|Year : 2006 | Volume
| Issue : 3 | Page : 169-171
A rare presentation of primary (AL) amyloidosis
K Subramanian, Sivaprakash, M Harris, V Raji
Institute of Internal Medicine, Madras Medical College, Government General Hospital, Chennai, India
Institute of Internal Medicine, Madras Medical College, Government General Hospital, Chennai - 600 003
Source of Support: None, Conflict of Interest: None
Primary amyloidosis is a multi-system disease, involving renal, cardiovascular, gastrointestinal, articular and nervous systems. Peripheral neuropathy occurs in 10-35% of patients and is the presenting feature in 10% of cases. Clinical involvement of the autonomic nervous system is well recognized, although uncommon. Most patients develop features of autonomic dysfunction including postural hypotension, impotence, gastrointestinal disturbances, impaired sweating and loss of bladder control. Nearly 25% develop a superimposed carpal tunnel syndrome caused by amyloid infiltration of the flexor retinaculum at the wrist. We report a case of a 53-year-old man, who presented with autonomic dysfunction, who on investigation was found to have systemic AL amyloidosis. The constellation of painful dysesthesia, autonomic dysfunction and a history of carpal tunnel syndrome should alert the physician of the possibility of amyloidosis.
Keywords: Autonomic neuropathy, multi-system disease, systemic (AL) amyloidosis
|How to cite this article:|
Subramanian K, Sivaprakash, Harris M, Raji V. A rare presentation of primary (AL) amyloidosis. Ann Indian Acad Neurol 2006;9:169-71
| Introduction|| |
Primary amyloidosis is a multi-system disease, involving renal, cardiovascular, gastrointestinal, articular and nervous systems. Deposition of amyloid fibrils in peripheral nerves occurs in upto 20% of AL cases and most patients have more prominent sensory symptoms; however, some individuals might have greater involvement of the autonomous nervous system and carpal tunnel., Autonomic neuropathy may cause orthostatic hypotension, diarrhea or impotence. Clinical involvement of the autonomic nervous system is well recognised, although uncommon, in the so-called primary amyloidosis. Among patients who develop polyneuropathy, autonomic dysfunction seems to be common. Trotter et al found orthostatic hypotension, diarrhea and impotence in most such patients Associated histopathological evidence exists in several case reports of amyloid deposition in sympathetic ganglia and chain., We report a case of a 53 year old man, who presented with autonomic dysfunction, who on investigation was found to have systemic AL amyloidosis.
| Case Report|| |
53-year-old male was admitted for complaints of postural unsteadiness with painful dysesthesia both lower limbs for 6 months duration, diarrhea for 8 months and loss of weight (15 kg) in the past 1 year. He noted erectile dysfunction for the past 6 months. He did not note any sweating abnormalities. He was a chronic alcoholic, nonsmoker, not addicted to drugs. His past medical and drug history were unremarkable. Clinical examination revealed a cachectic male with pallor and glossitis. Particularly he had no macroglossia, periorbital purpura or hyperpigmentation. He had orthostatic hypotension (systolic blood pressure fall of 40 mmHg) with a fixed heart rate of 64 per minute. His heart rate showed no variation with Valsalva maneuver. Respiratory examination was normal and abdomen was soft with no organomegaly. Neurological examination revealed normal higher mental functions and cranial nerves. He had glove and stocking type of sensory loss with no nerve thickening or signs of posterior column dysfunction. On investigations he was found to have normal counts, a normocytic, normochromic anemia and normal vitamin B12 levels. Fasting and 2 h postprandial blood glucose were normal. Renal functions revealed 3+ proteinuria, (3.5 gm in 24 h) with normal values of creatinine and urea. Serum electrolytes including calcium were normal. Liver enzymes showed elevated alkaline phosphatase 635 IU with rest of the panel normal. ECG showed poor progression of 'R' wave in the precordial leads. Echocardiogram showed moderate concentric left ventricular hypertrophy (IVS 18 mm; LVPW 13 mm), dilated atria and thickening of free wall of the right ventricle. HIV and VDRL were non reactive. CT scan of the abdomen was normal. Upper and lower GI endoscopy were normal and a rectal biopsy was done. The colonic mucosa showed amorphous deposit of eosinophilic material in the perivascular region, which showed congophila and apple green birefringence under polarised light [Figure - 1]. Urine for Bence jones protein was negative. Skeletal survey did not reveal lytic bone lesions. Serum immunofixation electrophoresis revealed a discrete lambda light chain band [Figure - 2]. Bone marrow aspiration showed mild lympho plasmacytosis (Plasma cells 8%; Lymphocytes 12%) with a mild decrease in erythroid series. Lower limb nerve conduction studies demonstrated bilateral sensorimotor asymmetrical axonal neuroapathy with no evidence of conduction block. Patient and his family members rejected a request for nerve biopsy. A final diagnosis of primary systemic amyloidosis was made involving the peripheral nerves, autonomic nervous, cardiovascular, renal, gastrointestinal, hepatic systems. Patient was started on Melphlan, prednisolone and symptomatic measures. He is now being followed up at the hematology outpatient department.
| Discussion|| |
Systemic AL amyloidosis is a protein conformation disorder associated with clonal plasma cell dyscrasia. In both AL amyloidosis and amyloidosis complicating Multiple Myeloma or Waldenstrom Macroglobulinemia the amyloid is composed of fragments of immunoglobulin light chains from amino-terminal variable regions or the complete immunoglobulin light chains. Amyloid fibrils from patients with familial amyloid neuropathy are composed of one of the three aberrant proteins caused by genetic mutations, transthyretin, apo-lipoprotein A1 and gelsolin.
Involvement of peripheral nervous system is not infrequent and may be the presenting feature of the disease process. In cases of primary AL amyloidosis peripheral neuropathy occurs in 10-35% and is the presenting feature in 10% of patients. In a study by Kyle et al at Mayo Clinic, neuropathy was the first manifestation of systemic amyloidosis in 17% of 229 patients. The majority have renal or cardiac manifestations with peripheral neuropathy as a late manifestation. Pain and temperature sensation are lost before light touch and vibration. Distal symmetrical weakness and pansensory loss evolves later in the course of the disease. Most patients develop features of autonomic dysfunction including postural hypotension, impotence, gastrointestinal disturbances, impaired sweating and loss of bladder control. Nearly 25% develop a superimposed carpal tunnel syndrome caused by amyloid infiltration of the flexor retinaculum at the wrist. The constellation of painful dysesthesia, autonomic dysfunction and a history of carpal tunnel syndrome should alert the physician of the possibility of amyloidosis. Electrodiagnostic studies show changes of axonal neuropathy with low amplitude or absent SNAPs and low amplititude CMAPS but preserved motor conduction velocities. Distal median motor latencies are prolonged in patients with carpal tunnel syndrome. EMG shows signs of active denervation. A monoclonal protein or light chainis detected in 90% of patients by immunofixation of serum or urine. Monoclonal lambda light chains are more common than kappa (3:1). Bone marrow examination reveals increased plasma cells with clonal dominance of a light chain isotype on immunohistochemical staining. The diagnosis of amyloidosis is established by histological demonstration of amyloid deposition in tissues. Abdominal fat pad aspiration, rectal biopsy or bone marrow aspirate yield positive results in 80% of cases. In patients suspected to have amyloid neuropathy combined muscle and sural nerve biopsy provides confirmation in 90% of cases. Results of sural nerve biopsy show amyloid deposition around blood vessels and within the endoneurial space, loss of myelinated and unmyelinated fibres and active axonal degeneration. The pathogenic mechanism of nerve fibre damage is unclear. The prognosis is poor with a median survival of less than 18 months. High dose melphlan with autologous blood stem cell transplantation has shown promising results in improvement of neurological deficits in selected patients. However its applicability is restricted to those with limited organ disease and no significant cardiac involvement.
| References|| |
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[Figure - 1], [Figure - 2]
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