Chronic aortic dissection as a cause of fever of unknown origin.

ABSTRACT

Chronic aortic dissection presenting as a prolonged febrile syndrome is an uncommon condition. We believe that only 22 cases have been previously reported. We present a case of a patient with an aortic dissection whose diagnosis was delayed because persistent fever, malaise, and night sweats dominated his clinical picture. These complaints may be accompanied by an increased erythrocyte sedimentation rate, leukocytosis, thrombocytosis, and anemia of chronic disease. Knowledge of this atypical presentation, a high degree of suspicion, and investigation using an adequate imaging method will help to avoid missing this potentially lethal entity.

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THE PRESENTATION of aortic dissection may be more subtle than' the classic textbook description of an acutely ill patient with excruciating chest pain of abrupt onset. (1) In rare cases, chronic aortic dissection can have atypical prominent features, such as persistent fever, night sweats, malaise, and elevated acute phase response laboratory parameters. (2-15) This misleading clinical picture may cause the underlying diagnosis to be delayed and may prompt an extensive but unfruitful search for a systemic illness. We describe one such case in which the patient had prolonged high fever associated with chronic dissection of the thoracic aorta that was not detected when he was first admitted to hospital. We also review reported cases of patients with chronic aortic dissection and prolonged febrile syndrome.

CASE REPORT

A 61-year-old man was admitted to our hospital for evaluation of self-limited, moderately intense upper abdominal pain radiating to the back, of sudden onset, associated with a 2-week history of fever and profuse night sweats. Seventeen days before admission, the patient was seen in the emergency department after an abrupt episode of dull retrosternal and upper abdominal pain that radiated to the left arm and was accompanied by diaphoresis. At that time, he was found to have blood pressure of 210/120 mm Hg and a tortuous aorta shown by a chest x-ray film, but normal findings on abdominal ultrasonography, unremarkable serial electrocardiograms, and normal cardiac enzyme values. Once the blood pressure was controlled, he was sent home. However, 2 days after this episode, night sweats and fever developed with daily temperature spikes up to 38.8[degrees]C (101.8[degrees]F). The patient's medical history was significant only for hypertension of 6 years' duration, treated with captopril and atenolol.

Physical examination on admission was unremarkable, except for a temperature of 39[degrees]C, an enlarged right axillary lymph node, and blood pressure of 160/100 mm Hg. Serial cardiac enzyme determinations and electrocardiographic findings were normal. A chest x-ray film disclosed only a tortuous aorta. Urinalysis, abdominal x-ray films, and ultrasonography showed no abnormalities. Initial laboratory data revealed a white blood cell count of 13,700/[mm.sup.3], a platelet count of 426,000/[mm.sup.3], and an elevated erythrocyte sedimentation rate (ESR) (84 mm/hr), with normal hemoglobin and biochemical test values. Serum albumin and globulin levels were normal, as were results of protein electrophoresis. Additional studies included several negative blood and urine cultures, repeated negative serologic tests for various infectious agents (syphilis, typhoid fever, brucella, rickettsiae, toxoplasma, hepatitis B and C viruses, Epstein-Barr virus, and cytomegalovirus) and autoantibodies, and normal C3 and C4 level s. Although a purified protein derivative skin test was positive, an extensive search for acid-fast bacilli (including mycobacterial cultures of samples from blood, urine, sputum, and right axillary lymph node) was negative.

Gallium and technetium scans, upper gastrointestinal series, abdominal computed tomography (CT), and ocular funduscopy were all unremarkable. Transthoracic echocardiography showed mild left ventricular hypertrophy, but no pericardial effusion or vegetations. However, thoracic CT revealed widening of the descending aorta and an intramural thrombus within a false lumen in the left anterolateral wall of the descending thoracic aorta, which extended from the level of the origin of the left subclavian artery to just above the diaphragm (Fig 1). This finding was confirmed by transesophageal echocardiography (Fig 2) and thoracic magnetic resonance imaging (MRI) (Fig 3).

Chronic aortic dissection type III was diagnosed, and conservative medical management was chosen after surgical consultations. Until the eighth hospital day, the patient had daily spiking temperatures to 39[degrees]C. During this time, he had only one brief episode of mild, dull, retrosternal pain, but electrocardiogram and cardiac enzyme levels remained normal. Over the subsequent days, fever spontaneously remitted, and he was discharged on the 23rd hospital day, receiving a regimen of hypotensive medications (captopril and atenolol at higher doses), which controlled his blood pressure at approximately 120/80 mm Hg. The patient has remained afebrile, and the laboratory parameters of acute inflammatory response have returned to normal levels.

DISCUSSION

Aortic dissection is usually an acute event characterized by excruciating chest pain and other classic symptoms of sudden onset, although it might also present in a more subtle manner, making diagnosis difficult. (1,16) Fever during the acute phase of aortic dissection is frequent; however, chronic aortic dissection manifested as a prolonged febrile syndrome associated with constitutional symptoms and an elevated ESR is extremely uncommon. (17) Previous case reports of chronic aortic dissection presenting as a prolonged febrile syndrome are listed in the Table. (2-15) Among the 23 cases to date (including our case), 10 of the aortic dissections occurred in hypertensive patients, but an absence of any known predisposing condition was not so uncommon. Although most of the patients first presented with chest, back, or abdominal pain, this was self-limited or of low intensity in many and was overshadowed by their systemic symptoms and laboratory findings, which dominated the clinical pictures. Aortography was the study that established the diagnosis in most cases reported before the development and widespread use of newer imaging methods.

Thus, aortic dissection may closely mimic other entities such as an infectious, neoplastic, or autoimmune disease, with persistent fever, night sweats, malaise, and increased laboratory parameters of acute phase reaction. As in our case, the systemic symptoms may dominate the clinical picture and mask the underlying diagnosis. On review of our patient's symptoms, it is evident that although he had some of the features of aortic dissection (chest and/or abdominal pain, hypertension, diaphoresis), these were misinterpreted because fever and night sweats became the prominent complaints, which along with an elevated ESR, raised the question of an underlying systemic disorder. (16) Fever prompted an extensive search that initially failed to reveal any infectious, neoplastic, or autoimmune disease to explain the pyrexia.

The mechanism by which aortic dissections may produce fever and a systemic inflammatory response remains a matter of conjecture. Some authors have postulated that active dissecting hematoma with marked tissue destruction can cause release of cytokines, which would be responsible for the inflammatory reaction. (2,3) Similarly, the cessation of the active dissection and the resolution of tissue ischemia (with resorption of the sequestered blood) may lead to the disappearance of both the fever and the inflammatory response.

Continued fever led to a thorough study for fever of unknown origin, which included thoracic CT. The incidental finding of a dissection involving the descending thoracic aorta was unexpected. The development of new reliable, less invasive diagnostic procedures such as MRI, helical CT, or transesophageal echocardiography has modified the approach to and evaluation of suspected aortic dissection, to the extent of even precluding the need for aortography. (18) Although MRI is currently considered to be the method of choice, this technique cannot be used on hemodynamically unstable patients. (19,20) On the other hand, helical CT and transesophageal echocardiography are not only more readily available in the emergency setting, but also can be done on patients who need to be closely monitored. (21,22) When the diagnosis of chronic aortic dissection is suspected, MRI is probably the preferred method to confirm the dissection and the most appropriate technique for preoperative evaluation, provided surgical interventi on is indicated. (18) Our patient's aortic dissection (type III DeBakey or type B Stanford) was managed medically after surgical consultations.

CONCLUSION

Important clinical, diagnostic, and therapeutic implications are associated with this challenging and potentially lethal condition. Chronic aortic dissection should be considered as a possible cause of fever of unknown origin, especially if there is evidence of previous hypertension and a relatively recent episode of chest, back, or abdominal pain. Knowledge of this atypical presentation and investigation using an appropriate imaging method will result in earlier diagnosis and better patient prognosis.

TABLE.

Reported Cases of Chronic Aortic Dissection Manifested as Prolonged
Febrile Syndrome (N = 23) (2-15)

                                             No. (%)

Sex
   Male                                      15 (65)
   Female                                     8 (35)
Medical history
   Hypertension                              10 (44)
   Unremarkable                              10 (44)
   Other                                      3 (13)
Clinical course
   Prolonged fever                           23 (100)
   Malaise                                   10 (44)
   Night sweats                               6 (26)
   Weight loss                                7 (30)
   Congestive heart failure                   3 (13)
   Pleural effusion                           4 (17)
   Pericardial effusion                       2 (9)
Laboratory abnormalities *
   Elevated elevated sedimentation rate      20 (91)
   Decreased hemoglobin/hematocrit values    11 (50)
   Increased white blood cell count           6 (27)
   Increased platelet count                   6 (27)
Diagnosis first established by
   Aortography                                5 (22)
   Abdominal ultrasonography                  2 (9)
   Computed tomography                       11 (48)
   Transthoracic echocardiography             2 (9)
   Transesophageal echocardiography           2 (9)
   Emergency thoracotomy                      1 (4)
Type of dissection (DeBakey classification)
   Type I                                    11 (48)
   Type II                                    3 (13)
   Type III                                   9 (39)
Type of treatment *
   Conservative                              11 (50)
   Surgery                                    9 (41)
   Initially conservative, surgery later      2 (9)

* Not reported in one case.

References

(1.) Butler J, Ormerod O, Giannopoulos N, et al: Diagnostic delay and outcome in surgery for type A aortic dissection. QJ Med 1990; 79:391-396

(2.) Murray HW, Mann JJ, Genecin A, et al: Fever with dissecting aneurysm of the aorta. Am J Med 1976; 61:140-144

(3.) Mackowiak PA, Lipscomb KM, Mills LJ, et al: Dissecting aortic aneurysm manifested as fever of unknown origin. JAMA 1976; 236:1725-1727

(4.) Ruderman A, Mackowiak PA, Smith JW: Fever as a manifestation of dissecting aneurysm of aorta. Am J Cardiol 1979; 44:581-582

(5.) Lesur G, LeBourgeois P, Dorra M, et al: Dissection aortique revelee par une fievre prolongee inexpliquee. Presse Med 1987; 16:31-32

(6.) Smith MA, Singer C: Fever of unknown origin: unusual presentation of dissecting aortic aneurysm. Am J Med 1988; 85:126-127

(7.) McKeown PP, Campbell NP: Pyrexia of unknown origin and aortic dissection. Int J Cardiol 1989; 25:124-126

(8.) Turner N, Pusey CD: Aortic dissection masquerading as systemic disease--the post-dissection syndrome. QJ Med 1990; 75:525-531

(9.) Giladi M, Pines A, Averbuch M, et al: Aortic dissection manifested as fever of unknown origin. Cardiology 1991; 78:78-80

(10.) Aranda JL, Guerra JM, Mendicote F: Diseccion aortica y fiebre de origen desconocido. Rev Clin Esp 1994; 194:66-67

(11.) Schattner A, Klepfish A, Caspi A: Chronic aortic dissection presenting as a prolonged febrile disease and arterial embolization. Chest 1996; 110:1111-1114

(12.) Veyssier-Belot C, de Gennes C, Papo T, et al: Une cause meconnue de fievere prolongee: a propos de six cas de dissection aortique chronique. Rev Med Interne 1998; 19:704-708

(13.) Miyairi T, Inaba H, Matsumoto J, et al: Dissecting aortic aneurysm presenting as pyrexia of unknown origin: report of a case. Surg Today 1998; 28:102-104

(14.) Geppert AG, Mahvi A, Hainaut P, et al: Chronic aortic dissection masquerading as systemic disease. Acta Clin Beig 1998; 53:19-21

(15.) Raza K, King P, Allison SP: Back pain and fever. Posigrad Med J 1999; 75:51-52

(16.) Dmowski AT, Carey MJ: Aortic dissection. Am J Emerg Med 1999; 17:372-375

(17.) Hirst AE, Johns VJ, Rime SW: Dissecting aneurysm of the aorta: a review of 505 cases. Medirine 1958; 37:217-279

(18.) Deutsch HJ, Sechtem U, Meyer H, et al: Chronic aortic dissection: comparison of MR imaging and transesophageal echocardiography. Radiology 1994; 192:645-650

(19.) Cigarroa JE, Isselbacher EM, DeSanctis RW, et al: Diagnostic imaging in the evaluation of suspected aortic dissection. old standards and new directions. N Engl J Med 1993; 328:35-43

(20.) Laissy JP, Blanc F, Soyer P, et al: Thoracic aortic dissection: diagnosis with transesophageal echocardiography versus MR imaging. Radiology 1995; 194:331-336

(21.) Zeman RK, Berman PM, Silverman PM, et al: Diagnosis of aortic dissection: value of helical CT with multiplanar reformation and three-dimensional rendering. AJR 1995; 164:1375-1380

(22.) Sommer T, Fehske W, Holzknecht N, et al: Aortic dissection: a comparative study of diagnosis with spiral CT, multi-planar transesophageal echocardiography, and MR imaging. Radiology 1996; 199:347-352

RELATED ARTICLE: KEY POINTS

* Chronic aortic dissection can misleadingly present with persistent fever, malaise, weight less, and elevated acute phase response laboratory parameters.

* This atypical presentation may prompt an extensive but unfruitful search for a systemic disorder.

* Chronic aortic dissection should be considered as a possible cause of fever of unknown origin, especially in hypertensive patients with a recent episode of chest, back, or abdominal pain.

* Investigation using an appropriate imaging technique will result in earlier diagnosis and better patient prognosis.

From the Departments of Radiology and Internal Medicine, La Paz University Hospital, Madrid, Spain.

Reprint requests to Luis Gorospe, MD, La Paz University Hospital, Department of Radiology, [P.sup.0] de la Castellana 261, 28046 Madrid, Spain.