Eosinophilic granulomatosis with polyangiitis

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Eosinophilic granulomatosis with polyangiitis (EGPA)
Other namesChurg–Strauss syndrome, allergic angiitis and granulomatosis. [1]
Churg-Strauss syndrome - high mag.jpg
Micrograph showing an eosinophilic vasculitis consistent with eosinophilic granulomatosis with polyangiitis. H&E stain. One of the American College of Rheumatology criteria for EGPA is extravascular eosinophil infiltration on biopsy. [2]
Specialty Immunology, rheumatology   OOjs UI icon edit-ltr-progressive.svg
Symptoms Fatigue, fever, weight loss, night sweats, abdominal pain, cough, joint pain, muscle pain, bleeding into tissues under the skin, a rash with hives, small bumps, or a general feeling of ill. [1]
Complications hypereosinophilia, granulomatosis, vasculitis, inner ear infections with fluid build up, inflammation of the moist membrane lining the surface of the eyelids, or inflammation of peripheral nerves. [1]
Risk factors History of allergy, asthma and asthma-associated lung abnormalities (i.e., pulmonary infiltrates). [1]
Diagnostic method antineutrophil cytoplasmic antibodies (ANCA); cluster of asthma, eosinophilia, mono- or polyneuropathy, nonfixed pulmonary infiltrates, abnormality of the paranasal sinuses, and extravascular eosinophilia. [1]
Treatment Suppress the activity of the immune system to alleviate inflammation. [1]
Medication Corticosteroid medications such as prednisone or methylprednisolone, and mepolizumab. [1] Proliferation inhibitor for those with the presence of kidney or neurological disease. [1]

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as allergic granulomatosis, [3] [4] is an extremely rare autoimmune condition that causes inflammation of small and medium-sized blood vessels (vasculitis) in persons with a history of airway allergic hypersensitivity (atopy). [5]

Contents

It usually manifests in three stages. The early (prodromal) stage is marked by airway inflammation; almost all patients experience asthma and/or allergic rhinitis. The second stage is characterized by abnormally high numbers of eosinophils (hypereosinophilia), which causes tissue damage, most commonly to the lungs and the digestive tract. [5] The third stage consists of vasculitis, which can eventually lead to cell death and can be life-threatening. [5]

This condition is now called "eosinophilic granulomatosis with polyangiitis" to remove all eponyms from the vasculitides. To facilitate the transition, it was referred to as "eosinophilic granulomatosis with polyangiitis (Churg–Strauss)" for a period of time starting in 2012. [6] Prior to this it was known as "Churg–Strauss syndrome", named after Jacob Churg and Lotte Strauss, who first published about the syndrome in 1951 using the term allergic granulomatosis to describe it. [3] It is a type of systemic necrotizing vasculitis.

Effective treatment of EGPA requires suppression of the immune system with medication. This is typically glucocorticoids, followed by other agents such as cyclophosphamide or azathioprine.[ citation needed ]

Signs and symptoms

Eosinophilic granulomatosis with polyangiitis consists of three stages, but not all patients develop all three stages or progress from one stage to the next in the same order; [7] whereas some patients may develop severe or life-threatening complications such as gastrointestinal involvement and heart disease, some patients are only mildly affected, e.g. with skin lesions and nasal polyps. [8] EGPA is consequently considered a highly variable condition in terms of its presentation and its course. [7] [8]

Allergic stage

The prodromal stage is characterized by allergy. Almost all patients experience asthma and/or allergic rhinitis, [9] with more than 90% having a history of asthma that is either a new development, or the worsening of pre-existing asthma, [10] which may require systemic corticosteroid treatment. [7] On average, asthma develops from three to nine years before the other signs and symptoms. [7]

The allergic rhinitis may produce symptoms such as rhinorrhea and nasal obstruction, and the formation of nasal polyps that require surgical removal, often more than once. [9] Sinusitis may also be present. [9]

Eosinophilic stage

The second stage is characterized by an abnormally high level of eosinophils (a type of white blood cell) in the blood and tissues as a result of abnormal eosinophil proliferation, impaired eosinophil apoptosis, and increased toxicity due to eosinophil metabolic products. [7] [11] A normal 5% eosinophil composition in total leukocyte count can be elevated to 60% in EGPA, and this local accumulation of eosinophil is involved in the pathogenesis of asthma described in the allergic stage by initiating and maintaining immune responses in inflammation. [12] [13] The symptoms of hypereosinophilia depend on which part of the body is affected, but most often it affects the lungs and digestive tract. [7] The signs and symptoms of hypereosinophilia may include weight loss, night sweats, asthma, cough, abdominal pain, and gastrointestinal bleeding. [7] Fever and malaise are often present. [14] The eosinophilic stage can last months or years, and its symptoms can disappear, only to return later. [7]

Vasculitic stage

The third and final stage, and hallmark of EGPA, is inflammation of the blood vessels, and the consequent reduction of blood flow to various organs and tissues. [7] The damage done to the blood vessels can be explained by the overabundance of eosinophils that are produced and flowing throughout the vasculature of the body; eosinophil production, while essential for assisting inflammatory responses to infections and diseases, can lead to tissue damage when it is done in excess. [15] Local and systemic symptoms become more widespread and are compounded by new symptoms from the vasculitis. [14]

Severe complications may arise. Blood clots may develop within the damaged arteries in severe cases, particularly in arteries of the abdominal region, which is followed by infarction and cell death, or slow atrophy. [14] Many patients experience severe abdominal complaints; these are most often due to peritonitis and/or ulcerations and perforations of the gastrointestinal tract, but occasionally due to acalculous cholecystitis or granulomatous appendicitis. [14]

The most serious complication of the vasculitic stage is heart disease, which is the cause of nearly one-half of all deaths in patients with EGPA. [14] Among heart disease-related deaths, the most usual cause is inflammation of the heart muscle caused by the high level of eosinophils, although some are deaths due to inflammation of the arteries that supply blood to the heart or pericardial tamponade. [14] Kidney complications have been reported as being less common. [16] Complications in the kidneys can include glomerulonephritis, which prevents the kidneys' ability to filter the blood, ultimately causing wastes to build up in the bloodstream. [17]

Diagnosis

Diagnostic markers include eosinophil granulocytes and granulomas in affected tissue, and antineutrophil cytoplasmic antibodies (ANCA) against neutrophil granulocytes. Two pathological subsets of EGPA are differentiated by the presence of antineutrophil cytoplasmic antibodies (ANCA), autoantibodies that mistakenly target and attack specific proteins found within the cytoplasm of neutrophils. [18] The ANCA+ subtype is characterized by predominantly vasculitis-like manifestations, while the ANCA- subtype is more commonly associated with eosinophilic-related symptoms. [18] Approximately 30-40% of EGPA cases are ANCA+. [18] While the pathogenic mechanisms are not fully understood, this finding suggests a role of B cells – the precursors of ANCA-producing plasma cells – in the pathogenesis of EGPA.

The American College of Rheumatology 1990 criteria for diagnosis of Churg–Strauss syndrome lists these criteria:[ needs update ]

For classification purposes, a patient shall be said to have EGPA if at least four of these six criteria are positive. The presence of any four or more of the six criteria yields a sensitivity of 85% and a specificity of 99.7%. [2] [ needs update ]

Risk stratification

The French Vasculitis Study Group has developed a five-point system ("five-factor score") that predicts the risk of death in Churg–Strauss syndrome using clinical presentations. These factors are: [19]

Having none of these factors indicates milder case, with a five-year mortality rate of 11.9%. The presence of one factor indicates severe disease, with a five-year mortality rate of 26%, and three or more indicate very severe disease: 46% five-year mortality rate. [20]

Imaging

On CT scan of the lungs, peripheral parenchymal opacification (pulmonary consolidation or ground-glass opacity) in the middle and lower zones is the predominant pattern. Interlobular septal thickening (septa separating the secondary pulmonary lobules can be due to pulmonary odema secondary to heart failure. [21]

Treatment

Treatment for eosinophilic granulomatosis with polyangiitis includes glucocorticoids (such as prednisolone) and other immunosuppressive drugs (such as azathioprine and cyclophosphamide). In many cases, the disease can be put into a type of chemical remission through drug therapy, but the disease is chronic and lifelong.[ citation needed ]

A systematic review conducted in 2007 indicated all patients should be treated with high-dose steroids, but in patients with a five-factor score of one or higher, cyclophosphamide pulse therapy should be commenced, with 12 pulses leading to fewer relapses than six. Remission can be maintained with a less toxic drug, such as azathioprine or methotrexate. [22]

On 12 December 2017, the FDA approved mepolizumab, the first drug therapy specifically indicated for the treatment of eosinophilic granulomatosis with polyangiitis. [23] Patients taking mepolizumab experienced a "significant improvement" in their symptoms. [23] Mepolizumab is a monoclonal antibody that targets interleukin-5, a major factor in eosinophil survival. [24]

In addition to mepolizumab, a number of emerging targeted biotherapies—including the anti-IgE monoclonal antibody omalizumab, immunomodulation with Interferon-α, and B cell therapy with rituximab—may lead to increasingly personalized treatment regimens for future EGPA patients. A review of EGPA treatments conducted in 2020 proposes integrating targeted biotherapies into EGPA management plans following failure of treatment with corticosteroids. [25]

History

Eosinophilic granulomatosis with polyangiitis was first described by pathologists Jacob Churg (1910–2005) and Lotte Strauss (1913–1985) at Mount Sinai Hospital in New York City in 1951, using the term "allergic granulomatosis" to describe it. [3] [26] They reported "fever...hypereosinophilia, symptoms of cardiac failure, renal damage, and peripheral neuropathy, resulting from vascular embarrassment in various systems of organs" [27] in a series of 13 patients with necrotizing vasculitis previously diagnosed as "periarteritis nodosa", accompanied by hypereosinophilia and severe asthma. [28] Churg and Strauss noted three features which distinguished their patients from other patients with periarteritis nodosa but without asthma: necrotizing vasculitis, tissue eosinophilia, and extravascular granuloma. [28] As a result, they proposed that these cases were evident of a different disease entity, which they referred to as "allergic granulomatosis and angiitis". [28]

Society and culture

The memoir Patient , by musician Ben Watt (of Everything but the Girl fame), deals with his experience with EGPA in 1992, and his recovery. [29] Watt's case was unusual in that it mainly affected his gastrointestinal tract, leaving his lungs largely unaffected; this unusual presentation contributed to a delay in proper diagnosis. His treatment required the removal of 5 m (15 ft) of necrotized small intestine (about 75%), leaving him on a permanently restricted diet. [29]

Umaru Musa Yar'Adua, the president of Nigeria from 2007 to 2010, reportedly had EGPA and died in office of complications of the disease. [30]

DJ and author Charlie Gillett was diagnosed with EGPA in 2006; he died four years later. [31]

Japanese ski jumper Taku Takeuchi, who won the bronze medal in the team competition in 2014, has the disease and competed at the Sochi Olympics less than a month after being released from hospital treatment. [32]

New Zealand reporter and television presenter Toni Street was diagnosed with the condition in 2015. [33] [34] Street has had health problems for several years, including removal of her gallbladder four months prior. [35]

American professional basketball player Willie Naulls died on 22 November 2018 in Laguna Niguel, California, from respiratory failure due to EGPA, [36] which he had been battling for eight years. [37]

Canadian stand-up comic Candy Palmater died on December 25, 2021, shortly after being diagnosed with EGPA. [38]

Filipino actress Kris Aquino, sister of former Philippine President Benigno Aquino III, revealed on 16 May 2022 that she was diagnosed with EGPA. [39]

Related Research Articles

<span class="mw-page-title-main">Eosinophil</span> Variety of white blood cells

Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells and basophils, they also control mechanisms associated with allergy and asthma. They are granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood, after which they are terminally differentiated and do not multiply. They form about 2 to 3% of white blood cells in the body.

<span class="mw-page-title-main">Eosinophilia</span> Blood condition

Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 5×108/L (500/μL). Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 × 109/L (i.e. 1,500/μL). The hypereosinophilic syndrome is a sustained elevation in this count above 1.5 × 109/L (i.e. 1,500/μL) that is also associated with evidence of eosinophil-based tissue injury.

<span class="mw-page-title-main">Vasculitis</span> Medical disorders that destroy blood vessels by inflammation

Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis. Vasculitis is primarily caused by leukocyte migration and resultant damage. Although both occur in vasculitis, inflammation of veins (phlebitis) or arteries (arteritis) on their own are separate entities.

<span class="mw-page-title-main">Granulomatosis with polyangiitis</span> Medical condition

Granulomatosis with polyangiitis (GPA), also known as Wegener's granulomatosis (WG), after the Nazi German physician Friedrich Wegener, is a rare long-term systemic disorder that involves the formation of granulomas and inflammation of blood vessels (vasculitis). It is an autoimmune disease and a form of vasculitis that affects small- and medium-size vessels in many organs but most commonly affects the upper respiratory tract, lungs and kidneys. The signs and symptoms of GPA are highly varied and reflect which organs are supplied by the affected blood vessels. Typical signs and symptoms include nosebleeds, stuffy nose and crustiness of nasal secretions, and inflammation of the uveal layer of the eye. Damage to the heart, lungs and kidneys can be fatal.

<span class="mw-page-title-main">Anti-neutrophil cytoplasmic antibody</span> Group of autoantibodies

Anti-neutrophil cytoplasmic antibodies (ANCAs) are a group of autoantibodies, mainly of the IgG type, against antigens in the cytoplasm of neutrophils and monocytes. They are detected as a blood test in a number of autoimmune disorders, but are particularly associated with systemic vasculitis, so called ANCA-associated vasculitides (AAV).

Microscopic polyangiitis is an autoimmune disease characterized by a systemic, pauci-immune, necrotizing, small-vessel vasculitis without clinical or pathological evidence of granulomatous inflammation.

Eosinophilic pneumonia is a disease in which an eosinophil, a type of white blood cell, accumulates in the lungs. These cells cause disruption of the normal air spaces (alveoli) where oxygen is extracted from the atmosphere. Several different kinds of eosinophilic pneumonia exist and can occur in any age group. The most common symptoms include cough, fever, difficulty breathing, and sweating at night. Eosinophilic pneumonia is diagnosed by a combination of characteristic symptoms, findings on a physical examination by a health provider, and the results of blood tests and X-rays. Prognosis is excellent once most eosinophilic pneumonia is recognized and treatment with corticosteroids is begun.

Interleukin 5 (IL-5) is an interleukin produced by type-2 T helper cells and mast cells.

Loeffler endocarditis is a form of heart disease characterized by a stiffened, poorly-functioning heart caused by infiltration of the heart by white blood cells known as eosinophils. Restrictive cardiomyopathy is a disease of the heart muscle which results in impaired diastolic filling of the heart ventricles, i.e. the large heart chambers which pump blood into the pulmonary or systemic circulation. Diastole is the part of the cardiac contraction-relaxation cycle in which the heart fills with venous blood after the emptying done during its previous systole.

<span class="mw-page-title-main">Eosinopenia</span> Medical condition

Eosinopenia is a condition where the number of eosinophils, a type of white blood cell, in circulating blood is lower than normal. Eosinophils are a type of granulocyte and consequently from the same cellular lineage as neutrophils, basophils, and mast cells. Along with the other granulocytes, eosinophils are part of the innate immune system and contribute to the defense of the body from pathogens. The most widely understood function of eosinophils is in association with allergy and parasitic disease processes, though their functions in other pathologies are the subject of ongoing research. The opposite phenomenon, in which the number of eosinophils present in the blood is higher than normal, is known as eosinophilia.

Mepolizumab, sold under the brand name Nucala by GlaxoSmithKline, is a humanized monoclonal antibody used for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis, and hypereosinophilic syndrome (HES). It recognizes and blocks interleukin-5 (IL-5), a signalling protein of the immune system.

An overlap syndrome is a medical condition which shares features of at least two more widely recognised disorders. Examples of overlap syndromes can be found in many medical specialties such as overlapping connective tissue disorders in rheumatology, and overlapping genetic disorders in cardiology.

Pauci-immune vasculitis is a form of vasculitis that is associated with minimal evidence of hypersensitivity upon immunofluorescent staining for IgG. Often, this is discovered in the setting of the kidney.

Necrotizing vasculitis, also called systemic necrotizing vasculitus, is a category of vasculitis, comprising vasculitides that present with necrosis. Examples include giant cell arteritis, microscopic polyangiitis, and granulomatosis with polyangiitis. ICD-10 uses the variant "necrotizing vasculopathy". ICD-9, while classifying these conditions together, does not use a dedicated phrase, instead calling them "polyarteritis nodosa and allied conditions".

Leukotriene receptor antagonist-associated Churg–Strauss syndrome may occur in asthma patients being treated with leukotriene receptor antagonists, occurring 2 days to 10 months after the antagonist has been started, with features of the syndrome including peripheral eosinophilia, pulmonary infiltrates, and less commonly neuropathy, sinusitis, and cardiomyopathy.

Jacob Churg was a Russian Empire-born Polish-American pathologist. Churg, together with Lotte Strauss, has given his name to Churg–Strauss syndrome, now known as eosinophilic granulomatosis with polyangiitis.

Lotte Strauss was a German-American pathologist.

Eosinophilic myocarditis is inflammation in the heart muscle that is caused by the infiltration and destructive activity of a type of white blood cell, the eosinophil. Typically, the disorder is associated with hypereosinophilia, i.e. an eosinophil blood cell count greater than 1,500 per microliter. It is distinguished from non-eosinophilic myocarditis, which is heart inflammation caused by other types of white blood cells, i.e. lymphocytes and monocytes, as well as the respective descendants of these cells, NK cells and macrophages. This distinction is important because the eosinophil-based disorder is due to a particular set of underlying diseases and its preferred treatments differ from those for non-eosinophilic myocarditis.

Lymphocyte-variant hypereosinophilia is a rare disorder in which eosinophilia or hypereosinophilia is caused by an aberrant population of lymphocytes. These aberrant lymphocytes function abnormally by stimulating the proliferation and maturation of bone marrow eosinophil-precursor cells termed colony forming unit-eosinophils or CFU-Eos.

Vasculitic neuropathy is a peripheral neuropathic disease. In a vasculitic neuropathy there is damage to the vessels that supply blood to the nerves. It can be as part of a systemic problem or can exist as a single-organ issue only affecting the peripheral nervous system (PNS). It is diagnosed with the use of electrophysiological testing, blood tests, nerve biopsy and clinical examination. It is a serious medical condition that can cause prolonged morbidity and disability and generally requires treatment. Treatment depends on the type but it is mostly with corticosteroids or immunomodulating therapies.

References

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  14. 1 2 3 4 5 6 Churg & Thurlbeck 1995, p. 426.
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  17. ↑ "Churg-Strauss syndrome-Churg-Strauss syndrome - Symptoms & causes". Mayo Clinic.
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  29. 1 2 Whiting S (10 April 1997). "Everything But the Final Song / Ben Watt lives to tell how he almost didn't". SFGate . Retrieved 30 June 2013.
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  35. ↑ "Toni Street's mystery illness revealed". NZ Herald. Retrieved 5 October 2015.
  36. ↑ Goldstein R (25 November 2018), "Willie Naulls, Knicks All-Star and Celtics Champion, Dies at 84", The New York Times
  37. ↑ Bolch B (25 November 2018). "Former UCLA great and integration pioneer Willie Naulls dies at 84". Los Angeles Times. Retrieved 26 November 2018.
  38. ↑ Média, Bell. "Comedian Candy Palmater dead at 53". www.iheartradio.ca.
  39. ↑ "Kris Aquino says her illness now considered 'life threatening'". CNN Philippines. 16 May 2022. Retrieved 3 June 2022.

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