A 54-year-old woman presented to the emergency department with a chief complaint of acute-onset chronic panniculitis involving the abdominal wall, along with new-onset tongue swelling, lesions on both ankles and bilateral leg swelling.
The patient’s past medical history was significant for hypothyroidism and chronic abdominal wall fat on the left side, which had been intermittently inflamed over the previous 2 years. Otherwise, her health was good. She reported no smoking, drinking or illicit drug use. Her family history was significant for autoimmune disease, with systemic lupus erythematosus (SLE) on her father’s side. She is postmenopausal.
The patient’s lab test results were significant for anemia, with a hemoglobin of 9.7 g/dL and a hematocrit of 29.1 mL/dL on complete blood count and 79% segmented neutrophils on differential. She had a large amount of occult hematuria on urinalysis and an elevated creatinine level of 1.2 mg/dL. She was afebrile and normotensive. Her erythrocyte sedimentation rate was elevated at 100 mm/h.
A computed tomography (CT) scan of the chest with and without contrast showed multiple lung nodules, suggesting benign entities such as granulomas or focal scars. These nodules had been noted on prior outpatient CT scans performed over 2 years, and they appeared to decrease and increase in size over time, suggesting autoimmune disease rather than an infectious process.
Further Evaluation
A biopsy of the pannus 2 years prior had shown lymphohistiocytic infiltrate with germinal centers and a preponderance of kappa light chains. Lymphohistiocytes often are associated with infections such as Epstein-Barr virus, cytomegalovirus and parvovirus, among others, as well as with autoimmune disorders and malignancies. Characterization of the T and B cells suggested that they were of nonmalignant origin.
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The patient was evaluated by the rheumatology and dermatology departments, and a biopsy of her ankle lesions was performed to correlate with the known pathology of her abdominal mass. Biopsy results indicated leukocytoclastic vasculitis – the presence of leukocytes in vessel walls, producing reactive damage to mural structures.
The patient underwent further workup for vasculitic syndromes. Her rheumatoid factor was 42 IU/mL (reference range 0-30 IU/mL), and an antinuclear antibody test was positive.
A proteinase 3 (PR3) antibody test was negative at < 6 U/mL (reference value < 3.5 U/mL). The patient also underwent an antineutrophilic cytoplasmic antibodies (ANCA) test. Perinuclear ANCA and cytoplasmic ANCA were reactive, suggesting Wegener’s granulomatosis (WG) or microscopic polyangiitis. Cryoglobulin test results were negative, ruling out cryoglobulinemia and SLE. A Jo-1 antibody test and an antiglomerular basement membrane (GBM) antibodies test to rule out anti-GBM antibody disease were negative. Myeloperoxidase (MPO) antibodies were > 100 U/mL (reference ranges: < 6.0 U/mL, negative; 6.0-9.0 U/mL, equivocal; > 9.0 U/mL, positive), also suggesting WG. Still, the negative PR3 results prohibited a definitive diagnosis, since positive PR3 test results occur in most people with WG.
Confirming the Diagnosis
The patient was started on 500 mg of methylprednisolone on admission, which appeared to improve her leg swelling.
Since lab results noted hematuria, renal histology was needed. Renal insufficiency is common in WG, and urinalysis often shows red blood cell casts and other casts due to glomerular inflammation and necrosis. Renal histology often provides evidence of vessel inflammation. In WG, inflammation of the smaller vessels, venules, capillaries and arterioles is common. In other vasculitides, such as Henoch-Sch”nlein purpura or anti-GBM antibody disease, biopsy reveals deposits of immunoglobulins A and G in the capillary walls, but in WG, no immune deposits (pauci-immune glomerulonephritis) can be found in the glomeruli.1
Renal biopsy showed pauci-immune glomerulonephritis, confirming the diagnosis of WG, which was MPO-positive and ANCA-positive but PR3-negative, a set of findings occurring in only a small percentage of WG patients.2
Wegener’s Granulomatosis
Vasculitic syndromes should be considered in patients with multiorgan symptoms; systemic symptoms such as weakness and fever; pulmonary-renal symptoms such as hemoptysis or hematuria suggesting glomerulonephritis; hypertension; and hepatitis C infection.
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WG, also known as granulomatosis with polyangiitis, is a vasculitis affecting small and medium blood vessels (Table 1). First described in 1954 by Goodman and Churg, WG is described pathologically as having a triad of features: systemic necrotizing angiitis, necrotizing granulomatous inflammation of the respiratory tract, and necrotizing glomerulonephritis.3
WG is classified as limited or severe based on criteria from the American College of Rheumatology (Table 2).4 The absence of hematuria, red blood cell casts, pulmonary involvement as measured by oxygen saturation, and disease in critical organs defines limited WG. Severe disease comprises everything else.3
Approximately 90% of WG cases are in people of northern European descent, with a slightly greater male-to-female ratio, and with women more likely to have limited disease.3 The mean age at diagnosis is between 45 and 50 years.5
Treatment with glucocorticoids and cytotoxic agents is initiated at diagnosis and continues until remission is induced.5 Treatment of patients with WG underwent a dramatic change in the early 1970s with the introduction of the combination of cyclophosphamide and high-dose glucocorticoids. Before 1970, 50% of patients with WG survived only 5 months after diagnosis, and 82% died within 1 year.5 With combination treatment, remission occurs in 75% of patients; still, more than 60% of patients relapse after 6 years.6
The patient was continued on steroids, which were tapered to prednisone 60 mg daily, and started on cyclophosphamide before being discharged with follow-up by nephrology for continued monthly cyclophosphamide treatments.
Grace A. Jordan is a PA at Sentara Pulmonary and Critical Care Specialists in Norfolk, Va. Gordon A. Ryan is a physician in internal medicine in Norfolk, Va. They have completed disclosure statements and report no relationships related to this article.
References
1. Haas M, et al. Etiologies and outcome of acute renal insufficiency in older adults: a renal biopsy study of 259 cases. Am J Kidney Dis. 2000;35(3):433.
2. Jennette CJ, Falk RJ. Small-vessel vasculitis. N Engl J Med. 1997;337(21):1512-1523.
3. Papadopoulos PJ. Wegener granulomatosis. Medscape Reference. http://emedicine.medscape.com/article/332622-overview. Updated Aug. 10, 2011. Accessed Oct. 31, 2011.
4. Leavitt RY, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis. Arthritis Rheum. 1990;33(8):1101-1107.
5. Wung PK, Stone JH. Therapeutics of Wegener’s granulomatosis. Nat Clin Pract Rheumatol. 2006;2(4):192-200.
6. Hoffman GS, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992;116(6):488-498.
