Continuing Education Activity

Shrinking lung syndrome (SLS) is a complication of systemic autoimmune disease, most commonly seen in systemic lupus erythematosus but also reported in Sjogren syndrome, rheumatoid arthritis, and scleroderma. It is characterized by dyspnoea with or without pleuritic chest pain, the elevation of the hemidiaphragm, and restrictive physiology on lung function testing, This rare condition can have serious complications including marked dyspnoea and more rarely, respiratory failure. To avoid the significant morbidity and mortality associated with this condition, it must be promptly diagnosed and treated. This activity reviews the evaluation and treatment of shrinking lung syndrome and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

Objectives:

• Identify the common causes of shrinking lung syndrome.

• Outline the typical presentation of a patient with shrinking lung syndrome.

• Describe the typical imaging findings associated with shrinking lung syndrome.

• Review how interprofessional team activity and open communication can improve patient outcomes in shrinking lung syndrome.

Introduction

Shrinking lung syndrome (SLS) is a rare complication of systemic autoimmune disease. It occurs most commonly in systemic lupus erythematosus but there are rare reports of it developing in systemic sclerosis, Sjogren's syndrome, and rheumatoid arthritis.[1][2] It should be suspected in a patient with a relevant autoimmune disease who presents with exertional shortness of breath with or without pleuritic chest pain with radiographic evidence of unilateral or bilateral elevation of the hemidiaphragm or diaphragms.

Reduced lung volumes and a restrictive deficit on lung function testing are typical. It is a diagnosis of exclusion and therefore other investigations such as computed tomography of the chest are undertaken to exclude competing diagnoses.[3][4]

Etiology

Shrinking lung syndrome occurs in the setting of systemic autoimmune diseases, most commonly in systemic lupus erythematosus and much less commonly in Sjogren's syndrome, scleroderma, and rheumatoid arthritis. Various etiologies have been postulated including pleural inflammation, diaphragm dysfunction, phrenic neuropathy, pleural adhesions, and myopathy.[5] However, the precise pathophysiological mechanism by which it occurs has yet to be proven.[6]

Epidemiology

The epidemiology of SLS has been best studied in SLE as there is not enough data to estimate its prevalence in other autoimmune diseases. It is estimated to occur in between 0.5% to 1.53% of all lupus patients, and it can occur at any point in the course of the disease.[3][7] SLE is a disease that affects women more than men, with a female to male ratio of 9:1.[8] Shrinking lung syndrome follows a similar distribution in SLE patients, with it being more prevalent in females with estimates ranging from (6:1) to (17:1) with an average age at diagnosis of 36.[9]

Pathophysiology

There is an ongoing debate about the pathophysiology of shrinking lung syndrome in SLE. Various theories have been suggested that have sought to explain the unique clinical features of this syndrome. Hypotheses have included reduced diaphragmatic muscle thickness, diaphragmatic dysfunction due to pleural adhesions, pleural inflammation chronically impairing deep inspiration reducing lung compliance, paralysis of the phrenic nerve, alterations in surfactant, and myositis.[9][10][11][12][13][14][9]

History and Physical

Shrinking lung syndrome is typically suspected in patients who present with dyspnoea with or without pleuritic chest pain and who have a background of a relevant systemic autoimmune disease, most commonly SLE.[6] Cough and orthopnoea are less common symptoms. Orthopnoea is thought to be secondary to diaphragmatic weakness. There may be a history of previous episodes of pleuritis. Patients can have co-existent active extra-thoracic features of lupus, including symptoms and signs such as arthralgia, rash, alopecia, and glomerulonephritis.[15] 

Reduced chest expansion and less commonly auscultatory crackles are possible examination findings. Patients may be tachypneic with shallow breathing. Approximately half of the patients have active extra-thoracic disease at the time of diagnosis.[3] It may be the presenting feature of systemic lupus erythematosus in a normal number of cases.[16]

Evaluation

The evaluation of shrinking lung syndrome requires exclusion of other causes of shortness of breath and pleuritic chest pain in SLE patients. Laboratory, radiographic and functional testing are all helpful both in demonstrating the characteristic features of SLS and also in excluding differential diagnoses. 

Routine blood testing is typically normal. A raised white cell count may be suggestive of infection. Raised levels of CRP may indicate serositis. The ESR may be raised in the context of active lupus. Renal function is expected to be normal unless there is co-existent lupus nephritis. Creatine kinase levels are typically normal unless active myositis elsewhere. The serological profile of the lupus patient should be clarified. A positive ANA is present in all cases. Positive antiphospholipid serology is noted in approximately 2/3 of patients. There may be evidence of hypocomplementemia, increased DNA binding (3/4 cases), and a positive ENA (including SS-A, SS-B, anti-RNP, and anti-Sm). However, these tests may also be normal and they neither confirm nor refute the diagnosis.[15] 

If the specific diagnosis of an autoimmune disease is unknown, then further testing to include a full autoimmune profile would be appropriate. Tests to consider would include rheumatoid factor, anti-CCP, and scleroderma-specific antibodies. Occasionally the connective tissue disease may be as of yet undifferentiated. 

Measurement of arterial blood gases is variable, with some patients demonstrating normal results and some showing mild hypoxemia, worse on exertion.[17]

Plain radiography of the chest is a crucial investigation. The most common finding is a unilateral or bilateral elevation of the hemidiaphragm, which is a characteristic feature of the condition. Reduced lung volumes are also common. Less common findings include linear atelectasis, pleural effusions, and pleural thickening.[18]

CT imaging of the chest is required to exclude parenchymal lung abnormalities and exclude common differentials such as interstitial lung disease and pulmonary emboli. An echocardiogram may be required in addition depending on the clinical context. 

Assessment of diaphragm motion by M-mode ultrasound is occasionally requested but not always diagnostic. It may demonstrate the abnormal diaphragmatic movement, which may be absent or paradoxical.[19]

Interestingly, one study demonstrated normal or approximately normal diaphragm contractility in a high proportion of SLE patients with SLS (9/12) using phrenic nerve stimulation, indicating that normal diaphragmatic movement cannot be used as a marker to exclude the condition.[20]

Pulmonary function testing classically demonstrates a restrictive deficit, along with reduced total lung capacity (TLC), reduced carbon monoxide transfer factor (DLCO), and reduced lung volumes.[3] Maximal respiratory and expiratory pressures are reduced in some cases.[5]

Treatment / Management

There are no evidence-based guidelines for the treatment of shrinking lung syndrome but treatment almost invariably involves corticosteroids in the first instance. The usual dose is between 0.5 to 1mg/kg of prednisolone daily and may be preceded by a short course of intravenous methylprednisolone depending on initial severity. Corticosteroids are typically successful as monotherapy. Adjunctive treatments include inhaled beta-2 agonists, theophylline, analgesia, and chest physiotherapy.

In treatment-refractory cases, rituximab has emerged as a promising option based, with case reports of success after the initial failure of treatment with steroids.[21][22][23] Indeed, other immunosuppressive agents such as cyclophosphamide, azathioprine, mycophenolate mofetil, and methotrexate have generally not been successful after treatment failure with steroids, although azathioprine has been effective as a steroid-sparing agent.[15]

Differential Diagnosis

Shrinking lung syndrome is a diagnosis of exclusion.

A wide variety of illnesses causing dyspnoea or pleuritic chest pain need to be excluded before making a diagnosis. This includes conditions such as pneumonia, viral or bacterial pleurisy, pericarditis, pulmonary embolism, interstitial lung disease, chronic obstructive pulmonary disease, heart failure, pulmonary hypertension, musculoskeletal chest wall disorders, and anxiety. 

If a raised hemidiaphragm is identified, as is almost ubiquitous in this condition, other causes that could be considered before making a diagnosis of shrinking lung syndrome include pulmonary atelectasis, pulmonary hypoplasia, prior lobectomy, prior pneumonectomy, phrenic nerve palsy, contralateral stroke, subphrenic abscess, distended stomach or colon or abdominal tumors. 

Finally, other causes of a restrictive lung deficit need to be considered and excluded. These include causes such as pulmonary fibrosis, large pleural effusions, kyphoscoliosis, morbid obesity, and neuromuscular disorders such as motor neuron disease and myasthenia gravis.

Prognosis

Shrinking lung syndrome has a good prognosis. Most patients achieve some improvement with appropriate immunosuppressive therapy. Clinical improvement is common, with most patients reporting symptomatic relief. There is stabilization or improvement in lung function testing in most cases.[3][7] Radiological improvement is less common, with 57% of cases in one study demonstrating improvement.[15] Complete recovery of clinical, functional, and radiographic abnormalities is uncommon.

Complications

The complications of untreated shrinking lung syndrome include severe symptomatic dyspnoea and, more rarely, respiratory failure.[24]

Deterrence and Patient Education

Shrinking lung syndrome is a rare complication of systemic autoimmune disease, most commonly SLE. This condition presents with exertional dyspnoea with or without pleuritic chest pain. It is rare, affecting approximately 1% of patients with SLE, and can occur at any point in the disease. In those patients with radiographic evidence of an elevated hemidiaphragm and restrictive physiology on lung function testing in the absence of another cause, it should be suspected. Initial treatment is usually with corticosteroids. More intense immunosuppression with disease-modifying and biologic drugs is sought in refractory cases. Most patients improve with treatment.

Pearls and Other Issues

Clinicians should consider shrinking lung syndrome as a possible diagnosis in SLE patients after excluding more common causes of shortness of breath. A raised hemidiaphragm is a key clue to identifying this condition.

Enhancing Healthcare Team Outcomes

Shrinking lung syndrome is a rare complication of SLE and requires a high index of suspicion to diagnose and prevent complications. While a rheumatologist will typically be supervising care, other specialists such as internists and pulmonologists plan an essential role in diagnosing and managing this condition, particularly in the exclusion of competing diagnoses. Nursing staff members are crucial in disease education and administering medications (including infusions of biologics where necessary). Pharmacists make a key contribution to the safe prescription of disease-modifying therapies. Physiotherapists and occupational therapists play a key role in rehabilitation from respiratory illness.

This condition has potentially deleterious consequences in the form of severe dyspnoea and potentially respiratory failure. Therefore, a high index of suspicion is needed, along with a meticulous evaluation in order to make an early diagnosis and prevent complications and improve prognosis.[25] [Level 5]