From the Department of Pathology Laboratory, Fars Legal Medicine Research Center, Shiraz, Iran.
Manuscript received August 17, 2012; accepted December 5, 2012.
The authors report no conflicts of interest.
Reprints: Marzieh Hosseini, MD, Department of Pathology Laboratory, Fars Legal Medicine Research Center, PO Box 71345-1864, Shiraz, Iran. E-mail: M.email@example.com.
Abstract: Acute arteritis of the aorta and the main pulmonary arteries is unusual in a newborn. This type of vasculitis should be described as a separate entity. There are many differences between this entity and polyarteritis nodosa or Takayasu disease. Moreover, neither Takayasu disease nor polyarteritis nodosa and other forms of classic primary large vessels vasculitis have been reported in a neonate until now. The presence of chronic inflammation, fibrosis, and calcification would suggest that this process had been present before birth.
We report a 27-day-old newborn with acute necrotizing aortitis. The feature of this entity is not those of any of the classic entities described in infants or children.
Inflammatory diseases of the arteries have been classified based on etiologic factors. These factors are the caliber of the affected vessels and the observed histologic appearance. The former is the most desirable but impractical, because the etiologic factor has been detected in a minority of the cases such as syphilitic, mycotic, or tuberculous arteritis. Division based on the vessel caliber is also useful. These divisions include the large vessel arteritis, the medium-sized vessel arteritis, and the small vessel arteritis. A group of related primary large vessel arteritis initially affects the aorta and its main branches. They are commonly seen in adults but have also been reported in children. Aortic arteritis can be seen in rheumatoid arthritis, ankylosing spondylitis, and scleroderma. Takayasu, which has a predilection for the aorta and its branches, results in absence of pulses in the upper extremities, ocular changes, and neurological manifestations. It mostly occurs in young females.1 Polyarteritis nodosa (PAN) is a classic example of chronic, systemic, and nongranulomatous necrotizing vasculitis of the medium-sized muscular arteries at the branching point. It causes tissue ischemia, infarction, and aneurysm formation.2 Polyarteritis nodosa is a rare condition in infants and children. Infantile form of PAN is a distinct clinicopathologic entity.3 Clinical and pathological features similarities of the infantile polyarteritis nodosa (IPN) and mucocutaneous lymph node syndrome (or Kawasaki disease) have suggested that these 2 entities may be different manifestations of the same basic disease process.4 However, whereas Kawasaki disease is usually diagnosed on clinical examination, diagnosis of IPN is frequently made at autopsy.3 Infantile polyarteritis nodosa generally occurs in the coronary arteries, often resulting in aneurysmal dilatation in these vessels.1 Neither Takayasu disease nor IPN and other forms of classic primary large vessel vasculitis have been reported in a neonate until now. The presented case is a large vessel vasculitis in a term newborn.
We report a 27-day-old male infant who was born at 38 weeks of gestation by natural abdominal delivery to a gravida 1, para 0, 25-year-old woman. The infant weighted 3300 g at birth. The Apgar score was 5 at 1 minute. He was good until presented with a low-grade fever (oral temperature, 38.2°C) and irritability 3 days before admission. On a workup on him, some data were found.
Physical Examination and Para Clinic Data
No significant findings were detected on physical examination except for a low-grade fever. The white blood cell count, along with the other components of the complete blood cell count results were as follows: white blood cell count, 24,000/mL (reference range, 9000–30,000/mL); segmented neutrophils, 78%; lymphocytes, 18%; monocytes, 2%; hemoglobin, 135 g/L (reference range, 130–162 g/L); and platelet count, 320,000/mL (reference range, 150,000–450,000/mL). Blood culture has shown no growth after 72 hours and after 2 weeks. Calcium levels of serum were 2.25 mmol/L (reference range, 2.22–2.56 mmol/L). Also, serologic testing for syphilis was negative in his parents. All other workups were normal.
He unexpectedly progressed to respiratory and cardiac arrest. External cardiac massage was performed. Despite cardiorespiratory resuscitation efforts, the infant died 2 hours after admission.
The body of a newborn weighted 4000 g, with no significant external abnormalities. An autopsy was done using the classic method. About 50 mL of clotted blood was present in the pericardial cavity. A site of rupture was seen just above the aortic origin. The external surface of the great vessels including ascending aorta, aortic arch, and pulmonary arteries showed a scattered petechial hemorrhage. A gritty sensation was encountered as the wall of the aorta and major pulmonary arteries were severed with scissors. The internal surface of the first portion of the aorta, aortic arch, and 3 to 4 cm of proximal of the descending aorta showed white to yellow elevated plaques and nodules from 0.1 to 0.8 cm in diameter. The heart, coronary arteries, cardiac valves, and ventricular chambers showed no evidence of gross abnormalities. The renal arteries were patent. The systemic vessels were grossly normal. The subclavian, carotid, celiac, and mesenteric vessels were grossly unremarkable. The parenchyma of the lung showed scattered irregular tan consolidated areas. The main pulmonary artery was similar to the aorta but the pulmonary artery and venous tree were patent. The liver weighted 160 g and was unremarkable. The gallbladder, biliary tree, gastrointestinal tract, pancreas, thymus, and thyroid were unremarkable. The kidney’s cortex, medulla, and the collecting systems including ureters and bladder were unremarkable. The brain weighted 350 g and was normal on cross section.
Microscopic examination of myocardium from the left and right ventricles and atria were normal, no inflammatory cell infiltration was observed. Sections of the aorta and great vessels showed acute necrotizing inflammation that involved all layers of the vessel wall (Fig. 1). There was an extensive calcification in the area of the intimate and superficial media in these involved vessels. Variable inflammatory infiltrates were observed in all layers of the vessel wall. In some areas, the infiltration was heavy, consisting predominantly of neutrophils with some lymphocytes and rare histiocytes. In other areas, there was fibrosis of the wall, with scattered histiocytes and lymphocytes. Plasma cells and multinucleated giant cells were absent. There are also focal fibrinoid necrosis and cell debris. No aneurysm formation was visible in any artery. Elastic tissue stains showed disruption of the elastic layer in the involved arteries. The carotid, coronary, subclavian, and celiac arteries showed normal histologic appearance except in 10% of their proximal origin that showed all of the previously mentioned microscopic changes. Sections of large pulmonary arteries showed also acute vasculitis and calcification similar to that described in the aorta and its branches, but small- and medium-sized pulmonary arteries were normal. No abnormal vessels were seen in several sections of the liver, kidneys, gastrointestinal tract, and other organs. Sections from central nervous system, gastrointestinal tract, kidneys, liver, and other organs were unremarkable. Polymerase chain reaction (PCR) for infectious agents such as tuberculosis and herpes simplex virus (HSV) showed no positive bands. The final diagnosis was nonspecific acute necrotizing aortitis and panarteritis.
Widespread aortitis and inflammation of large arteries without aneurysm formation in a newborn is unusual. A review of the literature indicated that only 1 case of the relatively similar picture is reported by Barlow et al5 in a female infant. According to our review of literature, it seems our case report is the second report of aortitis and large vessel arteritis in a newborn and the first report of a necrotizing vasculitis involving aorta and its major branches in a neonate. Treponema pallidum has been found to affect every organ in the human body. It has been found in every organ in stillborn syphilitic infants and in neonates that have died of syphilis. Syphilitic aortitis of congenital origin in young children has been reported by Yampolsky and Powel.6 Negative serological tests and the absence of plasma cells would make lues unlikely.5
Infectious arteritis of large vessels is associated with high mortality.7 Pulmonary vasculitis by Malassezia furfur in an infant on long-term intralipid therapy is described by Redline and Dahms.8 A characteristic vasculitis is an unusual but a well-recognized complication of Pseudomonas septicemia in the neonate. Pseudomonas vasculitis is a rare cause of intrauterine infection of the newborn. Moreover, pseudomonas vasculitis was described in a very premature infant accompanied with widespread skin necrosis.9
Tuberculous aortitis generally affects the distal aortic arch and the descending aorta that is close to the specific groups of mediastinal lymph nodes, but exceptionally it involves the ascending aorta.10 Moreover, the PCR for Mycobacterium tuberculosis was negative in our case. Disseminated HSV type 2 infection causes necrotizing vasculitis in the small- and medium-sized vessels of the lung and peripancreatic arteries. Nuclear inclusion characteristics of HSV were found in these arteries.11 The PCR for HSV was negative in our neonate. Takayasu arteritis is a disease of unknown cause involving the aorta and its major branches, and it has been reported in as young as a 6-month-old infant.12 However, it is histologically described that the presence of fibrosis and chronic inflammation of the vessel wall did not indicate acute inflammation or fibrinoid necrosis.1 Moreover, giant cells frequently seen in Takayasu were not seen in our case, and extensive calcification has not been described in Takayasu arteritis.5 Polyarteritis nodosa is a multifocal, segmental, necrotizing vasculitis involving small- and medium-sized muscular arteries. The infantile form of PAN is often considered a separate clinicopathologic entity. Infantile polyarteritis nodosa most commonly involves the coronary arteries, often resulting in the microaneurysm formation in these vessels and commonly manifests with congestive heart failure.3 These common features would make the diagnosis of IPN unlikely and the features of our case (absence of aneurysm formation and the presence of extensive calcification) were not like those of IPN. The presence of both acute and chronic inflammation with fibrosis and calcification in the involved vessels in this case report would suggest that the process had been initiated for some time before birth.5
Although the features of this presented case are relatively similar to the case reported by Barlow et al5 as a separate form of aortitis and large vessels arteritis, the fibrinoid necrosis and acute necrotizing vasculitis were certainly striking and had not been described in the cases previously reported by him.5 No case reported to date had quite the same features and it is worthy of description in the literature. Is it a distinct form of IPN or it is a separate entity?
1. Rosai J. Arteries. In: Rosai and Ackerman’s Surgical Pathology
. 10th ed. St. Louis, MO; C.V. Mosby (Elsevier); 2011: 2296–2297.
2. Ordones NG, Rosai J. Urinary tract kidney, renal pelvis, and ureter. In: Rosai and Ackerman’s Surgical Pathology
. 10th ed. St. Louis, MO; C.V. Mosby (Elsevier); 2011: 1142–1143.
3. Engel DG, Gospe SM Jr, Tracy KA, et al. Fatal infantile polyarteritis nodosa with predominant central nervous system involvement. Stroke
. 1995; 26 (4): 699–701.
4. Kelly PC, Pearl WR, Weir MR. Infantile polyarteritis nodosa with mucocutaneous lymph node syndrome treated with long-term corticosteroids. South Med J
. 1987; 80 (8): 1045–1048.
5. Barlow JF, Fraser B, Carter GA. Aortitis and large vessel arteritis in a newborn. Hum Pathol
. 1985; 16 (4): 427–429.
6. Yampolsky J, Powel CC. Syphilitic aortitis of congenital origin in young children. Am J Dis Child
. 1942; 63 (2): 371–389.
7. Postema PG, Legemate DA, Baeten DL, et al. Pneumococcal aortitis: an insidious diagnosis. Neth J Med
. 2011; 69 (1): 31–34.
8. Redline RW, Dahms BB. Malassezia pulmonary vasculitis in an infant on long-term Intralipid therapy. N Engl J Med
. 1981; 305 (23): 1395–1398.
9. Hughes JR, Newbould M, du Vivier AW, et al. Fatal Pseudomonas septicemia and vasculitis in a premature infant. Pediatr Dermatol
. 1998; 15 (2): 122–124.
10. Choi JB, Yang HW, Oh SK, et al. Rupture of ascending aorta secondary to tuberculous aortitis. Ann Thorac Surg
. 2003; 75 (6): 1965–1967.
11. Phinney PR, Fligiel S, Bryson YJ, et al. Necrotizing vasculitis in a case of disseminated neonatal herpes simplex infection. Arch Pathol Lab Med
. 1982; 106 (2): 64–67.
12. Kohrman MH, Huttenlocher PR. Takayasu arteritis: a treatable cause of stroke in infancy. Pediatr Neurol
. 1986; 2 (3): 154–158.
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