Clinical Practice Guidelines: Pulmonary Manifestations in Sjögren Syndrome

Patients with Sjögren syndrome often present with several pulmonary manifestations, highlighting the need for a multidisciplinary approach to caring for those with pulmonary complications, according to practice guidelines published in Chest. For this patient population, the multidisciplinary team might include a rheumatologist, primary care physician, pulmonologist, pathologist, radiologist, and, when necessary, an oncologist.

Pulmonary disease is often underdiagnosed in patients with Sjögren syndrome. Approximately 10% to 20% of patients with Sjögren syndrome present with pulmonary involvement, which can result in higher mortality rates and lower quality of life. Because up to 65% of patients with asymptomatic Sjögren syndrome will have abnormal pulmonary imaging, pulmonologists can play a significant role in the diagnosis of Sjögren syndrome as well as address any potential pulmonary complications. 

“Clinical practice guidelines for the diagnosis, management, and treatment of pulmonary manifestations of Sjögren’s were developed by the Sjögren’s Foundation after identifying a critical need for early diagnosis and improved quality and consistency of care,” the guideline authors note. The guidelines were created using a strength of evidence rating based on available evidence and were reviewed by the Pulmonary Topic Review Group (TRG) and the Consensus Expert Panel (CEP) members. Consensus agreement for the 102 questions used to form the recommendations had an agreement average of 98%.

Of the 1192 articles identified, the TRG generated 52 recommendations using the 150 abstracts that were qualified for inclusion. The most robust recommendations from the guidelines are included next. For the full list of recommendations, please see the original practice guidelines.

Evaluation for Lung Involvement

Sjögren syndrome is often diagnosed after an initial pulmonary disorder is recognized, namely in patients with airway disorders, indeterminate interstitial lung diseases, and pulmonary lymphoproliferative disorders. Because of the commonality of pulmonary involvement in Sjögren syndrome, baseline chest radiography is recommended; however, if there is greater concern for lung involvement, a high-resolution computed tomography (HRCT) scan is preferred. Baseline pulmonary function tests including spirometry, diffusing capacity of the lung for carbon monoxide, and lung volumes are also recommended at this stage of assessment. Although the panel did not provide specific guidance on the intervals for repeat testing, the majority of TRG members noted that they repeated pulmonary function tests every 6 to 12 months to form a longitudinal disease trajectory.

For the evaluation of pulmonary complications in patients with asymptomatic Sjögren syndrome, the guideline panel recommended that serologic biomarkers not be used to evaluate for pulmonary involvement in patients with confirmed Sjögren disease (intermediate evidence, strong recommendation). In asymptomatic Sjögren syndrome, the researchers also did not recommend routine echocardiography (intermediate evidence, strong recommendation). Clinicians must obtain a detailed medical history of respiratory symptoms in all patients with Sjögren syndrome on each visit due to the prevalence of pulmonary involvement in this patient population (high evidence, strong recommendation).

When evaluating patients with Sjögren syndrome who have pulmonary symptoms, patients with dyspnea are recommended to have an echocardiogram in the following situations: if patient is suspected to have pulmonary hypertension, if the patient has unexplained dyspnea after pulmonary etiologies have been excluded, and if the patient is suspected to have cardiac involvement (high evidence, strong recommendation).

When evaluating for Sjögren syndrome in patients with lung disease, clinical and serologic evaluation for Sjögren syndrome is recommended for patients who have uncharacterized interstitial lung disease, diffuse cystic lung disease, or pulmonary lymphoma (high evidence, strong recommendation).

Upper and Lower Airway Disorders

Some upper and lower airway diseases associated with or due to Sjögren syndrome include xerotrachea, dysphagia, laryngopharyngeal reflux, vocal cord cystic lesions, obstructive sleep apnea, bronchiectasis, bronchiolitis, obstructive lung disease, and reactive airway disease.

Chronic cough is prevalent in approximately 38% of patients with Sjögren syndrome, and unexplained cough associated with dry eyes may lead to confirmed Sjögren syndrome in nearly 36% of patients.

For patients with Sjögren syndrome who have chronic cough for longer than 8 weeks, an evaluation is warranted, beginning with an evaluation for common causes followed by an evaluation for pulmonary complications of Sjögren syndrome such as xerotrachea, interstitial lung disease, bronchiolitis, bronchiectasis, and pulmonary lymphoma.

For patients with Sjögren syndrome who present with signs or symptoms of airway disorders, clinicians should perform pulmonary function tests and HRCT scans to confirm the presence of airway disorders. For patients with asthma or chronic obstructive pulmonary disease, the researchers suggested management as per clinical practical guidelines, with inhaled corticosteroids and β-agonists as the mainstay of management and avoidance of anticholinergic drugs to prevent drying of secretions. In addition, a trial of inhaled corticosteroids with/without macrolides is suggested for patients with bronchiolitis, and nebulized saline and secretagogues are suggested for patients who exhibit xerotrachea.

When assessing and managing patients with Sjögren syndrome with upper and lower airway diseases, those with a dry bothersome cough and documented absence of lower airway or parenchymal lung disease should be evaluated for treatable or preventable etiologies other than xerotrachea such as gastroesophageal reflux, postnasal drip, and asthma (intermediate evidence, strong recommendation). Cessation of smoking is recommended in all patients with Sjögren syndrome (intermediate evidence, strong recommendation).

Interstitial Lung Disease

Among patients with Sjögren syndrome who have interstitial lung disease, many experience shortness of breath, cough, sputum production, or chest pain, with symptom severity ranging from symptomatic to minimal dyspnea on exertion to severe. Over time, the onset of interstitial lung disease increases with a prevalence of 10% in the first year of diagnosis to 20% after 5 years postdiagnosis. Subtypes of interstitial lung disease reported among patients with Sjögren syndrome include nonspecific interstitial pneumonia (45%), respiratory bronchiolitis (25%), usual interstitial pneumonia (16%), lymphoid interstitial pneumonia (15%), organizing pneumonia (7%), amyloid involvement (6%), and lymphoma (4%).

Among patients with Sjögren syndrome who are suspected to have interstitial lung disease, the panel members recommended the use of HRCT scanning with expiratory views (high evidence, strong recommendation) and oximetry testing as a part of the patient’s initial evaluation (high evidence, strong recommendation).

A surgical biopsy in patients with Sjögren syndrome with interstitial lung disease is not routinely recommended. However, following a multidisciplinary review, a lung biopsy may be considered if the biopsy could have significant management implications, such as in neoplastic and nonneoplastic lymphoproliferative disorders, other cancers, amyloid involvement, and progressive deterioration and suspected infection failing empiric therapies where less invasive testing proved undiagnostic (intermediate evidence, strong recommendation).

If the patient is asymptomatic for lung disease or demonstrates minimal impairment on pulmonary function tests or HRCT, the panel recommended serial monitoring via pulmonary function tests every 3 to 6 months to determine the disease trajectory and pharmacotherapy if serial studies indicate a significant decline in lung function (intermediate evidence, strong recommendation).

When considering nonpharmacologic and other management for patients with Sjögren syndrome with interstitial lung disease, the following are recommended:

• Vaccination: All patients with Sjögren syndrome must be immunized against influenza and pneumococcal infection (high evidence, strong recommendation).
• Pneumothorax and cystic lung disease: Patients with Sjögren syndrome with cystic lung disease may have a higher risk for pneumothorax; therefore, patients and caregivers must be educated about associated signs and symptoms and should be instructed to seek medical attention if experiencing such signs and symptoms (intermediate evidence, strong recommendation).
• Pulmonary rehabilitation: Patients with symptomatic Sjögren syndrome with interstitial lung disease and impaired lung function are recommended to be referred to pulmonary rehabilitation (intermediate evidence, strong recommendation).
• Oxygen: For patients with Sjögren syndrome who are suspected to have interstitial lung disease and clinically significant resting hypoxemia, long-term oxygen therapy is recommended (intermediate evidence, strong recommendation).
• Air travel: Discouraging air travel is not recommended for patients with Sjögren syndrome who have interstitial lung disease unless the patient develops signs and symptoms of pneumothorax or new-onset or unexplained chest pain or dyspnea prior to boarding (intermediate evidence, strong recommendation).
• Lung transplant: Among patients with Sjögren syndrome with interstitial lung disease whose condition is advanced with resting hypoxia or whose lung function is quickly deteriorating, evaluation for lung transplantation is recommended (intermediate evidence, strong recommendation).

Among patients with Sjögren syndrome with interstitial lung disease or a related disorder, health care providers should be aware of short- and long-term side effects of systemic corticosteroids (high evidence, strong recommendation). A full list of these potential side effects can be found in the original guideline.

When considering azathioprine, patients and health care providers must take into consideration drug-induced risks. Testing for thiopurine methyltransferase activity or genotyping prior to azathioprine initiation is recommended to reduce the risk for severe, life-threatening leukopenia due to complete lack of thiopurine methyltransferase activity (high evidence, strong recommendation).

Patients and health care providers must also be aware of potential side effects when considering the use of mycophenolate mofetil (high evidence, strong recommendation) and of potential risks and harms associated with rituximab (high evidence, strong recommendation).

For patients with Sjögren syndrome with interstitial lung disease who are rapidly progressing or presenting with acute respiratory failure, the panel recommended a trial of high-dose corticosteroids, such as intravenous methylprednisolone. They also noted that alternative etiologies including infections or lymphoproliferative disorders should be considered (intermediate evidence, strong recommendation).

When considering cyclophosphamide for patients with Sjögren syndrome and interstitial lung disease, significant risks must be reviewed and Pneumocystis jirovecii prophylaxis must be provided. Intravenous vs oral cyclophosphamide may greatly reduce the risk of bladder cancer (intermediate evidence, strong recommendation).

Finally, clinicians and patients should be aware of pulmonary complications linked to medications used to treat Sjögren syndrome and related connective tissue diseases, especially when patients are progressive or refractory to therapies (intermediate evidence, strong recommendation).

Lymphoproliferative Disease

Among patients with Sjögren syndrome who experience unexplained weight loss, fevers, night sweats, head and neck lymphadenopathy, or parotitis, the possibility of lymphoma should be further assessed (high evidence, strong recommendation). All patients with Sjögren syndrome should be clinically monitored for signs and symptoms of pulmonary lymphoproliferative disorders such as lymphoma and amyloid involvement (high evidence, strong recommendation).

Because abnormalities in HRCT and positron emission tomography (PET) scans are common in patients with Sjögren syndrome with or without lymphomatous complications, a multidisciplinary review with oncology may facilitate disease diagnosis and management. Because many clinicians in the US may not have payor authorization to order a PET scan, unless ordered by an oncologist or malignancy is histopathologically confirmed, accessibility to PET, costs, and insurance coverage should be considered. However, mucosa-associated lymphoid tissue and cystic lung disease linked to Sjögren syndrome often have an indolent course and may be managed conservatively.

“While most of the evidence would be considered of low quality due to the lack of randomized, placebo-controlled clinical trials, our recommendations and strength of the recommendations incorporate Sjögren’s-specific expertise in pulmonology, rheumatology, and hematology/oncology,” the guideline authors noted.

“The guidelines process also has led to identification of high priorities for future research. These priorities include epidemiological and risk analyses, blood-based and noninvasive biomarkers, quantitative imaging tools, optimal frequency of repeat [pulmonary function tests] and HRCT testing for each pattern of pulmonary disease, studies on etiology and treatment, and specifically on antifibrotics for Sjögren’s-[interstitial lung disease],” the panel members concluded.

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Lee AS, Scofield RH, Hammitt KM, et al; for the Consensus Expert Panel (CEP) Members. Consensus guidelines for evaluation and management of pulmonary disease in Sjögren’s. Chest. 2021;159(2):683-698. doi:10.1016/j.chest.2020.10.011