Microscopic polyangiitis in a pregnant woman. (Case Reports).

ABSTRACT: Patients who have vasculitis in pregnancy generally have a grim prognosis. Vasculitis occurring during pregnancy may have a more aggressive course and require more aggressive treatment than vasculitis occurring at other times. A 29-year-old woman who presented in the 16th week of her third intrauterine pregnancy was diagnosed as having active microscopic polyangiitis. Therapy consisting of high-dose methyiprednisolone and cyclophosphamide was instituted, but the patient died of pulmonary infection due to methicillin-resistant Staphylococcus aureus.

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MICROSCOPIC POLYANGIITIS (MPA) is a systemic, small-vessel vasculitis, primarily associated with necrotizing glomerulonephritis and pulmonary capillaritis. Patients with this disease have predominant involvement of glomerular capillaries, without the granuloma formation seen in Wegener's granulomatosis (WG). (1)

Limited information is available on pregnancy outcome and medication use in these patients, because primary vasculitis most often occurs m older individuals and is more common in men (23) Vasculitis involving the medium-sized arteries, such as polyarteritis nodosa (PAN), Churg-- Strauss syndrome (CSS), or WG, is more often reported in pregnant patients (2-6) We describe a fatal case of MPA during pregnancy.

CASE REPORT

A previously well 29-year-old multigravida woman who was 16 weeks pregnant was admitted to our hospital. She had a rash on her limbs and a 2-month history of fever and arthralgia. Three weeks before admission, she had fatigue, dyspnea, cough, and rash. She had hematuria, oliguria, and azotemia, and was transferred to our department.

She had no history of hypertension or renal disease, and family history was unremarkable. On physical examination, she was adynamic and pale. Systemic blood pressure was 130/80 mm Fig, and temperature was 38.20[degrees]C. At the extensor sides of the lower extremities, palpable pur-pura was present. Inspiratory and expiratory rales at both lung bases were noted on chest examination.

Laboratory values were erythrocyte sedimentation rate, 78 mm/hr (Westergren); C-reactive protein, 3.2 mg/dL (normal, <0.8 mg/dL); hemoglobin, 8.4 g/dL; white blood cell count, 22,000/[mm.sup.3] platelet count, 450,000/mm (3); blood urea nitrogen, 56 mg/dL; creatinine, 5.4 mg/dL, albumin, 2.8 g/dL; cholesterol, 176 mg/dL; and triglycerides, 188 mg/dL. The serum electrolyte levels were normal. The 24-hour urinary protein excretion was 3.2 g; the sediment contained 30 to 40 red cells and 10 to 15 white cells per high-power field. The prothrombin and partial thrombo-plastin times were normal. Antinuclear antibodies, anti-double-stranded DNA antibodies, anticardiolipin immunoglobulin (Ig) G, anticardiolipin IgM were all negative. Peri-nuclear antineutrophil cytoplasmic antibody (pANCA) test was found to be positive (64 IU/mL; normal, <4 IU/mL) with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) specificity. To protect the fetus from radiation, we did not perform any x-rays of the patient's lungs in the first clays after admission to our hospital. Kidneys were normal on ultrasonography. A percutaneous renal biopsy was performed on fourth day of hospitalization, and histology showed a small-vessel vasculitis of the MPA type, characterized by transmural inflammation of the arterial wall, with a heavy infiltrate of neutrophils, eosinophils, and mononuclear cells, destruction of the blood-vessel wall, and segmental fibrinoid necrosis (Figure). We were able to diagnose MPA due to the general arthralgia, myalgia, skin lesions, kidney failure, renal biopsy findings, and positive pANCA resuhs. The elevated pANCA level allowed us to distinguish this from WG. Therapy with methylprednisolone (1,000 mg/day for 3 days) and cyclophosphamide (500 mg for 1 day) was begun.

On the third day of therapy, spontaneous abortion occurred. Chest radiography the next day showed diffuse, reticulonodular pulmonary shadowing and pulmonary hemorrhage. After the pulse therapy, we continued the treatment with methylprednisolone (40 mg/day). Serum creatinine level decreased to 1.5 mg/dL on the 15th day of therapy.

Eighteen days after pulse therapy, the patient had severe respiratory infection with methicillin-resistant Staphylococcus aureus. On the 22nd day after admission, she died of respiratory failure related to acute respiratory distress syndrome.

DISCUSSION

Microscopic polyangiitis is a systemic vasculitis that is histologically characterized by small-vessel involvement; MPA was initially recognized as a particular type of polyarteritis nodosa (PAN), with rapidly progressive necrotizing glomerulonephritis in most cases, and sometimes involving lung hemorrhage. Unlike PAN, most patients with MPA present with or later have severe renal disease, particularly if the diagnosis is delayed. (1) In MPA, a perinuclear pattern of staining (pANCA) is usually seen, in contrast with the diffuse granular cytoplasmic staining (cANCA) seen in WG. Much of the initial clinical presentation of MPA is nonspecific. Systemic symptoms, such a malaise, anorexia, fever, and weight loss, predominate initially, and these are often accompanied by asynchronous episodes of rash, arthralgia, and myalgia. Renal disease presents clinically with microscopic hematuria and proteinuria in patients with MPA. More than 90% of patients have renal impairment, and in most series, no fewer than 30% of pa tients were oliguric by the time the diagnosis was made. Other clinical symptoms that occur in MPA, such as alveolar hemorrhage, constitute a pulmonary-renal syndrome similar to that observed in Goodpasture's syndrome or WG. (1,7-9)

If the clinical findings of MPA are life-threatening, therapy with high-dose corticosteroids and cyclophosphamide must be considered. Data are limited concerning vasculitis during pregnancy; most of the reported cases have been diagnosed with classic PAN, CSS, or WG. (2-6) Unfortunately, few data are available regarding the use of high-dose cyclophosphamide and methylprednisolone therapy in pregnancy. Most of the data come from case reports describing the use of chemotherapeutic drugs for various cancers, including leukemia, lymphoma, breast cancer, and Ewing's sarcoma. Cyclophosphamide is contraindicated during pregnancy, but data on its real fetal toxicity are limited. (10) Normal labor and delivery has been documented when cyclophosphamide therapy was begun after the second trimester of pregnancy. (5,11)

In our patient, treatment with pulse therapy was associated with a spontaneous abortion. After treatment, temperature decreased, urinary volume increased, and creatinine level decreased to within normal range. The patient died, however, because of sepsis from pneumonia. In MPA, similar to other vasculitides and collagen vascular diseases, death can result from disease activity or from various causes not necessarily related to the vasculitis. (12,13)

In this report, we emphasize that vasculitis in pregnant patients can develop rapidly, and evaluation and treatment should be the same as for a nonpregnant individual.

References

(1.) Adu D, Bacon PA: Classical polyarteritis nodosa, microscopic polyarteritis, and Churg-Strauss syndrome. Oxford Textbook of Rheumatology. Maddison PJ, Isenberg DA, Woo P, et al (eds). London, Oxford University Press, 1998, pp 1351-2365

(2.) Owen J, Hauth JC: Polyarteritis nodosa in pregnancy: a case report and brief literature review. Am J Obstet Gynecol 1989; 160:606-607

(3.) Reed NR, Smith MT: Periarteritis nodosa in pregnancy: report of a case and review of the literature. Obstet Gynecol 1980; 55:381-384

(4.) Burkett G, Richards R: Periarteritis nodosa and pregnancy. Obstet Gynecol 1982; 59:252-254

(5.) Dayoan ES, Dimen LL, Boylen CT: Successful treatment of Wegener's granulomatosis during pregnancy: a case report and review of the medical literature. Chest 1998; 113:836-838

(6.) Habib A, MacKay K, Abrons HL: Wegener's granulomatosis complicating pregnancy: presentation of two patients and review of the literature. Clin Nephrol 1996; 46:332-336

(7.) Falk RJ, Nachman PH, Hogan SL, et al: ANCA glomerulonephritis and vasculitis: a Chapel Hill perspective. Semin Nephrol 2000; 20:233-243

(8.) Franssen CF, Stegeman CA, Kallenberg CG, et al: Antiproteinase 3- and antimyeloperoxidase-associated vasculitis. Kidney Int 2000; 57:2195-2206

(9.) Brijker F, Magee CC, Tervaert JW, et al: Outcome analysis of patients with vasculitis associated with antineutrophil cytoplasmic antibodies. Clin Nephrol 1999; 52:344-351

(10.) Luisiri P, Lance NJ, Curran JJ: Wegener's granulomatosis in pregnancy. Arthritis Rheum 1997; 40:1354-1355

(11.) Auzary C, Huong DT, Wechsler B, et al: Pregnancy in patients with Wegener's granulomatosis: report of five cases in three women. Ann Rheum Dis 2000; 59:800-804

(12.) Duffy KN, Duffy CM, Gladman DD: Infection and disease activity in systemic lupus erythematosus: a review of hospitalized patients. J Rheumatol 1991; 18:1180-1184

(13.) Carder PJ, Harrison DJ: Opportunistic infection and antineutrophil cytoplasm antibodies in Wegener's granulomatosis. Respir Med 1989; 83:421-424

KEY POINTS

* Unlike polyarteritis nodosa, most patients with microscopic polyangiltis have severe renal disease, particularly if diagnosis is delayed.

* Microscopic polyangiitis is a systemic vasculitis that is histo-logically characterized by small-vessel involvement.

* Limited data are available on pregnancy outcome and medication use in these patients because primary vasculitis occurs most often in older individuals and is more common in men.

* Vasculitis occurring during pregnancy may have a more aggressive course and require more aggressive treatment than vasculitis occurring at other times.

From the Departments of Nephrology, Pathology, and Obstetrics and Gynecology, Ataturk University School of Medicine, Erzurum, Turkey.

Reprint requests to Ali Riza Odabas, MD, Ataturk Universitesi Postanesi PK:26, 25171, Erzurum, Turkey.