Granulomatosis with polyangiitis in pediatric patient: case report

Granulomatosis with polyangiitis in pediatric patient: case report
1 Universidade Positivo, Medicine - Curitiba - Paraná - Brazil. 2 Pequeno Príncipe Hospital, Nephrology - Curitiba - Paraná - Brazil.
Correspondence to: Marina Machado Ramos. Universidade Positivo. R. Prof. Pedro Viriato Parigot de Souza, 5300 - Ecoville, Curitiba, PR, Brazil. CEP: 81280-330 E-mail: [email protected]
CASE REPORT Submitted on: 03/03/2020 Approved on: 03/25/2020
DOI: 10.25060/residpediatr-2022.v12n1-280 This work is licensed under a Creative Commons Attribution 4.0 International License.
Marina Machado Ramos1, Jessika Cazarotto Masquieto1, Isabella Gazzi1, Karen Previdi Olandoski2
Abstract Objective: To report the case of a pediatric patient diagnosed with granulomatosis with poliangiitis (GPA) and progression to chronic renal failure, requiring renal replacement therapy, an extremely rare event in GPA being reported in less than 2% of cases. Case Report: Female patient had gastrointestinal symptoms and recurrent sinusitis during childhood. Symptoms evolved to asthenia and abdominal pain at 9 years of age, followed by headache, macroscopic hematuria, decreased diuresis, ascites and facial edema. The investigation suggested renal insufficiency, with subsequent biopsy and confirmation of the diagnosis of GPA with negative ANCA. Although she presented a good initial evolution to the dialysis treatment, the patient was readmitted for hypertensive peaks associated with headache and seizures. Imaging exams showed vasculitis of the central nervous system. Despite treatment, the patient developed septic shock, followed by cardiorespiratory arrest, and died. Comments: The present study demonstrates the importance of investigating GPA in patients with suspected symptoms in order to initiate early treatment and avoid adverse outcomes.
Headings: Granulomatosis with Polyangiitis, Nephrology, Anti-Neutrophil Cytoplasmic Antibody- Associated Vasculitis.
2 Residência Pediátrica; 2022: Ahead of Print.
INTRODUCTION
Granulomatosis with Polyangiitis ( GPA), formerly called Wegener’s Granulomatosis (WG), is a necrotizing vasculitis that affects mainly small to medium-sized vessels, including the group of vasculitis associated with anti - neutroplasmic cytoplasmic antibodies. phyla (ANCA)¹. GPA is quite rare in pe- diatric age, with an estimated annual incidence of 0.1:100,000 in children, with a mortality rate of 90% in one year after diagnosis if not treated, reasons for which we chose to report the present case¹.
Although the pathophysiology of GPA is not well es- tablished, the development of an autoimmune inflammatory process is suggested, with the involvement of neutrophils, endothelial cells and ANCA against neutrophil proteinase ( PR3) in individuals. duos with a genetic predisposition to en- vironmental triggers, such as airway infections, for example².
THE GPA can lead to the manifestation of Rapidly Pro- gressive Glomerulonephritis (RPGN), which is characterized by a rapid and progressive loss of renal function that occurs over weeks or months, associated with the presence of labo- ratory indications of glomerulonephritis, that is, hemat uria and protein uria. Histologically, the translation of this clinical syndrome is the presence of crescents in more than 50% of the glomeruli3.
The symptoms of GPA are quite varied and can affect different organs. Classically, more than 90% of patients have respiratory and auditory conditions. Renal manifestations occur in 70 to 77% of patients, resulting from necrotizing glomerulonephritis, which can be evidenced by changes in the urinary sediment, azotemia and arterial hypertension. In up to 60 % of individuals, cutaneous manifestations can be observed. Neurological and cardiac involvement, however, are quite rare, reaching up to 33.6% of patients1,4.
The diagnosis of GPA involves clinical, radiological, serological and anatomopathological criteria. The recom- mendation of the EULAR PRINTO PRES consensus is to fulfill
at least two of the diagnostic criteria (Table 1) - when three of the six criteria are present, there is a sensitivity of 93.3% and specificity of 99.2 % for diagnostic confirmation³. The histopathological manifestations of the disease are character- ized by parenchymal necrosis, vasculitis and granulomatous inflammation. C-ANCA, in turn, is an antibody marker targeting proteinase - 3 (anti-PR3), present in neutrophils. The titration of this marker is related to the activity of GPA, with 90% sen- sitivity and specificity, and should be followed up during the course of the disease5,6.
The American College of Rheumatology, on the other hand, proposes the diagnosis of GPA against at least 2 of the following diagnostic criteria (Table 2)7-9:
CASE DESCRIPTION
MGM, 9 years old, was admitted to the emergency department of a pediatric hospital with complaints of vomiting and diarrhea with 3 days of evolution. The mother reported that 8 months ago the patient started with asthenia, progress- ing to nausea, abdominal pain, fever peaks and headache, whose treatments were based on venous hydration and antiemetics. Past history of abdominal pain associated with grandmothers since 2 years of age and recurrent rhinitis and sinusitis since 5 years of age.
Ago, the patient presented macroscopic hematuria and decreased urine output, associated with lumbar and abdominal pain, when she was admitted to a hospital in her city in a regular general condition (REG), pale, with facial edema and mild ascites. On the same occasion, laboratory tests were requested that showed renal failure, which was given supportive treatment and abdominal computed to- mography (CT) was requested (normal report). Due to the reduction in diuresis and the evolution of the laboratory tests, the child was requested to be transferred to the In- tensive Care Unit (ICU), being then referred to a pediatric hospital in Curitiba.
Histopathology Granulomatous inflammation in the arterial wall or in the perivascular region
upper airway Chronic purulent or bloody rhinorrhea, recurrent epistaxis, nasal septum perforation, chronic or recurrent sinusitis
Laryngo-tracheo-bronchial involvement Subglottic, tracheal, or bronchial stenosis
lung involvement Chest X-ray or CT scan showing nodules, cavitations, or infiltrations
HIP ANCA positive by immunofluorescence or ELISA
kidney involvement Hematuria or pauci-immune necrotizing glomerulonephritis
Table 1. EULAR PRINTO PRES diagnostic criteria for GPA in the pediatric age group.
Oral or nasal inflammation Oral ulcers or purulent or bloody rhinorrhea
Changes on chest X-ray Nodules, cavitations or infiltrations
Change in urinary sediment Micro or macrohematuria
Granulomatous inflammation on biopsy Histological changes compatible with granulomatous inflammation in the arterial wall or in the perivascular region
Table 2. American College of Rheumatology diagnostic criteria for GPA in the pediatric age group.
3 Residência Pediátrica; 2022: Ahead of Print.
On physical examination at the time of admission, he had a weight of 32.5 kg (P50 -CDC) and height of 1.21 m (P5-CDC), REG, hypoactive, pale, hydrated, hypertensive, oli- goanuric, eupneic and afebrile. Presenting with facial swelling and moderate ascites.
On the second day of the first hospitalization, which lasted 56 days, the patient underwent a renal biopsy and un- derwent automated peritoneal dialysis. The initial diagnostic hypotheses were acute chronic renal failure (CRF), autoim- mune disease or rapidly progressive glomerulonephritis. Due to the latter hypothesis , a pulse of methylprednisolone 1000 mg/1.73m² / day for three days was started.
On the fifteenth day of hospitalization , peritoneal di- alysis proved to be poorly functioning and the exams showed gram negative bacilli in her fluid, with intraperitoneal cefazolin and amikacin being associated with intravenous cefepime.
On the eleventh day of hospitalization, the result of the renal biopsy material was obtained, identifying in the sample growing lesions in a proliferative/sclerosing phase, moderate granulomononuclear infiltrate with plasma cells and granu- lomas, al is m of fibrosis (30-40%) with proportional tubular atrophy. In the vascular compartment, the arterial vessels are slightly thickened.
In view of the clinical picture and the anatomopatho- logical findings, the hypothesis of GPA would be the most likely. ANCA, MGMT gene methylation by PCR (GBM), im- munoglobulins, chest CT, spirometry and MRI of the skull and sinuses were requested to aid in the diagnosis. This showed mucosal thickening covering the right maxillary sinus and a small cyst in the left maxillary sinus.
On the twenty-third day of admission, the diagnosis of GPA with negative ANCA was established , histopathologically compatible with renal biopsy and glomerulonephritis with crescents. Pulse therapy with methylprednisolone was then performed for five days, and on the last day of medication, a dose of cyclophosphamide was administered.
The patient improved with clinical parameters, until on the thirteenth day of hospitalization, due to the ineffectiveness of peritoneal dialysis, it was decided to switch to hemodialysis. The patient remained stable and asymptomatic, starting the second cycle of pulse therapy with methylprednisolone and cyclophosphamide. On the quinquag, the seventh day of hos- pitalization, he was discharged with outpatient hemodialysis.
Twenty-eight days after hospital discharge, the patient was hospitalized again for a hypertensive crisis associated with complaints of headache and seizures, and was referred to the ICU. Cranial MRI performed on that day showed acute and subacute ischemia due to generalized vasculitis. The diagno- ses so far were GPA, chronic dialysis kidney disease, central nervous system (CNS) vasculitis, manifesting seizures and SAH.
On the third day of the second hospitalization, he had hypoglycemia and hypotension at the end of hemodialysis. On physical examination, REG, pale, eupneic on room air, with cushingoid facies, BP of 92/65 mmHg (P50 for systolic pressure
and between P50-90 for diastolic pressure ), HR of 110 bpm, saturating 95% in room air, abdomen globular, distended and diffusely painful on palpation.
On the 7th day of the second hospitalization, the pa- tient reported respiratory difficulty . On examination, she was hypotensive, tachypneic, saturating 91% with O2 in a nasal catheter and presenting cutaneous neo-mucosal pallor. Pul- monary auscultation with diffusely diminished breath sounds. The central pulses were palpable and thin and the peripheral pulses were difficult to palpate. An oxygen mask was installed, piperacillin sodium was prescribed with sodium tazobactam and vasoactive amine. At the moment, he was discussed with the family about hypotheses of septic shock and imminent risk of needing intubation. The patient evolved with a sudden change in the level of consciousness and apnea. Positive pres- sure ventilation and subsequent orotracheal intubation were started, progressing to bradycardia, followed by cardiopulmo- nary arrest in asystole , and cardiopulmonary resuscitation was initiated. The patient remained in asystole and died.
DISCUSSION
The present study reports the case of a 9-year-old female patient diagnosed with GPA , a low-prevalence ANCA- associated necrotizing vasculitis in the pediatric age group. The diagnosis should be considered in patients who present respiratory symptoms - such as sinusitis, epistaxis, oral ulcers -, renal - such as hematuria , leukocytes and proteinuria -, constitutional symptoms - fever, weight loss, and fatigue, for example - gastrointestinal - chronic non - use, abdominal pain and persistent diarrhea - cutaneous and musculoskeletal6,10. For diagnostic confirmation, the diagnostic criteria of EULAR PRINTO PRES and the American College of Rheumatology are used. (Tables 1 and 2, respectively)5,7.
The diagnosis was sealed once the diagnostic criteria of both the EULAR PRINTO PRES and the American College of Rheumatology were met, presenting pulmonary , renal , upper airway involvement, associated with the biopsy findings. renal opsy that showed granulomas and pauci-reactivity5,7.
The GNRP picture was not manifested in the case of this patient, although it is associated with GPA in up to 15 % of the cases3. Negative ANCA, as presented by the patient, can occur in approximately 33% of patients4. In these cases, the search for anti-PR3 can greatly assist in the diagnostic elucidation of GPA, since it can be positive even in the face of negative ANCA.
CT, which may show pulmonary alterations such as consolidations and a ground -glass pattern11, was also nor- mal in the patient. The MRI of the sinuses, in turn, showed mucosal thickening and retention cyst with hypersignal on T1-weighted images in the left maxillary sinus, in agreement with the literature, which indicates, among the most common radiological abnormalities of the sinuses, the opacities, fluid levels and bone destruction12.
4 Residência Pediátrica; 2022: Ahead of Print.
The patient in question was initially treated with pulse therapy of methylprednisolone and, later, associated with cyclo- phosphamide, in agreement with the literature10. here are reports of the use of corticosteroids in 95% of patients and of cyclophos- phamide in 76%, being the most used drugs in the treatment of GPA8. Furthermore, the association of cyclophosphamide with corticosteroids in induction therapy increases disease remission rates from 55% to 85%13. The patient presented with acute CRF, requiring renal replacement therapy, an extremely rare event in GPA, reported in less than 2% of cases.
On the second admission, the patient presented a condi- tion suggestive of CNS vasculitis, triggering convulsive crises, hy- pertensive crisis, confirmed by brain MRI. The evolution continued with the condition of septic shock that led to the patient ‘s death , in agreement with the articles that define infectious processes as the main causes of death in patients with GPA8.
REFERENCES
1. Ribeiro C, Neto MSC, Silva GMC, Santos AA, Penido MGMG. Granulo- matose de Wegener: apresentação clínica e tratamento. J Bras Nefrol. 2006;28(2):114-7.
2. Pereira N, Amaro C. Primary systemic vasculitis in childhood. Revista SPDV. 2012 Abr;70(2):173-80.
3. Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis. Arthritis Rheum. 1990 Ago;33(8):1101-7.
4. Antunes T, Barbas CSV. Granulomatose de Wegener. J Bras Pneumol. 2005;31(Supl 1):S21-S6.
5. Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Buocompagni A, 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 Mai;69(5):798-806.
6. Bohm M, Fernandez MIG, Ozen S, Pistorio A, Dolezalova P, Brogan P, et al. Clinical features of childhood granulomatosis with polyangiitis (Wegener’s granulomatosis). Pediatr Rheumatol Online J. 2014 Mai;12(1):18.
7. Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis. Arthritis Rhem. 1990 Ago;33(8):1101-7.
8. Iudici M, Quartier P, Terrier B, Mouthon L, Guillevin L, Puéchal X. Chil- dhood-onset granulomatosis with polyangiitis and microscopic polyan- giitis: systematic review and meta-analysis. Orphanet J Rare Dis. 2016 Out;11:141.
9. Rodrigues CEM, Callado MRM, Nobre CA, Moura FEA, Vieira RMRA, Albuquerque LAF, et al. Prevalência das manifestações clínicas iniciais da granulomatose de Wegener no Brasil: relato de seis casos e revisão da literatura. Rev Bras Reumatol. 2010 Abr;50(2):150-64.
10. Antunes T, Barbas CSV. Granulomatose de Wegener. J Bras Penumol. 2005;31(1):21-6.
11. Ferreira MCF, Junior HP. Granulomatose de Wegener. Relato de caso. Rev Bras Clín Méd. 2011 Set/Out;9(5):389-92.
12. Silvera S, Vignaux O, Legmann P. Sinonasal and cerebral imaging findings in Wegener’s granulomatosis. Presse Med. 2007 Mai;36(5 Pt 2):913-21.
13. Kidney Disease: Improving Global Outcomes (KDIGO). Glomerulonephritis Work Group. KDIGO Clinical practice guideline for glomerulonephritis. Kidney Int. 2012 Jun;2(Supl 2):139-274.