eMedicine Specialties > Dermatology > Diseases of the Vessels

Churg-Strauss Syndrome (Allergic Granulomatosis): Treatment & Medication

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

Treatment

Medical Care

Churg-Strauss syndrome (CSS) is typically a corticosteroid-responsive disease; hence, they are first-line therapeutic agents. Most patients respond to corticosteroid monotherapy. Intravenous corticosteroids should be considered for patients with extensive disease. Dramatic response to therapy may be observed with improvement in eosinophilia counts, reduction of the erythrocyte sedimentation rate (ESR), and reduction in muscle enzyme levels within 1-2 weeks of initiation of treatment. Corticosteroids may be tapered once clinical improvement occurs. Importantly, note that patients with Churg-Strauss syndrome (allergic granulomatosis)–related neuropathy respond more slowly to treatment. Residual asthma or other symptoms may require the continuation of low-dose prednisone therapy.4

Cyclophosphamide should be initiated in severely ill patients who do not respond to initial therapy. Patients with life-threatening disease or those at risk of organ failure are potential candidates. The addition of cyclophosphamide appears to improve outcomes and reduces the incidence of relapses. For patients with systemic disease who are not at risk for major organ failure or death, methotrexate (MTX) may be given as a corticosteroid-sparing agent to reduce the cumulative dose. Other immunomodulatory medications include azathioprine (AZA) and mycophenolate mofetil, which may also be used as corticosteroid-sparing agents. AZA is best used for maintenance therapy rather than for induction of remission in refractory disease. Chlorambucil and plasma exchange have occasionally been used and are most effective when used in combination therapy.7

Agents that block tumor necrosis factor (TNF), such as infliximab and etanercept, have been used for a limited period in severe life-threatening cases. These agents, when combined with corticosteroids or other immunomodulatory agents, greatly increase the risk of infection due to immunosuppression. More data are needed to determine whether these drugs have a favorable risk-to-benefit ratio for use in Churg-Strauss syndrome (allergic granulomatosis) patients. Another infrequently used therapy is recombinant interferon (IFN) alfa, which can be effective when given on a short-term basis in otherwise refractory cases. One anecdotal case report has described the use of rituximab in a patient with recalcitrant Churg-Strauss syndrome (allergic granulomatosis).7,16

Consultations

Because Churg-Strauss syndrome (allergic granulomatosis) is a systemic disorder, consultation with an internist, rheumatologist, or other medical subspecialist is recommended.

Diet

No disease specific dietary interventions are required for Churg-Strauss syndrome (allergic granulomatosis) patients.

Medication

Corticosteroids are the mainstay of treatment in Churg-Strauss syndrome (allergic granulomatosis). The addition of other medications may be necessary in cases of life- or organ-threatening vasculitis.

Corticosteroids

These drugs have anti-inflammatory and immunosuppressive properties.


Methylprednisolone (Medrol, Solu-Medrol)

To treat inflammatory and immune reactions. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Adult

15 mg/kg/d IV bolus, then convert to prednisolone

Pediatric

Administer as in adults

Coadministration with digoxin may increase digitalis toxicity due to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor for hypokalemia with concurrent diuretics; antacids decrease absorption; amphotericin B and carbonic anhydrase inhibitors may lead to hypokalemia

Documented hypersensitivity; viral, fungal, or TB skin infections

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Transient adverse effects of pulse IV corticosteroids are bitter taste, facial flushing, headache, asthenia, significant rise in blood pressure, and temporary glucose intolerance; consider restricting breastfeeding in patients taking >20 mg/d or withhold breastfeeding for 4 h after dosing; weight gain, Cushingoid appearance, osteoporosis, and avascular necrosis; use may increase risk of or worsen preexisting viral, fungal, opportunistic, and parasitic infections; may cause reactivate TB; increased risk of peptic ulcer disease, especially in patients with history; posterior subcapsular cataract formation; CNS complications (psychosis, agitation, insomnia, depression); may induce or worsen preexisting hypertension and glucose and lipid abnormalities; skin changes include atrophy, alopecia, acneiform eruptions, poor wound healing, purpura, striae, hirsutism, and desquamation


Prednisolone (Econopred, Articulose-50, Delta-Cortef)

Decreases autoimmune reactions, possibly by suppressing key components of immune system.

Adult

20-60 mg PO qam or 1 mg/kg PO for 3 d

Pediatric

1-2 mg/kg PO qam

Decreases effects of salicylates and toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects of corticosteroids

Documented hypersensitivity; viral, fungal or TB skin lesions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperthyroidism, osteoporosis, cirrhosis, nonspecific ulcerative colitis, peptic ulcer, diabetes, and myasthenia gravis

Immunomodulators

These agents modulate immune responses to various stimuli.


Methotrexate (Folex PFS, Rheumatrex)

Unknown mechanism of action in treatment of inflammatory reactions; may affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness).

Adult

7.5 mg/wk PO once or 2.5 mg bid for 3 doses qwk; adjust dose gradually for satisfactory response

Pediatric

5-15 mg/m2/wk PO/IM single dose or 3 divided doses q12h

Oral aminoglycosides may decrease absorption and blood levels of concurrent oral MTX; charcoal lowers levels; coadministered etretinate may increase hepatotoxicity; folic acid or derivatives in some vitamins may decrease response; coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity; may increase plasma levels of thiopurines

Documented hypersensitivity; alcoholism, hepatic insufficiency, immunodeficiency syndromes, preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia)

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Monitor CBC counts monthly and liver and renal function q1-3mo during therapy (more frequently during initial dosing, dose adjustments, or with risk of elevated MTX levels [eg, dehydration]); toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if blood counts drop significantly; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly (increased toxicity with NSAIDs or salicylates not tested)


Azathioprine (Imuran)

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, lowering autoimmune activity.

Adult

1 mg/kg/d PO for 6-8 wk; increase by 0.5 mg/kg q4wk until response or 2.5 mg/kg/d

Pediatric

Initial dose: 2-5 mg/kg/d PO/IV
Maintenance dose: 1-2 mg/kg/d PO/IV

Allopurinol increases toxicities; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of MTX metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine

Documented hypersensitivity; thiopurine methyltransferase deficiency

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Increases risk of neoplasia; caution in liver disease and renal impairment; hematologic toxicities may occur; check thiopurine methyltransferase level before treatment; monitor CBC count and liver function periodically


Cyclosporine (Sandimmune, Neoral)

Cyclic polypeptide suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft vs host disease) in many organs. Base dosing on ideal body weight.

Adult

Initial PO dose: 14-18 mg/kg/d 4-12 h before organ transplantation
Maintenance PO dose: 5-15 mg/kg/d qd or divided bid
Initial IV dose: 5-6 mg/kg qd 4-12 h before organ transplantation
Maintenance IV dose: 2-10 mg/kg/d divided q8-12h

Pediatric

Administer as in adults

Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase with concurrent lovastatin

Documented hypersensitivity; uncontrolled hypertension or malignancies; PUVA or UVB radiation in psoriasis (may increase risk of cancer)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzymes; may increase risk of infection and lymphoma; reserve IV for those who cannot take PO


Interferon alfa 2a and 2b (Roferon-A [alpha-2a], Intron A [alpha-2b])

Recombinant DNA product. Mechanism of antitumor activity not clearly understood; direct antiproliferative effects against malignant cells and modulation of host immune response may be important.

Adult

2 million U/m2 SC 3 times/wk for 30 d

Pediatric

Not established

Theophylline may increase toxicity; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity, interleukin 2

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in brain metastases, severe hepatic or renal insufficiency, seizure disorders, multiple sclerosis, or compromised CNS

Alkylating agents

These agents are recommended as initial therapy of severe, life-threatening Churg-Strauss syndrome (allergic granulomatosis) and for patients who are not responsive to corticosteroids alone.


Cyclophosphamide (Cytoxan, Neosar)

Chemically related to nitrogen mustards. As an alkylating agent, mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Adult

0.6 g/m2 to 2.0 mg/kg/d infused over 1 h, followed by vigorous IV hydration; repeat 1 time/mo for 1 y; first pulse given on day 4 after third day of bolus methylprednisolone; sodium 2-mercaptoethane sulfonate (mesna) at 160% of cyclophosphamide dose separated into 4 doses at 0, 3, 6, and 9 h optional; may help prevent serious urologic adverse effects

Pediatric

Not recommended

Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity

Documented hypersensitivity; severely depressed bone marrow function

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Hematologic myelosuppression, primarily leukopenia, is most common adverse effect; nadir usually in 8-12 d; thrombocytopenia and anemia less frequent; GI adverse effects include anorexia, nausea, and emesis; PO ondansetron and dexamethasone may control nausea resistant to antiemetics; urologic adverse effects are dysuria, urgency, hematuria, bladder fibrosis, and necrosis; death from hemorrhagic cystitis has occurred (mesna may prevent); bladder cancer risk increased 45-fold; reproductive toxicities are azoospermia and amenorrhea; other adverse effects are hair loss, mucositis, and hyperpigmentation


Chlorambucil (Leukeran)

Alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription.

Adult

0.1-0.2 mg/kg/d PO or 3-6 mg/m2/d for 3-6 wk; adjust dose depending on blood counts

Pediatric

0.1-0.2 mg/kg/d PO qd for 5-15 wk

Documented hypersensitivity; previous resistance to this medication

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in seizure disorders and bone marrow suppression

Anti-TNF agents

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


Infliximab (Remicade)

Monoclonal antibody with human constant and murine variable regions; neutralizes biologic activity of TNF-alpha with high binding affinity to the soluble transmembrane forms of TNF-alpha and inhibits binding of TNF with receptors.

Adult

3-20 mg/kg IV; repeat infusions q2-6wk

Pediatric

Not established

Active infection, moderate-to-severe CHF, hypersensitivity to murine products or other components

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Severe infection (including sepsis) reported, especially with concomitant immunosuppressive infections; histoplasmosis, coccidioidomycosis, listeriosis, Pneumocystis TB, other bacterial and fungal infections reported; in patients in areas with endemic histoplasmosis or coccidioidomycosis, carefully weigh benefits and risks


Etanercept (Enbrel)

Fusion protein of TNF receptor and Fc portion of human IgG-1; binds TNF and blocks interaction of TNF-alpha and TNF-beta with cell-surface receptors, rendering TNF biologically inactive.

Adult

25-50 mg SC 2 times/wk

Pediatric

0.4 mg/kg/wk SC; not to exceed 25 mg

Concomitant use of anakinra increases infection risk

Active infection, immunization with live vaccines

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Allergic reactions reported; may worsen or increase infections; associated with life-threatening infectious disease besides TB (eg, candidiasis, histoplasmosis, aspergillosis, listeriosis); TNF-alpha antagonists often used with other immunosuppression, particularly glucocorticoids and MTX; increased rates of TB or other infections due to interactions among therapies unknown

More on Churg-Strauss Syndrome (Allergic Granulomatosis)

Overview: Churg-Strauss Syndrome (Allergic Granulomatosis)
Differential Diagnoses & Workup: Churg-Strauss Syndrome (Allergic Granulomatosis)
Treatment & Medication: Churg-Strauss Syndrome (Allergic Granulomatosis)
Follow-up: Churg-Strauss Syndrome (Allergic Granulomatosis)
Multimedia: Churg-Strauss Syndrome (Allergic Granulomatosis)
References
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References

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  2. Churg J, Strauss L. Allergic granulomatosis, alletic angiitis, and periarteritis nodosa. Am J Pathol. 1951;27:277.

  3. Oh MJ, Lee JY, Kwon NH, Choi DC. Churg-Strauss syndrome: the clinical features and long-term follow-up of 17 patients. J Korean Med Sci. Apr 2006;21(2):265-71. [Medline].

  4. Gota CE, Mandell BF. Systemic necrotizing vasculitis. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ. Fitzpatrick's Dermatology in General Medicine. 2. 7th. New York: McGraw Hill; 2008:1606-1616/165.

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  7. Piette WW. Primary systemic vasculitis. In: Sontheimer RD, Provost TT. Cutaneous manifestations of rheumatic diseases. 2nd. New York: Lippincott Williams & Wilkins; 2004:159-196/ Chp 8.

  8. Pagnoux C, Guilpain P, Guillevin L. Churg-Strauss syndrome. Curr Opin Rheumatol. Jan 2007;19(1):25-32. [Medline].

  9. Phillip R, and Lugmani R. Mortaility in systemic vasculitis: a systemic review. Clin Exp Rheumatol. 2008;26 (5 Suppl 51):S94-104.

  10. Lhote F, Guillevin L. Polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome. Clinical aspects and treatment. Rheum Dis Clin North Am. Nov 1995;21(4):911-47. [Medline].

  11. Neumann T, Manger B, Schmid M, Kroegel C, Hansch A, Kaiser WA. Cardiac involvement in Churg-Strauss syndrome: impact of endomyocarditis. Medicine (Baltimore). Jul 2009;88(4):236-43. [Medline].

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  13. Wong DA, Miller MK, Lawrence-Miyasaki L. Churg-Strauss Syndrome in patients treated with omalizumab. Chest [serial online]. May 2009;May 2009:Accessed July 15, 2009. [Medline]. Available at http://www.chestjournal.org/content/early/2009/05/01/chest.08-2990.long.

  14. Keogh KA, Specks U. Churg-Strauss syndrome: clinical presentation, antineutrophil cytoplasmic antibodies, and leukotriene receptor antagonists. Am J Med. Sep 2003;115(4):284-90. [Medline].

  15. Peen E, Hahn P, Lauwers G, Williams RC Jr, Gleich G, Kephart GM. Churg-Strauss syndrome: localization of eosinophil major basic protein in damaged tissues. Arthritis Rheum. Aug 2000;43(8):1897-900. [Medline].

  16. 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].

  17. [Guideline] Global Initiative for Asthma. Global strategy for asthma management and prevention. National Guideline Clearinghouse. 2008.

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Further Reading

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Keywords

Churg-Strauss syndrome, allergic granulomatosis, CSS, allergic granulomatosis and angiitis, allergic granulomatous angiitis, asthma, transient pulmonary infiltrates, hypereosinophilia, systemic vasculitis, allergic rhinitis, peripheral blood eosinophilia

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Contributor Information and Disclosures

Author

Claudia Hernandez, MD, Assistant Professor, Department of Dermatology, University of Illinois at Chicago College of Medicine
Claudia Hernandez, MD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for Laser Medicine and Surgery, Chicago Dermatological Society, Chicago Medical Society, Dermatology Foundation, National Hispanic Medical Association, and Society for Investigative Dermatology
Disclosure: Amgen Honoraria Speaking and teaching; Centocor Honoraria Speaking and teaching

Medical Editor

Jacek C Szepietowski, MD, PhD, Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland
Disclosure: Stiefel Salary Employment; Orfagen Consulting fee Consulting; Maruho Consulting fee Consulting; Astellas Consulting fee Consulting

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Catherine M Quirk, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania
Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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