Churg-Strauss Syndrome



Churg-Strauss Syndrome


Surya V. Seshan, MD





Key Facts


Terminology



  • Synonyms: Allergic granulomatosis and angiitis


Etiology/Pathogenesis



  • Triggers: Allergens, vaccines, drugs


  • T-helper cell and eosinophil activation


Clinical Issues



  • Occurs in any age, mostly 40-60 years


  • Asthma, eosinophilia, granulomatous inflammation


  • Positive MPO-ANCA (40-70%)


  • Typically relapsing disease (35-74%)


  • High renal incidence in ANCA(+) cases


  • Rapid renal failure, mild renal impairment, hematuria


  • Remission after initial treatment (90%)


  • Cyclophosphamide in steroid-resistant or relapsing disease


Microscopic Pathology



  • Acute, subacute, &/or chronic crescentic GN, pauci-immune


  • Occasional isolated eosinophilic interstitial nephritis


  • Small vessel vasculitis, fibrinoid necrotizing and granulomatous types


Ancillary Tests



  • Negative IF and nonspecific EM


  • No immune deposits


Top Differential Diagnoses



  • Granulomatosis with polyangiitis (Wegener) with renal involvement


  • Drug-induced vasculitis


  • Systemic parasitic infestation







Renal biopsy from a patient with CSS shows circumferential, transmural necrotizing arteritis surrounded by numerous eosinophils and by lymphocytes. Eosinophils invade the media image.






Periodic acid-Schiff stain of a glomerulus in CSS reveals segmental necrosis image, a cellular crescent in Bowman space, and rupture of Bowman capsule image with periglomerular inflammation.


TERMINOLOGY


Abbreviations



  • Churg-Strauss syndrome (CSS)


Synonyms



  • Allergic granulomatosis and angiitis



    • Defined by autopsy study in 1951 by Churg and Strauss


Definitions



  • American College of Rheumatology (ACR) criteria differentiate various forms of vasculitides once diagnosis of vasculitis is made



    • CSS diagnosis requires 4 of 6 following features



      • Asthma


      • Eosinophilia > 10%


      • Extravascular eosinophil infiltration


      • Pulmonary infiltrates


      • Paranasal sinus changes


      • Peripheral neuropathy


  • Chapel Hill Consensus Conference (pathology)



    • Criteria are diagnostic and generally exclude other forms of systemic vasculitides


    • Eosinophil-rich inflammatory infiltrate and granulomatous inflammation involving respiratory tract


    • Eosinophil-rich necrotizing vasculitis affecting small to medium-sized vessels


    • Associated with asthma and peripheral eosinophilia


  • Classified with antineutrophilic cytoplasmic antibody (ANCA) diseases


ETIOLOGY/PATHOGENESIS


Environmental Exposure



  • Trigger agents: Allergens, vaccinations, or drugs


Genetic



  • Associated with HLA-DRB4 gene, risk factor


Pathogenesis



  • Primarily cell-mediated tissue and vascular injury



    • CD4(+) T cells secrete interferon-gamma (Th-1 cytokine), promoting granulomatous inflammation


    • Eosinophil activation via IL-4, IL-5, and IL-13 secretion and CD95-CD95L pathway


    • Tissue damage by eosinophils due to release of cytotoxic eosinophilic cationic and major basic protein


    • Eotaxin-3 from endothelial cells chemotactic for eosinophils


  • ANCA probably contributes to pathogenesis



    • ANCA titers correlate with disease activity


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Rare: 3-11/1,000,000 worldwide


    • 16-27% have renal involvement from 3 large series


    • Lesser frequency and milder disease than other small vessel vasculitides involving kidney


  • Age



    • Peak age: 40-60 years; mean: ˜ 48 years


    • Younger adults may also be affected


  • Gender



    • No gender predilection


  • Ethnicity



    • No ethnic predisposition


Presentation



  • Multisystemic disease


  • 4 phases



    • Allergic



      • Constitutional symptoms


      • Asthma


      • Rhinitis


    • Eosinophilic



      • Peripheral eosinophilia



      • Tissue eosinophil infiltration (e.g., gastrointestinal, sinusitis)


      • Heart


    • Vasculitic



      • Skin purpuric rash


      • Peripheral neuropathy


      • Cerebral vessels


      • Lung


      • Kidney


    • Post vasculitic



      • Sequelae related to major organ damage and hypertension


  • Renal disease



    • Higher incidence in ANCA(+) cases


    • Progressive renal insufficiency


    • Acute renal failure (less frequent)


    • Hematuria (mild to severe)


    • Subnephrotic proteinuria, usually < 1.0 g/d


    • Asymptomatic (isolated) urinary abnormalities


    • Obstructive uropathy caused by ureteral stenosis


Laboratory Tests



  • Anemia, leukocytosis


  • Peripheral eosinophilia (10-20%)



    • May be lower or normal in patients previously treated with steroids for asthma


  • Elevated erythrocyte sedimentation rate


  • ANCA (40-70% positive)



    • Mainly p-ANCA (antimyeloperoxidase antibodies [MPO]); rarely c-ANCA or atypical


  • Rheumatoid factor (25% positive)


  • Elevated serum IgE levels and immune complexes containing IgE


Treatment

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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Churg-Strauss Syndrome

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