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Acute Aortic Insufficiency Associated With Wegener Granulomatosis

      Cardiac valvular involvement associated with Wegener granulomatosis is uncommon. We describe a 17-year-old male adolescent who sought medical attention because of a sore throat, arthralgias, low-grade fever, and fatigue of 3 weeks’ duration. A rash was noted on his elbows, hands, and ankles; subsequently, a crusting lesion was noted in his internal nares, and infiltrates were detected on chest radiography. Blood cultures were negative for pathogens. An echocardiogram disclosed mild left ventricular enlargement with grade 2 aortic insufficiency, and Wegener granulomatosis was diagnosed based on an antineutrophil cyto-plasmic antibody titer of 1:512. When blood cultures are negative for aortic valve endocarditis, a high index of clinical suspicion and antineutrophil cytoplasmic antibody testing may lead to the diagnosis of acute aortic insufficiency associated with Wegener granulomatosis.

      Abbreviations:

      ANCA (antineutrophil cytoplasmic antibody)
      Wegener granulomatosis was first described in the 1930s as a distinct clinical syndrome characterized by a necrotizing granulomatous lesion of the respiratory tract, vasculitis, and glomerulonephritis.
      • Fahey JL
      • Leonard E
      • Churg J
      • Godman G
      Wegener's granu-lomatosis.
      This disease entity targets primarily the kidneys and lungs. However, it can be disseminated and involve other organ systems. Clinical manifestations related to granulomatous or vasculitic lesions of the heart are uncommon.
      • Goodfield NER
      • Bhandari S
      • Plant WD
      • Morley-Davies A
      • Sutherland GR
      Cardiac involvement in Wegener's granulomatosis.
      We report a manifestation of Wegener granulomatosis involving the aortic valve.

      REPORT OF A CASE

      In 1992, a 17-year-old male adolescent presented to his internist because of a 3-week history of sore throat, arthralgias, low-grade fever, and fatigue. He became breathless while walking up 1 flight of stairs and had had an episode of minimal hemoptysis. A rash was noted on his elbows, hands, and ankles, but no alopecia, nasopharyngeal ulcers, or Raynaud phenomenon was evident. The leukocyte count was 15.4 ×109/L, hemoglobin level was in the reference range, and the erythrocyte sedimentation rate (Westergren method) was 39 mm/h. An antistreptolysin O titer, rheumatoid factor, mononucleosis spot slide test, and throat culture for streptococcal infections were negative.
      The patient was referred to a rheumatologist. On examination, he was afebrile; his blood pressure was 126/84 mm Hg, weight was 87.1 kg, and height was 200 cm. He had no marfanoid features. Findings on a general examination, including the heart, lungs, head, eyes, ears, nose, and throat, were unremarkable. An examination of his skin revealed symmetrical erythematous papules (2 × 4 mm) on his elbows, dorsum of his hands, and metacarpophalangeal joints, as well as around his ankles and the dorsum of his feet.
      Laboratory review revealed that a Lyme antibody and fluorescent antinuclear antibodies were negative. The thyroid-stimulating hormone level, prothrombin time, and partial thromboplastin time were in the reference ranges. A follow-up leukocyte count was 15.5 × 109/L. The differential cell count was 71% polymorphonuclear leukocytes, 23% lymphocytes, 2% mononucleocytes, and 2% eosinophils. Urinalysis revealed 30 mg of protein and 5 to 10 erythrocytes per high-power field without casts. Other laboratory results were as follows (reference ranges shown parenthetically): hemoglobin level, 7.1 g/dL; mean corpuscular volume, 89.6 fL; erythrocyte sedimentation rate, 38 mm/h; aldolase, 7.8 U/L (<7.4 U/L); aspartate aminotransferase, 34 U/L (<30 U/L); creatine kinase, 269 U/L (<75 U/L); and serum creatinine, 1.1 mg/dL. Two blood cultures were negative for pathogens. A cold ag-glutinin titer was 1:128. Initial chest radiography revealed a poorly defined alveolar infiltrate in the right midlung field.
      A punch biopsy of the skin lesions revealed subepider-mal bullae that contained a few polymorphonuclear leukocytes and perivascular infiltration by lymphoid cells mixed with a few eosinophils and plasma cells. No thrombi were seen in the vessels. The patient was given prednisone, 20 mg/d, for possible vasculitis; erythromycin, 500 mg 4 times a day, for possible mycoplasma pneumonia; and keto-profen, 75 mg 3 times a day, for his arthralgias.
      The patient returned to our clinic 6 days later without improvement and complained of epistaxis. A crusting lesion was noted in the internal nares, and a cardiac examination revealed a diastolic decrescendo murmur. Sinus radiography revealed air-fluid levels in the inferior recesses of each maxillary sinus. Findings on computed tomography of the brain and frontal sinuses were unremarkable. A biopsy of the nasal passages revealed acute and chronic inflammation but no granulomas or evidence of vasculitis. An echo-cardiogram disclosed mild left ventricular enlargement with grade 2 aortic insufficiency but no evidence of vegetations. Findings on electromyography of the extremities were unremarkable, and a deltoid muscle biopsy showed no inflammation.
      The patient became progressively breathless and was admitted to the hospital 2 weeks after the initial assessment. His blood pressure was 118/70 mm Hg, and the hemoglobin level was 8.4 g/dL. An arterial blood gas study while the patient was breathing room air revealed a Po2 of 42 mm Hg and a Pco2 of 41 mm Hg. The C3 and C4 complement levels were in the reference range, as was the C-reactive protein level at less than 0.4 mg/dL. During hospitalization, the patient's pulse pressure widened such that the systolic blood pressure was 170 mm Hg and the diastolic blood pressure was audible to 0 mm Hg. Electrocardiography showed no pronounced abnormalities. The patient was scheduled to undergo an open lung biopsy because of his worsening hypoxemia and the increased infiltrates on chest radiography. On the day before the scheduled lung biopsy, findings on chest radiography were normal, and the biopsy was canceled. Findings on ultra-sonography of the kidneys were normal. Urinalysis revealed a few erythrocytes per high-power field and less than 100 mg of protein. Six blood cultures were negative for pathogens. The antineutrophil cytoplasmic antibody (ANCA) titer was 1:512, with subsequent cytoplasmic ANCA specificity.
      Wegener granulomatosis was diagnosed. Oral cyclophosphamide was initiated at 150 mg/d, and the dosage of prednisone was increased to 40 mg/d. The patient was discharged from the hospital; his dermatitis, epistaxis, pulmonary dysfunction, and arthritis had resolved. On an outpatient basis, the new-onset aortic insufficiency was monitored, and transesophageal echocardiography showed no vegetations. Despite clinical remission of the Wegener granulomatosis, the aortic valve insufficiency worsened. The patient was referred to a cardiovascular surgeon and underwent aortic valve repair approximately 1 year after his symptoms had begun. At surgery, 2 perforations were noted in the aortic valve leaflets (Figure 1): 1 was in the left coronary cusp and 1 was in the noncoronary cusp. Each perforation was approximately 1 cm in diameter. Both perforations appeared to have a well-healed rim of fibrous tissue around their margins. They were repaired by using mitral leaflet tissue from a cryopreserved homograft. Resumption of the patient's cardiac function was good, and findings on an echocardiogram were unremarkable. Eventually, the prednisone and cyclophosphamide were discontinued. The patient was lost to follow-up until June 1994.
      Figure thumbnail gr1
      Fig. 1Perforation in the left coronary cusp with a fibrous rim around the perforation. The noncoronary cusp also had a perforation, which has been closed with a tissue patch (arrow).
      The patient returned for medical care in January 1995 because of a history of yellow productive cough, migratory arthritis, dermatitis, and fatigue of several weeks’ duration. The ANCA was positive at 1:512. The erythrocyte sedimentation rate was 5 mm/h, and the antinuclear antibody was negative. He was given trimethoprim-sulfamethox-azole and prednisone. However, his symptoms worsened, and cyclophosphamide was reinitiated; his symptoms and signs subsequently resolved. As of January 1999, the Wegener granulomatosis was in remission; the patient was taking trimethoprim-sulfamethoxazole and low-dose cyclophosphamide. He has no physical limitations, the aortic valve is intact, and he is employed as a construction worker.

      DISCUSSION

      The data on the cardiac complications of Wegener granulomatosis are sparse. A review by Forstot et al
      • Forstot JZ
      • Overlie PA
      • Neufeld GK
      • Harmon CE
      • Forstot SL
      Cardiac complications of Wegener granulomatosis: a case report of complete heart block and review of the literature.
      on cardiac complications associated with Wegener granulomatosis revealed pathologic findings of pericarditis, coronary arteritis, and myocarditis. Twenty-one percent of patients examined had valvulitis or endocarditis, and conduction system defects were described.
      Cardiac valvular involvement associated with Wegener granulomatosis is uncommon. Greidinger et al
      • Greidirtger EL
      • Lcmes V
      • Hellmann DB
      Cardiac valve disease in Wegener's granulomatosis [letter].
      summarized and reviewed aortic valve involvement in Wegener granulomatosis, including their description of a patient with aortic and mitral valve involvement. Six cases involved the aortic valve alone, and 2 involved the aortic and mitral valves. Davenport et al
      • Davenport A
      • Goodfellow J
      • Goel S
      • Maciver AG
      • Walker P
      Aortic valve disease in patients with Wegener's granulomatosis.
      described 2 patients with aortic valvular disease that progressed despite clinical remission of the noncardiac manifestations of Wegener granulomatosis after treatment had been initiated. Aortic valve histopathology revealed myxoid degeneration, and 1 patient had a valve replaced.
      Yanda et al
      • Yanda RJ
      • Guis MS
      • Rabkin JM
      Aortic valvulitis in a patient with Wegener's granulomatosis.
      described 1 patient with Wegener granulomatosis who developed congestive heart failure due to aortic valve involvement. The noncoronary cusp was abnormal, and the valve was replaced. The pathological examination revealed both myxomatous and collagenous degeneration. Gerbracht et al
      • Gerbracht DD
      • Savage RW
      • Scharff N
      Reversible valvulitis in Wegener's granulomatosis.
      described a patient with Wegener granulomatosis who had a myocardial infarction, and a subsequent echocardiogram revealed evidence of aortic valvulitis, which resolved with chemotherapy. In addition, Fox and Robbins
      • Fox AD
      • Robbins SE
      Aortic valvulitis complicating Wegener's granulomatosis.
      described a 20-year-old man with Wegener granulomatosis who developed aortic insufficiency that required valve replacement. The aortic valve cusps were opposed, but a discrete deficiency in the non-coronary cusp was identified.
      Valve abnormalities associated with Wegener granulomatosis are uncommon. Our patient had aortic valvular involvement with incompetence due to the development of intraleaflet abnormalities in 2 of the 3 cusps. This report illustrates that aortic valve involvement due to Wegener granulomatosis can masquerade as endocarditis, and when cultures are negative for infective endocarditis, the diagnosis and thus the appropriate treatment, as well as the potentially organ-saving and lifesaving treatment, of Wegener granulomatosis can be delayed.
      Although rare, mitral valve involvement has been documented to occur with Wegener granulomatosis.
      • Levine H
      • Madden TJ
      Wegener's granulomatosis: report of a case.
      In addition, Wegener granulomatosis has been reported in 1 case involving the tricuspid valve.
      • Kosovsky PA
      • Ehlers KH
      • Rafal RB
      • Williams WM
      • O'Loughlin JE
      • Markisz JA
      MR imaging of cardiac mass in Wegener granulomatosis.
      Most cases of cardiac involvement in Wegener granulomatosis have been associated with abnormal renal function and multisystemic disease with ear, nose, and throat as well as lung and kidney involvement. Our patient had urinary sediment abnormalities but normal renal function, as shown by the serum creatinine level. The urinary abnormalities promptly resolved with corticoste-roid treatment. The early diagnosis of Wegener granulomatosis in our patient may have contributed to the minimal findings of multisystemic disease of his lungs and kidneys.
      When blood cultures are negative for aortic valve endocarditis, a high index of clinical suspicion and ANCA testing may lead to the diagnosis of the rare complication of acute aortic insufficiency associated with Wegener granulomatosis.
      • Kallenberg CGM
      • Brouwer E
      • Weening JJ
      • Tervaert JW
      Anti-neutrophil cytoplasm it antibodies: current diagnostic and patho-physiological potential.

      ACKNOWLEDGMENTS

      We thank the St Mary's/Duluth Clinic Health System Education and Resource Division for technical support, Dr Carl E. Heltne, attending cardiologist, for his expertise in this case, and Barb Jablonski for her expert typing of the submitted manuscript.

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