Churg-Strauss syndrome

Churg-Strauss syndrome, more recently called 'allergic granulomatosis angiitis or eosinophilic granulomatosis with polyangiitis (EGPA), is a rare multisystem autoimmune disease. It is phased, starting with bronchial asthma and allergic symptoms, continuing with rising eosinofilia in the blood and tissues and culminating in Systemic vasculitis. The syndrome was first described in 1951 by Swedes Jakob Churg and Lotte Strauss, who characterized it as a granulomatosis variant of polyarteritis nodosa (so-called necrotizing vasculitis with extravascular necrotizing granulomas of various stages) with pronounced eosinophilic infiltrates in the wall of both vascular and perivacular vessels. Histologically, the syndrome is now characterized as necrotizing vasculitis of small and medium blood vessels with Granulomatous Inflammation and tissue infiltration of eosinophilia. It is a serious disease that fundamentally affects patients' quality of life and can also end in death. Early diagnosis and therapy greatly improve patients' survival and reduce the risk of developing chronic organ damage.

Epidemiology
IThe incidence of Churg-Strauss syndrome is reported as 2,4/1 000 000. The disease manifests between the ages of 14 and 75, the most common occurrence being in the 4th and 5th decenium. Men are slightly more likely to be affected by CSS.

Clinical picture
The clinical picture can be divided into three phases:
 * 1) Prodromal stage with Astma bronchiale and/or allergic rhinitis with nasal polyposis (3-8 years); repeated sinusitis, nasal polyps, bleeding, purulent nasal discharge and mesotitis
 * 2) Eosinophilia in blood and tissues, eosinophilic pneumonitis with transient infiltrates (RTGs, periphery, multiple, nodal, nodule-free, effusion with large amounts of eosinophils), eosinophilic gastroenteritis (abdominal pain dyspepsia, diarrhoea), eosinophilic peritonitis, pancreatitis, cholecystitis, alveolar haemorrhage and more.
 * 3) Systemic vasculitis.

CSS may be accompanied by other symptoms such as weight loss, temperatures, night sweats, arthralgia, mono- and polyarthritis, myalgia, myositis, head nerve paresis, mononeuritis multiplex, intracranial haemorrhage, convulsions, psychotic conditions, erythema, skin necrosis. The most common cause of death is cardiac failure (eosinophilic endo/myo/pericarditis, coronary artery vasculitis, valve damage). Non-specific renal parenchyma damage is uncommon but may present as glomerulonephritis with proteinuria and/or hematuria with hypertension. 250px|náhled| Mikroskopický obraz CSS

Churg-Strauss vasculitis diagnostic criteria
To confirm CSS diagnosis, a patient must meet at least four of the ACR (American College of Rheumatology) :
 * Astma bronchiale.
 * Eosinophilia - more than 10% of the differential budget.
 * Mono- or polyneuropatia.
 * Fleeting lung infiltrates.
 * Disability paranasal sinuses.
 * Finding of eosinophils extravascularly.

Laboratory findings in CSS patients
250px|náhled|p-ANCA
 * Non-specific-high sedimentation, increased CRP, anemia, positive rheumatoid factor, high IgE.
 * Eosinofilia.
 * ANCA antibodies in 30-40% of cases.

ANCA antibodies
The presence of ANCA (AntiNeutrophil Cytoplasmatic Antibodies) antibodies is crucial for the development of vasculitis. These are autoantibodies against cytoplasmic antigens Neutrophilic granulocytes, that stimulate neutrophils to produce oxygen radicals and secrete lysosomal enzymes, causing their destruction. The exact role of the ANCA in vasculitis pathogenesis is still not entirely clear, but they appear to contribute to the production of free oxygen radicals by neutrophils and facilitate leukocyte adhesion to the vascular endothelium. At the same time, they activate monocytes and increase the production of certain cytokines(TNF-α) and chemokines. ANCA antibodies can be determined by:
 * immunofluorescence (we recognise 3 subtypes),
 * c-ANCA (cytoplasmic),
 * p-ANCA (perinuclear) – typical for CSS,
 * a-ANCA (atypical),
 * ELISA method (can be distinguished by 7 ANCA specifiers)
 * anti-myeloperoxidase MPO (typical of CSS),
 * against proteinase 3 PR3,
 * against lactoferin LF,
 * human leukocyte elastase – HLE.

ANCAs are a useful laboratory indicator not only for diagnosis, but also for determining disease activity and assessing the effectiveness of therapy.

Treatment
In general, treatment of ANCA-positive vasculitis can be divided into treatment induction to induce disease remission and treatment maintenance to maintain remission. Corticosteroids are usually based on prednisone 1 mg/kg/day, and are gradually reduced after a month. Some authors recommend routine use of cyclophosphamide in all Churga-Strauss syndrome patients. The maintenance treatment is continued with corticosteroids at a dose of 5-10 mg/day  and cyclophosphamide, often replaced by the less toxic  (2 mg/kg/day). Other immunosuppressants- methotrexate, mycophenolate, or cyclosporin A - may also be used in maintenance treatment. U multiorgánového postižení refrakterního na kombinovanou léčbu se jako efektní ukázalo podání vysokodávkovaných imunoglobulinů nebo interferonu α.

Před zavedením kortikoidů umírala polovina pacientů do 3 měsíců od prvních projevů vaskulitidy a 5 let přežívalo méně než 5 % pacientů. V současnosti přežívá pět let díky kombinované léčbě více než 75 %.

Závěr
Vzácné systémové vaskulitidy spojené se zvýšením ANCA protilátek postihují především vitální orgány (plíce, ledviny), proto mají bez léčby velmi špatnou prognózu. Glukokortikoidy a cyklofosfamid mohou při včasné diagnóze výrazně prodloužit život pacientů a omezit rozvoj chronického selhávání ledvin při léčbě dialýzou nebo po transplantaci. V posledních letech se výzkum zaměřuje na syntézu nových léčiv s podobnou účinností, ale menší toxicitou.

Vzhledem k tomu, že se jedná o velmi vzácné onemocnění, jsou pacienti s CSS jednoznačně indikováni k péči ve specializovaných centrech a v podmínkách mezioborové spolupráce.

Související články

 * Systémové vaskulitidy

Zdroj
S laskavým svolením autora Jana Michálka

Doporučená literatura

 * [1] Churg J, Strauss L. Allergic granulomatosis, allergic angiitis and periarteritis nodosa. Am J Pathol. 1951; 27: 277–301. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1937314/pdf/amjpathol00493-0100.pdf [21.02.2012]
 * [2] Žurková M., Kolek V., Musilová K.: Syndrom Churg-Straussové. Interní medicína pro praxi 11(10)/2009 http://www.solen.cz/pdfs/int/2009/10/07.pdf [21.02.2012]
 * [3] Doležel Z., Macků M., Rybníček O., Tomanová Y., Fráňová J.: Eosinifilie – nesnadný hlavolam. Pediatrie pro praxi 1/2005 http://www.solen.sk/index.php?page=pdf_view&pdf_id=1823&magazine_id=4 [22.02.2012]
 * [4] Bartůňková, J.; Tesař, V.; Šedivá, A.: Diagnostic and pathogenetic role of antineutrophil cytoplasmatic antibodies, Clinical immunology 106 (2002) http://www.sciencedirect.com/science/article/pii/S1521661602000268 [22.02.2012]
 * [5] https://www.geum.org/sarko/10_Zurkova.htm/ [21.02.2012]