PERINEPHRIC HEMATOMA AND MASSIVE GASTROINTESTINAL HEMORRHAGE (GIB) COMPLICATING POLYARTERITIS NODOSA (PAN)

• Polyarteritis nodosa
• Perinephric hematoma
• Vasculitis

INTRODUCTION

PAN is a rare entity in the Chinese population [[1]]. It is characterized pathologically by systemic necrotizing vasculitis on median-sized vessels. Renal involvement from aneurysm formation is common, but perinephric bleeding, especially bilateral, is unusual. Prompt diagnosis and treatment is critically important in controlling bleeding, salvaging renal function and arresting progression of the vasculitic process. Morbidity and mortality are frequently owed to uncontrolled sepsis and bleeding.

We report a patient with classical PAN, which was complicated by perinephric hematoma and acute renal failure. Despite the initial well being of the patient, massive gastrointestinal bleeding supervened, which eventually triggered a series of fatal complications.

CASE

A 57-year-old lady complained of 4 weeks history of flu-like febrile illness. She was initially managed by a general practitioner with little improvement. Leg swelling and facial puffiness was then noticed and the patient was admitted into a private hospital for further investigation. Physical examination showed a raised jugular venous pressure and the kidneys were ballotable bilaterally. Left loin tenderness could also be elicited. Laboratory investigations showed that the hemoglobin was 4.8gm/dL, urea 34 mmol/L and creatinine 752mol/L. The daily urine output dropped progressively to less than 200 mL shortly after admission. Urine microscopy was unremarkable, however. Upper abdomen ultrasonogram (US) revealed kidney enlargement on both sides and computerized tomogram (CT) showed bilateral perinephric hematoma (Figure 1). Chest X-ray and sinus radiogram were normal. In view of the electrolyte disturbance and fluid overload, she was started on peritoneal dialysis and was transferred to our hospital for further treatment. On admission, the patient was normotensive and conscious. She was dialysis dependent and the kidneys were ballotable bilaterally even with the presence of two liters of peritoneal dialysate. Serology tests showed ANF1/20, anti-DNA negative, C3 166 mg/dL, C4 45 mg/dL, CRP 8.4 mg/dL. ANCA was positive and anti-myeloperoxidase (anti-MPO) staining was 52% (normal ≤ 3.9%). Hepatitis B and C markers were all negative. In view the large perinephric hematoma, renal biopsy was not performed. Pulsed methylprednisolone (500 mg each) was given for three days and she was maintained on prednisolone 40 mg daily. Cyclophosphamide was started at 2 mg/kg/day. Ranitidine was also given as prophylaxis for GIB. Renal arteriogram was requested but an urgent appointment was not entertained as serial US showed no progression in the size of the perinephric hematoma. One week after admission, the patient developed massive GIB. Upper endoscopy showed anterior wall duodenal ulcer. The bleeding was not controlled with intravenous omeprazole. Renal, coeliac and superior mesenteric (SMA) angiogram showed multiple microaneurysms in the intrarenal (Figure 2) and gastroduodenal artery territories (Figure 3). No active bleeding site was seen. Truncal vagotomy and pyloroplasty was performed and the patient started on hemodialysis. Histological examination of the resected bowel showed no evidence of small vessel vasculitis. She was managed in the intensive care unit with notable drop in the pANCA level. The patient remained dialysis-dependent but was otherwise stable. Two weeks later, she developed severe gram-negative chest infection, which progressed relentlessly to fulminant septicemia. Despite multiple antibiotics, she developed multi-organ failure and succumbed six weeks after admission.

Figure 1. CT showing bilateral perinephric hematoma (arrow).

Figure 2. Renal angiogram showing multiple microaneurysms in the intrarenal arteries (arrow).

Figure 3. Coeliac and superior mesenteric angiogram showed multiple microaneurysms in the gastroduodenal artery territories (arrow).

DISCUSSION

PAN is a systemic panmural necrotizing vasculitis of unknown origin with manifestations occurring in multiple organ systems. Kussmaul and Maier [[2]] first described this difficult-to-diagnose entity in 1866. The incidence of PAN has been estimated to be 0.7 to 6/100,000, occurring most commonly in middle-aged men [[3]]. Many patients with a small vessel vasculitis such as microscopic polyarteritis (MPA) also have evidence of medium-sized vessel involvement [[4]]. They are more likely to have renal involvement and systemic symptoms, and be positive for anti-neutrophil cytoplasmic antibody (ANCA) than patients with PAN alone. These entities should, therefore, be considered as a continuum rather than an “overlap” syndrome [[5]]. For our patient, renal histology was not available and the absence of florid urine casts was not in conformity with an active glomerulonephritis. Subsequent bowel histology also did not show evidence of microscopic polyarteritis. These findings, nonetheless, suggested that it was a case of classical polyarteritis nodosa.

Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against constituents of the primary granules of polymorphonuclear leucocytes (PMN) and lysosomes of monocytes. They are found in the sera of patients with pauci-immune necrotizing crescentic glomerulonephritis and systemic vasculitis, including Wegener's granulomatosis and microscopic polyarteritis. ANCA that produce an artifactual perinuclear staining by indirect immunofluorescence microscopy on alcohol-fixed PMN (p-ANCA) are usually specific for myeloperoxidase (MPO). Most ANCA that produce a cytoplasmic pattern by indirect immunofluorescence (cANCA) are directed against proteinase 3 (PR3). The specificity of ANCA for PR3 or MPO does not effectively differentiate between these clinicopathologic categories of disease. In the study by Hagen et al. [[6]], PR3-ANCA positivity was detected by EIA in 66% of patients with Wegener's granulomatosis, 26% with microscopic polyangiitis and 50% with idiopathic crescentic glomerulonephritis alone, whereas MPO-ANCA positivity was detected in 24% of patients with Wegener's granulomatosis patients, 58% with microscopic polyangiitis, and 64% with idiopathic crescentic glomerulonephritis alone. Li [[1]] also demonstrated that ANCA and anti-MPO antibody are not specific for MPA in the Chinese population. They would, however, alert the clinician of the possibility of vasculitis though a clinicopathological correlation is essential in making the diagnosis.

Spontaneous perinephric hematoma (SPH) of the kidney is a rare entity and SPH of both kidneys is even more unusual. SPH is generally caused by the rupture of intrarenal aneurysms formed by vasculitis. US and CT can detect the site of hematoma but provide no information on the cause of it. On the other hand, angiography discloses arterial wall irregularities, aneurysms, and hypoperfusion distal to aneurysms which are rather characteristic for PAN [[7]]. Though histologic examination of renal tissue remains the only way to ascertain the diagnosis of classical PAN, it may not be feasible in most circumstances unless a nephrectomy is planned. Appropriate treatment should be promptly given once the condition is identified. Combined therapy with corticosteroid and cyclophosphamide appears to confer a survival benefit [[8]]. In patients with uncontrolled bleeding, arterial embolization should be considered as a useful alternative to surgery [[9]]. Close patients monitoring is imperative to reduce morbidity [[10]] and the development of fatal complications.