EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Silicosis is one of the most common occupational disorders globally, caused by inhaling crystalline silicon dioxide or silica. Despite decades of preventative efforts, silicosis continues to be a global problem. In many industries, workers are exposed to respirable crystalline silica dust particles. The condition can be found worldwide, although it is more prevalent in low-income and middle-income countries. Lung transplant is the final treatment option for silicosis, which has no known curative treatment. There is a paucity of research on patients with silicosis who receive lung transplants. Long-term results in patients with silicosis who received a single-lung transplant are also of interest. Here, we present a case of secondary (AA) amyloidosis that developed in a patient who had a single-lung transplant to treat chronic complicated silicosis.

A 36-year-old patient who had a single-lung (right) transplant to treat silicosis 62 months previous to arrival at our clinic was admitted with complaints of progressive dyspnea, abdominal pain, and diarrhea. Informed consent was obtained from the patient. The patient had a history of working with the manufacture and application of non-stick coatings (polytetrafluoroethylene, also known as Teflon) for 8 years from the age of 18 years and was diagnosed with silicosis at age of 26 years.

The chest radiograph results revealed a diffuse nodular appearance in the right lung. Complete blood count, serum biochemistry, and inflammatory markers were within reference limits. No viral, fungal, or bacterial pathogens were observed in the throat, sputum, urine, stool, or blood samples. Empirical antibiotic treatment was started. Forced expiratory volume in 1 second was decreased by more than 20% versus the best result in the pulmonary function test. No significant change was observed in the native lung in the thorax computed tomography (CT) scan, whereas diffuse reticulonodular appearance was remarkable in the right lung (Figure 1a and 1b). Normal histological tissue was found throughout a bronchoscopic lung biopsy sample. The patient’s abdominal pain was not eased by medical treatment, so a biopsy was obtained from the edematous gastric antrum during an upper gastrointestinal system endoscopy. When the patient’s dyspnea worsened, an open lung biopsy was conducted.

A wedge biopsy was performed with a right lateral mini thoracotomy incision from the middle lobe. Hematoxylin-eosin staining revealed giant cells and granulomas consisting of epithelioid histiocytes in the lung tissue (Figure 2a). Crystal violet staining detected amyloid deposits in the vessel walls of the lung parenchyma (Figure 2b). Amyloid deposition was also observed in the gastric biopsy sample (Figure 2c). Immunohistochemical typing was compatible with AA amyloidosis (Figure 2d). The patient’s serum amyloid A level was increased (71 mg/dL). Previous pulmonary explant material was reexamined, and no amyloidosis was found.

Amyloidosis is a disorder that progresses with the accumulation of insoluble fibrils (amyloid) in the extracellular space due to misfolding of autologous proteins, which can lead to organ dysfunction and even death.² Dozens of different precursor amyloidogenic proteins have been identified, at least 17 of which cause systemic diseases.³ The most common type of systemic amyloidosis is primary systemic light-chain (AL) amyloidosis, in which amyloid forms from variable regions of monoclonal immunoglobulin light chains produced by an indolent plasma or B-cell clone.⁴ Although AA amyloidosis is a known complication of chronic inflammatory disorders, it is a rare disease with a reported incidence of 1 to 2 cases per million person-years.⁵ The development of AL amyloidosis due to plasma cell neoplasm is a common expectation in solid-organ recipients, which is also a component of posttransplant lymphoproliferative disease.^4-6

There is scarce research on the development of amyloidosis in solid-organ transplant recipients. One study investigated 5112 solid-organ recipients with a diagnosis of amyloidosis. Only 30 of these patients developed amyloidosis after transplant.⁷ Of these patients with poor survival, 14 had AL amyloidosis while, surprisingly, 11 had secondary (AA) amyloidosis. Chronic inflammation was identified as chronic bronchitis, gout, hepatitis, and tuberculosis with an aspergilloma in 5 of the patients who developed AA amyloidosis. The progress of AA amyloidosis is characterized by accumulation of serum amyloid A protein, an acute phase reactant, in many organs and tissues secondary to chronic inflammation.⁸ Although a case of AL amyloidosis has been reported in a patient who received a combined heart, lung, and kidney transplant, the development of amyloidosis in an isolated lung recipient has not been reported in the English literature. To our knowledge, we have presented the first reported case of AA amyloidosis in a lung transplant recipient.

There are a limited number of reports on patients who underwent lung transplant for silicosis. Although there have been reports of patients with silicosis who underwent bilateral sequential lung transplant, a single-lung transplant is not uncommon in patients with chronic complicated silicosis.^9,10 Long-term outcomes and complications in this unique group of patients, ie, single-lung transplant recipients, are worthy of further study. No signs of amyloidosis were found when the right lung explant material was reexamined, possibly because chronic inflammation due to silicosis had not yet produced any observable pathological changes during transplant. In our case, the native lung showed chronic and complex silicosis, which most likely caused persistent inflammation and resulted in AA amyloidosis. In addition, long-term transplant immunosuppression may predispose patients to chronic infections or chronic inflammation of undetermined origin.

We conclude that AA amyloidosis should be considered as a potential long-term complication of the native lung in patients with silicosis who undergo single-lung transplantation.

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