Advancing Understanding of Shrinking Lung Syndrome in SLE

First described in 1965, shrinking lung syndrome (SLS) is a rare complication of systemic lupus erythematosus (SLE). With a prevalence consistent with that of SLE,¹ a female to male ratio of 20:2 has been reported for SLS.² SLS is not unique to SLE; it has been reported in other connective tissue diseases, including Sjgren’s syndrome, scleroderma, and rheumatoid arthritis.² While the precise percentage of patients with SLE who present with SLS is unknown, the literature has reported a range of 0.5% to 1.1%,^3,4 although a recent study in Lupus by M Deeb, MD of the Toronto Lupus in Canada, and colleagues involving 1439 SLE patients reported an SLS prevalence of 1.5%.²

Presenting signs and symptoms of SLS include progressive exertional dyspnea, pleuritic chest pain with reduced lung volume, elevated hemidiaphragm, and the presence of a restrictive ventilator defect. It has been reported that SLS can manifest at any point during the SLE disease course, including in patients with inactive disease, and often in patients without previous or concomitant organ involvement.⁴

In the patient cohort in the Deeb, et al study, SLS occurred primarily during the first year after SLE diagnosis,² a finding thought to be the initial manifestation of SLE, as reported by Pillai, et al in 2014.⁵ However, given that SLE may remain undiagnosed for several years after initial disease onset, it is possible that SLS may also persist for several years after disease onset.⁴

The underlying pathophysiology of SLS is poorly understood, although several theories have been offered, including complications of pleuritis,⁶ respiratory muscle weakness, myopathy of the diaphragm, and phrenic nerve dysfunction.^2,7

According to Murray B. Urowitz, MD, director of the Centre for Prognosis Studies in the Rheumatic Diseases and professor of medicine at the University of Toronto, Canada, “The mechanism underlying this restrictive pulmonary condition with decreased lung volumes is not clear. The immunologic mechanisms involved in other major organ involvement in SLE are not obvious in this manifestation, although the response to steroids may be very good.”

When SLS is promptly diagnosed and effectively treated, long-term prognosis is good and mortality rates are low, with some patients achieving complete clinical and spirometric remission.⁴ Left untreated, SLS can result in severely compromised pulmonary function and therefore must be treated promptly and aggressively in order to stabilize pulmonary function.³

The challenge with managing SLS is 2-fold: (1) recognizing SLS as part of the differential diagnosis, and (2) early implementation of evidence-based treatment. Ruling out common pulmonary manifestations such as interstitial lung disease, rather than a clinical suspicion of SLS, is often the focus of the diagnostic approach in patients with SLE who present with progressive dyspnea.  Furthermore, in many cases standard pulmonary function tests (PFTs) do not include parameters such as maximal inspiratory pressure and maximal expiratory pressure, both of which would reveal respiratory muscle changes that are consistent with SLS.

In fact, a 2016 study by Borrell and colleagues reported that of 80 cases of SLS investigated, the diffusing capacity of the lungs for carbon monoxide (DLCO) was measured in only 32.⁴ Although used in some cases as a sole diagnostic tool for SLS,  DLCO alone is a non-specific finding, and both carbon monoxide transfer coefficient (KCO) and alveolar volume data should be obtained for SLS diagnosis.² Simultaneously reduced DLCO and KCO values correlate with an intrinsic restrictive disorder⁸ and should raise clinical suspicion of SLS in patients with SLE. These challenges can result in under-recognition and delayed or misdiagnosis of SLS.

Diagnostic delays of 11±20 months have been reported.⁴ Concluding a case report of a patient who presented with symptoms suggestive of SLS, Costa, et al, in a 2014 study said that “SLS, despite being rare, must be considered as a diagnostic possibility when patients diagnosed with SLE present dyspnea without heart insufficiency, anemia or diseases of the lung parenchyma.”⁹ According to Swamy Venuturupalli, MD, a rheumatologist with expertise in lupus in Beverly Hills, California, it is important to “rule out every other cause of shortness of breath first.”¹⁰