Vasculitis Of Medium-sized Vessels Research Articles

Eosinophilic granulomatosis with polyangiitis: a review article

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of ANCA-associated vasculitis (AAV) within the group of small vessel vasculitides. It is defined by vasculitis of small and medium-sized vessels with granulomatous inflammation and blood and tissue eosinophilia. Almost all patients have allergic symptoms with bronchial asthma and rhinosinusitis symptoms. Further clinical manifestations vary depending on the localisation, severity, and type of disease manifestation. Eosinophilic infiltration and inflammation may result in rhinosinusitis, pneumonitis, gastrointestinal involvement, and cardiomyopathy. The latter, in particular, is associated with a worse prognosis. As a necrotising pauci-immune small-vessel vasculitis, EGPA, similar to the other AAVs, can cause pulmonary infiltrates with alveolar haemorrhage, glomerulonephritis, cutaneous vasculitis with purpura as well as central and peripheral neurologic injuries. The presence of perinuclear ANCA (pANCA) with specificity against myeloperoxidase (MPO) is observed in approximately one-third of patients but is not specific to EGPA. MPO-ANCA-positive patients are more likely to have peripheral neurologic involvement and glomerulonephritis, whereas ANCA-negative patients are more likely to have cardiac and pulmonary involvement. What is frequently challenging in the clinical routine is to differentiate EGPA from the hypereosinophilic syndrome (HES). The therapeutic approach to EGPA depends on whether the severity of the disease is potentially organ or life-threatening. For severe forms of EGPA, acute therapy mainly includes glucocorticoids in combination with cyclophosphamide. Rituximab has come to be mentioned as an alternative treatment option in the guidelines. Various immunosuppressive therapies are available for remission maintenance. In EGPA without severe organ involvement, IL-5 blockade with mepolizumab is an approved treatment.

GRANULOMATOSIS WITH POLYANGIITIS: LITERATURE REVIEW

Wegener's granulomatosis (granulomatosis with polyangiitis) is a rare autoimmune disease characterized by vasculitis of small and medium-sized vessels and the formation of granulomas. Most often, Wegener's granulomatosis (WG) affects the upper respiratory tract, lungs, kidneys, and eyes. Without treatment, the disease progresses rapidly and leads to death. GV was first described at the end of the 19th century. The characteristic clinical picture of hepatitis B was described by the German pathologist Friedrich Wegener. After the reports of F. Wegener in 1936 and 1939. In cases of necrotizing vasculitis with granulomatous inflammation as a special nosological form of vasculitis, this disease became known as Wegener's granulomatosis. In 2006, F. Wegener’s connection with Nazism was discovered, and it was proposed to abandon the term “Wegener’s granulomatosis” in favor of the term “granulomatosis with polyangiitis,” which, in general, more reflects the modern view of the essence of this disease. The term "Wegener's granulomatosis", however, is today used along with the term "granulomatosis with polyangiitis".

A Case of Polyarteritis Nodosa and Antiphospholipid Antibody Positivity Presenting with Intramuscular Haematoma

Polyarteritis nodosa (PAN) is a medium-sized vessel vasculitis often presenting report as both stenotic and aneurysmal lesions. Association with antiphospholipid antibody (aPL) has also been described. Here, we reported a case of PAN with history of cutaneous vasculitis presenting as multiple territory ischemic stroke, mesenteric panniculitis, coronary artery stenosis on imaging; lupus anticoagulant (LA) was also identified, patient was treated with immunosuppressants and anticoagulation. Disease course was, however, complicated by development of thigh haematoma. Clinical manifestation of PAN and its association with aPL will be discussed.

Поражения глаз при гранулематозе Вегенера

Wegener's granulomatosis, also called granulomatosis with polyangiitis, is a primary systemic necrotizing vasculitis of small and medium-sized vessels with the formation of granulomatous inflammation. This is a severe, progressive disease, presumably of autoimmune nature, which without basic treatment – immunosuppressive therapy (suppression of disease activity, remission maintenance and episodic therapy) can lead to the death of the patient. Upper respiratory tract, eye, lung and kidney lesions prevail in the clinical picture of Wegener's granulomatosis. Ocular manifestations often appear at early stages of the disease and are associated with upper respiratory tract and/or middle ear inflammation. Wegener's granulomatosis can affect any segment of the eye, most often the anterior segment and much less often the posterior, and can present in the form of minor and moderate ocular inflammation (scleritis, keratitis, etc.) or severe disorders of all structures and orbits (pseudotumour) leading to low vision and even blindness. Difficulties in the diagnosis of Wegener's granulomatosis arise from a variety of forms and ways of clinical progression at early stages of the disease, when ophthalmic changes are not very specific. In order to establish the correct diagnosis, it is necessary to compare biopsy results (characterized by granulomatous inflammation and vasculitis of small vessels, areas of necrosis) with clinical laboratory assessments. The refractory course of pathological process in the orbit, eye and its appendages, especially if the patient has some atypically occurring pathological processes in the upper respiratory tract and/or sinuses and lungs, should be a warning sign for a doctor to use an interdisciplinary approach for the diagnosis and treatment. Key words: Wegener's granulomatosis, granulomatosis with polyangiitis, systemic necrotizing vasculitis, eye disorder, scleritis, orbital pseudotumour

A difficult to diagnose case of respiratory tract injury in granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA, Wegener's granulomatosis) is a rare autoimmune disease, characterized by vasculitis of small and medium-sized vessels, as well as the formation of granulomas and the most frequent involvement of the upper respiratory tract, lungs, kidneys and eyes in the pathological process. In the absence of treatment, the disease progresses rapidly and is fatal. The onset of the disease is possible at any age. Pharmacotherapy is aimed at suppressing the immunopathological reactions underlying the disease in order to achieve complete remission associated with anti-neutrophil cytoplasmic antibodies of systemic vasculitis (ANCA-SV). The article deals with a difficult case for diagnosis of respiratory tract damage in GPA in a 60-year-old woman.

CPC03 Triad of generalized rash, peripheral eosinophilia and coexisting obstructive airway disease

Abstract An 87-year-old woman was referred to the acute dermatology service with a 1-week history of a generalized painful rash. She was under the care of the medical team for treatment of pneumonia with symptoms of a cough, fevers and shortness of breath. Her past medical history included adult-onset asthma, hyponatraemia and hypertension. She had never smoked. On examination, she had erythematous smooth papules and plaques on her limbs and torso with palmoplantar involvement, alongside purple macules and patches where older lesions were present. There was no lymphadenopathy and no mucosal involvement. She had an oxygen requirement of 2 L per minute via nasal cannula. Initial blood tests showed eosinophils of 2.8 × 109 cells L−1 and a C-reactive protein (CRP) of 77 mg L−1. A chest radiograph showed bilateral ill-defined shadowing. Two skin punch biopsies were performed for histology and immunofluorescence. Vasculitis screen identified positive antinuclear antibodies (anti-Ro) and reduced complement C4 with negative antineutrophil cytoplasmic antibody (ANCA). The patient remained unwell with increasing CRP and peripheral eosinophilia (up to 9.2 × 109 cells L−1) with rash progressing to exhibit a reticular pattern. Alongside bilateral patchy ground glass opacification on chest computed tomography, a clinical diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) was made. Differential diagnoses included viral exanthem, erythema multiforme and urticarial vasculitis. Screening for cardiac, renal and sinus involvement was undertaken. The patient improved clinically following the initiation of systemic steroids and the peripheral eosinophilia returned to baseline. Skin histology reinforced the clinical diagnosis of EGPA, demonstrating a dermal and perivascular eosinophilic infiltrate with focal extension into vessel walls. EGPA is a rare small- to medium-sized vessel vasculitis with an annual incidence of 0.9–2.4 per million and a median age at diagnosis of 49–59 years. The clinicopathological hallmarks, as in this case, are asthma with peripheral eosinophilia and pulmonary eosinophilic infiltrates. Median time from onset of asthma to presentation with EGPA is 5–9 years. EGPA remains a clinical diagnosis, reinforced by serological and histological findings, although ANCA is reported to be negative in 60–70% of cases. Systemic steroids are the first-line therapy, with a role for second-line immunosuppressants such as methotrexate and rituximab. The key learning points from this case are to keep an open mind in considering a systemic cause for cutaneous manifestations, especially when the patient does not fulfil the usual demographic picture.

Anti-IL5 Monoclonal Antibodies Reduce Asthma Exacerbations and Corticosteroids Dose in Three Eosinophilic Granulomatosis with Polyangiitis Case Reports.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare multisystem necrotizing small and medium-sized vessel vasculitis with eosinophilic adult-onset asthma as part of its spectrum. Therapeutic choices include corticosteroids, immunosuppressive agents, and novel immunomodulators. Mepolizumab and benralizumab are monoclonal antibodies targeting Interleukin-5 (IL-5), which plays a leading role in every stage of production and maturation of eosinophils and are recently undergoing evaluation and administered in steroid-dependent, relapsing and/or refractory EGPA. Herein we describe the cases of three patients with a prior EGPA diagnosis, experiencing frequent asthmatic exacerbations despite oral and inhaled corticosteroid treatment (two patients) and adverse effects of corticosteroids (one patient). Two patients are under treatment with mepolizumab and one patient with benralizumab as an add-on supplemental regimen. In our case series anti-IL5 monoclonal antibodies proved efficient asthma-controlling and corticosteroid-sparing agents.

Dilated Cardiomyopathy in a Patient with Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare pathology that belongs to a group of diseases characterized by necrotizing vasculitis of small and medium-sized systemic blood vessels. Symptomatic cardiovascular involvement occurs in 27%–47% of cases of EGPA and is one of the most severe manifestations. The diagnosis is usually confirmed by eosinophilic infiltration observed in tissue biopsy, but with the recent inclusion of cardiac magnetic resonance imaging (MRI), the former can be replaced. Early diagnosis is important because timely treatment is often associated with improvement.

Overview of Guidelines for the Medical Treatment of Acute Kawasaki Disease in Japan (2020 Revised Version) and Positioning of Plasma Exchange Therapy in the Acute Phase.

Kawasaki disease (KD) is a medium-sized vessel vasculitis of unknown origin that predominantly affects infants and young children. As KD causes cardiac complications such as coronary artery lesions, it is known as a disease that causes sudden death in children with acquired cardiac disease. The clinical trials of prednisolone, infliximab and cyclosporin A have led to the insurance coverage of these drugs in the treatment of KD, in addition to intravenous immunoglobulin therapy, which was already indicated for the treatment of KD. Despite not being a drug, plasma exchange therapy as a procedure was also approved for insurance coverage in Japan. Furthermore, new guidelines for KD treatment were published by the American Heart Association in 2017 and the Single Hub and Access Point for Paediatric Rheumatology in Europe in 2019. In light of these circumstances, the Japanese Society of Pediatric Cardiology and Cardiac Surgery guidelines were revised. Here, we provide an overview of the revised guidelines and mention the position and actual practice of plasma exchange therapy as one of the ultimate treatment modalities.

Role of 18F-FDG PET/CT in Large Vessel Vasculitis and Polymyalgia Rheumatica.

Systemic vasculitides comprise a group of autoimmune diseases affecting blood vessels, including large vessel vasculitis (LVV) and medium-sized vessel vasculitis such as giant cell arteritis (GCA) and Takayasu arteritis (TAK). GCA frequently overlaps with polymyalgia rheumatica (PMR), a rheumatic inflammatory condition affecting bursae, tendons or tendon sheaths, and joints. 18F-FDG PET/CT plays an important role in the diagnostic work-up of GCA, PMR, and TAK and is increasingly used to monitor treatment response. This continuing education article provides up-to-date guidance on the role of 18F-FDG PET/CT in patients with LVV, medium-sized vessel vasculitis, and PMR. It provides a general introduction on the clinical presentation and challenges in the diagnostic work-up of LVV and medium-sized vessel vasculitis, with a focus on the 2 major LVV subtypes: GCA, including PMR, and TAK. Next, practice points to perform and interpret the results of 18F-FDG PET/CT are described in line with the published procedure recommendations. Furthermore, the diagnostic performance and its role for treatment monitoring are discussed, taking into account recent international recommendations for the use of imaging in LVV and medium-sized vessel vasculitis in clinical practice. This is illustrated by several clinically representative PET/CT scan examples. Lastly, knowledge of limitations and pitfalls is essential to understand the role of 18F-FDG PET/CT in LVV, medium-sized vessel vasculitis, and PMR. Challenges and opportunities, as well as future research and conclusions, are highlighted. Learning objectives provide up-to-date guidance for the role of 18F-FDG PET/CT in patients with suspected LVV, medium-sized vessel vasculitis, and PMR.

Cholecystitis: A Rare Presentation for Diffuse Eosinophilic Granulomatosis With Polyangiitis

Eosinophilic granulomatosis with polyangiitis is a rare disorder of small- to medium-sized vessel vasculitis that can affect a multitude of organ systems. It typically presents as asthma, with 50% of cases having some gastrointestinal involvement, but involvement of the gallbladder is very rare. We present a unique case report of a patient who presented for nonspecific symptoms, ultimately leading to a cholecystectomy, which officially histologically diagnosed them with eosinophilic granulomatosis with polyangiitis.

The effect of various forms of treatment of vasculitis on C3, C4 and C5a complement levels in infants and children attending Assiut University Children Hospital (AUCH)

Vasculitis is an umbrella term for various and heterogeneous disorders sharing the presence of inflammation of blood vessel walls (Geetha & Jefferson, 2020). Immune cell infiltrates involve the presence of leukocytes in the vessel with immune-complex deposition, which implies the activation of the complement system and then the swelling and destruction of vessel mural structures. The lumen is narrowed or occluded leading to ischemia and necrosis (Chimenti et al., 2015). It produces local symptoms resulting in hypoperfusion, infarction and hemorrhage and systemic symptoms with an increase in acute phase reactants (Salvador, 2020). According to the size of the blood vessel affected and the distribution of vascular injury, pediatric vasculitis is classified into small vessel vasculitis as in Henochonlein Purpura (HSP), medium-sized vessel vasculitis as in Kawasaki disease and large vessel vasculitides affecting the aorta and its proximal branches. Some forms of small vessel vasculitis are characterized by the presence of antineutrophil cytoplasmic antibodies (ANCAs), whereas others are associated with immune complex deposition in affected tissues. Clinical presentation supported by specific laboratory test, imaging, and confirmatory histology are necessary in order to perform vasculitides’ diagnosis (Sivaraman et al., 2020). To assess the severity of vasculitis and response to treatment, urinary biomarkers such as albumin/creatinine ratio (A/C ratio) in urine have been proved to be easily done and correlated well with both clinical and serological results (Zhang, 2020). Aim of Work: The aim of this study is to assess the effect of various forms of drugs, used in treatment of vasculitis, on the serum levels of complements (C3, C4, and C5a) and Antineutrophil cytoplasmic antibodies (ANCA), in infants and children attending Assiut University Children Hospital (AUCH). Conclusion: In conclusion, cases on combined Methotrexate and Steroid therapy scored best regarding the lowering of C5a level in serum, however, in our cases as a whole, the level of C5a didn’t differ significantly from its level in control. Although the 3 arms of therapy used in this study had good effect on C3 & C4 levels, yet their effect on C5a level was not significant from control. This finding could be explained by the fact that most of our studied cases were of the immune-complex deposition diseases type (which have no effect on C5a) and were ANCA negative. Therefore, C5a inhibitor drugs probably will not be suitable in treatment of most common causes of pediatric vasculitis encountered in this series. Perhaps, this type of therapy might be used in ANCA-Positive associated vasculitides, e.g. Wegener’s Granulomatosis. Further research with bigger number of ANCA positive cases is needed to decide whether such cases could benefit from the use of C5a inhibitors or not.

Beware of the master masquerader- A case series of cavitary lung disease with hearing loss.

Granulomatosis with polyangiitis (GPA) is an etiologically unknown systemic disease characterized by necrotizing granulomatous inflammation. Additionally, it is accompanied by vasculitis of small and medium-sized blood vessels. It manifests clinically as a triad involving the lungs, upper airways, and kidneys. It is estimated that 90% of patients will exhibit upper or lower airway symptoms and around 80% develops the renal disease. In this article, we describe three case scenarios with varying presentations. GPA should be considered among the possible etiologies of cavitary pulmonary lesions with ear manifestations including hearing loss with poor response to unusual treatment.

Neonatal medium-sized vessel vasculitis: A rare case report

Vasculitis is a rare disorder during the neonatal period. We present a term male neonate of consanguineous parents and birthweight of 4 030 g who presented at 11 days of life with an evolving skin rash. There was no history of drug exposure in the neonate except for routine care. On day 7 of life, multiple erythematous plaques with necrotic or pustular centres appeared. There were no signs of mucosal involvement or sepsis and laboratory findings were normal. Skin biopsy revealed small and intermediate vessel vasculitis. At follow-up 2 weeks after discharge from the hospital, the skin lesions persisted, and at age 2 months, the patient presented with features of severe pneumonia and subsequently died. Vasculitis was reported as the cause of death on postmortem biopsy.

A Case Report of Eosinophilic Granulomatosis with Polyangiitis in a Pediatric Patient

Introduction: Eosinophilic Granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), is a rare systemic vasculitis of small and medium-sized vessels that primarily develops in middle-aged individuals. It is characterized by asthma, blood eosinophilia, and extrapulmonary manifestations. In childhood, EGPA is extremely rare. Pulmonary and cardiac involvement is predominant in pediatric EGPA, and mortality is substantial. The key to the treatment of EGPA lies in the early diagnosis of the disease. When glucocorticoids and immunosuppressants are used early, they can improve both the symptoms and the overall outlook of EGPA.

Dilated cardiomyopathy in a patient with Eosinophilic Granulomatosis with Polyangiitis (Churg Strauss)

ResumenLa granulomatosis eosinofílica con poliangeítis (GEPA), anteriormente conocida como síndrome de Churg-Strauss, es una patología poco frecuente que pertenece al grupo de enfermedades caracterizadas por vasculitis necrotizante de vasos sanguíneos sistémicos de pequeño y mediano calibre. La afectación cardiovascular sintomática ocurre entre un 27% a un 47% de los casos de GEPA, siendo una de las manifestaciones más graves. El diagnóstico suele confirmarse con biopsia de tejido con infiltración de eosinófilos pero, en casos seleccionados, con la reciente inclusión de la resonancia cardíaca, podemos prescindir de ella.El diagnóstico precoz es importante debido a que el tratamiento oportuno suele asociarse con mejoría del cuadro.

Elevated Plasma Apurinic/Apyrimidinic Endonuclease 1/Redox Effector Factor-1 Levels in Refractory Kawasaki Disease.

Kawasaki disease (KD) refers to systemic vasculitis of medium-sized vessels accompanied by fever. The multifunctional protein apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) is a new biomarker for vascular inflammation. Here, we investigated the association between APE1/Ref-1 and KD. Three groups, including 32 patients with KD (KD group), 33 patients with fever (Fever group), and 19 healthy individuals (Healthy group), were prospectively analyzed. APE1/Ref-1 levels were measured, and the clinical characteristics of KD were evaluated. The mean age of all patients was 2.7 ± 1.8 years, but the Healthy group participants were older than the other participants. Fever duration was longer in the KD group than in the fever group. APE1/Ref-1 levels were significantly higher in the KD group (p = 0.004) than in the other two groups, but there was no difference between the healthy and fever groups. APE1/Ref-1 levels did not differ according to fever duration or coronary arterial lesion but were higher in refractory KD cases than in non-refractory cases. APE1/Ref-1 levels were significantly higher during the acute phase of KD. We propose that APE1/Ref-1 could be a beneficial biological marker for the diagnosis and prognosis of KD, especially in refractory KD.

Синдром змішаної кріоглобулінемії: особливості клінічного перебігу та лікування. Огляд літератури та опис клінічного випадку, асоційованого з COVID-19

Abstract. The aim of the study was to analyze the literature rewiew regarding modern methods of diagnosis and treatment of mixed cryoglobulinemia. Mixed cryoglobulinemia syndrome (MCS) is a unique systemic inflammatory syndrome, which includes small- and medium-sized vessel vasculitis caused by cryoglobulin-containing immune complexes. MCS is potentially caused by hepatitis C virus infection. It may also be associated with autoimmune or lymphoproliferative disorders or, rarely, may be idiopathic. The diagnosis of MCS should be suspected in any patient who presents with one or more of the following clinical features: palpable purpura, skin ulcers, arthralgias and/or arthritis, peripheral neuropathy, and/or microscopic hematuria or proteinuria with or without chronic kidney disease. The general approach of management of moderate to severe mixed cryoglobulinemia should include targeted treatment of the underlying disease causing the cryoglobulinemia along or with additional immunosuppressive therapy. In some cases, immunosuppressive therapy is started first, and then, after stabilization of disease, therapy for the underlying disease is added. The main indication for immunosuppressive therapy is a progressive systemic disease of the kidneys, nervous system, gastrointestinal tract, skin, or vasculitis with necrosis. The prognosis is variable and depends on the severity of the disease and the response of the underlying disease to therapy. In this publication, we also describe a rare clinical case of mixed cryoglobulinemia associated with COVID-19. Thus, the syndrome of cryoglobulinemia is quite difficult both in diagnosis, taking into account the heterogeneity of clinical and laboratory data, and in treatment which makes it necessary to select effective immunosuppressive therapy in specific clinical cases.

Granulomatoza sa poliangitisom - mogući endokrini aspekti

Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a necrotizing vasculitis of small and medium-sized blood vessels characterized by diffuse inflammation of vascular structures and perivascular and extravascular granulomatosis. In its systemic form, GPA predominantly affects the ear, nose and throat, with lung and kidney involvement with typically rapidly progressive necrotizing glomerulonephritis with extracapillary crescents, while the absence of kidney damage at the time of diagnosis is defined as a limited form of GPA with a more favorable prognosis (1, 2). Antineutrophil cytoplasmic antibodies (c-ANCA) with specificity for proteinase 3 (PR3) represent a biochemical diagnostic criterion. They are detected in 90% of generalized forms and in about 50% of limited forms of granulomatosis with polyangiitis (1, 2). In the absence of treatment, GPA is a disease of progressive evolution. Systemic corticosteroid therapy and immunosuppressive therapy significantly changed the prognostic aspect of the disease. Only a few sporadic observations have been published on endocrine disorders associated with GPA. We present a case of a man, 39 years old, with Wegener's granulomatosis who developed autoimmune thyroiditis 8 years after the initial diagnosis.

GRANULOMATOSE EOSINOPHILIQUE AVEC POLYANGEITE: PRESENTATIONS INHABITUELLES. EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS: UNUSUAL PRESENTATIONS

Introduction:Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis of unknown etiology, affecting small and medium-sized vessels and associating asthma,pulmonary involvement, peripheral eosinophilia and extravascular eosinophilic granulomas. We report three GEPA sightings of unusual revelations. Methods:These are three cases of GEPA from the internal medicine department B, Mohammed V military hospital in Rabat. Results:Three patients aged between 27 and 70 years. The most frequently found manifestations were pulmonary, cutaneous, neurological and digestive. All patients presented with peripheral eosinophilia. The ANCA were negative. All patients were treated with corticosteroids in one case, immunosuppressive therapy were used. Conclusion:In this article, GEPA was revealed by an acute surgical abdomen (appendicitis) in one case, a febrile rash in the second and liver damage in the third patient. Our patients responded well to corticosteroid therapy but the treatment must be adapted depending on the case.