AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Background

Allergic granulomatosis and angiitis is a systemic disorder characterized by asthma, transient pulmonary infiltrates, hypereosinophilia, and a systemic vasculitis. Churg and Strauss first described it in 1951, when they reviewed autopsy cases that were previously classified as polyarteritis nodosa. These cases were atypical in that they were associated Churg and Strauss syndrome with asthma and extravascular granulomas, as well as a systemic vasculitis. This disease is now known as allergic granulomatosis and angiitis or Churg-Strauss syndrome (CSS).

Pathophysiology

CSS has been divided into 3 distinct phases, which may or may not be sequential. The prodromal phase is characterized by asthma with or without allergic rhinitis. The second phase is marked by a peripheral blood eosinophilia and eosinophilic tissue infiltration that produces a picture similar to that of Loeffler syndrome, chronic eosinophilic pneumonia, or eosinophilic gastroenteritis. The third, or vasculitic, phase may involve any organ. The most frequent site of involvement is the heart, though other organs that may be involved are the lung, CNS, kidney, lymph nodes, muscle, and skin. Skin involvement occurs in more than two thirds of patients.

The diagnosis is challenging because of the phasic nature and because the 3 histologic features that Churg and Strauss initially described (ie, tissue infiltration by eosinophils, necrotizing vasculitis, and extravascular granulomas) may not be present in all biopsy specimens.

In 1990,¹ the American College of Rheumatology (ACR) developed criteria for epidemiologic and therapeutic studies. These criteria are as follows: (1) asthma, (2) eosinophilia greater than 10% on a differential WBC count, (3) mononeuropathy or polyneuropathy, (4) nonfixed pulmonary infiltrates, (5) paranasal sinus abnormalities, and (6) biopsy containing a blood vessel with extravascular granulomas. The finding of 4 of the 6 criteria yields a sensitivity of 85% and a specificity of 99.7%.

Frequency

United States

CSS is a rare disease and may be underreported.

International

CSS is a rare disease. In the general population, the frequency of the disorder is estimated at 2.4-4 per million patients. CSS may be underreported.

Mortality/Morbidity

The natural history of CSS is variable. The syndrome may range from an indolent process to a rapidly fatal vasculitis.

• Treatment with steroids improves patients' survival, with long-term overall remission rates of 81-82%. 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.

Sex

A slight male predominance exists. The male-to-female ratio is 1.3:1.

Age

The age of onset varies in range of 4-75 with a mean of about 50 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

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.

• Allergic phase
• • Rhinitis, sinus pain, headache
  • Cough
  • Wheezing
• Eosinophilic phase
• • General - Weight loss, fever, sweats
  • Gastrointestinal - Abdominal pain, diarrhea
  • Pulmonary - Cough
• Vasculitic phase
• • General - Malaise, lassitude, fever
  • Cardiac - Chest pain, dyspnea
  • Pulmonary - Cough, hemoptysis
  • Rheumatologic - Arthralgia, arthritis, myalgia
  • Neurologic - Weakness, numbness

Physical

The signs depend on the phase and organ systems involved.

• Allergic phase
• • Nasal polyps
  • Wheezing
  • Cough
  • Rhinitis
  • Sinus tenderness
• Eosinophilic phase
• • General - Weight loss, fever, sweats
  • Pulmonary - Cough, hemoptysis, rales, rhonchi
  • Gastrointestinal - Rebound, masses, obstruction, ascites, bleeding
• Vasculitic phase
• • General - 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 the 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 resembling erythema multiforme, hemorrhagic lesions ranging from petechiae to extensive ecchymoses, cutaneous and subcutaneous nodules, facial edema, livedo reticularis, urticaria, vesicles (Different morphologies may occur simultaneously. The lesions tend to occur in crops and may show remissions and exacerbations. Nodules frequently occur on the scalp and extensor surfaces of the extremities.)

Causes

The etiology of CSS remains unclear; however, the presence of asthma, eosinophilia, and increased immunoglobulin E (IgE) levels suggest an allergic process. Some authors have implicated drug sensitivities to penicillin, penicillamine, iodides, leukotriene modifiers, and mesalazine.²

A report from a workshop sponsored by National Institutes of Health concluded that the vasculitis in CSS is unmasked by the tapering of steroids rather than by an adverse effect of the leukotriene modifiers. The development of CSS after hyposensitization vaccination and associated with pulmonary infection suggest that these events could initiate an inflammatory cascade.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Other Problems to be Considered

Allergic bronchopulmonary aspergillosis
Cutaneous lymphoma
Leukocytoclastic vasculitis
Loeffler syndrome
Lymphomatoid granulomatosis
Polyarteritis nodosa
Rheumatoid arthritis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Lab Studies

• Determination of the CBC count with the erythrocyte sedimentation rate (ESR): Eosinophilia greater than 10% is a diagnostic criterion of the ACR. Treatment with steroids may mask this finding. Anemia, leukocytosis, thrombocytosis, and an elevated ESR usually accompany the vasculitic phase.
• Tests for rheumatoid factor (RF) and antinuclear antibody (ANA): Some patients may have weakly positive ANA and/or RF results.
• Test for antineutrophilic cytoplasmic antibodies (ANCA): Perinuclear ANCA (P-ANCA) directed predominantly against a myeloperoxidase was initially reported in as many as 75-80% of patients with CSS, but in one study showed that only 13% had positive p-ANCA findings. Because of the low sensitivity of this test, a negative ANCA result does not rule out CSS. Classic antineutrophilic cytoplasmic antibody (C-ANCA) directed against serine proteinase 3 is positive in about 10% of patients with CSS. High titers of C-ANCA are seen more often with Wegener granulomatosis than with CSS.
• Test for soluble thrombomodulin and soluble interleukin-2 receptor: A positive finding is correlated with disease activity.
• BUN and creatinine measurements: Kidney involvement in the form of focal segmental glomerulonephritis may occur, but it is typically mild. Severe kidney involvement is more common in the other systemic vasculitides, such as Wegener granulomatosis and polyarteritis nodosa, than in CSS.
• Liver function testing: Serum aspartate aminotransferase and serum alanine aminotransferase levels may indicate liver or muscle involvement.
• Creatine phosphokinase testing: Creatine phosphokinase (CPK) levels may indicate muscle or cardiac involvement.
• Urinalysis: Hematuria and proteinuria have been reported but are usually mild. Severe kidney involvement is more typical of the other systemic vasculitides than of CSS.

Imaging Studies

• Chest radiographs may be abnormal in both the eosinophilic stage and the vasculitic phase. Radiographs typically reveal transient patchy infiltrates, bilateral nodular infiltrates, or an interstitial pattern. Bilateral hilar adenopathy has also been reported.
• Sinus radiographs: Opacification of the paranasal sinuses is an ACR diagnostic criterion.
• ECGs: Cardiac involvement is the most common cause of death from pericarditis or ischemia in the vasculitic phase. Diffuse myocardial fibrosis from granulomatous infiltration can lead to valvular insufficiency.

Procedures

• Tissue biopsy: The skin and kidney are the most frequently selected biopsy sites.

Histologic Findings

Biopsy may show a variety of histologic changes, including leukocytoclastic or necrotizing vasculitis, eosinophilic infiltration, and vascular and extravascular granulomas. Small-to-medium vessels are typically involved. Nodular lesions frequently reveal characteristic extravascular granulomas. These extravascular granulomas were initially thought to be specific for CSS, but they have also been found in Wegener granulomatosis, polyarteritis nodosa, systemic lupus erythematosus, rheumatoid arthritis, lymphoproliferative disorders, and other immunoreactive disorders. The granulomas are composed of a central core of necrotic eosinophilic debris with degeneration of collagen and are surrounded by a peripheral palisade of epithelioid histiocytes with few, if any, giant cells. The nonnodular lesions most often demonstrate a vasculitis or a nonspecific perivascular infiltrate of eosinophils and mononuclear cells without vasculitis.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Medical Care

Corticosteroids are the first-line therapy. Mild disease may initially be treated with oral corticosteroids, but most authors suggest beginning therapy for extensive disease with intravenous (IV) corticosteroids. Treatment with steroids has improved the survival from 50% at 3 years to 75% at 8 years.

The patient's response to corticosteroids is often dramatic. Within 1-2 weeks eosinophilia, the ESR and muscle enzyme levels may normalize. Corticosteroids can then be tapered, and remission is normally sustained. Residual asthma or other symptoms may require the continuation of low-dose prednisone therapy.

If vasculitic symptoms are uncontrolled or if large doses of steroids are required, cyclophosphamide should be started.

In patients with severe disease and life- or organ-threatening manifestations, the addition of cyclophosphamide appears to improve outcomes and reduces the incidence of relapses. In patients with a seemingly better prognosis and less severe disease, methotrexate (MTX) can be given as a corticosteroid-sparing agent to reduce the cumulative dose of corticosteroids, which is generally high in most cases, as long-term administration of corticosteroids is often inevitable to control asthma even if the vasculitis is inactive.
 
In severe cases, agents that block tumor necrosis factor (TNF), such as infliximab and etanercept, may be added for a limited period. Because this intense immunosuppression increases the risk for infections, prophylaxis with sulfamethoxazole-trimethoprim is advised. As an alternative, the administration of recombinant interferon (IFN)-alpha can be effective when given on a short-term basis in otherwise refractory cases. One case report describes successful use of rituximab in a patient with recalcitrant CSS.³

Consultations

Because CSS is a systemic disorder, consultation with an internist, rheumatologist, or other medical subspecialist is recommended.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Corticosteroids are the mainstay of treatment in CSS. The addition of other medications may be necessary in cases of life- or organ-threatening vasculitis.

Drug Category: Corticosteroids

These drugs have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Drug Category: Immunomodulators

These agents modulate immune responses to various stimuli.

Drug Category: Antimalarial agents

These agents can be used to treat certain autoimmune disorders.

Drug Category: Alkylating agents

These agents are recommended as initial therapy of severe, life-threatening CSS and for patients who are not responsive to corticosteroids alone.

Drug Category: Anti-TNF agents

These agents are recommended in severe cases when corticosteroids and cyclophosphamide may be insufficient to induce remission.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Further Outpatient Care

• The major long-term complications of the vasculitic phase are hypertension and permanent peripheral nerve damage.
• Myocardial involvement may be so severe as to require valve replacement.
• Atrophic scars are the main complication of skin lesions.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Media file 1:  Granuloma with a central core of eosinophilic debris surrounded by a peripheral palisade of epithelioid histiocytes and eosinophils.
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Media file 2:  Bilateral papules and nodules with central necrosis.
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Media file 3:  Magnified view of papules and nodules with central necrosis.
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Media file 4:  Distal digital purpuric papule.
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REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

1. Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. Aug 1990;33(8):1094-100. [Medline].
2. Sinico RA, Sabadini E, Maresca AM. Mesalazine-induced Churg-Strauss syndrome in a patient with Crohn's disease and sclerosing cholangitis. Clin Exp Rheumatol. Mar-Apr 2006;24(2 Suppl 41):S104. [Medline].
3. Kaushik VV, Reddy HV, Bucknall RC. Successful use of rituximab in a patient with recalcitrant Churg-Strauss syndrome. Ann Rheum Dis. Aug 2006;65(8):1116-7. [Medline].
4. Abril A, Calamia KT, Cohen MD. The Churg Strauss syndrome (allergic granulomatous angiitis): review and update. Semin Arthritis Rheum. Oct 2003;33(2):106-14. [Medline].
5. Burrows NP, Lockwood CM. Antineutrophil cytoplasmic antibodies and their relevance to the dermatologist. Br J Dermatol. Feb 1995;132(2):173-81. [Medline].
6. Davis MD, Daoud MS, McEvoy MT, Su WP. Cutaneous manifestations of Churg-Strauss syndrome: a clinicopathologic correlation. J Am Acad Dermatol. Aug 1997;37(2 Pt 1):199-203. [Medline].
7. Dutz JP, Ho VC. Immunosuppressive agents in dermatology. An update. Dermatol Clin. Apr 1998;16(2):235-51. [Medline].
8. Gayraud M, Guillevin L, Cohen P, Lhote F, Cacoub P, Deblois P, et al. Treatment of good-prognosis polyarteritis nodosa and Churg-Strauss syndrome: comparison of steroids and oral or pulse cyclophosphamide in 25 patients. French Cooperative Study Group for Vasculitides. Br J Rheumatol. Dec 1997;36(12):1290-7. [Medline].
9. Gross WL. Churg-Strauss syndrome: update on recent developments. Curr Opin Rheumatol. Jan 2002;14(1):11-4. [Medline].
10. Hellmich B, Gross WL. Recent progress in the pharmacotherapy of Churg-Strauss syndrome. Expert Opin Pharmacother. Jan 2004;5(1):25-35. [Medline].
11. Lhote F, Cohen P, Guillevin L. Polyarteritis nodosa, microscopic polyangiitis and Churg-Strauss syndrome. Lupus. 1998;7(4):238-58. [Medline].
12. Schwartz RA, Churg J. Churg-Strauss syndrome. Br J Dermatol. Sep 1992;127(3):199-204. [Medline].

Article Last Updated: Nov 1, 2007