Churg-Strauss Disease Medication

Updated: Jul 21, 2020
  • Author: Nir Shimony, MD; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP  more...
  • Print
Medication

Medication Summary

The mainstay of treatment of Churg-Strauss disease (CSD), now known as eosinophilic granulomatosis with polyangiitis (EGPA), is combination of steroids and immunosuppressants agents. Corticosteroids assist in lowering the eosinophilia burden as well as diminished the tissue infiltrates. For most patients, EGPA is a readily treatable illness, and reports over the past few decades have shown better outcomes than were demonstrated in earlier case series. In part, this may be due to the inclusion of milder cases due to improved recognition. In particular, diagnostic sensitivity has been greatest for individuals whose initial presentation is with asthma (90% of cases in some case series). However, a major factor has been the availability of corticosteroids. Milder EGPA may respond well to orally administered corticosteroids.

The recommended initial medications for treatment of severe manifestations of EGPA, including patients with EGPA–related peripheral neuritis, are corticosteroids, which are administered at high doses. In mild disease 1 mg/kg of Prednisone can be  initiated. In more severe cases the use of intravenous methylprednisolone at doses of 15 mg/kg on 1-3 successive mornings is a better option. Rapid correction of eosinophilia, leukocytosis, and elevations of sedimentation rate and LDH are characteristic of EGPA. Failure to provoke such corrections early in the course of therapy is associated with elevated risk for poor long-term outcome.

Intravenous treatment is followed by oral prednisone at a dose of approximately 1 mg/kg/d (usual, but absolute maximal daily dose should not exceed 80 mg/d), with ensuing taper once clinical improvement is noted.

Many patients with EGPA manifest a favorable response to this monotherapeutic approach within a few days; however, in many cases, persistence of asthma prevents oral prednisone from being tapered to doses lower than 10-15 mg/d. In milder cases, initial treatment can be undertaken with the administration of oral corticosteroids at doses of 1 mg/kg/d (60 mg/d is the usual but not absolute maximal dose).

Corticosteroid treatment, whether oral or intravenous, has been combined with plasma exchange or plasmapheresis for cases that were difficult to treat. This combination appears to have conferred benefit in some patients. Some patients have demonstrated marked clinical improvement, accompanied by declining circulating pANCA titers, after treatment with intravenous immunoglobulin (IVIg). Some patients have been treated, either initially or during a subsequent phase of therapy, with the combination of daily oral prednisone and cyclophosphamide. This approach may enhance disease control and may have a sparing effect upon steroid dosage, thus diminishing steroid-related adverse effects. Prednisone taper in patients responding to the combined therapy can be undertaken after approximately 2 weeks.

The combination of high-dose corticosteroids and dapsone has been used in patients with severe Churg-Strauss disease and has proven effective in instances of Churg-Strauss myocarditis. [28]  Corticosteroid doses may be reduced after improvement in myocarditis is achieved. IVIg is considered in neuropathy or cardiomyopathy refractory to conventional therapy. [134]

Cyclophosphamide treatment (titrated to the neutrophil count) generally is continued for 6-12 months after remission is established. Pulse intravenous cyclophosphamide therapy in combination with corticosteroids appears to diminish the risk for various adverse effects seen in patients receiving oral cyclophosphamide daily. This form of therapy is also considered in patients whose disease responds poorly to corticosteroids. Dose, frequency, and total number of cyclophosphamide pulses are adjusted to disease response, blood counts, and renal function. Efficacy of this form of therapy is not, as yet, fully established.

Usually, collaborating with physicians specializing in renal medicine is the best way to undertake this form of therapy. Protocols must be utilized to ensure that renal function is preserved with regard to additionally administered medications and hydration. These protocols entail intense hydration and coadministration of 2-mercaptoethanesulfonate (mesna). Some studies have used initial pulse intravenous cyclophosphamide at doses as high as 0.6 g/m2 of body surface, but this dose must be reduced in accordance with the degree of impairment of renal function exhibited by the patient.

Azathioprine, methotrexate, or ribavirin have possible roles in the treatment of CSD, but these drugs require additional study and should not be used without the participation of a subspecialist who can provide recommendations concerning dosage, anticipated benefits, and adverse effects.

The suggestion has been made that males with CSD might attain some benefit from treatment with thalidomide. This approach requires considerable additional study and the participation of an expert who can provide information concerning appropriate dosage, anticipated benefits, and adverse effects. The use of thalidomide is contraindicated in women of childbearing age. None of the drugs noted in this paragraph should be used without the collaboration of subspecialists skilled in their use and familiar with the relative indications, dosage adjustments, potential benefits, and adverse effects. Therefore, none of these agents are reviewed in the following Medication section because the complex issues entailed with their use fall beyond the scope of this article.

Summary for treatment perspectives in EGPA can be: [135]

Induction of remission

Mild disease

Oral prednisone: 1 mg/kg daily for 3 weeks, then tapering 5 mg every 10 days to 0.5 mg/kg. Then taper 2.5 mg every 10 days to the minimal effective dosage, or until definite withdrawal

Or

Intravenous methylprednisolone pulse (15 mg/kg) followed by oral prednisone as above. This option can be used in all cases or selectively in the more severe presentations

Relapse

Oral azathioprine 2/mg/kg daily for at least 6 months

Or

Cyclophosphamide pulses (600 mg/m2) every 2 weeks for 1 month, then every 4 weeks after that

Severe disease in presentation

Three consecutive methylprednisolone pulses (15 mg/kg) on day 1 to 3 plus oral prednisone 

Plus

Either 12 cyclophosphamide pulses (600 mg/m2) every 2 weeks for 1 month, then every 4 weeks after that

Or

Short-course of cyclophosphamide (oral 2 mg/kg) for 3 months or 6 cyclophosphamide pulses (600 mg/m2) every 2 weeks for 1 month, then every 4 weeks after that, followed by azathioprine 2 mg/kg for 1 year or more

Maintenance of remission

Methotrexate (10–25 mg per week)

Cyclosporin A (1.5–2.5 mg/kg per day)

Azathioprine (2 mg/kg per day)

Refractory disease

Plasma exchange

IVIG (0.4 g/kg per day for 5 days)

Interferon-alpha (3 million IU 3 times per week subcutaneously). Interferon-alpha as well as Rituximab (anti-CD20) are especially good for ANCA related vasculitis [136]  

TNF inhibitors: Infliximab, etanercept, adalimumab

Rituximab (325 mg/m2 for 4 consecutive weeks)

Next:

Corticosteroids

Class Summary

These medications decrease the activity of the immune system in inflammatory reactions. The immune system is of critical importance in the pathophysiology of this disease.

Methylprednisolone (Medrol, Solu-Medrol, Depo-Medrol)

Moderate or severe cases often treated for 1-3 d with IV methylprednisolone (or equivalent dose of some other anti-inflammatory corticosteroid). Administer initial dose under close supervision, since rare instances of anaphylaxis after initial dose have been reported.

Prednisone (Sterapred)

Useful in initial management of mild cases (especially for asthma) and in taper and maintenance phases of therapy for Churg-Strauss disease.

Previous
Next:

Cytotoxic agents

Class Summary

These agents inhibit cell growth and proliferation, reducing the activity of the immune system.

Cyclophosphamide (Cytoxan)

Synthetic drug, chemically related to nitrogen mustards, developed as antineoplastic agent. Biotransformed in liver, where constituent alkylating metabolites activated. These activated compounds interfere with growth of susceptible rapidly proliferating cells. Mechanism of action with regard to tumor cells may involve cross-linking of tumor cell DNA.

Previous