|Year : 2019 | Volume
| Issue : 4 | Page : 129-132
Heavy chain disease: a rare case report of adult nephrotic syndrome
Sanjeev S Manjunath1, Chettipunyam Sounderrajan Chetan1, Satish Suchitha1, Gangadhar Chirag2
1 Department of Nephrology, JSSAHER, Mysore, India
2 Department of Pathology, JSSAHER, Mysore, India
|Date of Submission||18-Jun-2019|
|Date of Decision||15-Jul-2019|
|Date of Acceptance||22-Jul-2019|
|Date of Web Publication||25-Nov-2019|
Dr. Chettipunyam Sounderrajan Chetan
DNB Nephrology, Associate Professor in Nephrology, JSS AHER, Mysuru, Department of Nephrology, JSSAHER, Mysore
Source of Support: None, Conflict of Interest: None
Monoclonal immunoglobulin deposition disease is a systemic disorder characterized by the deposition of immunoglobulins as nonfibrillar material in various organs. Three subtypes have been reported: light chain deposition disease, light and heavy chain deposition disease and heavy chain deposition disease. Among these, light chain deposition disease is the most prevalent. Reports of light and heavy chain and heavy chain disease are rare, with fewer than two dozen documented cases in the world literature and very few from India. Heavy chain disease is characterized by glomerular, tubular, and vascular wall deposition of monoclonal heavy chains without associated light chains. We present the case of a 51-year man, who presented with a 3-month history of pedal edema, hypertension detected 3 months ago, and mild renal failure Estimated Glomerular filteration rate (eGFR) 66 ml/min/1.73 m2; histopathology showed heavy chain deposition disease. The case emphasizes the need for a thorough workup for plasma cell dyscrasias when we see membranoproliferative pattern in adult patients. This patient was treated with bortezomib-based regimen and after 3 months achieved near-complete remission of proteinuria with improvement in serum creatinine.
Keywords: heavy chain deposition disease, nephrotic syndrome, plasma cell dyscrasias
|How to cite this article:|
Manjunath SS, Chetan CS, Suchitha S, Chirag G. Heavy chain disease: a rare case report of adult nephrotic syndrome. J Egypt Soc Nephrol Transplant 2019;19:129-32
|How to cite this URL:|
Manjunath SS, Chetan CS, Suchitha S, Chirag G. Heavy chain disease: a rare case report of adult nephrotic syndrome. J Egypt Soc Nephrol Transplant [serial online] 2019 [cited 2020 Feb 28];19:129-32. Available from: http://www.jesnt.eg.net/text.asp?2019/19/4/129/271560
| Introduction|| |
Heavy chain deposition disease (HCDD) is one of the plasma cell dyscrasias which include monoclonal gammopathy of unknown significance, monoclonal gammopathy of renal significance, multiple myeloma, light chain deposition disease, HCDD, and plasmacytoma. HCDD is the least common among them with only a few cases reported in world literature  and very few from India.
| Case history|| |
A 51-year-old male patient presented with a 3-month history of pedal edema and newly detected hypertension. He did not have cardiac and respiratory symptoms and no hematuria. On evaluation the patient was averagely built, with a pulse rate of 72/min, blood pressure of 160/90 mmHg and was on antihypertensives (metoprolol and cilnidipine). Urine routine showed albumin 3+, nil erythrocytes, and pus cells of 1–2/hpf. Quantification of 24 h urine protein showed 2.8 g proteinuria. Serum creatinine was 1.3 mg/dl, Estimated Glomerular filteration rate (eGFR) of 66 ml/min/1.73 m2, Hb% of 12.8 g/dl, total counts of 8000/mm3 with a normocytic normochromic blood picture. Serology was negative for HIV, HBs antigen, hepatitis c virus (anti-HCV), perinuclear Anti Neutrophil cytoplasmic Antibodies (p-ANCA), and cytoplasmic Antineutrophilic cytoplasmic antibodies (c-ANCA). Ophthalmology examination revealed grade 1 hypertensive changes. 2D echocardiography showed mild left ventricular hypertrophy. The patient underwent renal biopsy which showed enlarged glomeruli with mild mesangial expansion with proliferation of mesangial cells. Nodularity was seen in almost all the glomeruli and were periodic acid Schiff and silver positive and ([Figure 1]) blue with trichrome stain. Tubulointerstitial compartment was unremarkable ([Figure 2] and [Figure 3]). Immunofluorescence showed staining of peripheral capillary walls with IgG (2+) and C3 (2+) ([Figure 4] and [Figure 5]). A diagnosis of membranoproliferative  glomerulonephritis was made and patient was treated with steroids, mycophenolate, and angiotensin receptor blockers. The patient was followed up regularly. Serum creatinine was normal, urine showed persistent 3+ proteinuria with serum albumin of 2.4 g/dl. Repeat 24-h quantification showed 5 g proteinuria. Complement C3 and C4 levels were in the normal range. In view of lack of response to treatment, the patient underwent repeat renal biopsy nearly 6 months after the first one. It was an adequate specimen and showed features of nodular glomerulosclerosis. The nodules were periodic acid schiff (PAS) and silver positive and blue with trichrome stain ([Figure 1],[Figure 2],[Figure 3]). Tubular atrophy and interstitial fibrosis of 10–15% of the sampled cortical area was seen. Congo red stain negative, immunofluorescence showed linear glomerular and tubular basement membrane staining for IgG (3+); IF was negative for lambda and kappa light chains. A diagnosis of HCDD was made, and the patient was referred to a hematologist. Electron microscopy was not done due to nonavailability. He underwent further diagnostic evaluation. Bone marrow aspiration and biopsy showed normoblastic erythroid hyperplasia with normal plasma cells. Serum protein electrophoresis did not show myeloma band.
|Figure 1 Nodular glomerulosclerosis (Hematoxylin Eosin stain (H&E), ×100).|
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| Discussion|| |
HCDD is a very rare disease and the least common even among the immunoglobulin deposition diseases. In some large series, it accounted for as little as 0.33% of the total biopsies in some. Normally a heavy chain without associated light chain undergoes proteasomal degradation . In heavy chain disease there will be alterations in the immunoglobulin heavy chain which avoids degradation resulting in free heavy chain without the associated light chains circulating in the serum or urine. This abnormally truncated heavy chain gets deposited in various tissues resulting in organ dysfunction . HCDD association with myeloma or other plasma cell dyscrasias is less common [1,4]. Diagnosis of HCDD remains challenging due to their rarity, nonspecific clinical presentation and nonavailability of all the investigations required at many centers. A close collaboration between clinicians and pathologists is required.
Although the abnormal heavy chain is distributed in many organs it is the renal involvement which makes the patient seek medical attention. HCDD is usually seen in the fifth decade with no gender predilection. Some patients were in the third decade of life. Patients present with proteinuria (80%) often in the nephrotic range, hematuria, hypertension (70%), and renal failure (90%) . Prognosis depends on the underlying dysproteinemic state and untreated cases have progressive renal failure. α-HCD which is the most common of the three occurs with Mucosa associated lymphoid tissue (MALT) lymphomas and gastrointestinal symptoms predominate; renal involvement occurs sporadically. γ-HCD occurs with lymphomas and present with systemic symptoms, lymphadenopathy, splenomegaly, anemia, and autoimmune manifestations in up to one-third. Monoclonal spike on electrophoresis was seen in 83% cases in one series . Hypocomplementemia is not uncommon and C3 deposition in the kidney can be seen. μ-HCD is the least common and has features resembling CLL/small lymphocytic lymphoma with anemia, hepatosplenomegaly, and lymphadenopathy. Some with μ-HCD have increased free light chain secretion, osteolytic lesions, and can develop cast nephropathy.
HCDD is characterized morphologically by the presence of nodular glomerulosclerosis, variable mesangial expansion or membranoproliferative or a crescentic pattern of injury with glomerular ([Figure 1]) and tubular nonamyloid tissue deposition of heavy chain without associated light chain. The Glomerular basement membrane (GBM) may show double contouring and tubulointerstitial fibrosis and atrophy is proportional to glomerular injury. The diagnosis of heavy chain disease is done by immunofluorescent demonstration of heavy chains (IgG, IgA, IgM) in the glomerular, tubular, and vascular basement membrane and in the mesangium and negative for kappa and lambda chain disease . A minority of cases show complement C3 deposits . Electron microscopy shows punctate, amorphous or ground pepper-like deposits Other causes for nodular glomerulonephritis include amyloid-Congo red positive, fibrillary glomerulonephritis-Congo negative, polyclonal IgG deposits, diabetic-no deposits, other MIDD-restriction to one light chain class or one light and heavy chain subclass only.Monoclonal immunoglobulin deposits can be seen on a background, proliferative glomerulonephritis. It is seen in the middle aged and the elderly and most often in women. Two-thirds present with nephrotic syndrome and renal failure and remaining one-third with lesser proteinuria and hematuria. Monoclonal gammopathy is seen in less than one-third cases and up to 25% patients may have reduced complement levels .
We present a case of HCDD presenting with nephrotic range proteinuria, mild renal insufficiency, hypertension. and who responded to a bortezomib-based, dexamethasone-based and cyclophosphamide-based regimen. After 6 months there was improvement in serum creatinine to 0.9 mg/dl, urine albumin 1+, 24 h urine protein of less than 500 mg. Blood pressure was better controlled requiring reduction in antihypertensives.
| Conclusion|| |
HCDD is the least common of the monoclonal immunoglobulin deposition diseases with only a few cases reported in the literature. An appropriate immunofluorescence evaluation using kappa and lambda light chains is essential in diagnosing HCDD and differentiating it from others. Early diagnosis and treatment might be the key to complete remission of disease.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]