Presentation of Sjogren Syndrome as Nodular Pulmonary Amyloidosis

Sjogren syndrome is an autoimmune disorder that leads to dryness in the eyes and mouth. Nodular pulmonary amyloidosis is a localized amyloid deposition pathology commonly seen with monoclonal lymphoproliferative disorders. We present a patient who came in with dyspnea and was found to have nodular pulmonary amyloidosis on biopsy. Commonly associated lymphoproliferative pathologies were ruled out and on further workup, the patient was found to have Sjogren syndrome. This case demonstrates pulmonary nodular amyloidosis as a rare presentation of Sjogren syndrome in the setting of relatively well-controlled symptoms. Detection of pulmonary nodular amyloidosis should prompt evaluation of associated conditions such as malignancy and autoimmune disorders to guide further management.


Introduction
Amyloidosis is a heterogeneous group of disorders associated with the deposition of proteins in an abnormal fibrillar form in tissues [1]. Light chain (AL) amyloidosis and reactive (AA) amyloidosis are the two most common types of amyloidosis. In AL amyloidosis, clonal plasma cells produce light chains (λ or κ) that are amyloidogenic [2]. AA amyloidosis occurs due to increased secretion of serum amyloid A (SAA) protein, a protein produced in inflammatory pathologies [3]. Along with the sustained elevation of SAA, genetic polymorphisms in SAA and the type of autoinflammatory syndrome facilitate conversion to SAA to betapleated sheet and deposition in organs [4]. Pulmonary involvement is usually insignificant in systemic amyloidosis, and localized pulmonary amyloidosis is infrequently reported [5]. Isolated pulmonary amyloidosis in Sjogren syndrome is also an uncommon phenomenon. Here we present a patient who was found to have pulmonary nodular amyloidosis with Sjogren syndrome.

Case Presentation
A 78-year-old lady presented to the emergency room with increasing shortness of breath and cough for the past two to three months. The patient had been using lubricant eye drops for the past many years for her dry eyes but did not have any past diagnosis of Sjogren syndrome. The patient had normal vital signs on presentation. Normal breath sounds were heard on auscultation. Complete blood count and basic metabolic profile were unremarkable. Chest x-ray showed multiple nodular lesions in the right lung fields ( Figure 1). Computed Tomography (CT) scan of the chest showed numerous bilateral pulmonary nodules, including a spiculated 11 cm-sized mass in the left lower lobe, suspicious of malignancy ( Figure 2). Positron emission tomography (PET)-CT scan showed fluorodeoxyglucose (FDG) activity in the lung nodules and FDG avid hilar region ( Figure 3). Due to high suspicion of malignancy and for staging and characterization, the patient underwent surgical resection and biopsy of the right upper lobe. Pathologic specimen showed nodular amyloidosis, confirmed on Congo-red stain. Interestingly, there was no evidence of any neoplastic process in the resected specimen, despite high FDG activity on the PET scan.  Table 1). The monoclonal protein screen showed polyclonal paraproteinemia with elevated kappa and lambda light chains. There was also a slight isolated Immunoglobulin (Ig) G rise with normal levels of other Igs ( Table 2).   In this scenario, the patient had persistent dry eyes and strongly positive SS-A and SS-B antibodies.
Neoplastic processes were ruled out on biopsy, which leaves Sjogren syndrome causing and presenting as nodular pulmonary amyloidosis.
All the possible options including immunomodulators such as rituximab were discussed with the patient for the treatment of amyloidosis. After weighing the treatment options with the possible risk of immunosuppression, particularly in the ongoing coronavirus disease 2019 (COVID-19) pandemic, a decision was made not to start any treatment. The patient was followed up in the Rheumatology and Hematology clinic and she remained largely asymptomatic. She has not reported any other occurrence of symptoms since the initial presentation.

Discussion
Lung amyloidosis has three main histologic presentations described as nodular pulmonary amyloidosis, tracheobronchial amyloidosis, and diffuse alveolar septal amyloidosis [6]. Nodular pulmonary amyloidosis usually represents localized AL or AL/heavy chain (AH) amyloidosis [7]. It is usually detected incidentally as the patients are largely asymptomatic on presentation. On detection, nodular amyloidosis is found to be isolated but may be present alongside a localized clonal proliferation of B-lymphocytes or plasma cells secreting light chains [8]. It has also been shown to be associated with an underlying lymphoproliferative disorder such as mucosa-associated lymphoid tissue (MALT) lymphoma [7].
Due to its frequent association with localized lymphoma and other lymphoproliferative disorders, surgical excision and biopsy are essential for the diagnosis of amyloidosis and exclusion of localized lymphoma, as management options vary. In the advent of worsening symptoms and extension of amyloidosis, surgical excision has been done successfully [9].
Sjogren syndrome is associated with multiple pulmonary disorders, most commonly being interstitial lung disease, bronchiolitis, chronic obstructive pulmonary disease, and reactive airway disease ( Table 3) [10]. The presence of pulmonary nodular amyloidosis as a presentation of Sjogren syndrome is not widely reported.  In the current case, the presence of multiple nodular lesions in lung fields with FDG-avid lesions warranted the workup for malignancy with resection and biopsy. On the pathologic specimen, there was no evidence of neoplastic processes, and amyloidosis was confirmed with the Congo-red stain. With the autoimmune panel results and the presence of xerophthalmia, the association of nodular amyloidosis with Sjogren syndrome was established.

Type of Lung Involvement Main Clinical Features
This case report presents an uncommon association of Sjogren syndrome with nodular pulmonary amyloidosis. Further exploration of the pathophysiology of autoimmune disorders and associated inflammation can explain systemic amyloidosis but isolated organ amyloidosis in such conditions is uncommon. Further research and understanding of single-organ amyloid deposition in systemic conditions may provide a suitable explanation.

Conclusions
Isolated nodular pulmonary amyloidosis is a condition most commonly associated with lymphoproliferative malignancies. Along with its evaluation, clinicians also need to consider autoimmune disorders in the differential. Sjogren syndrome is one such condition that can infrequently present as nodular pulmonary amyloidosis. In that setting, management is generally conservative with symptomatic management.

Additional Information Disclosures
Human subjects: All authors have confirmed that this study did not involve human participants or tissue.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.