Severe intestinal involvement as initial manifestation of systemic childhood polyarteritis nodosa: Report of two cases

Severe intestinal involvement as initial manifestation of systemic childhood polyarteritis nodosa: Report of two cases

Journal of Pediatric Surgery (2013) 48, 425–428 www.elsevier.com/locate/jpedsurg Independent Case Reports Severe intestinal involvement as initial ...

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Journal of Pediatric Surgery (2013) 48, 425–428

www.elsevier.com/locate/jpedsurg

Independent Case Reports

Severe intestinal involvement as initial manifestation of systemic childhood polyarteritis nodosa: Report of two cases☆ Roberta C. Gomes a , Victor L.S. Marques a , Erica G.N. Cavalcante a , Lucia M.A. Campos a , Adriana M. Sallum a , Uenis Tannuri c , Clovis A. da Silva a,b,⁎ a

PediatricRheumatology Unit, PediatricDepartment, Faculdade de Medicina da Universidade São Paulo, São Paulo, Brazil DivisionofRheumatology, Faculdade de Medicina da Universidade São Paulo, São Paulo, Brazil c DivisionofPediatricSurgery, PediatricDepartment, Hospital das Clínicas da Faculdade de Medicina da Universidade São Paulo, São Paulo, Brazil b

Received 10 September 2012; revised 26 October 2012; accepted 28 October 2012

Key words: Childhood; Polyarteritis nodosa; Vasculitis; Arterial hypertension; Abdominal angina

Abstract Systemic childhood polyarteritis nodosa (C-PAN) is a rare primary vasculitis involving medium or small sized arteries. Abdominal angina is an important and serious complication of PAN, occurring usually 15 to 30 min after food intake, and particularly in adult patients. However, to our knowledge, this involvement as the first manifestation of C-PAN was not described. Therefore, we reported herein two C-PAN cases that fulfilled the new criteria for this vasculitis. These patients were young boys that had malignant arterial hypertension and recurrent post-prandial cramping with acute abdomen. Both of them were submitted to laparotomy that revealed multiple and diffuse intestinal necrosis. One of our cases had a severe post-prandial cramping, even after drinking water, and the laparotomy evidenced multiple intestinal perforations. In spite of use of antihypertensive therapies, immunosuppressive agents (corticosteroids, cyclophosphamide and/or methotrexate) and intravenous immunoglobulin, they died possibly due to severe and disseminated activity disease. In conclusion, we described herein the first two fatal cases of C-PAN that presented severe abdominal pain as initial manifestation. We suggest that the diagnosis of PAN should be considered in patients under acute abdominal angina with no apparent etiology. © 2013 Elsevier Inc. All rights reserved.

Systemic polyarteritis nodosa (PAN) is a necrotizing angiitis characterized by the presence of aneurysmal nodules along the walls of small and medium sized vessels of whole



Funding: This study was supported by FAPESP (grants 2008/582384 to CAS), by CNPQ grant 302724/2011-7 to CAS, by Federico Foundation to CAS and by Núcleo de Apoio à Pesquisa “Saúde da Criança e do Adolescente” da USP (NAP-CriAd). ⁎ Corresponding author. Rua Araioses, 152/81-Vila Madalena, São Paulo-SP, CEP 05442-010 Brazil. Fax: + 55 11 2661 8503. E-mail address: [email protected] (C.A. da Silva). 0022-3468/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2012.10.057

body [1,2]. This primary vasculitis occurs rarely during childhood and the gastrointestinal tract is affected in up to 24% of pediatric population [2,3]. Of note, abdominal angina represents an important and serious complication of PAN, particularly in adult patients, and is characterized by significant postprandial abdominal pain, mainly due to mesenteric inflammation [4,5]. This involvement as the initial manifestation of PAN has been rarely described in the adult population [6], however, to our knowledge, there are no similar cases reported in the systemic childhood PAN (C-PAN) population.

426 Therefore, we report herein two fatal cases of C-PAN with multiple intestinal vasculitis that presented severe abdominal pain as the initial manifestation of the disease.

1. Case report 1.1. Case 1 A 4-year old boy had a daily and recurrent post-prandial cramping, generally occurring about 30 min after food intake. At 4 years and 6 months, he was hospitalized due to claudication of the lower limbs, rectal bleeding associated with severe abdominal pain and distension, and absence of hydro-aerial noises compatible with acute abdomen. Intestinal necrosis, mainly in distal ileum, was observed in abdominal laparotomy. On admission into the pediatric intensive care unit, he had arterial hypertension (arterial pressure of 112/70 mmHg) without fever. Laboratory findings showed hemoglobin 10.7 g/dL, hematocrit 31%, white blood cells (WBC) 15,200/mm3 (13% bands, 79% neutrophils, 3% lymphocytes, 6% eosinophils and 0% monocytes), platelets 192,000/mm3, erythrocyte sedimentation rate (ESR) 17 mm/1st hour, C-reactive protein 248 mg/L (normal b 5), urea 25 mg/dL (normal range 10– 42), creatinine 0.46 mg/dL (normal range 0.6–0.9), C3 1.23 mg/dL (normal range 0.5–1.8) and C4 0.21 mg/dL (normal range 0.1–0.4). Urinalysis was normal. The hepatitis B surface antigen (HBs Ag) was negative. The rheumatoid factor, antinuclear antibody (ANA), antidouble-stranded DNA (anti-dsDNA), anti-Sm, anti-RNP, anti-Ro and anti-La antibodies and antineutrophil cytoplasmic antibodies (ANCA) were all negative. The colonoscopy was normal. During the second day of hospitalization, he had oliguria and severe arterial hypertension (arterial pressure over 200/130 mmHg), requiring sodium nitroprusside and hydralazine treatment. On the 7th day of hospitalization, he maintained oliguria by acute kidney injury (urea 80 mg/dL and creatinine 0.96 mg/dL), requiring hemodialysis. At that moment, he was treated with methylprednisolone pulse therapy (30 mg/kg/day for 3 consecutive days) and intravenous cyclophosphamide (500 mg/m2). On the 14th day of hospitalization, thoracic and abdominal angiotomography revealed bilateral renal artery stenosis with almost total occlusion in the proximal and middle third of the right renal artery and middle third of the left renal artery. The intestinal histology showed necrotizing vasculitis of the small and medium sized arteries and transmural ischemia, with a marked vascular smooth muscle hypertrophy compatible with malignant hypertension. Therefore, he fulfilled the European League Against Rheumatism (EULAR)/Paediatric Rheumatology International Trials Organisation (PRINTO)/Paediatric Rheumatology European Society (PRES) validated classification criteria for PAN [7]. At that moment, he received

R.C. Gomes et al. pulses of methylprednisolone (30 mg/kg/day for 3 consecutive days) and intravenous immunoglobulin (2 g/kg), without improvement of renal function, blood pressure and intestinal bleeding. On the 17th day of hospitalization, he had septic shock with isolation of multiple agents (Klebsiella sp., Enterococcus sp., Escherichia coli and nonCandida albicans), requiring a broad-spectrum antibiotics and anti-fungal therapies (linezolid, meropenem, amikacin, polymyxin and caspofungin). In spite of mechanical ventilation, vasoactive drugs and transfusions of packed red blood cells and platelet concentrates, the patient died after 33 days of hospitalization.

1.2. Case 2 A 6-month old boy had a recurrent post-prandial cramping and irritability. At the age of 7 months, he was hospitalized due to severe arterial hypertension (arterial pressure over 240/120 mmHg), livedo reticularis and acute ischemic stroke in the left hemisphere. He was hospitalized in the pediatric intensive care unit, requiring sodium nitroprusside and hydralazine therapies, without improvement of arterial hypertension and fever. Laboratory findings showed hemoglobin 11.5 g/dL, hematocrit 33%, WBC 12,000/mm3 (80% neutrophils, 17% lymphocytes and 3% monocytes), platelets 350,000/mm3, ESR 23 mm/1st hour, C-reactive protein 6 mg/L, urea 20 mg/dL, creatinine 0.6 mg/dL, C3 1.1 mg/dL and C4 0.25 mg/dL. Urinalysis was normal. The rheumatoid factor, ANA, anti-dsDNA, antiSm, anti-RNP, anti-Ro, anti-La, IgM and IgG anti-cardiolipin antibodies and ANCA were all negative. HBs Ag was negative. Other causes of renovascular arterial hypertension were excluded. At the age of 8 months post-prandial cramping worsened, even after 15 to 30 min after drinking water, with anorexia. The upper endoscopy revealed severe and diffuse blanching of the intestinal mucosa and gastritis without perforation. The conventional angiography evidenced multiple aneurisms and stenosis of mesenteric, hepatic, splenic, renal and cerebral arteries. Therefore, he fulfilled the EULAR/PRINTO/PRES criteria for PAN [7]. For 6 consecutive months, he received various treatments that included pulses of methylprednisolone (30 mg/kg/day for 3 consecutive days, monthly), intravenous cyclophosphamide (500–1000 mg/m2/month), intravenous immunoglobulin (2 g/kg) and methotrexate (1.0 mg/kg/week). Despite multiple therapies, he died at the age of 15 months due to acute orchitis and complication of acute abdominal with severe and diffuse intestinal necrosis and multiple intestinal perforations, evidenced in laparotomy.

2. Discussion To our knowledge, we described the first cases of systemic C-PAN in two young boys with abdominal angina

Intestinal involvement initial manifestation of C-PAN and severe intestinal vasculitis. Remarkably, both patients had refractory disease to immunosuppressive agents with a fatal outcome. Of note, PAN is one of the rarest childhood primary vasculitis and it is characterized by the involvement of the small and medium sized arteries with four subtypes: systemic C-PAN, cutaneous PAN, microscopic PAN and HBs Ag classic PAN [8,9]. The peak of incidence of this disease occurs between the age of 9 and 10 years old and it affects equally both genders [10,11]. This vasculitis was rarely reported in infants, as observed in second case [2]. To the best of our knowledge, there are only three cases of C-PAN with intestinal involvement that the first manifestation occurred under the age of one year old [12]. Recently, the EULAR/PRINTO/PRES proposed new criteria for C-PAN diagnosis. According to those, a patient is classified with C-PAN in the presence of the following obligatory criteria: histopathologic findings (evidence of necrotizing vasculitis in medium or small sized arteries) or angiographic abnormalities (aneurysm, stenoses or occlusion of a medium or small sized artery, without other causes), plus any of the five following criteria: skin involvement, myalgia/ muscle tenderness, peripheral neuropathy, renal involvement and arterial hypertension. The new EULAR/PRINTO/PRES criteria studied 150 patients with C-PAN worldwide, including also our Brazilian patients. The sensitivity, specificity and area under the curve (AUC) observed according to these criteria were 89.6%, 99.6% and 94.6%, respectively [7]. Our two patients fulfilled those new criteria with a predominant vasculitis in various mid-sized arteries and severe arterial hypertension.

Table 1

427 Multiple systems can be involved in C-PAN patients, including the renal and cutaneous tracts, and central nervous system [10], as shown in the present cases. Renal involvement frequently leads to variable degrees of arterial hypertension and renal insufficiency [13]. Importantly, malignant hypertension occurs only in 4% of adult PAN population and severe hypertension crisis was rarely described in C-PAN [14], as also evidenced herein. Of note, gastrointestinal involvement, especially abdominal pain, occurs in 24%–100% of C-PAN patients [2,8,10– 12,15,16] (Table 1). Abdominal angina is another important manifestation of the gastrointestinal involvement, often with fatal outcome described particularly in adult PAN. It is characterized by abdominal pain consequent to obstruction, stenosis or aneurisms of at least two vessels that irrigate the mesentery arteries [4,5], manifesting usually 15 to 30 min after meals [4]. Interestingly, one of our cases had a severe post-prandial cramping, even after water intake. The C-PAN therapy includes various immunosuppressive agents (especially corticosteroids, cyclophosphamide and methotrexate) and intravenous immunoglobulin [8,9,11], as in our cases. In spite of these treatments, both of them died possibly due to severe and disseminated activity disease. The overall mortality rate of C-PAN varied from 0% to 43% [8,9,12], mainly associated with severe intestinal obstruction, perforation or mesenteric vascular occlusion [12]. In conclusion, we described herein the first two fatal cases of C-PAN that presented abdominal angina as initial manifestation. We suggest that the diagnosis of C-PAN should be considered in patients under acute abdominal angina with no apparent etiology.

Demographic data and clinical manifestations of systemic childhood polyarthritis nodosa (C-PAN) at diagnosis

Variables at diagnosis Demographic data Age b 5 years Male gender Constitutional symptoms Fever Myalgia GI involvement Abdominal pain Intestinal ischemia GI bleeding Renal involvement Arterial hypertension Articular involvement Skin lesions Nervous system symptoms Testicular pain

Present Ozen et al. Maeda et al. Mocan et al. Venuta et al. Adaletli et al. Kendirli et al. Crankson et al. [10] (n = 1) [15] (n = 1) cases [8] (n = 63) [11] (n = 14) [16] (n = 1) [12] (n = 1) [2] (n = 1) (n = 2) 2 2

NR 33

0 8

0 1

1 1

0 0

0 1

0 1

0 0

36 29

12 NR

NR NR

1 0

1 0

NR NR

1 NR

2 2 2 1 2 0 1 1

15 NR NR 6 13 25 45 14

6 0 1 NR 5 7 7 NR

1 1 1 1 1 NR NR NR

1 1 0 0 NR NR 1 NR

1 0 0 1 1 NR NR NR

1 1 1 1 1 1 NR NR

1 1 NR NR NR 1 1 NR

1

4

NR

NR

NR

-

NR

NR

Results are presented in number of patients with positive variables. NR: not related, GI: gastrointestinal.

428

References [1] Ozçakar ZB, Yalçinkaya F, Fitoz S, et al. Polyarteritis nodosa: successful diagnostic imaging utilizing pulsed and color Doppler ultrasonography and computed tomography angiography. Eur J Pediatr 2006;165:120-3. [2] Adaletli I, Ozpeynirci Y, Kurugoglu S, et al. Abdominal manifestations of polyarteritis nodosa demonstrated with CT. Pediatr Radiol 2010;40:766-9. [3] de Carpi JM, Castejón E, Masiques L, et al. Gastrointestinal involvement in pediatric polyarteritis nodosa. J Pediatr Gastroenterol Nutr 2007;44:274-8. [4] Tyson RL. Diagnosis and treatment of abdominal angina. Nurse Pract 2010;35:16-22. [5] Levy AD. Mesenteric ischemia. Radiol Clin North Am 2007;45:593-9. [6] Cengız C, Pampal K, Doğan S, et al. Acute abdomen due to intestinal ischemia as an initial presentation of polyarteritis nodosa. Turk J Gastroenterol 2010;21:473-4. [7] Ozen S, Pistorio A, Iusan SM, et al. EULAR/PRINTO/PRES criteria for Henoch–Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: final classification criteria. Ann Rheum Dis 2010;69:798-806.

R.C. Gomes et al. [8] Ozen S, Anton J, Arisoy N, et al. Juvenile polyarteritis: results of a multicenter survey of 110 children. J Pediatr 2004;145:517-22. [9] Ozen S, Bakkaloglu A, Dusunsel R, et al. Childhood vasculitides in Turkey: a nationwide survey. Clin Rheumatol 2007;26:196-200. [10] Kendirli T, Yüksel S, Oral M, et al. Fatal polyarteritis nodosa with gastrointestinal involvement in a child. Pediatr Emerg Care 2006;22: 810-2. [11] Maeda M, Kobayashi M, Okamoto S, et al. Clinical observation of 14 cases of childhood polyarteritis nodosa in Japan. Acta Paediatr Jpn 1997;39:277-9. [12] Venuta A, Ceccarelli PL, Biondini D, et al. Jejunal obstruction as initial presentation of polyarteritis nodosa in a 13-month-old boy. J Pediatr Surg 2011;46:27-9. [13] Blaustein DA, Kumbar L, Srivastava M, et al. Polyarteritis nodosa presenting as isolated malignant hypertension. Am J Hypertens 2004;17:380-1. [14] Belot A, Ranchin B, Canterino I, et al. Hypertensive crisis, hepatitis B virus and polyarteritis nodosa in a child. Pediatr Nephrol 2007;22:97-100. [15] Crankson SJ, Oda O, Al-Zaben AA, et al. Intestinal ischaemia in a child due to polyarteritis nodosa: a case report. Trop Gastroenterol 2006;27:41-3. [16] Mocan H, Mocan MC, Sen Y, et al. Fatal polyarteritis nodosa with massive mesenteric necrosis in a child. Clin Rheumatol 1999;18:88-90.