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Open Journal of Hematology

ISSN: 2075-907X
Volume 5, 2014

Patient with primary systemic amyloidosis presenting with intractable diarrhoea

Hemant Saha1, Ahmed Twahir1, Fatima Juma1, Ruchika Kohli2, *, Malkit S. Riyat1
The Aga Khan University Hospital, Nairobi, Kenya
Pathologists Lancet Kenya, Nairobi, Kenya

DOI: 10.13055/ojhmt_5_1_3.140526



Corresponding Address:
* P O Box 46203-00100, Nairobi, Kenya; Email: ruchikakohli@hotmail.com

Abstract

Introduction:

Primary systemic amyloidosis is the most common form of systemic amyloidosis. Clinical presentation commonly involves organs such as the kidney and heart. We report on a patient with systemic amyloidosis presenting as intractable diarrhoea. Numerous investigations had to be done before the diagnosis could be made highlighting the challenge in making a diagnosis due to the slow progression of the disease. This report is to increase awareness among physicians of this diagnosis and to emphasise the importance of identifying patients quickly.

Case Presentation:

A 63 year old male was admitted with a six months history of intractable, watery diarrhoea, anorexia and progressive renal failure. He had been investigated for proteinuria and deranged renal function prior to admission but no therapy was suggested and the diagnosis at that time was inconclusive. Extensive laboratory and radiological investigations were done. The diagnosis of systemic amyloidosis was made on serum free light chains which showed excess lambda chains and a terminal iliac and colonic biopsy which revealed eosinophilic thickening of the blood vessels with positive Congo red stain. Unfortunately the patient died prior to definitive management for the amyloidosis.

Conclusion:

This case emphasises the importance of early recognition of systemic amyloidosis so that management can be instituted.

Keywords: Amyloid, diarrhoea.

© Kohli et al.; licensee Ross Science Publishers
open-access license: ROSS Open Access articles will be distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided that the original work will always be cited properly.

Article Processing History:
Receiving date: 16-1-2014
Acceptance date: 26-5-2014
Electronic publication date: 26-5-2014
Year of Publication: 2014




Introduction

Primary systemic amyloidosis (AL) is a plasma cell dyscrasia characterized by fibrillar aggregates of monoclonal immunoglobulin kappa or lambda light chain type deposited extracellularly in vital organs [1]. It is the most common type of systemic amyloidosis [2].

Patients with amyloidosis usually present with a small plasma cell clone with evidence of dysfunction of one or more involved organs [3]. Typical AL amyloidosis syndromes include renal involvement (approximately 70% of patients) with nephrotic range proteinuria or renal failure in approximately 50%; cardiomyopathy in approximately 60% with thick walled heart, pericardial and pleural effusions [4]. However 30-60% of patients with amyloid also have gastrointestinal symptoms [5].

Patients with AL amyloidosis often have little intact monoclonal immunoglobulin; approximately 40% of patients have light chains only and about half the patients are missed if only serum protein electrophoresis is used for screening. Immunofixation electrophoresis to identify kappa or lambda light chains is more sensitive, and the combination of serum and urine immunofixation electrophoresis with serum free light chain (FLC) assay approaches 100% sensitivity for identifying a monoclonal protein in patients with AL amyloidosis [6]. It is also important to make every effort to characterise the immunoglobulin deposit.

AL amyloidosis should be suspected in any patient with nondiabetic nephrotic syndrome, or even non-ischemic cardiomyopathy with an echocardiogram showing concentric hypertrophy. Any patient who presents with any one of these syndromes should undergo a biopsy to detect amyloid deposits and a screening for monoclonal immunoglobulin light chains. If a monoclonal protein is present, a bone marrow examination should be performed to exclude the presence of multiple myeloma [4].

The major determinant of outcome in amyloidosis is the extent of cardiac involvement. Echocardiographic features of cardiac amyloidosis such as wall thickening, diastolic relaxation abnormalities, and reduced systolic function are associated with a poor outcome [7].

We report on a patient with intractable diarrhoea, a result of underlying AL amyloidosis in the gastro intestinal tract.


Case Report

History

A 63 year old male was admitted to the Aga Khan University Hospital in May, 2011 with a six months history of intractable, watery, non mucoid and non bloody diarrhoea, anorexia and renal failure, secondary to chronic interstitial nephritis.

Progressively, the patient developed lethargy with effort intolerance (New York Heart Association [NYHA] Class 3) with associated dyspnoea on exertion, lower limb oedema and oliguria. There was no orthopnoea, paroxysmal nocturnal dyspnoea, angina or chronic respiratory symptomatology. He also reported oliguria but no dysuria or hematuria.

He had been investigated for proteinuria and deranged renal function prior to admission but no therapy was suggested and the diagnosis at that time was inconclusive.

Past Medical History

The patient had a history of ischaemic heart disease. He was not a known hypertensive or diabetic and was not on any long term medications.

Examination

The patient was underweight with mild pallor and bilateral pitting lower limb oedema. There was no lymphadenopathy or organomegaly. He had an elevated jugular venous pressure but the heart sounds were normal; there were no murmurs or pericardial effusion noted. The remaining systemic examination was within normal limits.

Laboratory Investigations

The patient underwent an extensive laboratory and radiological work-up. Pertinent investigation findings are shown in table 1 below.

Table 1. Pertinent Laboratory and Radiology Investigations

Based on the above findings a diagnosis of primary amyloidosis was made. It is important that a bone marrow biopsy is performed for the work up of patients with amyloidosis as an aspirate alone may be insufficient to determine the plasma cell burden (our patient had only had a bone marrow aspirate).

Management

The patient was put on supportive management for his diarrhoea with octreotide. Haemodilaysis was required for the deteriorating renal function. Melphalan and Dexamathasone were considered for the amyloidosis but unfortunately the patient passed away before they could be instituted.

This patient had been ill for six months prior to the diagnosis of amyloidosis. Although a post mortem examination was not carried out it was thought that he may have succumbed to coexistant comorbid condtions.


Discussion

We describe a case of primary amyloidosis (AL) with deposition of amyloid in the terminal ileum and colon resulting in moderate malabsorption and odema of the legs.

Although in primary amyloidosis the involvement of the gastrointestinal tract is common, the clinical course and the prognosis are mainly determined by the extent of cardiac and renal amyloid deposition [8, 9].

Previous reports have shown that prominent presenting complaints in patients with gastrointestinal amyloidosis are weight loss, malabsorption, diarrhoea, steatorrhoea and hypoalbuminaemia [10]. Our patient had similar symptoms.

Diarrhea in patients with amyloidosis is often severe. It is thought to be due to a combination of autonomic neuropathy, amyloid infiltration of the submucosa resulting in malabsorption, and bacterial overgrowth [11]. Recent reports of the efficacy of somatostatin analogue in cases of refractory diarrhea suggest that a secretory mechanism may be involved [12].

Deposition of amyloid is usually greatest in the small intestine [13]. Amyloid deposition in our case was predominantly in the terminal ileum and colon. In the colon the presentation is similar to inflammatory bowel disease.

As highlighted in this case the diagnosis is usually difficult to establish primarily due to the slow progression of the disease and illustrates that awareness of diagnosis is necessary in order to identify patients quickly [14]. Numerous laboratory and radiological investigations were carried out before a definitive diagnosis was made.

Primary amyloidosis is treated with melphalan and dexamethasone, similar to the treatment of multiple myeloma. Newer agents such as bortezomib have also proven to be useful and research has shown that stem cell transplantation can offer a cure. With this therapy, median survival is prolonged [10, 15].

Our patient passed away within a few days after the diagnosis and as a result the patient was not put on any appropriate treatment.


Conclusion

Early diagnosis is essential for the optimal effect of treatment on patient survival and quality of life. In the future, it is hoped that clinicians will diagnose early, treat promptly, and halt the progress of an almost uniformly fatal disease [16].


Consent

A written informed consent was obtained from the patient’s next of kin for publication of this case report.


Competing Interests

None


Authors Contributions

HS, AT, MS and FJ were involved in the management of this patient. MS and RK were involved in assisting with the laboratory diagnosis. RK, FJ and MS were involved in writing of the manuscript.

All Authors read and approved the final manuscript.


References

[1] Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol. 1995; 32: 45–59. [PMID: 7878478]
[2] Kyle RA, Linos A, Beard CM, Linke RP, Gertz MA, O'Fallon WM, Kurland LT. Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood. 1992; 79: 1817–22. [PMID: 1558973]
[3] Merlini G, Stone MJ. Dangerous small B-cell clones. Blood. 2006; 108: 2520–30. [PMID: 16794250] [DOI: 10.1182/blood-2006-03-001164]
[4] Merlini G, Seldin DC, Gertz MA. Amyloidosis: pathogenesis and new therapeutic options. J Clin Oncol. 2011; 29: 1924–33. [PMID: 21483018] [PMCID: PMC3138545] [DOI: 10.1200/JCO.2010.32.2271]
[5] Friedman S, Janowitz HD. Systemic amyloidosis and the gastrointestinal tract. Gastroenterol Clin North Am. 1998; 27: 595–614 , vi. [PMID: 9891699] [DOI: 10.1016/S0889-8553(05)70022-4]
[6] Palladini G, Russo P, Bosoni T, Verga L, Sarais G, Lavatelli F, Nuvolone M, Obici L, Casarini S, Donadei S, Albertini R, Righetti G, Marini M, Graziani MS, Melzi D'Eril GV, Moratti R, Merlini G. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem. 2009; 55: 499–504. [PMID: 19131635] [DOI: 10.1373/clinchem.2008.117143]
[7] Falk RH. Diagnosis and management of the cardiac amyloidoses. Circulation. 2005; 112: 2047–60. [PMID: 16186440] [DOI: 10.1161/CIRCULATIONAHA.104.489187]
[8] Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med. 1997; 337: 898–909. [PMID: 9302305] [DOI: 10.1056/NEJM199709253371306]
[9] Pascali E. Diagnosis and treatment of primary amyloidosis. Crit Rev Oncol Hematol. 1995; 19: 149–81. [PMID: 7542006] [DOI: 10.1016/1040-8428(94)00135-G]
[10] Madsen LG, Gimsing P, Schiodt FV. Primary (AL) amyloidosis with gastrointestinal involvement. Scand J Gastroenterol. 2009; 44: 708–11. [PMID: 19242859] [DOI: 10.1080/00365520902783717]
[11] Camilleri. , . Gastrointestinal amyloidosis. 2001 [updated 2001; cited 2011 28th November;]. Available from: http://www.uptodate.com
[12] Yam LT, Oropilla SB. Octreotide for diarrhea in amyloidosis. Ann Intern Med. 1991; 115: 577. [PMID: 1883131] [DOI: 10.7326/0003-4819-115-7-577_1]
[13] Ebert EC, Nagar M. Gastrointestinal manifestations of amyloidosis. Am J Gastroenterol. 2008; 103: 776–87. [PMID: 18076735] [DOI: 10.1111/j.1572-0241.2007.01669.x]
[14] Janczewska I, Mejhert M, Hast R, Runarsson G, Sandstedt B. Primary AL-amyloidosis, ulcerative colitis and collagenous colitis in a 57-year-old woman: a case study. Scand J Gastroenterol. 2004; 39: 1306–9. [PMID: 15743012] [DOI: 10.1080/00365520410008105]
[15] Kyle RA, Gertz MA, Greipp PR, Witzig TE, Lust JA, Lacy MQ, Therneau TM. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N Engl J Med. 1997; 336: 1202–7. [PMID: 9110907] [DOI: 10.1056/NEJM199704243361702]
[16] Sammy Ho KRK. , . Practical Gastroenterology. 2003. Diarrhea in Gastrointestinal Amyloidosis; p. 74.-8.
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