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CASE REPORT
Ahead of print publication  

Secondary Amyloidosis with Fatal Outcome in a Child with Meningomyelocele: Need for a Closer Renal Surveillance


1 Department of Pediatrics, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India
2 Department of Pathology, GB Pant Institute of Postgraduate Education and Research, New Delhi, India

Date of Submission06-Jun-2021
Date of Decision14-Sep-2021
Date of Acceptance19-Nov-2021
Date of Web Publication24-Jun-2022

Correspondence Address:
Aashima Dabas,
Department of Pediatrics, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi 110002
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mamcjms.mamcjms_60_21

  Abstract 


Amyloidosis constitutes a group of diseases characterized by extracellular deposition of fibrils composed of low molecular weight subunits of a variety of proteins. Secondary amyloidosis may result from chronic inflammatory conditions such as familial Mediterranean fever, juvenile idiopathic arthritis, tuberculosis, and bronchiectasis. Myelomeningocele is reported rarely in literature as a cause of amyloidosis. We report here a case of 6-year-old boy with operated congenital lumbar myelomeningocele with paraparesis and neurogenic bladder, who was diagnosed with nephrotic syndrome with hypertension. He underwent a renal biopsy which showed amyloidosis. During the course of treatment, he acquired a perigenital infection and later succumbed to it. A closer follow-up of patients with neurogenic bladder can help identify and manage renal complications early.

Keywords: Infection, neurogenic bladder, SAA, steroid-resistant nephrotic syndrome



How to cite this URL:
Bharadwaj M, Dabas A, Mantan M, Batra V, Yadav S. Secondary Amyloidosis with Fatal Outcome in a Child with Meningomyelocele: Need for a Closer Renal Surveillance. MAMC J Med Sci [Epub ahead of print] [cited 2022 Nov 26]. Available from: https://www.mamcjms.in/preprintarticle.asp?id=348185




  Introduction Top


Amyloidosis constitutes a group of diseases characterized by extracellular deposition of fibrils composed of low molecular weight subunits of a variety of proteins. At least 25 different precursors of amyloid fibrils are known till date.[1] It can be classified as primary (AL) or secondary (SAA) on the basis of the underlying cause. Deposition of other proteins such as apolipoprotein A-I/A-II cystatin C, gelsolin, lysozyme, fibrinogen alpha chain, beta 2 microglobulin, and leukocyte chemotactic factor 2 has been detected with varied systemic and renal presentations.[2] Secondary amyloidosis (SAA) is the most common subtype in the pediatric age group.[3] Different case series report familial Mediterranean fever (FMF), juvenile idiopathic arthritis (JIA), tuberculosis, bronchiectasis, and chronic obstructive lung disease as common causes of secondary amyloidosis.[4] Myelomeningocele as a cause of amyloidosis is rarely reported in literature. Here we report a case of a 6-year-old boy with operated congenital myelomeningocele with steroid-resistant nephrotic syndrome[5] secondary to amyloidosis.


  Case Report Top


A 6-year-old male child, an operated case of lumbosacral myelomeningocele with ventriculoperitoneal shunt in situ, presented to our facility in July 2019 with complaints of swelling all over body with decreased urine output for 7 days. Child had paraparesis since birth with neurogenic bladder for which intermittent urinary catheterizations were advised but not carried out regularly. The parents had not consulted any physician for his bladder complaints after the surgery on follow-up. He had delay in motor milestones with mild delay in socioadaptive and cognitive domain, but did not report of any neurologic complications after the corrective surgery (performed in infancy). Child had no history of joint swellings, recurrent fever, rash, chronic cough, urinary tract infections, meningitis, or frequent antibiotic intake.

At presentation, the child had anasarca, hypertension, angular cheilitis, and paraparesis. Investigations showed normal kidney function (serum creatinine 0.7 mg/dL), nephrotic range proteinuria (urine protein/creatinine ratio >2), serum cholesterol 340 mg/dL, and serum albumin 1.4 mg/dL confirming the diagnosis of nephrotic syndrome. Ultrasonongraphy of the kidneys revealed thickened bladder wall with trabeculations without any evidence of hydrouretronephrosis. The kidneys were of normal size and maintained corticomedullary differentiation. The child was treated with furosemide, enalapril, and prednisolone. After 4 weeks of daily steroid therapy with 2 mg/kg of prednisolone, there was no reduction of proteinuria and parents refused a renal biopsy. They wanted us to start the specific therapy without biopsy; hence, tacrolimus was started for treatment of steroid-resistant nephrotic syndrome. The new guidelines for management of steroid-resistant nephrotic syndrome in children now recommend renal biopsy after 6 weeks of steroid therapy.[5] Eventually a renal biopsy was carried out when they consented for it; the biopsy showed mesangial, interstitial, tubular, and perivascular amyloid (SAA) deposits, confirmed as SAA type on immunohistochemistry, without any features of pyelonephritis [Figure 1].
Figure 1: (Original) Photomicrograph of kidney biopsy on hematoxylin
and eosinophil stain showing fluffy eosinophilic deposits in the
mesangium. (200× magnification). These deposits were positive for
SAA amyloid stain on immunohistochemistry (inset).


Click here to view


After the availability of this report, the immunosuppressants were stopped and only supportive therapy with diuretics and enalapril were continued. However, the child was readmitted after 3 weeks to the facility with persisting proteinuria, fever, and an ulcer around perianal region and genitalia. He was started on broad spectrum antibiotics and stress dose of steroids (0.75 mg/kg of prednisolone daily). Investigations revealed positive sepsis screen and acute kidney injury (AKI; serum creatinine 2.1 mg/dL). The blood, urine culture, and swab culture from the ulcer did not grow any organism. The child continued to deteriorate with increasing edema, poor perfusion, worsening glomerular filtration rate, and polymorphic leukocytosis. Keeping a possibility of worsening sepsis with shock with AKI, antibiotics were upgraded to injection meropenem and teicoplanin (renal-adjusted doses) and stress doses were made injectable hydrocortisone (75 mg/m2/day). The child, however, succumbed to the illness on day 17 of hospitalization.


  Discussion Top


Amyloidosis is a rare disease resulting from extracellular deposition of abnormal protein in different organ systems. Secondary amyloidosis is the most common cause of amyloidosis in children.[3] SAA is an acute-phase reactant produced by liver in chronic inflammatory disorders such as FMF, JIA, and cryopyrin-associated periodic syndromes or in chronic infectious diseases such as tuberculosis and bronchiectasis.[2],[3],[4] Amyloid deposits with Congo red stain give apple green birefringence on polarized light which can be confirmed with targeted amyloid protein on immunohistochemistry and immunofluorescence, as was performed in the index case.

Clinical features in amyloidosis depend on the organ system affected, kidney being the most common.[4] Rarely liver, gastrointestinal, cardiac, thyroid, and paranasal sinuses may be affected. Nephrotic syndrome is the most common presentation, others being, asymptomatic proteinuria, diabetes insipidus, and renal tubular acidosis,[6] as was observed in the index case. As the child had meningomyelocele with neurogenic bladder, a possibility of chronic renal inflammation with stasis of urine could be hypothesized to be a possible cause of secondary amyloidosis, even in the absence of overt hydronephrosis. In a similar single case, Carter et al. reported an 18-year-old Hispanic male with operated meningomyelocele with neurogenic bladder, diagnosed with nephrotic syndrome, secondary to amyloidosis (SAA) with hypertension at 18 years of age.[7]

Treatment of amyloidosis primarily involves treating the underlying cause and controlling the ongoing inflammation. Colchicines and biological such as interleukin 1 (IL1)/IL6 antagonists are used to prevent renal amyloidosis and end-stage renal disease for FMF and other rheumatologic disorders, respectively.[6],[8] The index case was advised intermittent catherization for neurogenic bladder to which he was not complaint. The management of steroid-resistant nephrotic syndrome remained challenging in this case, possibly attributed to chronic renal damage.To conclude, this was a case of operated congenital meningomyelocele who developed nephrotic syndrome secondary to amyloidosis, with a probable underlying state of chronic renal inflammation. The present case, being the first to highlight secondary amyloidosis in children with meningomyelocele, highlights the need for renal surveillance even in patients who do not have significant hydroureteronephrosis.

Authors’ contributions

AD, MM, and SY: idea conception, critical appraisal. MD and AD: analyzed the data, manuscript preparation and final draft of manuscript. VB: Histopathology and draft review. All authors have read and approved the final manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Perfetto F, Moggi-Pignone A, Livi R, Tempestini A, Bergesio F, Matucci-Cerinic M. Systemic amyloidosis: a challenge for the rheumatologist. Nat Rev Rheumatol 2010;6:417-29.  Back to cited text no. 1
    
2.
Shye M, Sisk A, Schulze C et al. A case of renal and splenic LECT 2 amyloidosis: a recently recognized cause of renal and systemic amyloidosis. Saudi J Kidney Dis Transpl 2020;31:508-14.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Bilginer Y, Akpolat T, Ozen S. Renal amyloidosis in children. Pediatr Nephrol 2011;26:1215-27.  Back to cited text no. 3
    
4.
Tuglular S, Yalcinkaya F, Paydas S et al. A retrospective analysis for aetiology and clinical findings of 287 secondary amyloidosis cases in Turkey. Nephrol Dial Transplant 2002;17:2003-5.  Back to cited text no. 4
    
5.
Trautmann A, Vivarelli M, Samuel S et al. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 2020;35:1529-61.  Back to cited text no. 5
    
6.
Tunca M, Akar S, Onen F et al. Turkish FMF study group: familial Mediterranean fever in Turkey. Results of a nationwide multicenter study. Medicine 2005;84:1-11.  Back to cited text no. 6
    
7.
Carter C, Shayan K, Mak R, Yorgin PD, Krous HF. Nephrotic syndrome in an 18-year-old boy with congenital myelomeningocele. Pediatr Nephrol 2013;28:1963-4.  Back to cited text no. 7
    
8.
Okuda Y, Ohnishi M, Matoba K et al. Comparison of the clinical utility of tocilizumab and anti-TNF therapy in AA amyloidosis complicating rheumatic diseases. Mod Rheumatol 2014;24:137-43.  Back to cited text no. 8
    


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