Differential Diagnosis of Spontaneous Pneumothorax

Appendix 2: Causes of spontaneous pneumothorax.1–3

Clinical and Chest imaging demographic (excluding findings Pulmonary function Genetics Cause features of pneumothorax) tests (Mendelian) Special tests

Primary Typically seen in Usually normal Usually normal Not applicable None, but spontaneous men during early thoracoscopy pneumothorax adulthood; patients performed for are usually tall and therapeutic reasons thin; strongly often shows associated with a subpleural blebs history of smoking COPD Prevalence May be normal in Airflow obstruction Not applicable None increases with age early disease; that is not fully (see separate from mid-adulthood findings in more reversible, often discussion of alpha on; strongly advanced disease with a decrease in 1-antitrypsin associated with a include diffusing capacity deficiency, below, history of smoking hyperinflation, which accounts for vascular deficiency, ~1-2% of cases of centrilobular COPD) emphysema, and bullae; classically upper lung- predominant Alpha 1-antitrypsin Development of May be normal in May be normal; Autosomal Alpha 1-antitrypsin deficiency early-onset (age early disease; airflow obstruction recessive level < 20 µmol/L; 30–40) and (or) findings in more that is not fully protease inhibitor severe emphysema advanced disease reversible, often protein phenotyping (including include with a decrease in emphysema that is hyperinflation, diffusing capacity not in proportion to vascular deficiency, history of smoking); panacinar possible emphysema and bronchiectasis and bullae; classically extrapulmonary lower lung- involvement (e.g., predominant liver disease) Asthma Development of Usually normal May be normal; Not applicable Bronchial paroxysmal or variable airflow hyperresponsiveness persistent airway obstruction, often challenges, allergy disorder with with a normal testing variable clinical diffusing capacity phenotype and age of onset; possible features of atopy Cystic fibrosis Bronchiectasis with Hyperinflation, Airflow obstruction Autosomal Sweat chloride level, bacterial upper lung- that is not fully recessive CFTR gene testing colonization, mostly predominant reversible, often commonly findings of with a decrease in beginning in bronchiectasis (eg. diffusing capacity childhood; frequent bronchial wall extrapulmonary thickening, mucous involvement (e.g., plugging, ring rhinosinusitis and shadows, tram lines, nasal polyps, cysts) exocrine and endocrine pancreatic disease, infertility)

Appendix to: Pierce CW, Hull PR, Lemire EG, Marciniuk D. Birt–Hogg–Dubé syndrome: an inherited cause of spontaneous pneumothorax. CMAJ 2011. DOI:10.1503/cmaj.092121. Copyright © 2011, Canadian Medical Association or its licensors

Appendix 2 continued

Clinical and Chest imaging demographic (excluding findings Pulmonary function Genetics Cause features of pneumothorax) tests (Mendelian) Special tests

Sequelae of Development of Variable, depending Not applicable Not applicable Dependent on pulmonary infection cystic and (or) on cause and clinical cavitary lesions on pathogen circumstances the basis of necrotizing pneumonia, TB, septic emboli, Pneumocystis infection LAM Pulmonary lesions, May be normal in May be normal, Not applicable; Consistent clinical almost exclusively in early disease; obstructive, associated tuberous and CT findings women of findings in more restrictive, or mixed, sclerosis is may suffice for childbearing age; advanced disease often with a autosomal dominant diagnosis; surgical also found in up to include decrease in lung biopsy is 40% of women with reticulonodular diffusing capacity. definitive TS (most infiltrates, cysts, (bronchoscopic prominently bullae, and pleural testing often dermatologic and effusion; lung nondiagnostic); neurologic volumes may be tuberous sclerosis is abnormalities); normal or increased diagnosed clinically, extrapulmonary and testing of TSC1 involvement and TSC2 loci is common (e.g., renal available angiomyolipomas) Pulmonary Development of Usually upper lung- May be normal, Not applicable Surgical lung biopsy Langerhans’ cell pulmonary lesions, predominant obstructive, (bronchoscopic histiocytosis (PLCH) in young adulthood reticulonodular restrictive, or mixed, testing often (e.g., age 20–30 infiltrate, cavitating often with a nondiagnostic) years); very strongly nodules, and cysts; decrease in associated with lung volumes may diffusing capacity. current and heavy be normal or smoking; occasional increased extrapulmonary involvement (e.g., bone lesions, diabetes insipidus) Birt–Hogg–Dubé Development of skin Chest radiograph Usually normal Autosomal dominant FLCN gene testing syndrome lesions, renal may be normal, is available tumours and chest CT may show pulmonary cysts cysts

Appendix 2 concluded

Clinical and Chest imaging demographic (excluding findings Pulmonary function Genetics Cause features of pneumothorax) tests (Mendelian) Special tests Marfan syndrome Musculoskeletal Usually normal; may Usually normal Autosomal dominant echocardiogram, slit abnormalities (e.g., show features of lamp examination; tall stature, long underlying chest FBN1 gene testing limbs, wall or is available arachynodactyly, cardiovascular chest wall lesions deformity), cardiovascular lesions (e.g., ascending aortic aneurysm and dissection, mitral valve prolapse), and ocular lesions (e.g., lens dislocation, myopia)

Ehlers–Danlos Characterized by Usually normal Usually normal Autosomal dominant Biochemical testing syndrome (type IV: thin/translucent skin, of type III vascular type) easy bruising, procollagen in characteristic facial fibroblasts, COL3A1 appearance, as well gene testing as arterial and visceral rupture

Note: CT = computed tomography, COL3A1 = collagen type III alpha 1, COPD = chronic obstructive pulmonary disease, FBN1 = fibrillin 1 , FLCN = folliculin, LAM = lymphangioleiomyomatosis, TS = tuberous sclerosis, TSC1 = tuberous sclerosis 1, TSC2 = tuberous sclerosis 2.

References

1. Kasper DL, Braunwald E, Fauci AS, et al. Harrison’s principles of internal medicine. 17th ed. New York (NY): McGraw- Hill Medical Publishing Division; 2008. p. 1635-40, p. 1648-50, p. 1660, p. 2465-69.

2. Mason RJ, Broaddus VC, Martin TR, et al. Murray and Nadel’s textbook of respiratory medicine. 5th ed. Philadelphia (PA): Saunders Elsevier; 2010. p. 883-902, p. 941-3, p. 985-1005, p. 1496-1507, p. 1766-70.

3. GeneReviews. GeneTests: Medical Genetics Information Resource [database]. Seattle (USA): University of Washington, Seattle; 1993–2010. Available: www.genetests.org (accessed 2010 Oct. 6)