eMedicine Specialties > Dermatology > Diseases of the Vessels

Churg-Strauss Syndrome (Allergic Granulomatosis)

Author: Claudia Hernandez, MD, Assistant Professor, Department of Dermatology, University of Illinois at Chicago College of Medicine
Contributor Information and Disclosures

Updated: Oct 26, 2009

Introduction

Background

Allergic granulomatosis and angiitis is a disorder characterized by extravascular granulomas, hypereosinophilia, and pulmonary and systemic small-vessel vasculitis. The combination of allergic granulomatosis and angiitis is associated with asthma, typically of adult onset, and allergic rhinitis.¹ Churg and Strauss first described this disorder in 1951, when they reviewed 13 autopsy cases that were previously classified as polyarteritis nodosa. These cases were atypical in that asthma and an eosinophilia preceded the systemic vasculitis. They named the syndrome "allergic angiitis and allergic granulomatosis," which has also come to be known as Churg-Strauss syndrome (CSS).²

Also see Churg-Strauss Syndrome (rheumatology focus) and Churg-Strauss Disease (neurology focus).

Pathophysiology

The diagnosis of Churg-Strauss syndrome (allergic granulomatosis) is challenging because of the highly variable presentation and course of the disease. Some patients have only mild manifestations, while others are affected by life-threatening conditions. Some investigators have divided Churg-Strauss syndrome (allergic granulomatosis) into 3 phases, as follows³ :

• A prodromal phase characterized by allergic manifestations followed by asthma
• A second phase of marked peripheral blood eosinophilia and eosinophilic tissue infiltration that produces a picture similar to that of Loeffler syndrome, chronic eosinophilic pneumonia, or eosinophilic gastroenteritis
• Systemic vasculitis

Pulmonary involvement, neuropathy, and skin lesions are common with each occurring in at least two thirds or more of affected patients. Other systemic features include polyneuropathy (symmetric or mononeuritis multiplex), ischemic bowel disease, nasal perforation, glomerulonephritis, ocular inflammation, coronary arteritis, and cardiomyopathy.⁴ Myocardial involvement or congestive heart failure is the most common cause of death. An extremely high eosinophilia count is present in all patients, averaging 1 X 10⁹/L, and approximately two thirds have a positive perinuclear antineutrophil cytoplasmic antibody (ANCA) titer, which targets primarily myeloperoxidase.⁵

More than one classification scheme exists for Churg-Strauss syndrome (allergic granulomatosis), including Lanham’s criteria, which emphasize clinical features, and the Chapel Hill Consensus Conference criteria, which emphasize pathology. A third option is the American College of Rheumatology (ACR) criteria, originally created for epidemiologic and therapeutic studies. The ACR diagnostic protocol requires the fulfillment of at least 4 of 6 criteria in the setting of vasculitis. These criteria are as follows⁶ :

• Asthma
• Eosinophilia count greater than 10% on a differential WBC count
• Mononeuropathy or polyneuropathy attributable to a vasculitis
• Transient pulmonary infiltrates
• Paranasal sinus abnormalities
• Biopsy specimen containing a blood vessel with extravascular eosinophils

The ACR criteria have a sensitivity of 85% and a specificity of 99.7%.⁷

Frequency

United States

Churg-Strauss syndrome (allergic granulomatosis) is a rare and likely underreported disease.

International

Churg-Strauss syndrome (allergic granulomatosis) is a rare disease. The annual incidence of the disorder is estimated at 2.4-4 cases per million general population, while among asthma patients, an average of 34.6 cases per million asthma population as been reported.⁸

Mortality/Morbidity

Since the introduction of immunosuppressive therapy, considerable improvement has been gained in patient survival. Five-year survival rates for Churg-Strauss syndrome (allergic granulomatosis) range from 68-100% depending on the study. Deaths occurring early in the course of disease are usually attributable to active systemic vasculitis resulting multiorgan failure and/or infection. Long-term adverse effects of therapy and the development of comorbidities account for deaths later in the course of disease.⁹

• Treatment with corticosteroids improves patient survival, with long-term overall remission rates nearly 82%. However, 26-28% of patients in remission have relapses. The overall mortality rate in treated patients who relapse is only 3.1%.
• A short interval from the onset of asthma to the development of the systemic vasculitis indicates an unfavorable prognosis.

Race

No racial predilection is currently recognized for Churg-Strauss syndrome (allergic granulomatosis).

Sex

Sexual predilection for Churg-Strauss syndrome (allergic granulomatosis) varies according to the source, with most sources citing a male predominance. The male-to-female ratio is 1.3:1.

Age

Churg-Strauss syndrome (allergic granulomatosis) may affect both children and elderly persons. The age of onset is wide (4-75 y), with a mean age of 38 years.¹⁰

Clinical

History

The 3 phases—allergic, eosinophilic, and vasculitic—do not necessarily follow one another in any particular order. Symptoms depend on the phase and organ systems involved. A careful history should include medication usage, infectious symptoms, and/or preexisting disease.¹¹

• Allergic phase of Churg-Strauss syndrome (allergic granulomatosis)
  • Rhinitis, sinus pain, headache
  • Cough
  • Wheezing
• Eosinophilic phase of Churg-Strauss syndrome (allergic granulomatosis)
  • General - Weight loss, fever, sweats
  • Gastrointestinal - Abdominal pain, diarrhea, bleeding
  • Pulmonary - Cough
• Vasculitic phase of Churg-Strauss syndrome (allergic granulomatosis)
  • General - Malaise, lassitude, fever
  • Cardiac - Chest pain, dyspnea
  • Cutaneous - purpura, papules
  • Pulmonary - Cough, hemoptysis
  • Rheumatologic - Arthralgia, arthritis, myalgia
  • Neurologic - Weakness, numbness

Physical

Clinical findings in Churg-Strauss syndrome (allergic granulomatosis) vary depending on the phase and organ systems involved.¹

• Allergic phase Churg-Strauss syndrome (allergic granulomatosis)
  • Nasal polyps
  • Wheezing
  • Cough
  • Rhinitis
  • Sinus tenderness
• Eosinophilic phase Churg-Strauss syndrome (allergic granulomatosis)
  • General - Weight loss, fever, sweats
  • Pulmonary - Cough, hemoptysis, rales, rhonchi
  • Gastrointestinal - Rebound, masses, obstruction, ascites, bleeding
• Vasculitic phase Churg-Strauss syndrome (allergic granulomatosis)
  • Constitutional symptoms - Fever, weight loss, adenopathy
  • Cardiac - Gallop, pericardial friction rub, jugular venous distension, peripheral edema
  • Pulmonary - Rales, rhonchi
  • Nervous system - Mononeuritis multiplex, diffuse peripheral neuropathy (most often in a glove-and-stocking distribution), loss of a visual field, cerebral hemorrhage, infarction
  • Renal - Mild proteinuria and hematuria
  • Genitourinary - Obstructive uropathy
  • Ocular - Episcleritis, panuveitis, marginal corneal ulceration, conjunctival infiltration, retinal infarction
  • Musculoskeletal - Joint swelling, muscle tenderness
  • Cutaneous
    • Erythematous macules and papules at times resembling urticaria: Papules are most commonly located symmetrically on the extremities and scalp.
    • Hemorrhagic lesions, including petechiae, extensive ecchymoses, and hemorrhagic bullae
    • Subcutaneous nodules, facial edema, and livedo reticularis

Causes

The etiology of Churg-Strauss syndrome (allergic granulomatosis) remains unclear. Several triggers are suspected, including environmental factors and medications. Inhaled allergens, vaccinations, infections (both bacterial and parasitic), and prescription drugs (eg, carbamazepine, quinine, macrolides, corticosteroid-sparing drugs used to treat asthma) have all been implicated. A class of medications known as leukotriene inhibitors (montelukast, pranlukast, zafirlukast) has also been associated with Churg-Strauss syndrome (allergic granulomatosis). However, whether they are a direct cause or simply associated with the disease remains unclear at this time. Substantial tapering of corticosteroids with the use of leukotriene modifiers may allow unmasking of a previously unsuspected underlying disease, but some patients have never been on corticosteroids.¹²

Another possible drug association with Churg-Strauss syndrome (allergic granulomatosis) is omalizumab, an anti-immunoglobulin E (IgE) antibody used to treat asthma. Once again, whether omalizumab use is truly responsible for Churg-Strauss syndrome (allergic granulomatosis) or simply unmasks it after corticosteroid tapering remains unclear.^13,14

A foreign or infectious agent has been suggested to initiate an inflammatory cascade in an individual with a susceptible genetic background. The inflammation then leads to eosinophilia. High levels of cytotoxic enzymes released by eosinophils have been found in the urine, sera, and bronchoalveolar lavage fluids of Churg-Strauss syndrome (allergic granulomatosis) patients. These enzymes could result in oxidative tissue damage.¹⁵ ANCA antibodies activate neutrophils in vitro, producing greater quantities of reactive oxygen species, which may result in endothelial cell damage. ANCA-positive patients typically have more prominent vasculitic manifestations.¹² However, the etiology of Churg-Strauss syndrome (allergic granulomatosis) remains incompletely understood, particularly in ANCA-negative patients.

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