Autonomic failure in primary amyloidosis.
ABSTRACT Amyloidosis is an uncommon plasma cell dyscrasia affecting Multisystem, characterized by deposition of amyloid proteins in extracellular spaces and the tissues. Reported incidence of amyloidosis is 8 cases per million per year. Deposition of amyloid fibrils occurs in peripheral nerves in 20% of the cases in Primary Amyloidosis. Though. polyneuropathy is one of the presenting manifestations in cases of Primary Amyloidosis, pure autonomic failure without involving peripheral nerves is not a documented entity. Here, we present a case of Primary Amyloidosis presenting as Pure Autonomic Failure (Dysautonomia).
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ABSTRACT: Chronic orthostatic hypotension is caused by a variety of disorders. Frequently patients withdraw from social interactions, are prone to adverse drug reactions and inappropriate diagnoses, and are bed-bound by the time of diagnosis. Applying basic principles of cardiovascular physiology and pharmacology usually permits these patients to lead active lives and to live longer. Much of the management is based on common sense and knowledge of the basic pathophysiology of the disorder and depends on thorough patient education and close monitoring of blood pressure in many of the activities of daily living.Western Journal of Medicine 01/1993; 157(6):652-7.
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ABSTRACT: Amyloidosis is a rare plasma cell proliferative disorder. The annual incidence in Olmsted County, Minnesota, is 8 in 1,000,000 patients. This is a difficult disorder to diagnose, because the symptoms at presentation are vague and include dyspnea, paresthesias, edema, weight loss, and fatigue. The clinical syndromes at the time of presentation include nephrotic-range proteinuria with or without renal failure, cardiomyopathy, "atypical multiple myeloma," hepatomegaly, and autonomic or peripheral neuropathy. The serum immunoglobulin free light chain assay has been an important step forward in classifying systemic amyloidosis as an immunoglobulin light chain form and in monitoring therapy. Recently, the importance of serum cardiac biomarkers in assessing outcome has been recognized. New therapies developed over the past 5 years include high-dose chemotherapy with stem cell reconstitution, combinations of alkylating agents with dexamethasone, and, most recently, thalidomide.Clinical Lymphoma & Myeloma 12/2005; 6(3):208-19. · 1.13 Impact Factor
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ABSTRACT: Light-chain (AL) amyloidosis is the most common form of systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. The disease often is difficult to recognize because of its broad range of manifestations and what often are vague symptoms. The clinical syndromes at presentation include nephrotic-range proteinuria with or without renal dysfunction, hepatomegaly, congestive heart failure, and autonomic or sensory neuropathy. Recent diagnostic and prognostic advances include the serum free light-chain assay, cardiac magnetic resonance imaging, and serologic cardiac biomarkers. Treatment strategies that have evolved during the past decade are prolonging survival and preserving organ function in patients with this disease. This review outlines approaches to diagnosis, assessment of disease severity, and treatment of AL amyloidosis.Clinical Journal of the American Society of Nephrology 12/2006; 1(6):1331-41. · 5.07 Impact Factor
© JAPI • VOL. 56 • DECEMBER 2008 www.japi.org 995
proteins.1-3 Six types of amyloidosis have been described
in literature – primary, secondary, haemodialysis-related,
hereditary, senile and localized. Primary amyloidosis (AL)
is associated with monoclonal light chains in serum/urine
with 15% of patients having multiple myeloma. Secondary
amyloidosis (AA) is associated with inflammatory, infectious,
and neoplastic causes3. As the symptoms like fatigue,
shortness of breath, edema, parasthesias and weight loss,
remain vague most of the times, the diagnosis is difficult
to reach. However, patients may present as nephrotic
range proteinuria with or without renal insufficiency,
cardiomyopathy, hepatomegaly, symptomatic peripheral
neuropathy, and autonomic failure.1,2 Autonomic failure
is always a part of symmetric peripheral neuropathy in
reported cases of primary amyloidosis. Here, we report a
case of Pure Autonomic Failure without involving peripheral
nerves in case of Primary Amyloidosis.
Mr. ABS, 50 years old previously healthy male presented
with history of giddiness for 1 and ½ years, especially while
getting up from lying down position and when beginning
to start walking. It was associated with feeling of blackout
sensation which used to get relieved on sitting down. The
giddiness progressively increased from initial 2-4 episodes
per week to present 2-4 episodes per day. There is no history
of increase in giddiness on movement of neck. There is no
history of rotation of surroundings, diplopia, tinnitus or
myloidosis is a rare multisystem disorder,
characterized by extracellular deposition of abnormal
There is no history of headache, weakness in limbs,
dysarthria, dysphagia, change of speech, paraesthesias
or dysaethesias, imbalance of gait, falls, tendency to fall
backwards, tremors or seizures. There is no history of
chest pain or palpitations. There is no history of bladder
involvement, hyper- or hypohydrosis. No history of drug
intake or toxins could be elicited. No history suggestive of
abnormal pigmentation was noted. Patient denied history
of Diabetes Mellitus and alcoholism.
Patient gave history of impotency for the same duration
– inability to get erection and ejaculation, no early morning
tumulescence and loss of libido associated with increased
frequency of stools.
There are no family members suffering from similar
Examination revealed severe orthostatic hypotension (BP
supine – 100/70 mm Hg and BP standing – 62/50 mm Hg).
His general and systemic examination was unremarkable.
Central nervous system (CNS) examination didn’t reveal
any involvement of pupils, cerebellar system or peripheral
nerves. All sensations were intact without any thickening
of peripheral nerves. ENT examination was normal. Patient
was evaluated in detail for cardiac autonomic neuropathy
as follows :
1. Postural hypotension – BP supine – 100/70 mm Hg and
BP standing 62/50 mm Hg (abnormal)
2. Sustained hand grip response – DBP 60 mm Hg initially
and DBP 64 mm Hg at the end of the test (abnormal)
3. Valsalva manoeuvre : RR/rr ratio – 1.0 (abnormal)
4. Heart rate response to standing : 30/15 RR ratio – 1.065
5. Heart rate response to deep breathing – RR max – RR
*Resident, Internal Medicine **Senior Nephrologist ***HOD Medicine
and Cardiology, Bharat Ratna Dr. Babasaheb Ambedkar Memorial
Hospital, Central Railway, Byculla, Mumbai - 400 027.
Received : 19.6.2008; Revised : 11.7.2008; Accepted : 2.9.2008
Autonomic Failure in Primary Amyloidosis
Aditi Pandit*, Savita Gangurde**, SB Gupta***
Amyloidosis is an uncommon plasma cell dyscrasia affecting Multisystem, characterized by deposition of amyloid
proteins in extracellular spaces and the tissues. Reported incidence of amyloidosis is 8 cases per million per year.
Deposition of amyloid fibrils occurs in peripheral nerves in 20% of the cases in Primary Amyloidosis. Though.
polyneuropathy is one of the presenting manifestations in cases of Primary Amyloidosis, pure autonomic failure
without involving peripheral nerves is not a documented entity. Here, we present a case of Primary Amyloidosis
presenting as Pure Autonomic Failure (Dysautonomia). ©
996 www.japi.org © JAPI • VOL. 56 • DECEMBER 2008
min – 1.0 (abnormal)
He underwent Head Tilt Test – positive with reproduction
of symptoms – heart rate accelerated to 102 bpm and BP
dropped to 60mm Hg systolic.
His hematological and biochemical reports were normal
except severe dyslipidaemia (Total Cholesterol – 341 mg%,
Triglycerides – 247 mg%, LDL Cholesterol – 262.3 mg%
and HDL Cholesterol – 29.3 mg%). His urine examination
revealed 3+ proteinuria with normal microscopy and 24
hours urinary proteins were 5.0 Gms. His ECG, 2-D Echo,
and Holter monitoring were normal. His MR Brain and
4-vessel MR Angio were normal. His NCV/EMG studies
were normal. His serum cortisol, aldosterone and thyroid
hormones were normal. USG Kidneys were normal. Serum
immunoelectrophoresis report revealed light chain
gammopathy (IgA lambda isotype).
Patient was subjected for renal biopsy which revealed
mesangial deposits, positive for Congo Red stain with
green fluorescence on UV light, confirming the diagnosis
of Primary Amyloidosis (Light Chain – AL).
A wide variety of medical conditions can present as
autonomic disorders – Primary conditions like Shy-Drager
syndrome, the Riley-Day syndrome, the Bradbury-Eggleston
syndrome or Secondary due to Diabetes, Alcoholism,
Nutritional deficiency, Toxins, drugs, paraneoplastic,
amyloidosis and others.4,5 Light-chain (AL) amyloidosis
is the most common form of systemic amyloidosis.6
Peripheral neuropathy and autonomic neuropathy is one
of the presenting manifestations of Primary Amyloidosis.4,5
Autonomic neuropathies are inherited or acquired (as
in amyloidosis) in which the autonomic nerve fibers are
selectively or disproportionately affected.7 Several familial
cases of amyloidotic polyneuropathy (FAP) have been
reported in literature.8,9 A case has also been reported
with primary amyloidosis with progressive hypotension.10
However, intensive search has not revealed a single case
of Autonomic Failure without involvement of peripheral
nerves due to primary amyloidosis. Our case emphasizes
the need of good clinical history and examination with
full investigational work up which revealed autonomic
neuropathy as the cause of orthostatic hypotension.
His neurological work up ruled other causes of primary
autonomic failure and his renal profile confirmed the
diagnosis of Primary Amyloidosis and the likely cause of his
pure autonomic failure. Chemotherapy with Thalidomide is
contemplated in the case.
Primary amyloidosis is a rare disease. Though peripheral
neuropathy with autonomic neuropathy is common
manifestation of primary amyloidosis, pure autonomic
failure in a case of primary amyloidosis is an unreported
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Res Clin Haematol 2005;18:709-27.
Gertz MA, Lacy MQ, Dispezieri A, Hayman SR. Amyloidosis : diagnosis
and management. Clin Lymphoma Myeloma 2005;6:208-19.
Ebert EC, Nagar M. Gastrointestinal manifestations of amyloidosis.
Am J Gastroenterol 2008;103:776-87.
Hollister AS. Orthostatic hypotension – Causes, Evaluation and
Management. West J Med 1992;157:652-57.
Wichser J, Vijayan N, Dreyfus PM. Dysautonomia – Its
Significance in Neurological Disease. Calif Med 1972;117:
Sanchorawala V. Light-chain (AL) amyloidosis : diagnosis and
treatment. Clin J Am Soc Nephrol 2006;1:1331-41.
Low PA, Vernino S, Suarez G. Autonomic dysfunction in peripheral
nerve disease. Muscle Nerve 2003;27:646-61.
Drugge U, Andersson R, Chizari F, Danielsson M, et al. Familial
amyloidotic polyneuropathy in Sweden : A pedigree analysis. J Med
Zalin A, Darby A, Vaughan S, Raftery EB. Primary
Neuropathic Amyloidosis in Three brothers. BMJ 1974;1:
10. Campbell TN, Goldman R. Primary amyloidosis with death due to
progressive hypotension. Calif Med 1966;104:208-11.