Discussion
Amyloidoses are a typology of rare diseases characterized by the
accumulation of protein fibrillary aggregates in heart, kidney,
gastrointestinal tract, peripheral and autonomic nerves, skin, joints
and blood vessels of all tissues1.The proteins
typically are antiparallel β-sheets, which show X-Ray diffraction,
orange-red appearance under light microscopy and apple-green
birefringence under polarized light2. Primary or light
chain (AL) amyloidosis is the most frequent type of systemic
amyloidosis. AL is caused by abnormal proliferation of resident bone
marrow monoclonal plasma cells producing unstable light chains. Lambda
subtype accounts for 75% of all cases. Those amyloidogenic free light
chains can then accumulate in tissues evolving in progressive organ
dysfunction. Typically, plasma cells are less than 10% at the bone
marrow biopsy3. Symptoms depend on the organ
involvement, ranging from heart failure with preserved ejection
fraction, nephrotic syndrome, organomegaly (mainly tongue and salivary
glands) to peripheral neuropathies and unspecific symptoms such as
fatigue, asthenia and body weight loss. The most common cause of the
death in patients with amyloidosis is heart failure4.
Clinical suspicion of AL amyloidosis will require biopsy of the involved
organs, preferably the fat pad or, more rarely, kidney, salivary gland,
heart and liver5. Currently, there are no clear
guidelines on systemic AL amyloidosis treatment. However, since both AL
amyloidosis and multiple myeloma (MM) are monoclonal plasma cell
dyscrasias, AL amyloidosis treatment strategies and medications are
derived from the anti-plasma cell therapy used for
MM6,7.
In our case report, the patient presented non-specific symptoms and
signs (hypotension, severe asthenia, limitation in ordinary activity due
to fatigue and dyspnea, itching, recurrent low-grade fever, DVT).
Laboratory tests showed nephrotic-range proteinuria and monoclonal IgA
lambda. The first clinical suspicion of infiltrative disease arose from
the low QRS voltage in V1-6 and limb leads. Amyloidosis EKG often shows
QRS voltage less than 0,5 mm in the peripheral leads and less than 1 mm
in precordial leads; the Sokolow/Lyon index which represents the sum of
the S wave in V1 and R wave in V5 and V6 (SV1+RV5/6) is usually
< 1.5 mV and is typically found in 30-70% of patients with AL
amyloidosis8. Echocardiography usually documents
hypertrophic cardiomyopathy, with no prior history of
hypertension9. Cardiac MRI was suggestive of amyloid
accumulation (Figure 2 ). Myocardial scintigraphy and genetic
exams were even performed to rule out transthyretin (ATTR) amyloidosis.
Despite cardiac MRI sensitivity and specificity is
85-90%9, the gold standard exam to diagnose
amyloidosis is histological evidence of amyloid deposition in the
tissues10. In our case, given the negativity of fat
pad aspiration (58% sensitivity and 100% specificity in AL
amyloidosis), cardiac involvement and high clinical suspicion, renal
biopsy was mandatory to confirm diagnosis.
HBV and HIV are typically associated with AA
amyloidosis11. Only few studies describe development
of AL amyloidosis after HBV and HIV infection and there is no unique
consensus about the etiopathogenesis12. The main
hypotheses are that HBV is responsible for chronic immunological
stimulation, while HIV antigens act like superantigens and stimulate B
cell proliferation determining immunoglobulins production; on the other
hand HIV infection causes CD4+ T cell depletion which induces
immunodeficiency13. Immunoglobulins can misfold and
accumulate as amyloid fibrils and lead to amyloidosis. Moreover, some
studies correlate monoclonal proliferation of plasma cells and
HIV13,14. In particular, the prevalence of MGUS in HIV
patients is higher compared to the general population, especially at
younger age (from 3-4% to 26%). In these patients, MGUS usually
recover after receiving antiviral therapy15.
Conclusion Our clinical case represents a rare case of HIV and HBV-associated AL
amyloidosis with IgA Lambda monoclonal component. Physiopathological
links between HIV, HBV and AL amyloidosis need to be accurately studied.
Our case report suggests that HIV-associated immune dysregulation might
be critical for pathogenesis of plasma cell dyscrasias and then AL
amyloidosis. Thus, we hypothesize that early immune restoration in our
patient is important to remodulate the activity of HIV-induced immune
system and, hopefully, to respond to anti-plasma cell neoplasm therapy.
We believe that this unusual observation presented as clinical
case might be important for infectious disease specialist, general
practitioners, cardiologists, and nephrologists to rapidly recognize
risk factors for AL amyloidosis and thus facilitate the diagnosis and to
start specific treatment.
AUTHOR CONTRIBUTIONS A.P., G.C, and O.M collected data, A.P., G.C, O.M
and M.P. interpreted data and wrote the manuscript, all authors reviewed
and approved the final version of the manuscript.
KEY MESSAGE Chronic viral infections as potential risk factor for AL
amyloidosis
FUNDING INFORMATION This article was produced without any funding.
CONFLICT OF INTEREST STATEMENT The Authors declare that there are no
potential conflicts of interest.
DATA AVAILABILITY STATEMENT Not applicable.
ETHICS STATEMENT This article does not contain any studies with human
participants or animals performed by any of the authors.
PATIENT CONSENT STATEMENT The patient provided informed consent for the
use of his clinical data.
ORCID Mariangela Palladino https://orcid.org/0000-0001-5993-8034