Cardiovascular pathology in vasculitis.

Vasculitides are diseases that can affect any vessel. When cardiac or aortic involvement is present, the prognosis can worsen significantly. Pathological assessment often plays a key role in reaching a definite diagnosis of cardiac or aortic vasculitis, particularly when the clinical evidence of a systemic inflammatory disease is missing. The following review will focus on the main histopathological findings of cardiac and aortic vasculitides.

Pulmonary artery sarcoma affecting the pulmonary valve mistaken as pulmonary vasculitis: a case report and comparative literature review.

Pulmonary arterial sarcomas (PAS) are rare aggressive tumours occurring mainly in the pulmonary trunk. We report a case of PAS involving the pulmonary trunk wall and valve, with uniform wall thickening which represents an atypical imaging manifestation of this tumour. A 63-year-old male presented with vague respiratory symptoms with rapid progression. CTPA showed low density filling defects in both pulmonary arteries and PET scan showed increased uptake in the pulmonary trunk, which along with raised ESR suggested Pulmonary Vasculitis. Echo imaging showed Right ventricular hypertrophy and pulmonary stenosis. Response to steroid therapy was minimal and his symptoms worsened. A referral for second opinion was made and he was diagnosed with PAS. He underwent Pulmonary thromboendarterectomy with Pulmonary valve replacement. Post-operative histopathology confirmed the diagnosis. PAS is rare and frequently misdiagnosed. Surgical resection is not curative, but together with chemotherapy can prolong survival.

Unilateral Toxoplasma retinochoroiditis with frosted branch angiitis: a multimodal imaging study.

A woman in her late 30s presented with sudden diminution of vision, redness and pain in the right eye (OD) of 10 days' duration. Best corrected visual acuity (BCVA) was 20/160 in OD and 20/20 in the left eye (OS). Anterior segment of OD showed keratic precipitates, flare 3+, cells 2+ and a festooned pupil. Vitreous haze and cells were seen in OD. Frosted branch angiitis (FBA) was seen in all quadrants in OD and old Toxoplasma scar was seen in both eyes. Serum toxoplasma immunoglobulin G (IgG) was positive and IgM negative, and PCR of an aqueous humour sample was negative for Toxoplasma She was diagnosed with toxoplasa retinochoroiditis in OD and treated with intravitreal clindamycin injections, oral anti-Toxoplasma antibiotics and steroids. Three months later, her BCVA in OD was 20/40 with resolving inflammation. She presented 2 months later with a new focus of retinochoroiditis without FBA and an old Toxoplasma scar.

Pulmonary pathology in vasculitis.

Pulmonary involvement is frequent in vasculitis, particularly in ANCA-associated small vessel vasculitis. Laboratory and radiological data alone are often sufficient to confirm the clinical hypothesis, but sometimes the pathologist plays a crucial role in the differential diagnosis and the patient's management. In this review, the pathologic features of pulmonary vasculitis and the pathologist's role in this field are illustrated.

A specific diagnostic metabolome signature in adult IgA vasculitis.

INTRODUCTION: IgA vasculitis diagnosis relies primarily on clinical features and is confirmed by pathological findings. To date, there is no reliable noninvasive diagnostic biomarker. OBJECTIVE: We aimed to explore the baseline serum metabolome of adult patients with IgA vasculitis to identify potential diagnostic biomarkers. METHODS: We performed a study comparing the serum metabolome of patients with IgA vasculitis to that of patients with inflammatory condition, namely spondyloarthritis. Serum analyses were performed by high-performance liquid chromatography-mass spectrometry. RESULTS: Fifty-five patients with IgA vasculitis and 77 controls with spondyloarthritis (age- and sex-matched) were included in this study. The median age of IgA vasculitis patients was 53 years. Two-thirds of patients were female (n = 32). At the time of vasculitis diagnosis, 100% of patients had skin involvement and 69% presented with glomerulonephritis (n = 38). Joint and digestive involvement were observed in 56% (n = 31) and 42% (n = 23) of patients. Four discriminative metabolites between the two groups were identified: 1-methyladenosine, L-glutamic acid, serotonin, and thymidine. The multivariate model built from the serum metabolomes of patients with IgA vasculitis and spondyloarthritis revealed an accuracy > 90%. As this model was significant according to the permutation test (p < 0.01), independent validation showed an excellent predictive value of the test set: sensitivity 98%; specificity 98%, positive predictive value 97% and negative predictive value 98%. CONCLUSION: To our knowledge, this study is the first to use the metabolomic approach for diagnostic purposes in adult IgA vasculitis, highlighting a specific diagnostic metabolome signature.

[Laboratory diagnostics for vasculitis beyond antineutrophil cytoplasmatic autoantibodies]. / Labordiagnostik bei Vaskulitiden jenseits von antineutrophilen zytoplasmatischen Autoantikörpern.

The diagnosis of systemic vasculitis (SV) is a major clinical challenge due to the very different forms of presentation and requires an interdisciplinary approach. Targeted laboratory diagnostics support making the diagnosis, differential diagnosis and classification and are also a key component in the detection of active organ manifestations and treatment complications. The basic laboratory tests include the erythrocyte sedimentation rate (ESR), C­reactive protein (CRP), blood count, serum creatinine, urinalysis, specific autoantibodies, complement, immunoglobulins, cryoglobulins and hepatitis B and C serology. Antineutrophil cytoplasmic autoantibodies (ANCA), antiglomerular basement membrane antibodies (anti-GBM antibodies) and anti-C1q antibodies are valuable laboratory markers for the diagnosis of the various forms of small vessel vasculitis. There are no specific laboratory tests for the diagnosis of medium and large vessel vasculitis. Despite advances in our understanding of the pathogenesis of vasculitis, no biomarkers have yet been identified that can be reliably used to guide treatment or that are useful in distinguishing vasculitis from other inflammatory diseases such as infections or treatment complications.

Lesson of the month: Large vessel vasculitis: A rare cause of transaminitis.

We present the case of a 73-year-old male with pyrexia of unknown origin (PUO). He was a returned traveller from Southern Africa and underwent extensive investigation to rule out an infective cause. This was mostly unrevealing but there was a notable transaminitis (ALT predominant) with normal bilirubin level. He showed no serological or clinical improvement despite antibiotic treatment. Subsequent CT-PET showed high mural uptake in the thoracic and abdominal aorta and its major branches, confirming the diagnosis of Large Vessel Vasculitis (LVV). This case highlights the importance of considering LVV in patients with PUO and with transaminitis.

Idiopathic membranous nephropathy and synchronous mononeuritis multiplex secondary to idiopathic small vessel vasculitis.

Membranous nephropathy has been associated with demyelinating polyneuropathies and antiglomerular membrane disease; however, an association with vasculitic neuropathy has not been described. This case describes a patient with biopsy-proven idiopathic membranous nephropathy and synchronous mononeuritis multiplex secondary to idiopathic small vessel vasculitis, who presented with lower limb microvascular ischaemia, peripheral neuropathy and active urinary sediment. Her extensive non-invasive screening for immunological disease and radiological investigations for occult malignancy were unremarkable. The patient received intravenous methylprednisolone and intravenous rituximab induction therapy resulting in complete remission of both the idiopathic membranous nephropathy and small vessel vasculitis at 7 months post treatment.

A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and Future.

The clinical association of purpura, arthralgia, and arthritis was first described in 1837 in a publication by Johann Lukas Schönlein, a German physician. In 1874, Eduard Henoch, a student of Schönlein, reported cases of children with purpura, abdominal pain, bloody diarrhea, and joint pain. IgA vasculitis, or Henoch-Schönlein purpura, is a systemic hypersensitivity vasculitis caused by the deposition of immune complexes in small blood vessels, including the renal glomeruli and mesangium. In the skin, the presentation is with non-thrombocytopenic purpura or urticaria. Worldwide, IgA nephropathy is the most common cause of primary glomerulonephritis. Detection of IgA deposition in small blood vessels and the renal glomeruli is diagnostic in most cases. This article aims to review the history, current classification, epidemiology, presentation, and diagnosis of IgA vasculitis and nephropathy, disease associations or trigger factors, including infections, vaccines, and therapeutic agents, and highlights some future approaches to improve diagnosis and clinical management.

[Immunoglobulin A vasculitis]. / Immunglobulin-A-Vaskulitis.

The immune-mediated small vessel vasculitis is known as Schoenlein-Henoch purpura predominantly from pediatrics and in these cases occurs more frequently after infections of the upper airways. In adults, immunoglobulin A (IgA) vasculitis often proceeds more severely und recurrently with the classical tetrad of skin manifestations in the sense of leukocytoclastic vasculitis, joint affection, gastrointestinal involvement and IgA nephritis, in contrast to the mostly mild and self-limiting course in children. The background of this systemic vasculitis with formation of IgA immune complexes is considered to be an altered glycosylation of IgA, as this causes the exposure of binding sites for autoantibodies so that an immune complex reaction can be elicited. This ultimately leads to perivascular deposition of IgA and a further activation of neutrophils. Groundbreaking in the diagnostics is the histological detection of leukocytoclastic vasculitis and in cases of renal manifestations a kidney biopsy with characteristic deposits of immune complexes, which cannot be clearly differentiated from IgA nephropathy. The treatment is aimed at the respective manifestation and is mostly based on consensus recommendations due to the lack of randomized studies. In addition to immunosuppressive medication, in the presence of a chronic kidney disease general nephroprotection is becoming increasingly more important also by inhibition of sodium-glucose transporter 2 (SGLT2). The type and extent of kidney involvement and also rare cardiac manifestations are the main determinants of the prognosis. Continuous medical accompaniment of those affected is necessary due to the possible progression of the disease and the risk of recurrence.

[Secondary vasculitides]. / Sekundäre Vaskulitiden.

Vasculitides that occur in association with underlying primary diseases are called secondary vasculitides. In the diverse differential diagnostics of vasculitides, a large variety of secondary vasculitides have to be considered. Secondary vasculitides cover the full spectrum of vasculitides, presenting in manifold clinical manifestations. This article provides an overview of systemic diseases and etiological factors, such as infections, drugs, and malignancies, which can be associated with vasculitides. The possible associations with infectious agents are too numerous to be comprehensively covered and are discussed in an exemplary fashion and with a western European focus. Especially in atypical and refractory disease courses, a secondary vasculitis should be considered. In light of the diversity of differential diagnoses and the particular challenges posed by secondary vasculitides, interdisciplinary collaboration is the key for an accurate and early diagnosis as well as for successful treatment management. Treatment of the primary disease should always be prioritized and, if a drug-induced vasculitis is suspected, immediate cessation of the culprit drug is mandatory.

Kikuchi-Fujimoto disease, a rare benign disease with atypical histomorphology: more than meets the eye.

Kikuchi-Fujimoto disease (KFD) is a benign self-limiting condition primarily affecting young females. It usually presents with fever and cervical lymphadenopathy of unknown aetiology with a preponderance of the Asian population. Histopathology is critical in making an accurate diagnosis. While the typical microscopic features include paracortical necrosis with debris, histiocytosis with immunoblasts, and absent neutrophils, rarely, KFD can show atypical features like marked immunoblastic proliferation mimicking lymphoma, demonstrate vasculitis mimicking lupus erythematosus, etc. The diagnosis is extremely challenging if such features occur in cases with generalised lymphadenopathy, which is infrequent in KFD. The study aims to describe the morphological, clinical, and immunohistochemical features of KFD and determine the frequency of the atypical features. We also analysed the subtle histological and immunohistochemical features that aid in the diagnosis of atypical cases. Cases reported as KFD over a period of 6 years were retrieved from the archives of histopathology. The morphological features were categorised as typical and atypical. In the atypical cases, the features that aided in the correct diagnosis of KFD were analysed. Out of the 42 cases evaluated, 23.9% (n=10) had generalised lymphadenopathy; 57.2% (n=24) were women with a median age of 25 years. Leukopenia was observed in 42% (n=13) of patients. Typical features were present in 76.2% (n=32) cases and 23.8% (n=10) presented with atypical features. Eight cases were antinuclear antibody-positive. Atypical features included five (50%) cases with vasculitis and panniculitis, and three (30%) cases with large, atypical cells for which immunohistochemistry (IHC) was performed. In two of these cases, the patent sinuses, absence of neutrophils, and IHC with CD68 aided the diagnosis. There is an overlap of clinical and histopathological features between KFD and malignant lymphomas and systemic lupus erythematosus. Given the fact that the atypical features (23.8%) are not rare occurrences in KFD, correlations with clinical findings and ancillary studies are essential to avoid misdiagnosis and inadvertent therapy.