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Shivraj et al., Int J Med Res Health Sci. 2014;3(4):1058-1060

International Journal of Medical Research
&
Health Sciences
www.ijmrhs.com Volume 3 Issue 4 Coden: IJMRHS Copyright @2014 ISSN: 2319-5886
Received: 9
th
Aug 2014 Revised: 10
th
Sep 2014 Accepted: 18
th
Sep 2014
Case report
NEW INSIGHTS IN TO SYSTEMIC AMYLOIDOSIS: PRIMARY AMYLOIDOSIS ASSOCIATED
WITH TUBERCULAR LYMPHADENITIS
*Shivraj Meena
1
, Nirmal Ghati
2
, Rita Sood
3
, Naval Kishore Vikram
4
1
Senior Resident,
2
Junior Resident,
3
Professor,
4
Additional Professor, Department of Medicine, All India
Institute of Medical Sciences, New Delhi, India
*Corresponding author email: shivraj.aiims@gmail.com
ABSTRACT
Tuberculosis is generally followed by secondary amyloidosis. The association of primary systemic amyloidosis
with tuberculosis is very rare. There is only one case thus far reported in literature. We report such a rare case of
primary amyloidosis with tuberculous lymphadenopathy. A 45 year old woman presented at the medicine
department of all India institute of medical sciences , New Delhi with on & off erythematous rashes over both
eyes for 1 year; low grade fever, fatigue and significant weight loss for 4 months, dysphagia for solid food since 1
month. Main finding on examination were pallor, macroglossia, bilateral periorbital erythematous rashes (racoon
eyes), hepatomegaly & cardiomegaly. She had raised serum alkaline phosphatase level. Chest x-ray revealed
cardiomegaly. USG abdomen revealed multiple retroperitoneal mesenteric lymph nodes and hepatomegaly. USG
guided FNAC from mesenteric lymph node showed acid fast bacillus. Histological examination of liver biopsy
showed amyloid deposition on congo red stain. Patient was treated with DOTS category I ATT with Bortezomib
and Dexamethasone based weekly chemotherapy.
Keywords: Amyloidosis, Tubercular lymphdenopathy, Bortezomib
INTRODUCTION
The term amyloid was introduced in 1854 by the
German physician scientist Rudolph Virchow
(reviewed by Cohen, 1986).
1
Rudolf Virchow first
described amyloidosis as an extracellular deposition
of carbohydrate. What we know now is that there is
an extracellular deposition of proteinaceous material
which, when stained with Congo red gives apple
green birefringence under polarized light. In 1838,
Mathias Schleiden, a German botanist, coined the
term amyloid for the amylaceous constituents of
plants. In 1854, Rudolf Virchow adopted the term to
describe abnormal extra-cellular material that he
encountered in the liver during autopsy.
2
Divry and
associates
3
recognized that the amyloid deposits
showed apple-green birefringence when specimens
stained with Congo red were viewed under polarized
light. This observation remains the sine qua non of
the diagnosis of amyloidosis. We report a case of
uncommon association of primary AL amyloidosis
with a common disease.
CASE REPORT
A 45 year old woman presented with on & off
erythematous rashes over both eyes for 1 year; low
grade fever, fatigue and significant weight loss for 4
months, dysphagia for solid food since 1 month;
intermittent spasmodic pain at umbilical region since
20days. Her BP was 100/70 mm/Hg, PR: 102/ min,
RR:22/ min. She had pallor, macroglossia (figure1),
petechial rashes over right arm & bilateral periorbital
erythematous rashes (racoon eyes). On abdomen,
DOI: 10.5958/2319-5886.2014.00054.x
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Shivraj et al., Int J Med Res Health Sci. 2014;3(4):1058-1060
tenderness at right hypochondrium and enlarged firm
tender liver (24 cm) were present. CVS examination
revealed cardiomegaly only.
Fig 1: Showed macroglossia
Blood test showed Hb: 11.4g/dl, WBC: 14300/cu
mm, Platelet: 561000/ul, ESR: 05mm/hr. She had
isolated raised ALP: 840 IU/L) level. Urine routine
microscopy and 24 hr. urinary protein were normal.
Chest x-ray revealed cardiomegaly. Her ECG
revealed low voltage QRS complex in the limb leads
with poor progression of R wave in precordial leads.
As a suspected case of infection - HIV, hepatitis viral
markers, blood & urine gram stain culture done were
negative. Though toxic granules containing
neutrophils were present, no atypical malignant cells
in the blood. Lactate dehydrogenase level was
normal. Serum & urine protein electrophoresis
showed no M band, but elevated lambda light chain
level (=152. 53 mg/L) in serum free light chain
assay. kappa & lambda light chain ratio was low
(k:=0.06). Total protein & albumin globulin ratio
were normal.
USG abdomen revealed multiple retroperitoneal
mesenteric lymph nodes, hepatomegaly, mild ascites
and bilateral mild pleural effusion. Contrast enhanced
computed tomography (CECT) of chest and abdomen
confirmed the USG finding. USG guided Fine needle
Aspiration Cytology (FNAC) from mesenteric lymph
node showed Acid Fast Bacilli (AFB). Bone marrow
biopsy showed 7% mature plasma cells, but it was
negative for lymphoma deposits or amyloids.
Abdominal fat pad biopsy was equivocal for
amyloidosis. Subsequently liver biopsy was done and
histopathologicaly revealed amyloid deposition
(figure II). Immunohistochemistry of liver biopsy
showed predominant lambda light chain deposition
around blood vessels in the background of
nonspecific lambda and kappa light chain deposition
in the sinusoids.
Fig 2: A Section of the liver stained with congo red
reveals pink-red deposits of amyloid (arrow) along
with sinusoids. (40x).
As the patient had progressive dysphagia, barium
swallow was showed sluggish peristalsis with tertiary
contraction in thoracic oesophagus but subsequent
upper G.I. endoscopy was normal. Autonomic
function tests revealed severe dysfunction, but the
nerve conduction test was normal. Echocardiography
showed bi-ventricular hypertrophy, bi-atrial
enlargement, thickened IVS and posterior wall,
granular sparkling of myocardium, severe left
ventricular dysfunction (EF 27%) & mild pericardial
effusion. Subsequent Holters study and BNP level
were normal.
Based on the above, a final diagnosis of primary
Amyloid Light-chain (AL) amyloidosis with
abdominal Koch was made. For tuberculosis,
category I anti tubercular treatment (ATT) and for
amyloidosis, Bortezomib and Dexamethasone based
weekly chemotherapy started. Though her symptoms
improved temporarily in the form of decreased
dizziness, fatigue, but after the third chemotherapy,
she developed decompensated chronic heart failure
(CHF) followed by diarrhoea. Appropriate treatment
started & Bortezomib based chemotherapy withheld
in the fear of drug induced diarrhoea. Later she
started having direct hyperbilirubinemia with
leucocytosis. ATT modified & broad spectrum
antibiotics started as all the investigations to localize
the infection were negative. Because of deranged
LFT, Bortezomib chemotherapy stopped and
Cyclophosphamide & Dexamethasone based weekly
chemotherapy started. But the patients condition
deteriorated rapidly and she died of septic shock with
aspiration pneumonia after 4 weeks.
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DISCUSSION
Amyloidosis is a heterogeneous group of diseases
associated with the common pathological process of
extracellular protein deposition in various organs,
leading to organ dysfunction and death.
Inspite of the fact that hepatic involvement in
systemic amyloidosis is common histologically
occurring in 60-100% of liver specimens
4
clinically
apparent liver disease is infrequent. The patient had
markedly elevated serum alkaline phosphatase which
suggests an early phase of intrahepatic cholestasis.
Jaundice is usually a terminal feature and most
probably would have appeared if the patient had lived
long enough. Intrahepatic cholestasis secondary to
amyloidosis has been reported by several other
workers.
5,6
Other parameters of liver function which
reflect the integrity of the hepatic parenchymal cells,
such as bilirubin level, serum albumin and
prothrombin time were normal because hepatic
amyloidosis is primarily an infiltrative disorder.
Tuberculosis is generally followed by secondary
amyloidosis. The association of primary systemic
amyloidosis with tuberculosis is very rare. Only one
case thus far reported in literature.
7
Diagnosis of
tuberculosis in presence of systemic amyloidosis can
be challenging as Amyloid material in a lymph node
can masquerade as caseous necrosis in cytology.
8
Our
patient had AFB in the abdominal lymph nodes which
regressed completely with ATT. The present case
outlines the challenges in management of atypical
cases where liver involvement with amyloid and use
of potentially hepatotoxic drugs was required for the
treatment of the patient.
There was no identifiable chronic inflammatory,
infective or neoplastic disorder to account for
amyloid deposition. Serum protein electrophoresis
did not show abnormal band. There was no bence-
jones protein in urine and bone marrow examination,
did not show expansion of plasma cell. This suggests
that the amyloidosis is most likely to be primary, but
unrelated to any overt immunocyte dyscrasia.
Our patient had primary amyloidosis with Liver,
Cardiac, ANS and GIT involvement with abdominal
tuberculous lymphadenopathy. Bortezomib with
dexamethasone is a proven therapy for primary
amyloidosis.
9
Our patient was started on this
treatment. Since she developed side effects, therapy
was changed to cyclophosphamide. But she
succumbed to her disease.
CONCLUSION
We conclude that tuberculosis is generally followed
by secondary amyloidosis. The association of primary
systemic amyloidosis with tuberculosis is very rare,
but in this case we can also think that primary
systemic amyloidosis can be associated with
tuberculosis.
ACKNOWLEDGMENT
This work was done in the department of medicine at
AIIMS, Hospital without any additional financial
support. Authors thanks to all participants in this
study. They are also grateful to Dr A B Dey for their
advice to patient care and management.
Conflict of interest: The authors declare no conflict
of interest.
REFRENCES
1 Jean DS, Alan SC. History of the Amyloid Fibril.
Journal of Structural Biology. 2000;130:8898.
2 Virchow VR. Ueber einem Gehirn and
Rueckenmark des Menschen auf gefundene
Substanz mit chemischen reaction der Cellulose.
Virchows Arh Pathol Anat.1854;6:135-8.
3 Divry P, Florkin M. Sur les prorietes optiques de
lamyloide. CR Seances Soc Biol.1927;97:1808-
10.
4 Gertz MA, Kyle RA. hepatic amyloidosis clinical
appraisal in 77 patients. Hepatology.
1997;25:118-21
5 Mc Donald P, Usborne C, Playfer JRA. Case of
intrahepatic choestasis due to amyloidosis. Int. J.
Clin. Pract. 1988;52:201-02
6 Gornka MK, Bhasin DK, Vasisth RK,Dhawan S.
Hepatic amyloidosis presenting with severe
intraheptic cholestasis. J. Clin Gastroenterol.
1996;23:134-36
7 Fekih L, Boussoffara L, Fenniche S, Hassene H.
Enigmatic evolution of an association of
pulmonary tuberculosis and amyloidosis. Rev
Mal Respir. 2011;28(5):691-5
8 Sharma N, Sharma S, Bindra R. Plasmacytoma
with amyloidosis masquerding as tuberculosis on
cytology. J Cytol. 2009;26:161-3
9 Kastritis E, Anagnostopoulos A.Treatment of
light chain (AL) amyloidosis with the
combination of bortezomib and dexamethasone.
Haematologica. 2007;92(10):1351-58