CAN CAUSE ANGINA DUE TO MICROVASCULAR ABNORMALITIES.
Medical Care: The initial management of PAN includes high-dose GCs, usually administered as pulse intravenous methylprednisolone (15 mg/kg per dose IV, repeated q24h for 1-3 d). Subsequently, start daily oral prednisone at 1 mg/kg/d. As the patient's clinical status and ESR normalize, usually within 1 month, the prednisone dosage can be tapered progressively over a period of 9-12 months and then stopped. When prednisone is combined with CY, the steroid dose is tapered more rapidly to reduce the increased risk of infection. Most patients with PAN require immunosuppressive therapy with CY in addition to GCs.
" When CY is necessary in the treatment regimen, intravenous pulse CY is generally preferred to oral CY. Intravenous pulse CY has a more rapid onset of action, allows a lower cumulative dose of CY to be administered, and exposes the patient to potential toxicity for shorter periods. However, in some cases, daily CY (either oral or parenteral) is needed for a satisfactory therapeutic response. Long-term adverse effects, especially the risks of bladder cancer and hematologic malignancies, are correlated with the cumulative dose of CY. Other major toxicities of CY include hemorrhagic cystitis, bladder fibrosis, bone marrow suppression, and ovarian failure. Patients are also at especially high risk of severe infections while receiving CY and high-dose GCs, usually in the initial phase of treatment of severe PAN.
" Intravenous pulse dosing regimens vary from 0.5-2.5 g at intervals of 1 week to 1 month and are individualized according to the patient's hematologic and renal function. Follow pulse therapy with intense intravenous hydration. Some also use mesna (2-mercaptoethanesulfonate salt), which detoxifies CY metabolites in the kidneys.
" Plasma exchange, or plasmapheresis, has not been found to add treatment benefit to either a regimen of GCs or a regimen of GCs and CY in the initial management of patients with PAN. However, plasmapheresis does play a role in refractory PAN and in patients who are dialysis-dependent, as well as in patients with HBV-related PAN.
" PAN in the setting of HBV is a special situation. Standard therapies for systemic PAN, including GCs and CY, enhance prognosis and control of the polyarteritis. However, they are also associated with persistence of HBV infection and failure to seroconvert from positive hepatitis B surface antigen (HBsAg+) to positive hepatitis B surface antibody (HBsAb+) and from positive hepatitis B e antigen (HBeAg+) to positive hepatitis B e antibody (HBeAb+). In fact, GCs are known to react with a GC response element in the HBV genome that accelerates viral replication, while CY inhibits any immune response directed at the virus.
" In 1995, Guillevin and colleagues treated 41 patients with HBV infection and PAN who had HBsAg+ and HBeAg+ serology with a regimen of GCs, antiviral agents, and plasmapheresis. The 7-year survival rate was 83% in this group of patients, with seroconversion observed in 51%, a stable (not increasing) viral titer in 56%, and total viral clearance in 24%. The specific regimen based on this data involves initial short-term prednisolone therapy 1 mg/kg/d administered for the first week to rapidly control the most severe life-threatening manifestations of PAN. The steroids are then tapered rapidly in the second week. Then antiviral agents, vidarabine or interferon alfa-2b, are administered to enhance immunologic clearance of HBV-infected hepatocytes and favor seroconversion. Plasma exchanges are used as adjunctive therapy to control the course of PAN in an effort to avoid the further use of GCs or CY.
" Isolated case reports have demonstrated benefit from the further addition of famciclovir and granulocyte-macrophage colony-stimulating factor (GM-CSF) to a regimen of antiviral therapy to cause seroconversion and viral clearance in patients who did not seroconvert and clear HBV infection with antiviral therapy alone.
" Treatment duration with a regimen of GCs with or without cytotoxic agents is usually 12 months; preferably, therapy does not exceed 18 months because disease activity is usually well controlled by then and toxicities related to treatment can be substantial.
PATIENT MONITORING
β’ CBC, urinalysis, renal and liver profi les
β’ Careful monitoring for infection
β’ Delayed appearance of neoplasms
β’ Angiographic changes may improve rapidly with combination steroid/cyclophosphamide therapy
β’ Acute phase reactants such as Interleukin-6 and C-reactive protein may be useful in diagnosis and
monitoring activity level during treatment and followup
POSSIBLE COMPLICATIONS
β’ Glomerulonephritis
β’ Renal failure
β’ Thrombosis
β’ Infarction
β’ Tissue/organ necrosis
β’ Stroke
β’ Myocardial infarct
β’ Mononeuritis multiplex
EXPECTED COURSE/PROGNOSIS
β’ Expected course of untreated polyarteritis nodosa is poor
β’ 5 year survival rate 13%
β’ Steroid and cytotoxic therapy treatment may increase percentage survival rate signifi cantly.
β’ Renal and GI signs most serious prognostic factors
β’ Patients with microscopic polyangiitis