Sjögren’s syndrome (SS) is a chronic autoimmune disorder primarily affecting exocrine glands, characterized by dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca). However, systemic manifestations, including pulmonary complications, are increasingly recognized. Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening presentation of SS, typically associated with vasculitis or coagulation abnormalities. We report the case of a 19-year-old male presenting with dyspnea and hemoptysis, later diagnosed with primary Sjögren’s syndrome (pSS). Initial clinical assessment revealed respiratory failure with low blood oxygen levels (hypoxemia), bilateral ground-glass opacities on chest computed tomography (CT), and iron-storing macrophages (hemosiderin-laden) in bronchoalveolar lavage fluid, consistent with DAH. Subsequent autoimmune serology confirmed positivity for anti-Ro/Sjögren’s-syndrome-related antigen A autoantibodies (SSA) and anti-La/Sjögren’s-syndrome-related antigen B autoantibodies (SSB), while other autoimmune markers, including anti-neutrophil cytoplasmic antibodies (ANCA), were negative. Labial salivary gland biopsy demonstrated focal lymphocytic sialadenitis, confirming pSS according to European League Against Rheumatism (EULAR) criteria. Treatment involved high-dose corticosteroids, leading to complete resolution of symptoms and significant improvement in imaging results. The patient remained stable at follow-up. DAH should be considered a potential presentation of pSS, even in the absence of classical symptoms. Increased awareness of this rare complication can facilitate early diagnosis and improve outcomes.

autoimmune disease, diffuse alveolar hemorrhage, hemoptysis, pulmonary complications, Sjögren’s syndrome

Sjögren’s syndrome (SS) is a chronic autoimmune disorder primarily characterized by the infiltration of lymphocytes into exocrine glands, leading to the hallmark symptoms of dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca). However, it is increasingly recognized that SS can have systemic manifestations, including significant pulmonary complications. SS can be classified as primary (pSS) or secondary (sSS).^[1,2] Primary SS occurs in isolation, while secondary SS is associated with other autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus.

The etiology of SS is multifactorial, involving genetic predisposition, environmental triggers, and hormonal factors. The disease process is characterized by the dysregulation of immune mechanisms. Lymphocytic infiltration, particularly of CD4+ T cells and B cells, leads to the destruction of glandular tissue and the production of autoantibodies, including anti-Ro/SSA and anti-La/SSB. This immune response is not limited to exocrine glands; it can also affect other organ systems, including the lungs.^[3,4]

Pulmonary hemorrhage in the context of SS is a rare complication often associated with pulmonary vasculitis or associated conditions. The mechanisms underlying pulmonary hemorrhage can include vasculitis, characterized by inflammation of blood vessels, leading to vascular damage and subsequent hemorrhage. The inflammation can result in the destruction of small- to medium-sized pulmonary vessels, causing rupture and bleeding into the alveolar spaces.^[5] The presence of anti-neutrophil cytoplasmic antibodies (ANCA) may further complicate this scenario, contributing to small-vessel vasculitis. Patients with SS may experience coagulopathy due to autoimmune processes affecting the coagulation cascade. This dysfunction can predispose individuals to abnormal bleeding, including pulmonary hemorrhage. The presence of antiphospholipid antibodies may also increase the risk of thromboembolic events, leading to pulmonary embolism and subsequent hemorrhage.^[6] Chronic inflammation and impaired mucociliary clearance in SS can lead to recurrent respiratory infections. Severe infections, particularly those caused by opportunistic pathogens, can result in localized pulmonary hemorrhage due to necrotizing pneumonia or abscess formation. Patients with SS are at an elevated risk for developing lymphoproliferative disorders, particularly non-Hodgkin lymphoma (NHL). Pulmonary involvement in these malignancies can manifest as nodules, effusions, or parenchymal infiltration, potentially leading to pulmonary hemorrhage.^[5-8]

The purpose of this article is to present a rare case of diffuse alveolar hemorrhage (DAH) as the first manifestation of pSS in a young male, highlighting the clinical, radiological, and pathological features that led to the diagnosis, as well as to emphasize the importance of considering SS in the differential diagnosis of pulmonary hemorrhage, even in atypical presentations.

A 19-year-old male presented to the emergency room with a chief complaint of sudden-onset dyspnea lasting two hours, accompanied by recurrent episodes of hemoptysis. The hemoptysis involved bright red blood, amounting to approximately 200 mL in total. The patient had no known medical history and no reported comorbidities. He denied any history of smoking, vaping, or illicit drug use.

Upon presentation, he was hemodynamically stable but exhibited mild respiratory failure. Arterial blood gas (ABG) analysis revealed a partial pressure of oxygen (PO ₂ ) of 54 mmHg (normal range: 75–100 mmHg), a pH of 7.46 (normal range: 7.35–7.45), and a partial pressure of carbon dioxide (PCO ₂ ) of 32 mmHg (normal range: 35–45 mmHg). Laboratory investigations showed normal hemoglobin levels, an elevated white blood cell count of 12,000/μL (normal range: 4,000–11,000/μL), normal platelet levels, elevated D-dimer levels at 2,500 ng/mL (normal range: ≤500 ng/mL), and a mildly elevated C-reactive protein (CRP) level (50 mg/L; normal range: ≤5 mg/L). Coagulation tests revealed a prothrombin time (PT) of 13.2 seconds (normal: 11-15 seconds), an activated partial thromboplastin time (aPTT) of 30.1 seconds (normal: 25-35 seconds), and a fibrinogen level of 360 mg/dL (normal: 200-400 mg/dL). Renal function tests showed a serum creatinine level of 0.9 mg/dL (normal: 0.6-1.3 mg/dL) and a blood urea nitrogen (BUN) level of 14 mg/dL (normal: 7-20 mg/dL).

A chest X-ray revealed bilateral alveolar infiltrates predominantly in the basal areas of both lungs (Fig. 1) . Given the patient’s clinical symptoms and elevated D-dimer levels, pulmonary embolism was considered a differential diagnosis. Consequently, a computed tomography pulmonary angiography (CTPA) was performed, which ruled out pulmonary embolism but showed findings consistent with diffuse pulmonary hemorrhage, specifically widespread ground-glass opacifications (Fig. 2) . A transthoracic echocardiogram revealed normal cardiac function, with an ejection fraction (EF) of 60%.

Figure 1.

Chest X-ray on admission. Bilateral infiltrates predominantly in lung bases.

Figure 2.

Chest computed tomography with diffuse bilateral ground glass opacities as was recorded in the day of our patient’s admission.

On the second day of hospitalization, a bronchoscopy was conducted. Analysis of bronchoalveolar lavage (BAL) fluid revealed that 22% of the macrophages were hemosiderin-laden, fulfilling the commonly used BAL criterion for DAH. BAL differential cell counts showed 65% macrophages, 20% lymphocytes, 10% neutrophils, and 5% eosinophils.

Further history-taking revealed that the patient had experienced xerostomia and keratoconjunctivitis sicca for the past year. These findings raised clinical suspicion for an underlying autoimmune etiology. BAL cultures were negative for bacterial, fungal, and mycobacterial infections, ruling out an infectious cause for the pulmonary hemorrhage.

An extensive autoimmune antibody panel was subsequently ordered. The results were positive for anti-Ro (Sjögren’s-syndrome-related antigen A autoantibodies, SSA) and anti-La (Sjögren’s-syndrome-related antigen B autoantibodies, SSB) antibodies, while tests for perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA), cytoplasmic ANCA (c-ANCA), anti-glomerular basement membrane (anti-GBM), anti-cyclic citrullinated peptide (anti-CCP), anti-double-stranded DNA (anti-dsDNA), anti-centromere antibodies (ACAs), anti-Jo-1, anti-RNP, and anti-Scl-70 antibodies were negative. These results directed the diagnostic focus towards pSS.

To confirm the diagnosis, a labial salivary gland biopsy was performed. Histological examination revealed classical features of focal lymphocytic sialadenitis, with a focus score of 2 foci per 4 mm ² (focus score ≥1 is diagnostic) (Fig. 3) . According to the European League Against Rheumatism (EULAR) classification criteria for pSS ^[9] , the patient achieved a score of 6, which confirmed the diagnosis of pSS.

Figure 3.

Salivary gland biopsy with distinct focal lymphocytic sialadenitis with a focus score of 2 foci/4 mm².

The patient was initially treated with high-dose intravenous methylprednisolone at 1 g/day for three days, followed by an oral prednisone tapering regimen starting at 60 mg daily, gradually reduced by 10 mg every two weeks until reaching a maintenance dose of 10 mg/day.

Supportive care included oxygen therapy (1–2 L/min), broad-spectrum antibiotics, intravenous fluids, and oral tranexamic acid for five days. The maintenance dose of corticosteroids was continued for six months, with plans for further gradual tapering based on clinical response and follow-up evaluations. The patient did not experience further episodes of hemoptysis, and a follow-up chest CT scan after one month showed significant improvement compared to the initial findings (Fig. 4) .

Figure 4.

Follow-up chest computed tomography scan showed significant improvement compared to the initial findings (after 1 month).

The patient was discharged in stable condition and instructed to consult with a rheumatologist for ongoing pSS management.

This is a rare case of pulmonary hemorrhage as the first manifestation of SS. To the best of our knowledge, very few similar reports have been described in the literature.^[10-13] Tomita et al. described a 75-year-old male with SS who developed DAH followed by rapidly progressive pulmonary fibrosis (f-NSIP). Despite aggressive immunosuppressive therapy, the patient did not survive. Autopsy revealed extensive alveolar hemorrhage and interstitial fibrosis, but no cryoglobulinemia or vasculitis. The case highlighted the rare occurrence of DAH in SS without cryoglobulinemia.

Johnston et al.^[11] presented a 47-year-old female with DAH and cryoglobulinemic vasculitis associated with primary SS. The patient experienced severe renal and pulmonary involvement, necessitating steroids, plasmapheresis, and cytotoxic therapy. The case demonstrated the impact of cryoglobulinemia in exacerbating SS complications and required ongoing immunosuppressive therapy.

Parimi et al.^[12] reported a 37-year-old woman with SS, DAH, cryoglobulinemia, and thrombotic microangiopathy (TMA), a rare combination of manifestations. The patient was resistant to corticosteroid treatment, and plasmapheresis was initiated. Despite interventions, her condition worsened, and she succumbed. Post-mortem findings confirmed TMA with renal involvement.

Yagyua et al.^[13] described a 75-year-old female with SS who developed DAH associated with myeloperoxidase (MPO)-ANCA positivity and antiphospholipid syndrome (APS). The condition was managed successfully with steroids, cyclophosphamide, and plasmapheresis. The case highlighted the diagnostic challenges and management complexities in patients with overlapping autoimmune conditions.

The clinical presentation of pulmonary hemorrhage in SS can be variable. Patients may exhibit hemoptysis, dyspnea, cough, chest pain (often pleuritic in nature, associated with lung inflammation or hemorrhage), and systemic symptoms (fatigue, fever, and malaise may present alongside respiratory manifestations).^[8] Given the nonspecific nature of these symptoms, a high index of suspicion is necessary for timely diagnosis.

Diagnosis of pulmonary hemorrhage in patients with SS requires a comprehensive approach. High-resolution computed tomography (HRCT) of the chest is essential in assessing lung parenchyma and vascular structures. It can help identify interstitial lung disease, bronchiectasis, and any signs of pulmonary hemorrhage, such as ground-glass opacities or consolidations. Pulmonary function tests are crucial for evaluating the extent of lung impairment. Restrictive patterns may indicate interstitial lung disease, while obstructive patterns may suggest bronchial involvement. Bronchoscopy can provide direct visualization of the airway and obtain BAL fluid for cytological and microbiological analysis. This procedure can help identify infectious causes of hemorrhage or malignancy.^[5-8,14]

Lastly, serological testing for autoantibodies, including anti-Ro/SSA, anti-La/SSB, and ANCA, can assist in confirming the diagnosis and identifying underlying autoimmune processes. In cases where malignancy is suspected, tissue biopsy may be necessary to establish a definitive diagnosis. Histopathological examination can reveal lymphoid hyperplasia or malignancy.^[5-8,14]

Management of pulmonary hemorrhage in SS involves a multidisciplinary approach, focusing on both the underlying autoimmune condition and the acute hemorrhagic event. High-dose corticosteroids are often the first-line treatment for managing pulmonary hemorrhage associated with vasculitis. They help reduce inflammation and stabilize the vascular integrity, thereby minimizing further bleeding. For patients with severe or refractory cases, additional immunosuppressive agents such as mycophenolate mofetil, azathioprine, or rituximab may be indicated. These agents aim to modulate the immune response and prevent further damage to pulmonary tissues. If coagulopathy is identified, management may include anticoagulation therapy or the use of agents to correct any underlying clotting deficiencies. Close monitoring and adjustment of treatment are essential to prevent thromboembolic complications. In cases of pulmonary hemorrhage secondary to infection, appropriate antibiotic therapy is crucial. Broad-spectrum antibiotics may be initiated, with adjustments made based on culture results.^[1,3,15] Lastly, if a lymphoproliferative disorder is diagnosed, oncological treatment, including chemotherapy or radiation therapy, may be necessary. Early intervention is critical to improve outcomes in these patients.^[14]

This case emphasizes the importance of including pSS in the differential diagnosis of DAH, even in unusual presentations such as young male patients with no prior history of autoimmune disease. The early recognition and diagnosis of pSS were facilitated by detailed clinical, radiological, and serological evaluations, as well as biopsy confirmation. Prompt treatment with high-dose corticosteroids led to rapid symptom resolution and significant radiological improvement. This case underscores the necessity for clinicians to maintain a high index of suspicion for autoimmune etiologies when evaluating pulmonary hemorrhage, particularly in the absence of common triggers. Moreover, it adds to the limited literature on DAH as the initial manifestation of pSS, contributing valuable insights into its clinical spectrum and management.

Not applicable

The authors declared that no clinical trials were used in the present study.

The authors declared that no experiments on humans or human tissues were performed for the present study.

The authors declared that they obtained written informed consent from the patient for publication of this case report and any accompanying images.

The authors declared that no experiments on animals were performed for the present study.

The authors declared that no commercially available immortalised human and animal cell lines were used in the present study.

The authors have declared that no competing interests exist.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The AI tool ChatGPT was used to improve the manuscript’s readability and language; subsequently, the authors revised and edited the content generated by the AI tool as needed, accepting full responsibility for the final content of the present manuscript.

The datasets generated and analyzed during the current study are not publicly available; however, they are available from the corresponding author upon reasonable request.

KD: conceptualization, methodology, writing–original draft, data collection, writing–review and editing; TVK: clinical laboratory analysis, data interpretation, data collection, literature review; VEG: data collection, writing–review and editing, project administration, supervision.

The corresponding author confirms that all authors meet the criteria for authorship as outlined by the International Committee of Medical Journal Editors (ICMJE), have read the manuscript, and have agreed to its publication.

The authors have no support to report.