A rare presentation of pulmonary transthyretin amyloidosis

Virchow described amyloidosis in 1853. Amyloidosis is the extracellular deposition of an insoluble misfolded polymerized tetramer of fibrillary protein that accumulates within tissues leading to organ dysfunction. Amyloidosis affects 10 people per one million every year. Specific varieties of amyloidosis result from diversely involved proteins. Tissue involvement can lead to multiorgan system dysfunction. Lung involvement from amyloidosis is very rare, and tissue biopsy is crucial for diagnosis. Genetic testing might be requested based on the suspected type. Lung involvement is very rare and mainly asymptomatic, and some cases are only diagnosed postmortem. When symptomatic, the clinical manifestations are nonspecific and include cough, dyspnea, and respiratory infections. The infiltrative process might affect pulmonary mechanics producing abnormal pulmonary function testing. Radiological manifestations of pulmonary amyloidosis involve the pleura, the tracheobronchial tree, the alveoli, and the mediastinal lymph nodes. Treatment of pulmonary amyloidosis is based on treating the underlying disease process. We present herein a case of 78-year-old male with senile cardiac amyloidosis, who presents to our clinic with multiple nodular pulmonary opacities.

The term amyloid was used for the first time in literature in 1853 by Rudolph Virchow [1,2]. Amyloidosis refer to the extracellular deposition of an insoluble misfolded, dissociated and polymerized tetramer of fibrillary protein in the tissue leading to organ dysfunction [[3], [4], [5]]. The incidence of amyloidosis is 10 cases per one million per year [6], hence the rarity of the diagnosis.

There are four types of amyloidosis caused by changes in four different protein structures: protein A amyloidosis (AA), immunoglobulin light chain amyloidosis (AL), transthyretin protein (ATTR) and Beta 2 microglobulin.

Protein A amyloidosis (AA) is associated with chronic inflammatory disease (systemic lupus erythematosus, rheumatoid arthritis, familial Mediterranean fever, etc.), whereas, the immunoglobulin light chain amyloidosis (AL), Kappa (K) or Lambda (L), is associated with blood cell dyscrasia (multiple myeloma, Waldenstrom macroglobulinemia, asymptomatic monoclonal gammopathy, Sjogren disease with associated lymphoma). Transthyretin protein (ATTR) can be either associated with genetic mutation (ATTRm) or without genetic mutation known as the senile or wild type (ATTRwt) seen in elderly males. Beta 2 microglobulin is seen in dialysis patients [[3], [4], [5], [6], [7], [8], [9], [10]]. AL amyloidosis is the most common type [4].

Amyloidosis may be localized or systematic and may affect many organs such as the heart, lung, kidney, nerves, tendons and gastrointestinal tract [5,10,11]. Amyloidosis may manifest as infiltrative cardiomyopathy with heart failure, arrythmia, atrial fibrillation, renal failure and carpal tunnel syndrome [3,5]. The most common type of systemic amyloidosis is, as mentioned earlier, light chain amyloidosis with a prevalence of one case per 100 000, followed by AA amyloidosis [10].

Amyloidosis of the lung parenchyma and airways was first time reported by Lesser in 1877 [12]. Primary pulmonary amyloidosis is more common than secondary amyloid pulmonary deposit [13]. Amyloidosis of the respiratory tract can be localized to the lung or part of systemic amyloidosis [4,11]. Lung involvement from amyloidosis is frequently seen in AL but can be seen with senile ATTR or ATTRwt [10] and the highest frequency of pulmonary amyloidosis occurs with Lambda light chains followed by Kappa light chains, then comes AA amyloidosis, and lastly the wild transthyretin protein [14]. Pulmonary involvement from amyloidosis is a rare entity [4] with male predilection [14,15].

A rare presentation of pulmonary transthyretin amyloidosis

Abstract

1. Introduction