Eosinophilic Granulomatosis With Polyangiitis Following COVID-19 Vaccination: A Case Report.

The current emergence of the coronavirus disease 2019 (COVID-19) pandemic and the possible side effects of COVID-19 mRNA vaccination remain worrisome. Few cases of vaccination-related side effects, such as vasculitis, have been reported. Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome, is a type of vasculitis characterized by the histological richness of eosinophils, asthma, polyneuropathy, sinusitis, and skin or lung involvement. Here, we report the first case of new onset EGPA following COVID-19 vaccination in Korea. A 71-year old woman developed a skin rash and presented with progressive weakness of the upper and lower extremities after the BNT162b2 vaccination (Pfizer-BioNTech). She was diagnosed with EGPA and her symptoms improved after systemic steroid and immunosuppressant therapy. Although it is very rare, clinicians should be aware that EGPA may occur after COVID-19 vaccination.

Eosinophilic Granulomatosis With Polyangiitis: Newer Therapies.

PURPOSE OF REVIEW: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic disseminated vasculitis associated with extravascular granulomas in patients suffering from asthma and tissue eosinophilia. Current therapies to achieve remission and prevent relapse include glucocorticoids and immunosuppressants like cyclophosphamide. RECENT FINDINGS: With the right treatment, clinical prognosis is favorable, so concerted efforts have been made in recent years to find new alternatives for treating severe EGPA. Monoclonal antibodies such as omalizumab, rituximab, and mepolizumab are among these new options. This review summarizes the pathogenesis and clinical manifestations of EGPA and critically examines current and emerging therapies.

Development of eosinophilic granulomatosis with poliangiitis (Churg-Strauss syndrome) and brain tumor in a patient after more than 7 years of omalizumab use: A case report.

Omalizumab is a monoclonal anti-immunoglobulin E antibody used for the treatment of severe perennial allergic asthma. Previous reports have suggested that omalizumab treatment can be associated with the development of eosinophilic granulomatosis with poliangiitis (EGPA) (formerly known as Churg-Strauss syndrome) and an increased risk of malignancy. Long-term risks of omalizumab treatment are not very well defined. Here, we report the case of a 75-year-old woman with concurrent occurrence of EGPA and brain tumor after more than 7 years of omalizumab treatment. The possibility of EGPA should be borne in mind during long-term treatment with omalizumab. Despite the absence of definitive data, an association may also exist between the development of malignancy and omalizumab use.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): evolutions in classification, etiopathogenesis, assessment and management.

PURPOSE OF REVIEW: Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss syndrome) is a peculiar hybrid condition of a systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and a hypereosinophilic disorder with frequent lung involvement that occurs in people with asthma. This review focuses on areas of evidence or persistent uncertainty in the classification, epidemiology, clinical presentation, diagnosis, prognosis and management of EGPA and attempts to identify clues to the mechanisms in the development or course of the disease. RECENT FINDINGS: The 2013 revision of the EGPA definition formally placed the disease in the subset of ANCA-associated vasculitides. Recently published large case series underlined that the presence of ANCAs, found in 30-40% of EGPA, determines distinct but partly overlapping disease expression and the major detrimental effect of heart involvement on survival. There is some evidence that asthma in EGPA resembles a nonallergic eosinophilic asthma phenotype. Encouraging results have been reported for the treatment of EGPA with rituximab or with the eosinophil-targeted antiinterleukin-5 agent mepolizumab. SUMMARY: The understanding of EGPA continues to advance, but many gaps in knowledge remain. The nomenclature remains a source of conceptual variance in terms of demonstrated presence or not of vessel inflammation or ANCAs in the diagnosis of EGPA. Distinguishing EGPA from hypereosinophilic syndromes can be problematic, and an understanding of the mechanistic relation between the vasculitis and the eosinophilic proliferation is profoundly lacking. Some evidence suggests distinct disease phenotypes, but this concept has not yet been translated to phenotype-adapted therapy.

Churg-Strauss Syndrome Following Vaccination Against 2010 Influenza A (H1N1): A Case Report.

PURPOSE AND BACKGROUND: Churg-Strauss syndrome (CSS) is a systemic inflammatory disorder characterized by asthma, transient pulmonary infiltration, hyper-eosinophilia, and systemic vasculitis. Reported triggering factors include infections, drugs, allergic desensitization, and vaccinations, although cases involving the latter two are extremely rare. Herein, we describe a patient who developed CSS after receiving an H1N1 vaccination. CASE REPORT: A 55-year-old woman presented with fever, skin eruptions, and sensory impairment of her feet within one week after an H1N1 vaccine injection. A chest X-ray showed pulmonary infiltrations in both lower lung fields. Eosinophilia was noted in a hematological test, and an electrophysiological study revealed a pattern of mononeuritis multiplex. A skin biopsy was performed which revealed palisading necrotizing granuloma around a degenerated dermis and eosinophilic infiltration of the blood vessel walls. These findings combined with the hematological and electrophysiological findings met the criteria of CSS according to the American College of Rheumatology. The patient recovered well after steroid treatment. CONCLUSION: This case highlights the possibility that the H1N1 vaccination can trigger CSS. Due to the rarity of reported autoimmune events after vaccine administration and the obscure causal association between autoimmunity and a vaccine, further post-marketing surveillance and research are necessary to clarify the relationship and identify risk factors.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): state of the art.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss, EGPA) is a systemic small-vessel vasculitis associated with asthma and eosinophilia. Histology of EGPA shows tissue eosinophilia, necrotizing vasculitis, and eosinophil-rich granulomatous inflammation. EGPA commonly presents with upper airway tract and lung involvement, peripheral neuropathy, cardiac and skin lesions. Antineutrophil cytoplasmic antibodies (ANCA) are positive in ~40% of the cases and more often in patients with clinical manifestations due to small-vessel vasculitis. The pathogenesis of EGPA is multifactorial: the disease can be triggered by exposure to allergens or drugs, but a genetic background has also been recognized, particularly an association with HLA-DRB4. Th2 responses are prominent, with up-regulation of IL-4, IL-13, and IL-5; however, Th1 and Th17 responses are not negligible. Eosinophils are activated, have a prolonged lifespan and probably cause tissue damage by releasing their granule proteins; their tissue recruitment can be regulated by chemokines such as eotaxin-3 and CCL17. Humoral immunity is also dysregulated, as demonstrated by prominent IgG4 and IgE responses. EGPA promptly responds to glucocorticoid therapy, although combinations of glucocorticoids and immunosuppressants (e.g., cyclophosphamide, azathioprine) are eventually required in most cases. Newer therapeutic options include the anti-IL5 antibody mepolizumab, whose efficacy has been described in small clinical trials, and the B-cell-depleting agent rituximab, reported in several case series.

New-onset severe eosinophilic granulomatosis with polyangiitis following the third dose of mRNA COVID-19 vaccine: A case report.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a complex multifactorial disease that results in multisystemic inflammation of the small- and medium-sized arteries. The exact pathogenesis of this syndrome is poorly understood, but it is postulated to result from a combination of eosinophilic dysfunction, genetic predisposition, and the development of autoantibodies after exposure to an unknown stimulus. We describe a case of new-onset EGPA following the third dose of the Pfizer-BioNTech mRNA vaccine in an infection-naive middle-aged man with a background history of allergic respiratory symptoms. The patient developed acute onset of mononeuritis multiplex, pauci-immune glomerulonephritis, and leucocytoclastic vasculitis 10 days after receiving the booster dose. His laboratory markers including eosinophil count, antineutrophil cytoplasmic antibodies, and renal function tests improved markedly after the initiation of pulse steroid therapy and rituximab infusion. However, his peripheral muscle weakness and neuropathic pain did not respond to the initial therapy but improved later with intravenous cyclophosphamide and intravenous immunoglobulin. To the best of our knowledge, this is the fourth case report of post-coronavirus disease 2019 vaccination precipitation of EGPA. All reported cases including our report were in patients with previous allergic manifestations who received mRNA-based coronavirus disease 2019 vaccines, and all the patients developed mononeuritis multiplex at presentation. Despite the few reported cases of post-vaccination autoimmune phenomena, the temporal association between vaccination administration and disease onset does not indicate causality, given the mass vaccination programmes employed. However, the novel use of the mRNA platform in vaccine delivery necessitates vigilant monitoring by the scientific committee.

[Rapid course of Churge-Strauss syndrome--since appearance of asthma till development of renal failure and neurological complication]. / Gwaltowny przebieg zespolu Churge-Strauss--od rozpoznania astmy oskrzelowej do rozwoju niewydolnosci nerek i powiklan neurologicznych.

Churge-Strauss Syndrome belongs to systematic, necrotic inflammation of medium and small vessels diseases. In this paper it is presented a case of 63 years old man with benign asthma, recognized six month earlier. Later occurs fever, difficulties with breathing, cough, fast progressing paresis of tree limbs, thinning and nephrotic syndrome with fast growing renal failure. Base for recognition was clinical picture and laboratory tests which showed elevetion of inflammation parameters (CRP, ESR), eosinophilia (18%) and p-ANCA antibodies. Treatment with glucocorticosteroids and cyclophosphamide was started. After six month proteinuria decreased. Paresis regressed and patient's movement abilities were improved. Renal failure stayed in fourth stadium of chronic renal disease. The aim of this paper is presentation diagnostic difficulties of Churge-Strauss Syndrome of atypical course with fast growing renal failure with neurological complications.

Pathogenesis of lung vasculitis.

Vasculitides that affect the lung represent a diverse group of diseases with various systemic clinical manifestations, and include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis), Churg-Strauss syndrome (CSS), and anti-glomerular basement membrane (anti-GBM) disease (Goodpasture syndrome). The etiologies of these diseases remain largely unknown. Although the pathogenic mechanisms of each differ, these diseases overlap by the presence of anti-neutrophil cytoplasmic autoantibodies in the vast majority of patients with MPA and GPA, and a substantial minority of patients with CSS and anti-GBM disease. This article reviews the current understanding of the pathogenesis of these four disease entities.

Epidemiology and etiology of wegener granulomatosis, microscopic polyangiitis, churg-strauss syndrome and goodpasture syndrome: vasculitides with frequent lung involvement.

This review focuses on the epidemiological characteristics and etiologies of four primary systemic vasculitides with frequent lung involvement, namely Wegener granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS), and Goodpasture syndrome (GPS). Elucidation of the mechanisms underlying these vasculitides with frequent lung involvement is complicated by their rarity, which hampers the undertaking of large-scale studies; difficulties in classification; and their multifaceted clinical presentations, which infer the existence of several etiologic pathways. Notwithstanding, epidemiological research showed some evidence for international, interethnic, and temporal variations of the frequencies of these four vasculitides; led to the identification of several genetic and environmental risk factors; and provided insight on the extent to which genes and environment might contribute to their development. Available data support the concept that WG, MPA, CSS, and GPS have unique and shared risk determinants. Although the precise causes of these vasculitides are not yet fully understood and the development of prevention strategies is out of our reach at present, current knowledge enables the formulation of etiologic hypotheses to provide caregivers and their patients with valuable information on the nature of these rare entities.

What targeting eosinophils has taught us about their role in diseases.

Eosinophil-associated disease is a term used to encompass a range of disorders from hypereosinophilic syndrome to asthma. Despite the longstanding belief that eosinophils can be primary contributors to disease pathophysiology, it is only in recent years that direct and selective reduction or elimination of eosinophils can be achieved in animals or human subjects. These developments have been made possible in mice through clever targeting of eosinophil production. Antibodies and other agents that target soluble eosinophil-related molecules, such as IL-5, or cell-surface structures, such as CCR3, have also proved useful in reducing blood and tissue eosinophil counts. In human subjects the only eosinophil-selective agents tested in clinical trials thus far are neutralizing antibodies to IL-5, with promising but mixed results. At the very least, such forms of pharmacologic hypothesis testing of the role of eosinophils in certain airway, gastrointestinal, and hematologic diseases has finally provided us with new insights into disease pathogenesis. At its optimistic best, these and other targeted agents might someday become available for those afflicted with eosinophil-associated disorders. This review summarizes what has been learned in vivo in both preclinical and clinical studies of eosinophil-directed therapies, with an emphasis on recent advances.

Churg Strauss syndrome: a review.

BACKGROUND: Churg Strauss syndrome is a medical condition of unknown aetiology characterized by asthma, eosinophilia and finally vasculitis involving small vessels in the limbs and nasal sinuses and the lungs. The purpose of this review is to highlight the natural history of this condition, the pathogenesis, clinical features and treatment modalities available and the prognosis. METHODS: Literature on the subject was reviewed using manual library search, articles in journals, internet search and conference abstracts. RESULT: Churg Strauss syndrome has been reported to be predominantly common in middle aged individuals in their middle age of life with a history of new onset or worsened asthma. The condition has a male predisposition. Prior to the advent of steroid therapy this condition invariably leads to death, but since the introduction of prednisolone therapy and other immunosuppressive therapy the outlook has improved for sufferers and long-term survival has been seen. CONCLUSION: Suspicion of this condition should be based on a good history, physical examination and laboratory investigations and diagnosis based on the criteria that has been drawn by the American College of Rheumatology.

Progress in pediatric vasculitis.

PURPOSE OF REVIEW: To examine recent advances in the pathophysiology and therapy of pediatric vasculitis. RECENT FINDINGS: The past 2 years have been marked by significant progress in extending novel techniques to the investigation of the two most common pediatric vasculitis syndromes, Henoch-Schonlein purpura and Kawasaki disease. Study of other vasculitides, such as Wegener granulomatosis, Churg-Strauss syndrome, and microscopic polyangiitis, is impeded by the small number of pediatric patients. Nonetheless, national and international registries are beginning to provide the foundation for generation of testable hypotheses regarding pathogenesis and optimal treatment. Thus, recent data from the study of children suggest that disorders in the control of inflammation, such as those that underlie familial Mediterranean fever and other autoinflammatory diseases, may predispose to vasculitis. Improved knowledge of mechanisms of disease, in turn, should pave the way for more targeted, effective, and tolerable therapies for children with systemic vasculitis. SUMMARY: International collaboration to study rare disorders such as pediatric vasculitis are demonstrating disorders of inflammatory regulation that predispose to these diseases and may point toward new treatment approaches.

New advances in the pathogenesis of ANCA-associated vasculitides.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of autoimmune disorders including Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS) and renal-limited vasculitis (RLV). This paper reviews updated information on the pathogenesis of AAV. Additional clinical evidence for a pathogenic role of ANCA comes from the observation that patients with severe acute renal failure treated with plasma exchange had a lower risk for progression to end-stage renal disease than patients who received intravenous methylprednisolone therapy, both in addition to standard treatment. Recent data also suggest that antibodies to complementary proteinase-3 (cPR3), probably cross-reacting with plasminogen, may induce PR3-ANCA. Furthermore, a new ANCA, directed against human lysosome membrane protein-2 (LAMP-2), concurrent with PR3-ANCA or MPO-ANCA, was described as a sensitive and specific marker for renal AAV. In vitro, ANCA can further activate primed neutrophils to release reactive oxygen species and lytic enzymes, and, in conjunction with neutrophils, damage and lyse endothelial cells. In vivo, transfer of splenocytes from myeloperoxidase-deficient mice immunized with mouse myeloperoxidase into wild-type mice resulted in pauci-immune systemic vasculitis. A similar experiment in PR3-deficient mice did not cause significant vasculitic lesions. In the anti-MPO induced vasculitis mouse model, a critical role of complement activation was suggested. The anti- LAMP-2 antibody can also induce pauci-immune necrotizing crescentic glomerulonephritis in rats. Rats developed both cross-reactive antibodies to LAMP-2 and crescentic glomerulonephritis when immunized with FimH, an adhesin from Gram-negative bacteria which has strong homology with human LAMP-2. Together, clinical, in vitro and in vivo data support a pathogenic role for ANCA in AAV, although this role is more evident for myeloperoxidase-ANCA than for PR3-ANCA. The role of anti- LAMP-2 requires further studies.

Churg-Strauss syndrome presenting as myositis following unaccustomed exercise.

A 68-year-old woman with a 4 year history of bronchial asthma developed marked myalgia in the extremities following exercise to which she was unaccustomed. Examination on admission, 11 days after onset, revealed myalgia, muscular weakness and cutaneous hemorrhagic bullae. Blood tests revealed eosinophilia (9160/mm(3)) and elevation of creatinine kinase and C-reactive protein. Muscle biopsy in the quadriceps femoris showed small vessel vasculitis and eosinophilic infiltration. Skin biopsy revealed leukocytoclastic vasculitis with neutrophilic and eosinophilic infiltration and fibrinoid necrosis. We diagnosed her as having Churg-Strauss syndrome (CSS). Corticosteroid treatment relieved her symptoms and resulted in normalization of the laboratory test results. Myositis is rare as an initial manifestation of CSS. The previous studies on immunological changes after eccentric exercise suggest that unaccustomed exercise could induce an increase in the serum level of interleukin-6 and trigger the onset of CSS.

[Antineutrophil cytoplasmic antibodies]. / Anticorpi anti-citoplasma dei granulociti neutrofili (ANCA).

Antineutrophil cytoplasmic antibodies (ANCA) are predominantly IgG autoantibodies directed against constituents of primary granules of neutrophils and monocytes lysosomes. Although several antigenic targets have been identified, those ANCA directed to proteinase 3 or myeloperoxidase are clinically relevant, whereas the importance of other ANCA remains unknown. Both are strongly associated with small vessel vasculitides, the ANCA-associated vasculitides, which include Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, and the localised forms of these diseases (eg, pauci-immune necrotising and crescentic glomerulonephritis). ANCA is a useful serological test to assist in diagnosis of small-vessel vasculitides. 85-95% of patients with Wegener's granulomatosis, microscopic polyangiitis, and pauci-immune necrotising and crescentic glomerulonephritis have serum ANCA. ANCA directed to either proteinase 3 or myeloperoxidase are clinically relevant, yet the relevance of other ANCA remains unknown. Besides their diagnostic potential, ANCA might be valuable in disease monitoring. In addition, data seem to confirm the long-disputed pathogenic role of these antibodies. There is increasing evidence that myeloperoxidase-ANCA are directly involved in the pathogenesis of necrotizing vasculitis. This is less clear for proteinase 3-ANCA, markers for Wegener's granulomatosis. With respect to proteinase 3-ANCA, complementary proteinase 3, a peptide translated from the antisense DNA strand of proteinase 3 and homologous to several microbial peptides, may be involved in induction of proteinase 3-antineutrophil cytoplasmic autoantibodies.

[A case of Churg-Strauss syndrome following corticosteroid withdrawal].

A 56-year-old man with bilateral hearing impairment who had taken betamethasone combined with dexchlorpheniramine maleate for 7 years to treat chronic sinusitis developed a dry cough after discontinuing this medication and was diagnosed with asthma, and after which he sensed impaired bilateral hearing. Based on the presence of numerous eosinophilic leukocytes in otorrehea, we made a diagnosis of eosinophilic otitis media, and he was prescribed predonisolone to control the asthma, but discontinued it on his own. He then developed fever, maniphalanx stiffness, testicular pain, and facial hyperesthesia, eruptions, and the lower-limb numbness. The detection of a positive serum reaction for MPO-ANCA and evaluated of eosinophilic leukocyte levels yielded a definitive diagnosis of CSS, for which the man was treated with predonisolone and cyclophosphamide. His symptoms were relieved, even though the onset of neutropenia, necessitated the discontinuation of cyclophosphamade administration.

Oral Corticosteroid Use for the Treatment of Chronic Eosinophilic Disease: A Patient's and His Physician's Experience.

This article, coauthored by a patient with eosinophilic granulomatosis with polyangiitis (EGPA) initially presenting as severe eosinophilic asthma and his physician-specialist, discusses the use and management of oral corticosteroid (OCS) treatment. It also considers the importance of early diagnosis of a rare disease and patient education. The patient describes his journey from progressive worsening of asthma and eventual diagnosis of EGPA to long-term OCS treatment and then participation in a clinical trial for this rare disease, involving the introduction of targeted biologic therapy with OCS tapering. The physician describes the importance of patient referral to obtain a correct diagnosis and optimal maintenance treatment, the balance between risk of adverse events associated with long-term OCS use and benefits of disease control, and various aspects of patient participation in clinical trials. Finally, the patient describes the role of continual patient education in the management of disease and OCS treatment. These considerations can apply to all chronic inflammatory diseases requiring maintenance OCS treatment.Funding: AstraZeneca.