Isolated intestinal polyarteritis nodosa in an elderly patient

Abstract

Background

Polyarteritis nodosa (PAN) is a necrotising vasculitis involving medium-sized and small-sized vessels without the involvement of the arterioles, capillaries or venules and the absence of antineutrophil cytoplasmic antibodies (ANCA).¹ The incidence is estimated at 2–9 cases per million. However, since the Chapel Hill Criteria revision in 2012 and the exclusion of PAN secondary to hepatitis B, the incidence has decreased.² There is no significant difference between sexes; however, some authors have observed a slight predominance in men.^{3 4} Onset of disease usually occurs between 40 and 60 years of age. Although it is not common in the elderly population, few studies reporting PAN in patients ≥65 years of age have been described.^{5 6}

PAN is characterised by segmental transmural necrotising inflammation of small-sized to medium-sized arteries. Vessels of the kidneys, heart, liver and gastrointestinal (GI) tract are involved in descending order of frequency.¹ Lesions usually involve only part of the vessel circumference with a predilection for branch points. The inflammatory process weakens the arterial wall and can lead to aneurysms or even rupture. Impaired perfusion with ulcerations, infarcts, ischaemic atrophy or haemorrhages may be the first sign of the disease.¹ This systemic vasculitis involves the GI tract in up to 50% of patients, most commonly the small bowel.^{7 8} This disorder can also involve a single organ or system.¹ This unusual presentation of PAN is often diagnosed when there is histopathological evidence of vasculitis in a single organ without other systemic manifestations.⁹ Cases of limited PAN involving the GI tract are rare.^{7 10} Herein, we present a case of a 73-year-old woman who presented with PAN isolated to the jejunum.

Case presentation

A 73-year-old-woman with osteoarthritis and osteoporosis, treated with acetaminophen and denosumab, was hospitalised because of severe abdominal pain. Two days prior to admission, she presented with acute abdominal pain described as persistent, severe, diffuse and non-radiating that progressively worsened. Pain was associated with nausea and vomiting episodes of gastric content. Acetaminophen and non-steroidal anti-inflammatory drugs did not relieve her symptoms. She had a 20 lb weight loss in a 6-month period. She had no history of fever, tiredness, melena, haematochezia, diarrhoea, changes in eating habits, jaundice, dysuria, cough, shortness of breath or haemoptysis.

On initial physical examination, temperature was 37.2°C, heart rate was 108 beats per minute and blood pressure was 128/80 mm Hg. She had diffuse abdominal pain on superficial and deep palpation with rebound tenderness. Bowel sounds were present, and no masses, hepatomegaly or splenomegaly were noticed. Musculoskeletal exam showed Heberden’s nodes. No synovitis or joint effusions were observed. Pulmonary, cardiac, head and neck, neurological and skin examination was normal.

Investigations

Laboratory tests revealed a white blood cell (WBC) count of 12.8x10⁹/L, haemoglobin of 15.6 g/dL, platelet count of 237x10⁹/L, absolute neutrophil count of 10.0x10⁹/L, serum creatinine of 0.77 mg/dL, albumin of 3.9 g/dL and elevated lactic acid at 22.8 mg/dL. Liver tests were normal: alkaline phosphatase of 80 mg/dL, total bilirubin of 1.2 mg/dL, aspartate aminotransferase of 13 mg/dL and alanine aminotransferase of 11 mg/dL. Lipase and amylase serum levels were normal. Urinalysis showed 0–2 red blood cells/high-power field (hpf), 0–4 WBC/hpf, and no casts or proteinuria. Westergren erythrocyte sedimentation rate (ESR) (50 mm/hour) and the C reactive protein (CRP) (21.3 mg/L) were elevated. Rheumatoid factor was positive at 24.2 u/mL (normal range=0–18 u/mL). Antinuclear antibodies, ANCA and cryoglobulins were negative. C3 complement was mildly decreased at 79.9 mg/dL, and C4 was normal. Viral hepatitis panel for hepatitis B and C and HIV tests were negative. Abdominal CT with intravenous contrast showed small bowel inflammatory changes at the right side of the pelvis and right mesentery congestion with fat stranding. The kidneys were normal in size without hydronephrosis and no evidence of aneurysms or arterial luminal irregularities. Mesenteric angiography showed an irregular pattern of the distal portion of the superior mesenteric artery at the right lower quadrant, ileocolic and right colonic mesenteric arteries with multifocal areas of segmental dilation and areas of narrowing in a bead-like pattern.

Differential diagnosis

One day after admission, she developed hypotension and further elevation of lactic acid. She underwent an exploratory laparotomy and was found with multiple areas of necrosis of the jejunum for which bowel resection was performed. A segment of the bowel measuring 20 cm in length by 3 cm in diameter was removed and sent for pathological assessment. Gross pathological description of the resected bowel showed dull and congested scattered purplish-coloured lesions ranging in size from 0.5 cm to 1 cm in greatest dimension with yellow lobulated adipose tissue along the mesenteric border extending up to 4 cm. The mucosa was dull and congested with scattered areas of ischaemic changes. Histopathological examination demonstrated numerous foci of submucosal haemorrhages, distorted medium-sized vessels with aneurysmal dilations, thickened walls and mixed inflammatory infiltrates involving all the vessel layers. Some of the vessel walls had necrotic debris suggestive of fibrinoid necrosis (figure 1). Also, mucosal flattening, atrophy and narrowing of the muscular layers evidenced the long-standing impaired perfusion (figure 2). These findings were consistent with PAN.

Figure 1

(A) Deformed artery with thickened wall and inflammatory infiltrate (black arrow/H&E 40×). (B) Artery with irregular lumen due to segmental damage with focal aneurysmal dilatation (H&E 100×). (C) Portion of necrotic arterial wall with mixed inflammatory infiltrates (black arrow/H&E 100×).

Figure 2

(A) Intestinal wall with mucosal atrophy (black arrow), narrow muscular layers (green arrow) and subjacent haemorrhage (white arrow/H&E 40×). (B) Similar to (A), intestinal wall with haemorrhage (white star/H&E 40×). (C) Haemorrhage in mesenteric adipose tissue (H&E 40×).

Treatment

After surgery, her clinical course was complicated with septic shock requiring vasopressors and intravenous antibiotic therapy for intra-abdominal infection with Pseudomonas aeruginosa and bacteremia. Also, she was started on intravenous methylprednisolone 60 mg daily for 4 days followed by prednisone 60 mg orally daily. She had a remarkable clinical improvement. Hypotension, abdominal pain, nausea and vomiting resolved. Four days after surgery, she was able to tolerate food without abdominal pain or other associated symptoms. She was discharged home on prednisone 60 mg daily. At that moment, cyclophosphamide therapy was declined by the patient as she was afraid of potential drug toxicities.

Outcome and follow-up

One month after discharge, she was doing well without abdominal discomfort, nausea, diarrhoea, fever or chills. Prednisone dose was decreased to 40 mg orally once daily. Two months later, she continued stable without abdominal symptoms. She had no clinical evidence of systemic manifestations. ESR decreased to 43 mm/hour and CRP to 0 mg/L. Prednisone dose was gradually decreased to 20 mg daily. Six months after the initial presentation, she developed an acute episode of colicky lower quadrant abdominal pain, non-radiating and with associated nausea. Abdominal CT showed partial bowel obstruction that resolved spontaneously after oral gastrografin was given for imaging study. Laboratory tests revealed a WBC count of 12.1x10⁹/L, haemoglobin of 14.1 g/dL, platelet count of 191x10⁹/L absolute neutrophil count of 10.5x10⁹/L, serum creatinine of 0.70 mg/dL and albumin of 3.4 g/dL. ESR was normal at 17 mm/hour. Given this relapse, she was started on cyclophosphamide 50 mg orally daily. Two weeks after starting cyclophosphamide, she was instructed to increase the dose to 100 mg daily, but she developed nausea, vomiting and diarrhoea for which cyclophosphamide dose was decreased back to 50 mg daily. Five months later, she remained asymptomatic without recurrence of vasculitis. Prednisone dose was gradually decreased to 5 mg daily. During the follow-up period, she did not develop systemic manifestations of PAN.

Discussion

We present a case of PAN isolated to the small bowel in an elderly patient. Both age at onset of PAN and clinical presentation are very uncommon. Our patient developed an acute abdomen requiring urgent surgical resection followed by immunosuppressive therapy. Even though GI manifestations are relatively common in PAN, localised intestinal vasculitis in the absence of other systemic manifestations has only been reported in a small number of cases.^{11 12} Delay in recognising and treating this atypical presentation may be associated with significant morbidity and mortality.^{8 12}

PAN in elderly patients is rare. Furthermore, few studies have examined the clinical presentation of PAN in this subset of patients. In a series of 38 patients ≥65 years of age with PAN and Churg-Strauss syndrome, older patients were more likely to present with peripheral neuropathy than younger individuals.⁶ No differences were found for musculoskeletal, cutaneous, GI or renal involvement. Noteworthy, older age (≥65 years) and GI tract involvement were associated with increased mortality in this study. Similarly, other studies have shown that older patients with PAN have an increased risk of relapse as well as mortality.^{3 13 14} These findings are not only related to the systemic involvement of the disease but also associated comorbidities and an increased number of adverse events related to immunosuppressive treatment.⁶

As in our patient, abdominal pain is the most common symptom of intestinal involvement in PAN.^{15 16}Other manifestations include nausea, vomiting, melena, haematochezia, diarrhoea, intra-abdominal bleeding and acute abdomen. The latter is associated with a worse prognosis.¹⁷ Moreover, patients presenting with GI manifestations have an increased risk of mortality.^{3 16} In a study of 348 PAN patients, the 1-year, 5-year and 10-year survival rates of those requiring surgery for intestinal involvement were 60%, 48% and 38%, respectively.³

Although PAN usually presents with multisystem disease, cases of isolated vasculitis have been reported including the male and female reproductive systems, bladder, breasts, muscle, kidneys and GI system involving the gallbladder, pancreas, liver, colon and small bowel.^{12 15 18–30} Among patients with isolated small bowel involvement, the most frequent finding observed by angiography is stenosis of the superior mesenteric and coeliac arteries. Only few cases of localised bowel vasculitis have been described, but as in our case, these are mainly limited to the small bowel, particularly the jejunum.^{12 30} In general, clinical outcomes of localised intestinal vasculitis vary in severity. Limited involvement to the gallbladder and pancreas is usually associated with a good prognosis after surgical intervention.¹⁰ Conversely, in patients with small bowel involvement requiring abdominal surgery, clinical outcomes are unfavourable with a significant impact on the morbidity and mortality.^{3 6} GI manifestations and age (≥65 years) are considered poor prognostic factors, for which even in the absence of systemic manifestations, as in our case, early treatment with immunosuppressive drugs may reduce mortality rates.³¹

Severe systemic PAN is usually treated with corticosteroids and cyclophosphamide. Patients with severe disease, manifested by major organ/system involvement or life-threatening disease, are usually treated with intravenous methylprednisolone pulse (1000 mg daily for 3 days), followed by high-dose prednisone 1 mg/kg/day (or equivalent).³² Although our patient presented with severe disease, we administered high-dose methylprednisolone at 1 mg/kg/day, rather than a pulse regimen, to avoid further immunosuppression given that her hospitalisation was complicated with abdominal infection and bacteremia. Also, initiation of cyclophosphamide treatment was delayed because the patient was afraid of adverse events. Nonetheless, she had a favourable clinical response and outcome.

Given the increased risk of adverse events and complications in elderly patients, lower immunosuppressive regimens are recommended for this group of patients to decrease drug toxicities.³³ Cases of single-organ involvement vasculitis may be managed only with surgical excision without the need for immunosuppressive therapy.³⁴ Nonetheless, in severe cases, corticosteroid therapy on its own may not be sufficient, for which immunosuppressive drugs may be required.³² This was the case of our patient who had recurrent vasculitis despite surgical resection and high-dose corticosteroid therapy.

In summary, we report an elderly woman with PAN limited to the jejunum. Clinicians should be aware of this unusual presentation and consider vasculitic entities such as PAN in the elderly even in the absence of systemic manifestations. Early recognition and treatment can prevent the development of life-threatening disease and organ damage.

Footnotes

References