eMedicine Specialties > Rheumatology > Vasculitis
Microscopic Polyangiitis: Treatment & Medication
Updated: Jan 20, 2010
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Microscopic polyangiitis (MPA) can manifest as a mild systemic vasculitis with mild renal insufficiency, or it can manifest as a full blown acute disease with rapid deterioration of renal function and respiratory failure due to pulmonary capillaritis. Treatment depends on the extent of disease, the rate of progression, and the degree of inflammation (see Medication).
Consultations
- A rheumatologist would be the main consultant who helps with the diagnosis and immunosuppressive therapy.
- Base consultations on the specific organ system involvement, as follows:
- Consult a pulmonologist for the management of hemoptysis due to pulmonary alveolar capillaritis. Additionally, consult a pulmonologist to help with the management of respiratory failure associated with diffuse alveolar hemorrhage and with the diagnosis of pulmonary involvement.
- Consult a nephrologist for help with the diagnosis and management of renal involvement and possible need for dialysis.
- Consult a gastroenterologist, if necessary, for the management of gastrointestinal bleeding.
- Consult a surgeon in cases involving catastrophic events in gastrointestinal or other organ systems.
- Consult a hematologist if plasmapheresis is considered.
Diet
- The nutritional requirement depends on the particular clinical situation, such as renal failure, respiratory failure, or pancreatitis.
Medication
Treatment of microscopic polyangiitis (MPA) consists of 3 phases.
- First phase - Remission induction with oral prednisone and cyclophosphamide
- For induction of remission, cyclophosphamide is started at 1.5-2 mg/kg/d. The patient should be monitored for leukocytopenia and neutropenia. Prednisone is started at 1 mg/kg/d and is continued for one month. If significant improvement is seen, the prednisone dose is decreased by 5 mg/wk. Once the dose of 10 mg/d is reached, the dose can be changed to 10 mg every other day. After complete remission, the maintenance phase is started.
- For induction of remission in patient with milder manifestations of MPA, a combination of methotrexate and prednisone can be used. However, a significantly higher relapse rate was observed with this combination than with the combination of cyclophosphamide and prednisone.
- In cases involving life-threatening alveolar capillaritis with pulmonary alveolar hemorrhage, plasmapheresis in addition to intravenous cyclophosphamide and pulse doses of steroids may be used.
- Glucocorticoid monotherapy is not recommended because of lower remission rates.
- Second phase - Remission maintenance
- The preference is to replace cyclophosphamide, which has high toxicity, with either methotrexate or azathioprine. If the serum creatinine concentration is greater than 2 mg/dL, methotrexate is no longer an option. At this phase, prednisone is continued and cyclophosphamide is replaced with azathioprine at 2 mg/kg/d for 12 months. After a year, the dose of azathioprine is decreased to 1.5 mg/kg/d. If methotrexate is used for maintenance treatment, it can be started at 0.3 mg/kg once a week, with the maximum dose of 15 mg/wk. This is increased by 2.5 mg/wk (maximum 20 mg/wk).
- This phase is continued for 12-24 months. Prednisone can be continued at 10 mg/d or every other day.
- Third phase - Treatment of relapse (The treatment of relapse MPA is the same as that of remission induction [see First phase].)
- Other therapies include the following:
- The use of sulfamethoxazole/trimethoprim is controversial in the prevention of relapse. The use of this treatment for Wegener granulomatosis has shown promising results.7,8 The relationship between Staphylococcus aureus colonization and the relapse rate has shown a debatable correlation.
- The use of mycophenolate mofetil in the treatment of MPA has been limited. In several small studies, mycophenolate mofetil was effective in maintaining remission in patients with MPA, even in those with moderate-to-severe renal impairment.9,10,11
- Cyclosporine is used for maintenance therapy.
- Intravenous immunoglobulin has been used in treatment of refractory disease.
Pneumocystis carinii pneumonia (PCP) (Pneumocystis jiroveci) prophylaxis via low-dose sulfamethoxazole/trimethoprim given as one double-strength tablet 3 times weekly is prudent.11
Corticosteroids
First line of treatment for induction of remission and usually for maintenance. For induction of remission, use IV methylprednisolone. For maintenance, use prednisone.
Methylprednisolone (Adlone, Medrol, Solu-Medrol)
Steroids ameliorate effects immune reactions and may limit biphasic anaphylaxis.
Adult
Pulse dose: 7 mg/kg/d IV for 3 d, followed by tapering dose
Pediatric
Not established
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia with concurrent diuretics
Documented hypersensitivity; viral, fungal, or tubercular 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
Observe for weight increase, edema, hypertension, and excessive potassium excretion and for less obvious signs of adrenocortical steroid-induced untoward effects; monitor for negative nitrogen balance due to protein catabolism; evaluate blood pressure and body weight and perform routine laboratory studies, including 2-h postprandial blood glucose and serum potassium and a chest radiograph at regular intervals during prolonged therapy
Steroid psychosis characterized by delirious or toxic psychosis with clouded sensorium; other symptoms may include euphoria, insomnia, mood swings, personality changes, and severe depression; onset of symptoms usually occurs within 15-30 d; predisposing factors include doses >40 mg prednisone equivalent, female predominance, and, possibly, a family history of psychiatric illness
Prednisone (Deltasone, Orasone, Sterapred)
Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.
Adult
40-60 mg PO qd; once ESR decreases to normal and patient is asymptomatic, reduce to 5-10 mg q1-2wk; once dose is down to 15 mg qd, reductions should be no more than 1-mg decrements every several weeks
Pediatric
Not established
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Immunosuppressive agents
These agents inhibit immune reactions that result from diverse stimuli.
Methotrexate (Folex PFS, Rheumatrex)
Should not be used if serum creatinine clearance is >2.0 mg/dL.
Unknown mechanism of action in treatment of inflammatory reactions; may affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust dose gradually to attain satisfactory response. An alternative form of less toxic therapy only for localized and nonaggressive disease is combination of MTX and prednisone.
Adult
10-25 mg PO/IV/IM qwk until adequate response achieved
Pediatric
Not established
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral MTX; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained 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; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency; methotrexate-induced pulmonary disease
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor CBC counts monthly and liver and renal function every 1-3 mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels, eg, dehydration); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood counts; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly with MTX (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested)
Azathioprine (Imuran)
Immunosuppressive agent; antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.
Adult
Initial dose: Approximately 1 mg/kg (50-100 mg) PO/IV qd or bid
Dose may be increased, beginning at 6-8 wk and thereafter in steps at 4-wk intervals, if no serious toxicities develop and if initial response unsatisfactory; use dose increments of 0.5 mg/kg/d, not to exceed 2.5 mg/kg/d
Pediatric
Not established
Toxicity increases with allopurinol; 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; low levels of serum thiopurine methyl transferase (TPMT)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level prior to therapy and follow liver, renal, and hematologic function; pancreatitis rarely associated
Cyclophosphamide (Cytoxan, Neosar)
Chemically related to nitrogen mustards.
As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Adult
0.5 g/m2/mo; adjusted to 1 g/m2 according to WBC count; maintenance treatment usually continues for 12 mo
Pediatric
Not established
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 rate of 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
Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis
More on Microscopic Polyangiitis |
| Overview: Microscopic Polyangiitis |
| Differential Diagnoses & Workup: Microscopic Polyangiitis |
 Treatment & Medication: Microscopic Polyangiitis |
| Follow-up: Microscopic Polyangiitis |
| Multimedia: Microscopic Polyangiitis |
| References |
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Further Reading
Keywords
microscopic polyangiitis, MPA, small vessel vasculitis, microscopic polyarteritis nodosa, microscopic PAN, small vessel vasculitides, systemic vasculitis, Wegener granulomatosis, Wegener's granulomatosis, Churg-Strauss syndrome, polyarteritis nodosa
