A Case of Hodgkin Lymphoma Presenting as Nephrotic Syndrome

Paraneoplastic glomerulopathy has been reported in patients with malignancy1. Nephrotic changes as part of the paraneoplastic syndrome are rare in lymphoid malignancies2. In particular, the association of nephrotic syndrome (NS) with Hodgkin’s Lymphoma (HL) is rare and there are few reports in the literature3,4,5. In the paediatric population an incidence of 1% has been described in France (5 patients out of 483 children with HL)6. Minimal change nephropathy is the most frequently observed renal lesion whereas this association appears, either simultaneously or within several months of each other2,3,5,6,7.


Introduction
P araneoplastic glomerulopathy has been reported in patients with malignancy 1 .Nephrotic changes as part of the paraneoplastic syndrome are rare in lymphoid malignancies 2 .In particular, the association of nephrotic syndrome (NS) with Hodgkin's Lymphoma (HL) is rare and there are few reports in the literature 3,4,5 .In the paediatric population an incidence of 1% has been described in France (5 patients out of 483 children with HL) 6 .Minimal change nephropathy is the most frequently observed renal lesion whereas this association appears, either simultaneously or within several months of each other 2,3,5,6,7 .

The Case
A 12-year-old, boy was admitted with complaints of periorbital and lower-extremities oedema, weight gain.There was no history of fever or night sweats.There was no lymphadenopathy or hepatosplenomegaly.His serum albumin was 1.6 gm/dl and serum cholesterol was 268mg/dl.Urine protein was 3+ and urine protein creatinine ratio was 2. The association of NS and HD having an incidence of 0.4% has been published in a large study on more than 1700 cases of HD and a similar percentage (0.6%), without sex predominance, has been reported in a more recent paper on 661 children affected by HD 9,10 .
It shows that the most common morphological subtype of HD (71.4%) is nodular sclerosis 11 and MCNS is a predominant kidney disease with some rare cases of HD associated to Focal Segmental Glomerulosclerosis (FSGS), IgA nephropathy, membranous glomerulopathy (which is a type of NS predominating in solid tumours) or membranoproliferative glomerulonephritis 10,11,12,13 .Until now a clear pathophysiologic link between malignancy  and renal disease has not been established, even though it is postulated that the cause of MCNS could be T cell dysfunction with abnormal secretion of cytokines, altering the permeability of the glomerular basement membrane, whereas, in case of other kidney diseases, such as membranous glomerulopathy, the pathogenesis could be mediated by immunocomplexes 12 .In the majority of HD cases associated with NS, selective serious albuminuria with normal renal function is the typical manifestation, with nodular sclerosis being predominant histological variety and almost ever, reversal of the renal disease is reported when the treatment against HD (chemotherapy and/or radiotherapy) results in complete remission.
On the contrary, steroids, especially in NS predating lymphoma, are often, more or less ineffective 11 .However our patient responded well to prednisolone.Finally, it is our opinion that in the case of nephritic syndrome that does not respond or responds very poorly to steroid therapy or has atypical features, nephrologists should suspect an occult lymphoma.

Conclusion
Nephrotic syndrome is a common renal disease seen by paediatricians.Most of the cases are because of Minimal change disease and are managed empirically with prednisolone.However as shown in our case, the adolescents presenting with nephritic syndrome should be investigated for secondary aetiology.

2 .
With the diagnosis of NS, the initial treatment consisted of prednisolone.He achieved remission in 2 weeks.After 6 weeks of daily steriods he was put on alternate day prednisolone.Two months later while on alternate day prednisolone, in an ultrasound examinationon he was found to have had retroperitonial mesentric Lymphadenopathy (Fig 1).Lab parameters were Hb-8.5gm%,TLC-11700 /cm, Urine: protein 4 + , A/G: 3.0/2.0,Serum cholesterol: 198, Blood urea/ S Cr: 35/0.7 mg/dl, Na/K: 141/3.8mmol/l, HBV/HCV/HIV: 1 Dr. Yogesh Rambhau Dakhane, MBBS, MD Resident, 2 Dr. Rajesh Kumar Singh, MBBS, MD Pediatrics, Assistant Prof, 3 Dr.Rajeev Kumar Thapar, MBBS, MD Paediatrics, Professor.All from the Department of Paediatrics, Command Hospital (CC) Lucknow, Uttar Pradesh, India.Discussion NS is a rare complication of Hodgkin's disease.Minimal change is most common NS seen with Hodgkin's disease.In 90% cases, NS is idiopathic.Approximately 10% cases of idiopathic NS are associated with different neoplastic disorders including solid tumours, carcinomas, lymphoma.Amongst lymphoma, nephrotic syndrome is ten times more common in patients with Hodgkin's disease.The kidney can be involved in neoplastic diseases in many ways: direct infiltration, renal vein thrombosis, renal artery or ureter compression, biochemical abnormalities (hypercalcemia, hyperuricemia), amyloidosis and paraneoplastic disease.NS is well known as a paraneoplastic manifestation of HD and there are several cases in which the recurrence of lymphoma is reported in conjunction with a recurrent episode of NS 8.