Pleural and pulmonary involvement in systemic lupus erythematosus

doi:10.1016/j.lpm.2010.11.004

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Volume 40, Issue 1, Part 2, January 2011, Pages e41-e51

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Summary

Systemic lupus erythematosus (SLE) is a rare complex autoimmune disease with a multisystem involvement. The clinical manifestations of this disease include an erythematous rash, oral ulcers, polyarthralgia, nonerosive arthritis, polyserositis, hematologic, renal, neurologic, pulmonary and cardiac abnormalties. The involvement of the respiratory system is frequent. Pleuro-pulmonary manifestations are present in almost half of the patients during the disease course and may be the presenting symptoms in 4–5% of patients with SLE. Complications directly associated to the disease include pleuritis with or without pleural effusion, alveolitis, interstitial lung disease, lupus pneumonitis, pulmonary hemorrhage, pulmonary arterial hypertension, and pulmonary thromboembolic disease. Complications due to secondary causes include pleuro-pulmonary manifestations of cardiac and renal failure, atelectasis due to diaphragmatic dysfunction, opportunistic pneumonia, and drug toxicity. The prevalence, clinical presentation, prognosis and response to treatment vary, depending on the pattern of involvement. As with other connective tissue diseases, early and specific therapeutic intervention may be indicated for many of these pleuro-pulmonary manifestations.

Section snippets

Pleural involvement

Pleural disease represents the most common intrathoracic manifestation of SLE, with pathologic evidence of pleuritis or pleural fibrosis in 50–83% of patients at autopsy and pleural effusion in 16–50% on chest radiographs. Pleural involvement may be the first manifestation of SLE and is commonly associated with pericarditis [5]. Clinically lupus pleuritis is characterized by chest pain, dyspnea, cough and possibly fever. Pleuritic pain can be present without radiographically detectable chest

Pulmonary infections

Patients with SLE are more susceptible to bacterial and opportunistic infections due to immunosuppressive therapy with glucocorticoids or an immunomodulatory agent as well as characteristic immunologic dysfunction including immunoglobulin deficiency, acquired and inherited complement deficiencies, defects in chemotaxis and phagocytosis and functional asplenia which may account for the increased susceptibility to pneumococcal and Salmonella sepsis [6], [7], [8], [9]. Underlying parenchymal

Acute pulmonary diseases

Acute lupus pneumonitis (ALP) and diffuse alveolar hemorrhage (DAH) are uncommon, acute life-threatening syndromes associated with SLE resulting from acute injury to the alveolar-capillary unit [20]. ALP occurs in 1–4% of patients with SLE. It can reveal a previously unknown SLE in up to 50% of patients or may occur in the course of the disease. The clinical presentation of ALP is non specific and is characterized by the sudden onset of fever, cough and dyspnea with hypoxemia and hypocapnia,

Chronic pulmonary diseases

Diffuse interstitial lung disease (ILD) is relatively less common in SLE than in other CTDs, although it may dominate the clinical picture in some patients. The involvement of the lung affects 3–8% of SLE patients, with a progressive increase in prevalence with disease duration [49], [50]. However, different high resolution computed tomography (HRCT) series have demonstrated a higher rate of ILD features (about one third of SLE patients), suggesting that subclinical lung disease is common [51],

Pulmonary embolism

SLE patients are at increased risk for coagulation problems. Pulmonary embolism should be suspected in patients who have antiphospholipid antibodies (aPL) with acute respiratory symptoms such as pleuritic chest pain and dyspnoea. Antiphospholipid antibodies are a family of acquired autoantibodies that are associated with vascular thrombosis and may be present in up to two thirds of patients with SLE [69], [70]. The two most well known and clinically important are the lupus anticoagulant (LA)

Pulmonary arterial hypertension

CTDs such as systemic sclerosis (SSc) and SLE can be complicated by severe pulmonary arterial hypertension (PAH) [76]. Previous studies have largely concentrated on SSc-associated PAH (SSc-PAH), with a disease prevalence estimated to be between 7.5 and 12% [77], [78]. Some degree of PHT complicates the course of SLE in 5–14% of the patients [79], [80], [81]. PHT prevalence and severity of disease in patients with SLE tend to increase with time [82]. Autopsy findings from patients with SLE and

Myopathies and muscle dysfunction

Shrinking lung syndrome (SLS) is a manifestation of SLE characterized by progressive dyspnea, the characteristic chest radiographic findings of small lung volumes, elevated hemidiaphragms and bibasilar atelectasis, with a restrictive ventilatory defect and a preserved carbon monoxide transfer coefficient. The exact prevalence of SLS in patients with SLE is unknown; occurrence has been described in 18 to 27% of patients [91], [92]. The pathogenesis of this condition is still not entirely known.

Conclusion

To conclude, pulmonary manifestations of lupus erythematosus are myriad. CT scan has emerged as a very useful tool in the early diagnosis and management of pulmonary diseases associated with SLE. The necessity of ruling out infection and establishing the diagnosis of acute pulmonary involvement such as alveolar haemorrhage, lupus pneumonitis, pulmonary embolism or acute alveolitis in ILD is vital as these conditions need immediate treatment and any delay can result in increased morbidity and

Conflicts of interests

None.

Glossary

aCL: anticardiolipin antibodies
ALP: acute lupus pneumonitis
aPL: antiphospholipid antibodies
APS: antiphospholipid syndrome
BAL: bronchoalveloar lavage
CAPS: catastrophic APS
CTD: connective tissue diseases
DAD: diffuse alveolar damage
DAH: diffuse alveolar hemorrhage
DLCO: carbon monoxide diffusing capacity
HRCT: high-resolution computed tomography
ILD: diffuse interstitial lung disease
LA: lupus anticoagulant
LIP: lymphocytic interstitial pneumonia
NSIP: nonspecific interstitial pneumonia
OP: organizing pneumonia
PAH: pulmonary arterial

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Approximately forty percent of patients with autoimmune diseases suffer from interstitial lung disease (ILD). There are currently no specific screening guidelines for these patients. ILD causes substantial morbidity and mortality; early recognition and diagnosis are essential to avoid treatment delays. The gold standard for management incorporates a multidisciplinary approach (MMD) with input from various specialties, such as pulmonary, rheumatology, radiology, and pathology, to reach a consensus regarding diagnosis and treatment. In this article, we will discuss the most common forms of ILD that affect patients with autoimmune diseases, as well as how to promptly and effectively diagnose and treat these conditions.
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La enfermedad pulmonar intersticial en el lupus es una entidad que se presenta con poca frecuencia y en la mayoría de los casos tiende a ser de progresión lenta. A pesar de esto, se desconoce en gran medida el enfoque terapéutico de los casos moderados a severos, debido a que la mayor parte de la evidencia proviene de reportes de caso y muchos de ellos fueron anteriores al advenimiento de los nuevos tratamientos para el lupus que se conocen hoy en día. Adicionalmente, se ha avanzado poco en entender su fisiopatología, los conceptos actuales provienen de otras enfermedades del tejido conectivo como la esclerosis sistémica que en ocasiones son agrupadas dentro del grupo de neumonías intersticiales con características autoinmunes. Esto de cierta forma ha sido un obstáculo para la investigación en este campo, sin que se haya logrado un enfoque diagnóstico y terapéutico unificado. Por ello, se realiza una búsqueda avanzada con el objetivo de tener la mayor evidencia disponible hasta la fecha en cuanto a los métodos diagnósticos y las terapias emergentes, ofreciendo al clínico una visión práctica para lograr su abordaje integral.
Interstitial lung disease in lupus is an entity that occurs infrequently and tends to progress slowly in most cases. Despite this, the therapeutic approach for moderate to severe cases is largely unknown because most of the evidence comes from case reports, many of which predate the advent of today's known treatments for lupus. Additionally, little progress has been made in understanding its pathophysiology and current concepts come from other connective tissue diseases such as systemic sclerosis or are grouped within the group of interstitial pneumonias with autoimmune characteristics. This, to an extent, has been an obstacle for research in this field, and to date there is no unified diagnostic and therapeutic approach. Therefore we conducted a state of the art search of the best evidence available to date, in terms of diagnostic methods and emerging therapies, to offer the clinician a practical vision for a comprehensive approach.
Shrinking lung syndrome. A rare pulmonary manifestation of lupus: A case report
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Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by protean clinical manifestations. Shrinking lung syndrome (SLS) is a rare pulmonary complication of this disease. It is characterized by progressive dyspnea, pleuritic chest pain, and decreased lung volume without signs of parenchymal disease. We report the observation of a 71-year-old patient with systemic lupus for 46 years, whose SLS is evoked by unexplained chronic dyspnea, convincing imaging, and respiratory functional exploration.
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Pulmonary manifestations in late versus early systemic lupus erythematosus: A systematic review and meta-analysis
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Citation Excerpt :
Moreover, in non-lupus populations, lung fibrosis increases with advanced age, raising our interest in examining these relationships in lupus [6]. Pulmonary involvement is common in SLE, and pulmonary features are the presenting symptom in 5% of patients [7]. The most common pulmonary manifestation, pleuritis, occurs in up to 50% of all lupus patients.
Phenotypes differ between late- and early-onset systemic lupus erythematosus (SLE). Prior studies suggested that there may be more pulmonary disease among late-onset patients. Our objective was to perform a systematic review and meta-analysis to evaluate the differences in pulmonary manifestations in late- versus early-onset SLE.
We searched the literature using PubMed, CINAHL, Web of Science, Cochrane Library, and EMBASE. We excluded studies that did not include American College of Rheumatology SLE classification criteria, an early-onset SLE comparison group, or those that defined late-onset SLE as <50 years of age. We rated study quality using the Newcastle–Ottawa Quality Scale. We used Forest plots to compare odds ratios (95% confidence intervals) of pulmonary manifestations by age. Study heterogeneity was assessed using I².
Thirty-nine studies, representing 10,963 early-onset and 1656 late-onset patients with SLE, met eligibility criteria. The odds of developing several pulmonary manifestations were higher in the late-onset group. Interstitial lung disease (ILD) was nearly three times more common (OR = 2.56 (1.27, 5.16)). Pleuritis (OR = 1.53 (1.19, 1.96)) and serositis (OR = 1.31 (1.05, 1.65)) were also more common in the late-onset group. The mean Newcastle–Ottawa Quality Scale score for study quality was moderate (6.3 ± 0.7, scale 0–9).
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Citation Excerpt :
Pleural effusions may be either unilateral or bilateral, equally distributed between the left and right hemithorax, rarely become massive, and tend to be recurrent. Diagnostic thoracentesis is always recommended, because these patients may have effusions for many different reasons including infection, pulmonary embolism (PE), renal failure, and cardiac failure.49,51,53,54 The pleural fluid is typically a sterile yellow or serosanguineous exudate with a variable cell count, predominantly consisting of polymorphonuclear neutrophils or lymphocytes.
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SLE is an autoimmune disease characterized by a variety of clinical and laboratory abnormalities. It may affect many organs and pulmonary involvement is a common finding in SLE. The purpose of this study was to disclose the pulmonary involvement in early SLE patients not more than 2 years of disease duration using the computed tomography (CT) as well as the pulmonary function tests as ways of pulmonary involvement assessment.
Forty-two patients aged 29 ± 12.5 with early SLE not more than 2 years of disease duration were recruited for the study. All patients were assessed clinically for their SLE with BILAG which was utilized for disease activity determination.
Nine and half percent of our patients were found to be clinically involved by ILD, where 28.6% have abnormal HRCT finding, 26.2% with abnormal PFT. Variants that were associated with an abnormal forced vital capacity FVC < 80% in a significant manner were: smoking, long disease duration, self-reported pulmonary symptoms (p 0.001), BILAG global score (p 0.006), Anti dsDNA (p 0.001), Antiphospholipid (IgM or IgG) (p 0.01), anti Sm (p 0.002), anti-RNP (p 0.005), HRCT abnormalities (p 0.001), current medication of steroid (any dose) (p 0.005), immunomodulator therapy (p 0.002), and Rituximab therapy (p 0.001).
ILD occurs as early as in the first 2 years in the course of SLE patients. There was a clear predilection of ILD with certain variables in our cohort of patients.

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Pleural and pulmonary involvement in systemic lupus erythematosus

Summary

Section snippets

Pleural involvement

Pulmonary infections

Acute pulmonary diseases

Chronic pulmonary diseases

Pulmonary embolism

Pulmonary arterial hypertension

Myopathies and muscle dysfunction

Conclusion

Conflicts of interests

Glossary

Semin Arthritis Rheum

Best Pract Res Clin Rheumatol

Semin Arthritis Rheum

Chest

Clin Chest Med

Am J Med

Clin Chest Med

Chest

Semin Arthritis Rheum

J Comput Assist Tomogr

Crit Care Clin

Semin Arthritis Rheum

Chest

Semin Arthritis Rheum

Semin Arthritis Rheum

Am Heart J

Chest

Chest

Chest

Mayo Clin Proc

Chest

Chest

Semin Arthritis Rheum

Late-onset systemic lupus erythematosus: a personal series of 47 patients and pooled analysis of 714 cases in the literature

Medicine (Baltimore)

The 1982 revised criteria for the classification of systemic lupus erythematosus

Arthritis Rheum

Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. I. A descriptive analysis of 704 European lupus patients. European Consensus Study Group for Disease Activity in SLE

Clin Exp Rheumatol

The respiratory system in connective tissue disorders

Allergy

Complement components and receptors: deficiencies and disease associations

ImmunolSeries

Fatal infections in systemic lupus erythematosus: The role of opportunistic organisms

Medicine

European Working Party on Systemic Lupus Erythematosus: Morbidity and mortality in systemic lupus erythematosus during a 10- year period. A comparison of early and late manifestations in a cohort of 1000 patients

Medicine (Baltimore)

Immunogenicity and safety of pneumococcalvaccination in patients with rheumatoid arthritis or systemic lupus erythematosus

Clin Infect Dis

Coexisting pneumocystis carinii and cytomegalovirus pneumonia in systemic lupus erythematosus

HK J Paediatr (new series)

Risk factors and prognostic influence of infection in a single cohort of 87 adults with systemic lupus erythematosus

Ann Rheum Dis

Infections in systemic lupus erythematosus: a prospective and controlled study of 110 patients

Lupus

The nature and outcome of infection in systemic lupus erythematosus

Lupus

Invasive fungal infection in systemic lupus erythematosus: an analysis of 15 cases and a literature review

Rheumatology

Pneumocystis carinii pneumonia after discontinuation of hydroxychloroquine in 2 patients with systemic lupus erythematosus

J Rheumatol

Pulmonary manifestations of systemic lupus erythematosus

J Thorac Imag

Diffuse alveolar hemorrhage and systemic lupus erythematosus: clinical presentation, histology, survival, and outcome

Medicine

Pulmonary hemorrhage in systemic lupus erythematosus

Semin Arthritis Rheum

Diffuse alveolar hemorrhage in systemic lupus erythematosus: a single center retrospective study in Taiwan

Renal Failure

Diffuse alveolar hemorrhage in Colombian patients with systemic lupus erythematosus

Clin Rheumatol

Pulmonary hemorrhage in Oriental patients with systemic lupus erythematosus

Lupus

Diffuse alveolar hemorrhage in lupus nephritis

Clin Nephrol

Microangiitis in lupus-induced pulmonary hemorrhage

Am J Clin Pathol