Primary Sjögren’s syndrome complicated by pleuritis and pleural effusion: a case report and review of the literature

Abstract

Introduction and importance

Pleural effusion is a rare manifestation of primary Sjögren’s syndrome (pSS), especially in elderly patients with comorbidities such as hypothyroidism and chronic obstructive pulmonary disease (COPD). Diagnosis can be challenging as respiratory symptoms may mimic community-acquired pneumonia or COPD exacerbations. Reporting rare presentations aids early recognition and tailored management.

Case presentation

An 82-year-old woman with pSS, hypothyroidism, and COPD presented with progressive dyspnea, productive cough, and bilateral leg swelling. Chest X-ray posteroanterior view revealed consolidation with blunting of the left costophrenic angle, pointing toward pleural effusion. Subsequent pleural fluid analysis demonstrated lymphocyte predominance along with normal glucose levels, suggesting effusion due to pSS. She received empiric antibiotics, oxygen, and supportive care.

Clinical discussion

Common causes of pleural effusion in an elderly patient include cardiovascular conditions such as heart failure, malignancy, infections such as pneumonia and tuberculosis, and autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. Sjögren’s syndrome rarely causes pleural effusion. Pleural fluid analysis helps in differentiating the cause of effusion. In pSS, pleural fluid analysis reveals lymphocytic predominance and exudation with normal glucose levels and pH, and low pleural fluid adenosine deaminase levels.

Conclusion

This case underscores the importance of thorough evaluation, early recognition, and tailored management in pSS patients with respiratory symptoms to prevent misdiagnosis and improve outcomes.

Introduction

Sjögren’s syndrome is a systemic autoimmune disease that primarily affects exocrine glands, causing sicca symptoms such as dry eyes (xerophthalmia) and dry mouth (xerostomia)[1]. It is classified as primary, which occurs on its own, and secondary if it is associated with other collagen disorders, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and scleroderma[2]. In addition to sicca symptoms, it can also cause multisystem involvement, causing polyarthritis, vasculitis, renal involvement, lymphoma, and pulmonary involvement[1].

Pulmonary manifestations are varied and include interstitial lung disease, airway disease, lymphoproliferative disorders, pulmonary infections, and thromboembolic disorders. Rarely, pleural effusion may also occur in less than 1% of cases, with only a few case reports describing it in the literature[3]. Pleural effusion in primary Sjögren’s syndrome is exudative with predominant lymphocytes and low complement, as well as low adenosine deaminase (ADA) levels[4]. In this case, we present an 80-year-old woman who had bilateral pleural effusion secondary to primary Sjögren’s syndrome (pSS). This case has been reported in accordance with the SCARE and TITAN Guidelines 2025^[5,6^].

HIGHLIGHTS

• Rare bilateral pleural effusion in primary Sjögren’s syndrome.

• Occurred in elderly patients with COPD and hypothyroidism.

• Diagnosis confirmed by imaging, laboratories, and autoimmune markers.

• Managed with antibiotics, oxygen, bronchodilators, and supportive care.

• Highlights need for early recognition to prevent misdiagnosis.

Case presentation

An 82-year-old Hindu woman presented to the hospital with progressive shortness of breath for the past 4 days, increased frequency of productive cough, and bilateral lower limb swelling. She had a history of Sjögren’s syndrome, diagnosed 2 years earlier based on serological tests, including positive ANA (Hep-2), Ro-52, and SS-A markers, and treated with steroids. Additionally, she had hypothyroidism, diagnosed around the same time and treated with levothyroxine (100 µg daily). The patient was a former smoker with a 5-pack-year history. She had recently been diagnosed with chronic obstructive pulmonary disease (COPD) but had not received the necessary vaccinations or domiciliary oxygen therapy. Three months before this presentation, she underwent surgical repair of a right neck of femur fracture. The patient also reported intermittent gum bleeding and dryness of the mouth, but she had not been compliant with her medication for Sjögren’s syndrome. She denied dry eyes, altered consciousness, or bruising, and also experienced weight loss, poor appetite, and disturbed sleep–wake cycles. There was no history of dry eyes or altered consciousness. Her family history included pulmonary tuberculosis and hyperuricemia in her son and a rheumatological disorder in her granddaughter.

Upon examination, the patient was alert and oriented. She showed signs of pallor and bilateral pitting pedal edema up to the mid-thigh (right > left), more significant on the right side. There were no signs of cyanosis, clubbing, or palpable lymphadenopathy. Her vital signs were stable, with a pulse rate of 74 beats per minute, blood pressure of 120/80 mmHg, and a respiratory rate of 20 breaths per minute. On auscultation, bilateral inspiratory wheezes were heard in the infraclavicular and supraclavicular regions, with decreased breath sounds in the infra-axillary regions. Cardiovascular, abdominal, and neurological examinations were otherwise unremarkable.

The results of laboratory tests are described in Table 1. In addition to these, coagulation studies were done, revealing normal results. Arterial blood gas showed mild respiratory alkalosis (pH 7.47), likely due to hyperventilation. Urinalysis revealed pyuria, suggesting possible urinary tract infection or inflammation. Microbiological testing of sputum yielded no significant growth, and acid-fast bacilli were not detected, excluding tuberculosis. Autoantibody tests were highly positive for ANA (Hep-2), Ro-52, and SS-A, confirming the diagnosis of Sjögren’s syndrome. Echocardiography showed dilated left and right atria, moderate tricuspid regurgitation, mild eccentric mitral regurgitation, and grade I left ventricular diastolic dysfunction, with a preserved left ventricular ejection fraction of 60%.

Table 1.

Serial blood investigation results of the patient.

Parameters	At presentation	Reference range
Total leukocyte count	12 000	4000–11 000 (/µL)
Hemoglobin	8.9	12–16 (g%)
Platelets	90 000	150 000–400 000 (/µL)
Peripheral blood smear	Anisopoikilocytosis, polychromasia, pencil cells, and target cells	-
Serum iron	30	50–170 (µg/dL)
Total iron binding capacity	150	250–450 (µg/dL)
Ferritin	300	15–150 (ng/mL)
Serum albumin	2.3	3.5–5 (g/dL)

Chest X-ray posteroanterior view (Fig. 1) revealed consolidation with blunting of the left costophrenic angle, pointing toward pleural effusion. Subsequent pleural fluid analysis demonstrated lymphocyte predominance (76%) along with normal glucose levels (70 mg/dL), normal ADA level (20 U/L). Cytology revealed the absence of malignant cells. In the clinical context, these findings, along with the patient’s history of Sjögren’s syndrome, were consistent with Sjögren’s-related pleural effusion. Axial computed tomography (CT) images (Fig. 2) of the chest in lung window reveal patchy fibrotic changes involving both lung fields, more marked in the peripheral and basal regions. Mild left-sided pleural effusion is noted, with fluid tracking along the left pleural space. Mediastinal window images (Fig. 3) confirm bilateral pleural effusion – minimal on the right side and mild on the left side.

Figure 1.

Chest X-ray posteroanterior view shows homogenous opacity in the left lower lung zone with blunting of the left costophrenic angle, suggestive of left-sided pleural effusion. There is associated increased density overlying the left mid and lower lung fields, which may represent underlying consolidation. The cardiac silhouette is partially obscured on the left side. The right lung fields appear clear, and the trachea is central. No obvious bony abnormalities are noted.

Figure 2.

Axial CT images of the chest in lung window reveal patchy fibrotic changes involving both lung fields, more marked in the peripheral and basal regions. Mild left-sided pleural effusion is noted, with fluid tracking along the left pleural space.

Figure 3.

Mediastinal window images confirm bilateral pleural effusion – minimal on the right side and mild on the left. Cardiac silhouette and mediastinal structures are within normal limits, with no significant mediastinal lymphadenopathy observed.

The patient was started on empiric broad-spectrum intravenous antibiotics to cover possible bacterial pneumonia, along with supplemental oxygen therapy and inhaled bronchodilators to help alleviate respiratory distress. Her thyroid hormone therapy was continued, and her autoimmune therapy was adjusted to optimize care. Nutritional support and physiotherapy were also initiated to prevent complications from her comorbidities. She was carefully monitored for fluid balance and pleural effusion. She was also started on prednisolone 40 mg. Over the course of a 7-day hospital stay, the patient showed improvement, with gradual resolution of her respiratory symptoms and a reduction in lower limb swelling. She was discharged with a follow-up plan to monitor her autoimmune condition and respiratory status, and to reassess the pleural effusion. After 2 weeks of taking steroids, the pleural effusion had subsided.

This case is notable for the rare occurrence of bilateral pleural effusion in a patient with Sjögren’s syndrome, highlighting the complexity of diagnosing and managing patients with autoimmune diseases and comorbid conditions. While pleural effusion is infrequently seen in Sjögren’s syndrome, it can occur, especially when compounded by pneumonia, hypothyroidism, and COPD. This case underscores the importance of early recognition and appropriate management in elderly patients with autoimmune diseases. Timely diagnosis, tailored therapy, and careful monitoring are essential for such complex cases.

Discussion

We report a case of bilateral pleural effusion in an 80-year-old woman with Sjögren’s syndrome, along with a literature review of all published cases since 2000 (Table 2). Pleural effusion in Sjögren’s syndrome is rare, and the possibility of association with other conditions, such as SLE and RA, should be explored[7]. A study conducted by Strimlan et al found that only 31 (9%) out of 343 patients with Sjögren’s syndrome had pulmonary involvement, and among these 31 patients, only 2 had pleural effusion[8].

Table 2.

Literature review of all published cases of Sjögren’s syndrome with pleural effusion since 2000.

Authors	Year of publication	Age and sex of the patient	Presenting complaints	Management
Horita et al[16]	2000	73 Y/M	Dyspnea	Prednisolone 30 mg
Teshigawara et al[2]	2008	65 Y/M	Cough and dyspnea	Prednisolone 30 mg
Makimoto et al[17]	2012	63 Y/M	Cough, dyspnea, and chest pain	Prednisolone 40 mg
Ma et al[15]	2015	42/F	Chest pain	Hydroxychloroquine 100 mg + total glucosides of peony
Cruz-Pérez et al[18]	2015	69 Y/F	Cough and chest pain	Methylprednisolone 120 mg + prednisolone 20 mg
Ferreiro et al[19]	2017	40 Y/F	Xerostomia and xeropthalmia with intermittent fibromyalgia	Spontaneous resolution of effusion
Hosoda et al[20]	2017	71 Y/F	Dyspnea	Prednisolone 25 mg
Usami[21]	2021	81 Y/F	Dyspnea	Prednisolone 30 mg
Alnabwani et al[22]	2021	69 Y/F	Dyspnea and chest tightness	Not mentioned
Shimoda et al[4]	2021	84 Y/F	Dyspnea	Prednisolone 20 mg
Abou Ziki et al[23]	2022	78 Y/F	Eye and mouth dryness and dyspnea	Prednisolone (dose not mentioned)
Fernandes et al[1]	2023	65 Y/F	Dyspnea, cough, and fever	Pulse methylprednisolone 500 mg for 3 days, then oral prednisolone
Varkey et al[11]	2024	Mid 20s/F	Dyspnea, productive cough and pleuritic chest pain	Video-assisted thoracoscopic surgery and decortication.

Pleural fluid analysis is crucial for differentiating whether the effusion is due to Sjögren’s syndrome or another cause. Pleural effusions are divided into exudative and transudative based upon Light’s criteria. Heart failure and cirrhosis are the common causes of transudative effusions, and nephrotic syndrome, constrictive pericarditis, superior vena cava obstruction, and urinothorax are the less common causes. Exudative effusions are commonly caused by pneumonia, malignancy, and thromboembolism[9]. Exudative effusions further need to be tested to identify the specific cause. These tests include cell count and differential, glucose levels, ADA, and cytologic analysis. If infection is suspected, bacterial culture and pH should also be tested[9]. Tuberculosis exhibits increased ADA levels. Malignancy exhibits lymphocytosis, and increased red blood cell count and decreased glucose levels[9]. In contrast, pleural fluid analysis in pSS reveals lymphocytic predominance and exudation with normal glucose levels and pH, and low pleural fluid ADA levels, as in our case^[1,10^]. However, effusions due to other autoimmune causes display a neutrophil-rich exudate[11]. Additionally, patients with lupus have reduced levels of complement, and in patients with RA, low glucose levels are present[4].

Lymphocytic infiltration of the glandular exocrine tissue is the primary pathophysiology of Sjögren’s syndrome, characterized by immune complex and T-cell lymphocyte deposition in the skin, joints, and organs. This is also evident in biopsy findings, which reveal more than 50 lymphocytes along with some macrophages and plasma cells^[11,12^]. Alongside these, positive clinical testing for sicca symptoms, such as the Schirmer test, sialography, and tear film stability test, can be used in the objective assessment of glandular dysfunction, helping in the diagnosis. Additionally, the presence of pSS-specific antibodies, such as anti-Ro (SS-A) and anti-La (SS-B), strongly suggests the diagnosis of pSS[12].

Cough and dyspnea are the most common pulmonary complaints of patients with Sjögren’s syndrome. In addition to these complaints, due to dryness of the nasal and oropharyngeal mucosa, epistaxis, sinusitis, difficulty swallowing, and hoarseness may occur[13]. Cough and dyspnea were also the presenting complaints in our case, and she also complained of frequent sinusitis.

Pulmonary involvement in pSS can also be demonstrated by radiology and pulmonary function tests (PFTs), with reduced diffusion capacity of lungs for carbon monoxide being the most common abnormality in PFT. Radiographic abnormalities include interstitial changes with reticulation, ground-glass opacities, consolidation, honeycombing, cysts, nodules, and bronchiectasis. Rarely, effusion may also be seen in the CT scans, as was present in our case^[3,13^].

The management approach of both pSS and secondary Sjögren’s syndrome is the same and includes non-pharmacological measures such as smoking cessation, patient education, dietary counseling, and immunization. Tear drops, along with a secretagogue (pilocarpine), can also be used in some patients[14]. Pulmonary manifestations are treated with high-dose glucocorticoids, which can be used alone or in combination with cyclophosphamide and mycophenolate mofetil. Rituximab can also be considered in some cases^[14,15^]. Pleural effusion secondary to any autoimmune disease should be resolved after the use of steroids. Rarely, steroid-resistant pleural effusions may occur in some collagen disorders, which may be treated with talc poudrage, tetracycline pleurodesis, and pleurectomy[16]. We did not require these therapies as the effusion subsided with steroid therapy for 2 weeks.

The key learning point from our case is that although pleural effusion rarely occurs in pSS, it should be considered as one of the causes, especially if pleural fluid analysis reveals lymphocytic predominance. Another learning point is the importance of the timely use of corticosteroids to relieve pulmonary symptoms, as seen in the literature review.

Conclusion

This case highlights the rare occurrence of bilateral pleural effusion as a pulmonary manifestation of pSS, particularly in an elderly patient with multiple comorbidities. Although pleural effusion is reported in less than 1% of pSS cases, it should remain a differential consideration when lymphocytic, exudative effusions are encountered – especially in patients with positive autoimmune markers. Early recognition, appropriate evaluation of pleural fluid characteristics, and timely initiation of targeted therapy can significantly improve outcomes. Our case underscores the need for clinicians to maintain a high index of suspicion for atypical presentations of autoimmune diseases, as prompt diagnosis and tailored management are crucial in preventing morbidity and improving quality of life in this vulnerable patient population.

Ethical approval

Our Institutional Research Committee does not mandate Institutional Review Board approval for case report writing.

Consent

Written informed consent was obtained from the patient’s parents/legal guardian for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Sources of funding

None.

Author contributions

N.B., M.P., and B.S. played a central role in the research, contributing to conceptualization, data curation, formal analysis, and methodology. N.B. was responsible for project administration and took the lead in writing the original draft, as well as in the review, editing, and visualization processes. S.D. and S.R. also helped in writing the original draft and the revision.

Conflicts of interest disclosure

None.

Research registration unique identifying number (UIN)

None.

Guarantor

Niraj Bam.

Provenance and peer review

Not commissioned, externally peer reviewed.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.