Shrinking Lung Syndrome as an Early Manifestation of Systemic Lupus Erythematosus: A Case Report With Literature Review

ABSTRACT

Systemic lupus erythematosus (SLE) can involve the respiratory system through various manifestations, including the rare pulmonary complication known as shrinking lung syndrome (SLS). SLS is characterised by progressive dyspnoea, pleuritic chest pain, diaphragmatic elevation, reduced lung volumes, a restrictive pattern on pulmonary function tests, and decreased diffusing capacity for carbon monoxide. Diagnosing SLS is challenging, as it requires ruling out interstitial lung disease and significant pleural pathology. While the onset of SLS varies, it typically occurs around 4 years after SLE diagnosis. Here, we report the case of a 33‐year‐old woman with SLE who developed SLS as an unusual early manifestation of the disease. SLS should be considered in the differential diagnosis of respiratory symptoms in patients with suspected or confirmed SLE, even in its early stages. Early recognition and appropriate management are essential for optimising outcomes.

We report the case of a 33‐year‐old woman with systemic lupus erythematosus (SLE) who developed shrinking lung syndrome (SLS) as an unusual early manifestation of the disease. SLS should be considered in the differential diagnosis of respiratory symptoms in patients with suspected or confirmed SLE, even in its early stages. Early recognition and appropriate management are essential for optimising outcomes.

1. Introduction

Respiratory complications are frequent in patients with systemic lupus erythematosus (SLE), impacting disease morbidity. Shrinking lung syndrome (SLS), a rare pulmonary manifestation occurring in 0.5%–1.5% of SLE patients [1], presents with a constellation of symptoms including progressive dyspnoea, pleuritic chest pain, radiographic evidence of diaphragmatic elevation, a restrictive pattern on pulmonary function tests (PFTs) demonstrating reduced lung volumes, and a diminished diffusing capacity for carbon monoxide (DLCO) [2]. The diagnostic process for SLS is complex, necessitating the exclusion of interstitial lung diseases and significant pleural pathology [2]. The underlying pathophysiology of SLS remains incompletely understood, with proposed mechanisms encompassing diaphragmatic myopathy or myositis, chronic pleural inflammation and adhesions, microatelectasis secondary to surfactant dysfunction, and phrenic nerve involvement [3]. Currently, there is a lack of established treatment guidelines for SLS. Corticosteroids and immunosuppressive agents are commonly utilised, yet their therapeutic effectiveness remains debated. Adjunctive therapies, such as beta‐adrenergic agonists and theophylline, have been investigated, but their clinical benefits have not been definitively demonstrated [2]. This case report details the presentation of early‐onset SLS as an initial manifestation in a young woman with previously undiagnosed SLE.

2. Case Report

A 33‐year‐old woman presented to the emergency department with progressive dyspnoea and shortness of breath, which had worsened over the preceding 3 months. Her respiratory symptoms began following an upper respiratory tract infection. Her past medical history was unremarkable; however, she reported a three‐year history of arthralgia, arthritis, and erythematous lesions over the distal interphalangeal joints of her hands and knees. Her family history included suspected rheumatologic diseases in her aunt and sister.

On presentation, the patient's oxygen saturation was 90% on room air without overt respiratory distress. Physical examination revealed diminished breath sounds over the left lung and small, palpable cervical and axillary lymphadenopathy. No active arthritis or skin lesions were observed. Neck and axillary ultrasound demonstrated hypoechoic lymphadenopathy with increased vascularity, consistent with reactive or inflammatory changes. Chest X‐ray (CXR) showed bilateral pleural effusions, predominantly on the left (Figure 1A).

FIGURE 1.

Imaging findings throughout the course of illness. (A) Initial chest x‐ray: bilateral pleural effusion (left‐dominant). (B) Chest x‐ray at SLS diagnosis: right hemidiaphragm elevation. (C) Follow‐up chest x‐ray (6 months): significant improvement.

A diagnostic and therapeutic thoracentesis yielded 4 L of pleural fluid. Cytological analysis revealed a predominantly lymphocytic profile, suggestive of an inflammatory or autoimmune aetiology. Rheumatologic laboratory investigations revealed positive antinuclear antibody (ANA), anti‐double‐stranded DNA (anti‐dsDNA), and fluorescent antinuclear antibody (FANA) with a homogeneous pattern. Anti‐phospholipid IgM antibodies were detected, and complement levels (C3 and C4) were reduced. Other rheumatologic markers were within normal limits. The patient's laboratory data and PFT results are summarised in Table 1.

TABLE 1.

Laboratory and pulmonary function test (PFT) results.

Test	Patient result	Reference range
Rheumatologic tests
ANA	3.42	Negative: < 0.9; Equivocal: 0.9–1.1; Positive: > 1.1
FANA	1/160 (Homogenous pattern)	Negative: < 1/80
Anti‐dsDNA	> 800 IU/mL	Negative: < 100; Positive: ≥ 100
CH50	106 U	70–150 U
C3	5 mg/dL	10–40 mg/dL
C4	53 mg/dL	90–180 mg/dL
C‐ANCA	2.89 U/mL	Negative: < 12; Borderline: 12–18; Positive: > 18
Anti‐cardiolipin IgG	1.41 GPL/mL	Negative: < 12; Borderline: 12–18; Positive: > 18
Anti‐phospholipid IgG	9.24 U/mL	Negative: < 12; Borderline: 12–18; Positive: > 18
Anti‐phospholipid IgM	21.14 U/mL	Negative: < 12; Borderline: 12–18; Positive: > 18
β2‐glycoprotein IgG	12.4 RU/mL	Negative: < 20; Positive: ≥ 20
β2‐glycoprotein IgM	13 RU/mL	Negative: < 20; Positive: ≥ 20
Rheumatoid factor	35 IU/mL	< 20 IU/mL
Creatinine	0.8 mg/dL	0.5–1 mg/dL
Protein	7 g/dL	6–8 g/dL
LDH	200 U/L	140–280 U/L

Test	Initial result	Follow‐up result
Spirometry
FEV1	1.29 L (46%)	2.48 L (75%)
FVC	1.48 L (45%)	2.92 L (80%)
FEV1/FVC	87%	93%
TLC	2.93 L (63%)	3.82 L (82%)
RV	1.87 L (134%)	1.41 L (110%)

CO diffusion
KCO	0.89 mmol/min/kPa/L (47%)	1.08 mmol/min/kPa/L (60%)
TLCO	2.32 mmol/min/kPa (27%)	4.12 mmol/min/kPa (49%)
VA	2.6 L (55%)	3.81 L (82%)

Test	Result	Reference range
Pleural fluid analysis
Sugar	105 mg/dL	> 60 mg/dL
Cholesterol	67 mg/dL	< 45 mg/dL
ADA	26 U/L	< 30 U/L
LDH	133 U/L	< 200 U/L
Protein	5.8 g/dL	< 3.0 g/dL
WBC	210 cells/μL (Neutrophils: 22%, Lymphocytes: 78%)	< 500 cells/μL

Abbreviations: β2‐glycoprotein IgG, beta‐2 glycoprotein immunoglobulin G; β2‐glycoprotein IgM, beta‐2 glycoprotein immunoglobulin M; ADA, adenosine deaminase; ANA, anti‐nuclear antibody; Anti‐dsDNA, anti‐double stranded DNA; C3, complement component 3; C4, complement component 4; C‐ANCA, antineutrophil cytoplasmic autoantibody, cytoplasmic; CH50, 50% haemolytic complement; CO, carbon monoxide; FANA, fluorescent anti‐nuclear antibody; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; KCO, carbon monoxide transfer coefficient; LDH, lactate dehydrogenase; RV, residual volume; TLC, total lung capacity; TLCO, transfer factor for carbon monoxide; VA, alveolar volume; WBC, white blood cells.

The diagnosis of SLE was established based on the 2019 EULAR/ACR classification criteria. The patient met the diagnostic criteria due to the presence of ANA at a titre > 1:80, pleural effusion, joint involvement, low C3 and C4 levels, and positive anti‐dsDNA antibodies. A rheumatologist confirmed the diagnosis, and treatment was initiated with oral prednisolone (0.5 mg/kg/day) and hydroxychloroquine (200 mg twice daily).

Despite appropriate treatment, including successful thoracentesis and pleural fluid drainage, the patient continued to experience dyspnoea. Further evaluation revealed normal erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP). Cardiac evaluation and transthoracic echocardiography demonstrated mild to moderate mitral and tricuspid regurgitation, with pulmonary hypertension (pulmonary artery pressure: 38 mmHg) and preserved left ventricular systolic function (ejection fraction: 55%). Lung sonography and repeat chest X‐ray, performed 1 week after the initial imaging, showed resolution of the pleural effusion but revealed elevation of the right hemidiaphragm (Figure 1B).

Given the hemidiaphragm elevation, alternative causes were systematically excluded. Central nervous system (CNS) pathology, such as stroke or multiple sclerosis, was deemed unlikely due to the absence of neurological symptoms (e.g., dysphagia, limb weakness, autonomic dysfunction) and the lack of clinical indication for neuroimaging. Phrenic nerve disorders (e.g., trauma, compression) and spinal cord pathology (e.g., cervical cord compression, Guillain–Barré syndrome) were excluded based on the absence of prior surgeries, trauma, or neurological deficits; chest and spinal imaging showed no compressive lesions or masses. Neuromuscular junction disorders (e.g., myasthenia gravis) were not suspected due to the lack of ptosis, bulbar symptoms, or fluctuating weakness. Primary muscular disorders (e.g., inflammatory myopathies) were considered unlikely given normal serum creatine kinase and aldolase levels and no evidence of proximal muscle weakness. Subdiaphragmatic causes (e.g., hepatosplenomegaly, subphrenic abscess) were ruled out via abdominal ultrasound and chest imaging.

PFTs demonstrated a restrictive ventilatory defect with reduced alveolar volume and reduced DLCO (Table 1). The absence of structural lung disease and the patient's favourable response to immunosuppressive therapy suggested an inflammatory mechanism related to SLS [4]. A second rheumatology consultation confirmed the diagnosis of SLS. Treatment was intensified with an increased dose of prednisolone (1 mg/kg/day) and the addition of mycophenolate mofetil (1 g/day, divided twice daily). Although thoracentesis led to initial relief of chest discomfort, the patient's dyspnoea persisted, indicating that pleural effusion alone did not fully account for her symptoms. This clinical course prompted escalation of immunosuppressive therapy.

The patient was discharged and followed up for 6 months. During this period, she experienced significant improvement in respiratory symptoms. Follow‐up pulmonary function tests showed progressive improvement in lung volumes and diffusing capacity, indicating a favourable response to treatment (Table 1). Chest imaging demonstrated marked resolution of previous abnormalities, with near‐complete normalisation of radiologic findings (Figure 1C). Prednisolone was gradually tapered over the six‐month follow‐up period based on sustained clinical and functional recovery. Mycophenolate mofetil was continued as maintenance immunosuppressive therapy to ensure long‐term disease control.

3. Discussion

SLS can manifest at any point during the course of SLE, with onset ranging from 1 month to 35 years post‐diagnosis, with an average onset around 4 years [5, 6]. A review of literature identified cases where SLS preceded the diagnosis of SLE (Table 2), highlighting its potential as an early manifestation [7, 8, 9, 10, 11, 12]. This highlights the importance of considering SLS in the differential diagnosis of respiratory symptoms, even in patients without a confirmed SLE diagnosis. Early rheumatologic evaluation and referral are warranted when SLS is suspected.

TABLE 2.

The cases of shrinking lung syndrome as a precursor to systemic lupus erythematosus diagnosis.

Year, country	Age, sex	Clinical manifestation of SLE	Presenting features of SLS	Imaging results	PFT pattern	SLS treatment	Follow‐up	Outcome
2023, Our case	33, F	Arthralgia, arthritis, and erythematous lesions in the distal interphalangeal joints of her hands and knees, pleural effusion	Dyspnoea, chest pain	Right hemidiaphragm elevation	Restrictive pattern with reduced DLCO	Corticosteroids, mycophenolate mofetil	6 months	Significant clinical improvement
2014, USA [7]	18, M	Arthritis, persistent fever, pleural effusion, pericardial effusion	Dyspnoea, chest pain	Elevation of right diaphragm	Restrictive pattern	Corticosteroids, azathioprine, hydroxychloroquine	18 months	Significant clinical improvement
2006, Kuwait [8]	21, F	Prolonged fever, polyarthritis	Dyspnoea, respiratory muscle dysfunction, pleuritic chest pain	Small lung volumes, elevated right hemidiaphragm, basilar atelectasis	Mild to moderate restrictive defect with normal diffusion	Corticosteroids	3 years	Significant clinical improvement
2004, France [9]	26, F	Prolonged fever, polyarthralgia, malar rash	Dyspnoea, chest pain, cough	Small lung volumes, elevated right hemidiaphragm	Restrictive pattern with low DLCO	Corticosteroids, hydroxychloroquine, theophylline, physiotherapy	8 months	Improved dyspnoea and cough, persistent chest pain
2001, France [10]	36, NR	Arthralgia, oscillating fever, weight loss	Dyspnoea	Bilateral reduction in lung volumes with a bilaterally elevated diaphragm	Restrictive pattern with reduced DLCO	Corticosteroids, cyclophosphamide	2 years	Improved diaphragm function, unchanged PFT and CXR
1990, Australia [11]	52, M	Fatigue, cough, night sweets, polyarthralgia, facial photosensitivity, scaly erythematous rash in face	Dyspnoea, chest pain and cough	Bilateral elevation of diaphragm and reduced lung volumes	Restrictive pattern with reduced DLCO	Corticosteroids, azathioprine	15 months	Significant clinical improvement
1965, NR [12]	23, F	Persistent fever, arthritis, butterfly rash, pleural effusion	Dyspnoea, chest pain	Elevation of right diaphragm and reduced lung volumes	Restrictive defect	Corticosteroids	NR	Significant clinical improvement
	39, F	Pleural effusion, arthralgia, weight loss	Dyspnoea, cough	Bilateral elevation of diaphragm	Restrictive defect	Corticosteroids	4 years	Increasing diaphragm elevation and dyspnoea

Abbreviations: CXR, chest x‐ray; DLCO, diffusing capacity for carbon monoxide; F, female; M, male; NR, not reported; PFT, pulmonary function tests; SLE, systemic lupus erythematosus; SLS, shrinking lung syndrome.

Delayed diagnosis of SLS is common, necessitating a high index of clinical suspicion. The prognosis is generally favourable, with a low mortality and improvement in PFTs with immunosuppressive therapy. While the timing of SLS onset varies, early diagnosis, rather than the timing of onset, is crucial for guiding appropriate treatment and preventing pulmonary decline [13]. Recognising SLS in SLE patients with unexplained dyspnoea allows for early initiation of targeted immunosuppressive therapy, potentially halting disease progression and improving outcomes.

SLS can significantly impair quality of life, emphasising the need for timely intervention. The primary diagnostic challenge lies in the exclusion of other pulmonary manifestations, such as interstitial, alveolar, pleural, or vascular involvement. A thorough clinical evaluation, imaging studies, and PFTs are essential to exclude other causes of respiratory symptoms and confirm SLS [2].

In this case, SLS was diagnosed based on persistent dyspnoea, absence of pleural or vascular abnormalities, and a restrictive ventilatory defect, reduced alveolar volume, and reduced diffusion capacity on PFTs (Table 1). The decline in the carbon monoxide transfer coefficient (KCO) raised concern for possible pulmonary vascular involvement [14].

Given the presence of mild to moderate mitral and tricuspid regurgitation with pulmonary hypertension (PAP: 38 mmHg), it is likely that pulmonary vascular dysfunction contributed to the observed diffusion impairment. Pulmonary hypertension (PH) is known to reduce KCO by impairing capillary recruitment and increasing vascular resistance [15].

In patients with SLE, PH is a recognised, albeit uncommon, complication that may arise through multiple overlapping mechanisms, including immune‐mediated pulmonary arterial hypertension (Group 1), secondary PH due to valvular disease or left ventricular dysfunction (Group 2), and PH associated with chronic thromboembolic disease or interstitial lung involvement (Groups 3 and 4), particularly in those with coexisting antiphospholipid syndrome [16].

The pathogenesis of SLE‐related PH remains incompletely understood but appears to involve a combination of immune dysregulation, genetic susceptibility, endothelial dysfunction, and inflammatory vascular remodelling [16]. In this case, the PH is likely multifactorial, potentially related to valvular heart disease and lupus‐associated pulmonary vasculopathy. Contrast‐enhanced CT pulmonary angiography ruled out thromboembolic disease, and chest CT showed no evidence of interstitial lung disease or structural parenchymal abnormality.

While the exact pathophysiology of SLS remains unclear, mechanical and functional factors dominate. Pleural inflammation and pain may induce diaphragm dysfunction through reflex inhibition, leading to impaired lung expansion. Pleuritic pain contributes to muscle guarding, increased thoracic rigidity, and shallow breathing patterns, which collectively reduce lung volumes [17].

Although a reduced DLCO is often associated with interstitial lung disease, SLS presents a distinct, non‐parenchymal mechanism of gas exchange impairment. In SLS, factors such as diaphragmatic dysfunction, pleuritic pain leading to shallow breathing, and microatelectasis contribute to reduced lung volumes and alveolar surface area, which can lower DLCO even in the absence of structural lung disease [18].

In this case, the observed decline in DLCO coincided with the presence of pulmonary hypertension (PAP: 38 mmHg), which may further impair diffusion by reducing capillary recruitment and increasing vascular resistance. However, we do not attribute the pulmonary hypertension to SLS itself. Instead, it is considered a concurrent manifestation of SLE, potentially resulting from immune‐mediated pulmonary arterial hypertension or secondary to mitral valve regurgitation.

The optimal treatment for SLS is not well‐defined, but corticosteroids and immunosuppressive agents remain the mainstay. Reported immunosuppressive treatments include cyclophosphamide, rituximab, azathioprine, methotrexate, mycophenolate mofetil, and belimumab, alongside hydroxychloroquine. Theophylline and beta‐agonists have been suggested as adjunctive therapies, although their efficacy is uncertain [17].

The response to treatment in SLS is generally favourable, with most patients experiencing clinical improvement [17]. In this case, the patient's symptoms, chest radiography, and PFTs showed significant improvement within 6 months of initiating immunosuppressive therapy, demonstrating the beneficial role of immunosuppression in controlling inflammation and preventing disease progression.

In conclusion, SLS is a rare but important pulmonary complication of SLE that is often under‐recognised and presents a diagnostic challenge, particularly in early‐stage or undiagnosed cases. SLS should be suspected in SLE patients with normal lung parenchyma, diaphragmatic elevation, and unexplained lung volume reduction on imaging studies and PFTs. Early recognition and diagnosis are crucial to minimising morbidity and preserving long‐term pulmonary function. Early identification of SLS as an initial SLE manifestation is crucial for timely intervention and improved outcomes.

Author Contributions

Conceptualization: N.K.R., B.R., H.A., H.K. Data curation: G.R., M.Y.M. Investigation: N.K.R., G.R. Methodology: N.K.R., G.R. Supervision: H.A., H.K. Writing – original draft preparation: G.R., H.K. Writing – review and editing: N.K.R., H.A., G.R.

Ethics Statement

Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.

Conflicts of Interest

The authors declare no conflicts of interest.

Roostaei G., Kazemizadeh H., Rahimi B., Abtahi H., Yousefi Mokri M., and Khoshnam Rad N., “Shrinking Lung Syndrome as an Early Manifestation of Systemic Lupus Erythematosus: A Case Report With Literature Review,” Respirology Case Reports 13, no. 7 (2025): e70255, 10.1002/rcr2.70255.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author, (Niloofar Khoshnam Rad), upon reasonable request.