Unusual presentation of transthyretin (ATTR) cardiac amyloidosis: A case report of pruritus as a possible initial symptom and challenging diagnosis

Background: Amyloidosis is characterized by the accumulation of misfolded proteins in various organs throughout the body. While any organ in the body can be affected by amyloidosis, the heart is the most commonly affected organ (۷۰%), followed by the kidney, liver, gastrointestinal system, and soft tissue, which are involved in ۶۰%, ۲۰%, ۱۵%, and ۱۰% of cases, respectively. Cardiac amyloidosis (CA) can lead to heart failure, cardiac arrhythmias, sudden cardiac death, and deposition of proteins in coronary arteries. Although the accumulation of proteins in soft tissues, including the skin, is not usual, but can present a range of symptoms, including pruritus. This symptom is typically localized to a single site; however, in some cases, it can affect multiple areas. In this report, we present a case of CA in which the patient initially presented with pruritus. Later, during the workup, the detection of ascites fluid raised a series of questions, ultimately leading to the diagnosis of CA. The case underscores the importance of considering amyloidosis in patients presenting with nonspecific symptoms, particularly those affecting the skin, and highlights the need for increased awareness of the disease among clinicians.Case presentation: A ۷۰-year-old man presented with a mild generalized pruritus that had been ongoing for ۱ month without any associated skin lesions. The patient denied experiencing any constitutional symptoms, including fever, weight loss, night sweating, gastrointestinal symptoms, jaundice, or urine or stool color alterations. Except for a reduction in mean corpuscular volume (MCV) (۷۰fL) with normal hemoglobin levels (۱۳mg/dL), and slightly elevated AlkP levels (۴۰۳U/L), all other tests were normal. An abdominopelvic sonography was then performed, revealing no pathologic findings. Subsequently, a MRCP was performed, revealing a mild dilation of the main pancreatic duct and common biliary duct, beginning at the level of the ampulla of Vater, with a normal intrahepatic biliary tree. EUS was also performed, which did not reveal any pathologic findings. Further blood tests, including AMA, ANA, ASMA, HBsAg, anti-HCV Ab, and anti-HIV Ab, were negative. A serum protein electrophoresis showed a reduction in albumin, along with elevated levels of β۱, β۲, and Ɣ, with a normal level of total protein and albumin to globulins ratio of ۱.۰۱. In order to rule out autoimmune hepatitis, a liver core needle biopsy was performed, which revealed chronic active hepatitis without significant fibrosis, with a histological activity index (HAI) of ۶, which was not specific enough to provide an exact diagnosis. Three months after the initial visit, an abdominopelvic CT scan with IV contrast showed ascites fluid in the abdomen and pelvis, along with an abnormal cardiothoracic ratio, dilated inferior vena cava (IVC), and hepatic veins. Another abdominal ultrasound was performed, showing significant systolic reflux flow into the hepatic vein, suggesting that congestive heart failure (CHF) caused by tricuspid valve (TV) regurgitation was the probable reason for the formation of the ascites fluid. Based on the presented clinical findings, transthoracic echocardiography (TTE) was conducted and showed biatrial enlargement, severe left ventricular (LV) hypertrophy with a LV ejection fraction of ۵۰%, mild right ventricular (RV) dilation with mild systolic dysfunction, and moderate to severe TV regurgitation. An ECG also depicted a right bundle branch block with low voltage in limb leads, which suggested restrictive cardiomyopathy (Figure ۱). To further evaluate the condition, cardiac magnetic resonance imaging (CMR) was performed, revealing biatrial enlargement with atrial wall and interatrial septum (IAS) hypertrophy, LV hypertrophy with wall thickening, reduced LV global longitudinal strain (−۸%), and mild RV hypertrophy with moderate systolic dysfunction and severe TV regurgitation. In the gadolinium study, a subendocardial to transmural enhancement (reverse myocardial nulling) was observed in the wall of all four chambers, strongly suggesting CA. In order to ascertain our hypothesis, an abdominal wall fat pad biopsy was obtained, and a Congo red staining was performed on the sample, showing apple-green birefringence when viewed under polarized illumination (Figure ۲). A technetium-۹۹m pyrophosphatase (Tc۹۹mPYP) study was conducted to investigate further, showing significant diffuse PYP activity throughout LV and RV myocardial regions, which was more prominent in the LV apex and septum, with a quantitative visual score of ۳. The Tc۹۹m-PYP scan findings indicated a myocardial PYP uptake greater than rib uptake and a heart-to-contralateral lung PYP uptake ratio of ۱.۵۲, suggestive of transthyretin amyloidosis. Finally, an endoscopy was conducted, revealing no esophageal varices. Ultimately, given the subtype diagnosis, our intended course of treatment involved the administration of diuretics as the general management due to the heart failure symptoms, alongside tafamidis. However, the patient expressed reluctance to comply with the suggested treatment and did not consent for further therapeutic plans.