In 96%, nerve damage was distally accentuated, but most had concurrent proximal weakness. Diagnostic sensitivity was 58% for superficial peroneal nerve/peroneus brevis muscle biopsy and 47% for sural nerve biopsy. Combination corticosteroid/cytotoxic therapy was more effective than corticosteroid monotherapy in inducing remission and improving disability, with trends toward reduced relapses and chronic pain. Treatment with cyclophosphamide for >6 months decreased the relapse rate, which was 46% for all patients. Disease/treatment-related mortality was 10%. Six percent developed cutaneous involvement. Although chronic pain persisted in 60% of survivors, 80% had good outcomes. NSVN nearly always presents as an asymmetric, distally accentuated, painful, sensorimotor polyneuropathy. Risks for systemic spread and death are small, and, aside from pain, neurologic prognosis is unexpectedly good. Although this was not a randomized controlled trial, combination therapy produced the best outcome in this cohort.

Ischaemic Cerebrovascular Events in HIV Infection

Several case reports and series described ischaemic cerebrovascular events in HIV infection. However, the exact prevalence and the clinical features of these events are unknown. We performed a cohort study on 772 consecutive HIV infected patients and evaluated the rate of transient ischaemic attacks (TIA) and of completed stroke. A total prevalence of 1.9% for TIA (0.8%) and stroke (1.2%) was calculated resulting in an annual incidence rate of 216 per 100,000. The prevalence was highest in the later stages of the infection. Stroke patients had a poorer immunological state than the TIA and the cohort patients. Probable (n = 3) and possible (n = 2) vasculitis and cardiogenic embolism (n = 2) could be detected as aetiology, the remaining patients had a cryptogenic event. Our data suggest that ischaemic cerebrovascular events are more common in HIV infected patients than in the general population and that a part of these events might be caused by HIV associated vasculitis or vasculopathy.

Late recurrence of postdural puncture headache: Case report

Background and Objectives. Postdural puncture headache can recur following an epidural blood patch but usually does so within the first week. However, a late recurrence was encountered in a 31-year-old woman with probable lupus vasculitis. Methods. The patient underwent a diagnostic lumbar puncture and suffered a postdural puncture headache. She was treated with an epidural blood patch and had complete resolution of her headache. Five weeks later, she suffered a sudden recurrence of an identical headache and underwent a repeat epidural blood patch. Results. The second headache, like the first, was immediately and completely resolved. Conclusions. A review of risk factors for postdural puncture headache and the role of an epidural blood-patch suggests a possible explanation for the late recurrence in this case.

Antinuclear autoantibodies specific for lamins. Characterization and clinical significance.

In 11 patients, sera displaying a ringlike nuclear immunofluorescent staining on sections of rat liver tissue were shown by Western blotting to contain antibodies to lamins. Sera from 8 patients contained autoantibodies reacting with lamin B, whereas sera from the other 3 patients reacted with lamins A and C. All patients (9 women and 2 men) had a chronic autoimmune disorder, which rarely fulfilled the usual criteria for a diagnosis of systemic lupus erythematosus. The disorder was characterized by acute or chronic (active or granulomatous) hepatitis; steroid-responsive blood cytopenia, often associated with a circulating anticoagulant, or anticardiolipin antibodies, or both; and cutaneous leukocytoclastic angiitis or probable brain vasculitis. Eight patients had at least two of these three conditions. Antilamin autoantibodies may thus be a marker for an unusual subset of autoimmune diseases.