Renal amyloidosis secondary to childhood tuberculosis: A report of two casesS Krishnamurthy, D Samanta, S Yadav
Department of Pediatrics, Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi - 110 002, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0022-3859.52843
Source of Support: None, Conflict of Interest: None
Childhood renal amyloidosis is a rare entity and is mostly secondary in nature. We describe two cases of renal amyloidosis in association with childhood tuberculosis. The first case was a 10-year-old girl who presented with abdominal tuberculosis and nephrotic syndrome, while the second case was a 5-year-old boy who presented with disseminated tuberculosis and nephrotic syndrome. They were found to have amyloidosis on renal biopsy. The former was treated with anti-tubercular drugs, while the latter required anti-tubercular drugs and steroids. Both the cases showed clinical improvement with remission of nephrotic syndrome. Successful treatment of tuberculosis can result in remission of nephrotic syndrome due to secondary renal amyloidosis. It is important, especially in developing countries, to be aware that tuberculosis continues to be part of the differential diagnosis of amyloidosis in children.
Keywords: Renal amyloidosis, nephrotic syndrome, tuberculosis
Tuberculosis continues to thrive in developing countries and is re-emerging in the industrialized world. Childhood renal amyloidosis is a rare entity and is mostly secondary in nature, in contrast to primary tuberculosis, which is encountered in adults. The association of tuberculosis with renal amyloidosis is common in adults;  however, to the best of our knowledge, in the last 10 years, only two pediatric cases have been described in English literature. , We describe two cases of secondary amyloidosis in association with childhood tuberculosis. Our report serves as a timely reminder that tuberculosis continues to be an important cause of amyloidosis in developing countries.
A 10-year-old girl presented with fever, weight loss, anorexia, and constipation alternating with diarrhea for four months, and bilateral periorbital and pedal edema for one week. There was no history of hepatic, cardiac, joint involvement, hematuria or oliguria. There was no history of contact with tuberculosis. She was malnourished. Abdomen was doughy with presence of free fluid. Chest examination was normal. Investigations showed hemoglobin concentration of 10.1 g/l, a normal chest roentgenogram and ulcerative Mantoux test with an induration of 25 mm. Ultrasonography of the abdomen revealed enlarged mesenteric and para-aortic lymph nodes with thickening of bowel loops and ascites. Abdominal paracentesis showed lymphocytic exudative fluid; acid fast bacilli were seen on Ziel Nielson stain. The patient had serum albumin level 1.8 g/L, proteinuria 4+ and hypercholesterolemia (324mg/dl). Liver function tests, blood urea, serum creatinine concentrations and urine microscopic examination were normal. Test for HBsAg was negative.
In view of abdominal tuberculosis with nephrotic syndrome, renal biopsy was done which showed excess extracellular hyaline amorphous material (amyloid) occupying the glomerular mesangium [Figure 1]. A potassium permanganate stain followed by Congo red staining revealed absence of apple green birefringence on polarized light, suggestive of secondary amyloidosis. , Anti-tubercular drugs were prescribed, to which she showed clinical improvement in 6 weeks, with subsidence of proteinuria and increase in serum albumin levels. She continues to be under follow up for the last 1 year. Nephrotic syndrome continues to be in remission. There is no azotemia or proteinuria.
A 5-year-old boy presented with complaints of fever, cough, decreased appetite and progressively increasing spinal deformity for 10 months, and bilateral periorbital edema for 5 days. His mother was under treatment for sputum positive pulmonary tuberculosis. Severe kyphotic deformity was noticed in the lumbar region. A positive Mantoux test (induration 15 mm) right para-tracheal lymphadenopathy and right lower zone collapse-consolidation on chest radiograph and loss of disc spaces between lumbar 3-4 vertebrae on spine radiograph were suggestive of tuberculous infection. MRI spine revealed spondylitis involving lumbar 3-4 vertebrae with destruction of vertebral body, cord edema, and cold abscesses. The child had serum albumin level 1.9 g/dl, proteinuria 4+ and hypercholesterolemia (310 mg/dl). Liver function tests, serum creatinine concentration, and urine microscopic examination were normal. HBsAg and HIV-ELISA were negative. He was diagnosed as a case of disseminated tuberculosis with nephrotic syndrome. Renal biopsy showed deposits of amyloid in most of the glomeruli. A potassium permanganate stain followed by Congo red staining showed absence of apple green birefringence on polarized light. He was started on antitubercular drugs. Prednisolone was given (due to clinical features consistent with neurotuberculosis) in a dose of 2 mg/kg/d for 6 weeks daily which was tapered over the next 6 weeks and then stopped. Proteinuria subsided 4 weeks after commencement of treatment. During hospital stay, he developed paraparesis and underwent anterolateral decompression.
He is under follow up for the last 14 months during which he has shown clinical improvement. There is no proteinuria. Blood urea and serum creatinine levels are normal.
He has no neurological deficits. Power, tone, and reflexes in the lower limbs are normal.
Amyloidosis occurs rarely in children. It is characterized by extracellular deposition of insoluble fibrillar amyloid proteins in various body tissues. The deposits are composed of seemingly homogeneous eosinophilic material that stains pink to orange-red with Congo red dye and in polarized light, demonstrates the pathognomonic apple-green birefringence of amyloid.
Primary amyloidosis, characterized by deposition of monoclonal light chain of immunoglobulin (AL type) is the commonest form in adults, but extremely rare in children. Secondary amyloidosis occurs due to deposition of amyloid A protein (AA), an acute phase reactant. This explains the presence of AA amyloid in chronic inflammatory conditions. Only secondary amyloidosis affects children in appreciable numbers. Most cases of secondary amyloidosis described in children are secondary to juvenile rheumatoid arthritis (JRA) and familial meditteranean fever (FMF). , JRA has become the most common cause of secondary amyloidosis in children in European countries,  while FMF has been reported mostly in Turkish children.  Other reported etiologies in children include tuberculosis , and Hodgkin Disease. 
The association of tuberculosis with amyloidosis is fairly common in adults (3.6-50%),  but only infrequently reported in children. , Tank et al,  described a 12-year-old girl with disseminated tuberculosis and amyloidosis who did not respond to anti-tubercular therapy, while Ozkaya et al,  have described a 13-year-old girl with Down syndrome who had pulmonary tuberculosis-related renal amyloidosis.
Renal amyloidosis is diagnosed by demonstration of amyloid on renal biopsy. In contrast to primary amyloidosis, the apple-green birefringence is abolished in secondary amyloidosis if the specimen is treated with potassium permanganate before Congo red stain.  This phenomenon was observed in both the cases described by us.
Management of secondary amyloidosis involves treatment of underlying cause, as remission has been reported following treatment of the underlying disorder.  The cases described by us had remission of nephrotic syndrome following treatment of tuberculosis. This is in conformity with the observations of some authors. , Renal amyloidosis has a relatively poor prognosis with a median survival of 50 months. 
To conclude, it is important, especially in developing countries, to be aware that tuberculosis continues to be part of the differential diagnosis of amyloidosis in children. Successful treatment of tuberculosis can result in remission of nephrotic syndrome due to secondary renal amyloidosis.