Case Report
A crazy cause of dyspnoea: pulmonary alveolar proteinosis Prashilla Soma, Shiraz Ellemdin, Natalie J Roche Lancet 2014; 384: 714 Deparment of Physiology (P Soma MB) and Deparment of Internal Medicine, University of Pretoria, South Africa (S Ellemdin MMed, N J Roche MMed) Correspondence to: Dr Prashilla Soma, Department of Physiology, Faculty of Health Sciences, University of Pretoria, Private Bag x323, Arcadia 0007, South Africa [email protected]
In March, 2013, a 37-year-old woman presented to the emergency department with a 6 month history of worsening dyspnoea, fatigue, insomnia, and generalised body pains. She had no cough or haemoptysis, was a non-smoker, and had no background medical or surgical history or occupational risk factors for pulmonary disease. Before her admission she had been treated by different general practitioners with multiple courses of empirical antibiotics and bronchodilators without resolution of her symptoms. On admission she was alert and orientated. Her vital signs were blood pressure 125/79 mm Hg, respiratory rate 24 breaths per min, heart rate 116 beats per min, and oxygen saturation 48% on room air. She was afebrile with central cyanosis. Chest examination showed good air entry with no abnormal sounds. The rest of the physical examination was normal. Her full blood count, C-reactive protein, antinuclear antibodies, and complement levels were normal, but she had a raised lactate dehydrogenase (LDH) concentration of 5·13 μkat/L (normal: 2·0–3·84 μkat/L). Chest radiograph showed bilateral consolidation, and high resolution CT (HRCT) confirmed dense bilateral reticulonodular infiltrates involving the upper and mid lung regions, in keeping with the so-called crazy paving pattern typical of pulmonary alveolar proteinosis (figure). Anti-granulocyte macrophage-colony stimulating factor (anti-GM-CSF) antibody concentrations, the gold standard for diagnosis of pulmonary alveolar proteinosis, is not available in South Africa. A transbronchial biopsy sample showed alveolar lumina filled with eosinophilic proteinaceous material that stained pink with Periodic Acid Schiff stain, consistent with pulmonary alveolar proteinosis. There were no infective organisms or granulomata. We treated the patient with whole lung lavage. At last follow-up in April, 2014, she was asymptomatic and repeat chest radiograph was normal. She has been followed up three monthly and might need repeat lung lavage if she becomes symptomatic. Pulmonary alveolar proteinosis is a rare pulmonary disease with specific features caused by alveolar
Figure: Pulmonary alveolar proteinosis Chest radiographs showing diffuse bilateral reticulonodular infiltrate with thickened septae, typical of the crazy-paving pattern.
714
accumulation of surfactant, composed of proteins and lipids, due to dysfunctional alveolar macrophages. It has an estimated annual prevalence of 3·7 cases per million population.1 There are three main categories of pulmonary alveolar proteinosis: congenital, secondary, and acquired.2 Autoimmune disease, an acquired form associated with anti-GM-CSF antibodies,1,2 accounts for almost 90% of cases of pulmonary alveolar proteinosis. The clinical presentation of pulmonary alveolar proteinosis is non-specific. Examination findings include inspiratory crackles (50% of patients), cyanosis (25%), and digital clubbing in a small percentage.2 Radiological signs are specific, however, with HRCT showing patchy, ground-glass opacifications with superimposed interlobular and intralobular septal thickening that gives rise to the so-called crazy-paving pattern.2 Whole lung lavage is the current standard treatment of choice. Other treatment options are inhaled aerosol GM-CSF, subcutaneous injected GM-CSF, plasmapheresis, and rituximab, a monoclonal antibody directed against the CD20 antigen on B lymphocytes.4,5 The natural history of pulmonary alveolar proteinosis falls into one of three types: spontaneous resolution, persistent symptoms, or progressive deterioration.2,3 Cough and dyspnoea are common symptoms seen by medical practitioners. It is sometimes difficult to distinguish between patients needing minimal investigation and conservative treatment, and those needing extensive evaluation and aggressive treatment. In our patient, despite the lack of remarkable findings on chest examination, the hypoxaemia and central cyanosis could not be ignored, and the impressive radiological findings demanded further invasive investigation. LDH is commonly elevated in pulmonary alveolar proteinosis and may be a useful marker of severity.2 Bilateral diffuse lung infiltrates can be caused by infection, inflammation, or malignancy. When a patient’s condition does not improve despite appropriate therapy, the clinician must critically appraise the original diagnosis. Contributors SE cared for the patient. PS and NJR wrote the report. Written consent to publish was obtained. References 1 Borie R, Danel C, Debray MP, et al. Pulmonary alveolar proteinosis. Eur Respir Rev 2011; 20: 98–107. 2 Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med 2003; 349: 2527–39. 3 Mazzone P, Thomassen MJ, Kavuru M. Our new understanding of pulmonary alveoloar proteinosis: what an internist needs to know. Cleve Clin J Med 2001; 68: 977–93. 4 Campo I, Kadija Z, Zorzetto M, et al. Novel treatment options for autoimmune pulmonary alveolar proteinosis. EMJ Respir 2013; 1: 122–28. 5 Campo I, Kadija Z, Mariani F, et al. Pulmonary alveolar proteinosis: diagnostic and therapeutic challenges. Multidiscip Respir Med 2012; 7: 4.
www.thelancet.com Vol 384 August 23, 2014
A crazy cause of dyspnoea: pulmonary alveolar proteinosis Prashilla Soma, Shiraz Ellemdin, Natalie J Roche Lancet 2014; 384: 714 Deparment of Physiology (P Soma MB) and Deparment of Internal Medicine, University of Pretoria, South Africa (S Ellemdin MMed, N J Roche MMed) Correspondence to: Dr Prashilla Soma, Department of Physiology, Faculty of Health Sciences, University of Pretoria, Private Bag x323, Arcadia 0007, South Africa [email protected]
In March, 2013, a 37-year-old woman presented to the emergency department with a 6 month history of worsening dyspnoea, fatigue, insomnia, and generalised body pains. She had no cough or haemoptysis, was a non-smoker, and had no background medical or surgical history or occupational risk factors for pulmonary disease. Before her admission she had been treated by different general practitioners with multiple courses of empirical antibiotics and bronchodilators without resolution of her symptoms. On admission she was alert and orientated. Her vital signs were blood pressure 125/79 mm Hg, respiratory rate 24 breaths per min, heart rate 116 beats per min, and oxygen saturation 48% on room air. She was afebrile with central cyanosis. Chest examination showed good air entry with no abnormal sounds. The rest of the physical examination was normal. Her full blood count, C-reactive protein, antinuclear antibodies, and complement levels were normal, but she had a raised lactate dehydrogenase (LDH) concentration of 5·13 μkat/L (normal: 2·0–3·84 μkat/L). Chest radiograph showed bilateral consolidation, and high resolution CT (HRCT) confirmed dense bilateral reticulonodular infiltrates involving the upper and mid lung regions, in keeping with the so-called crazy paving pattern typical of pulmonary alveolar proteinosis (figure). Anti-granulocyte macrophage-colony stimulating factor (anti-GM-CSF) antibody concentrations, the gold standard for diagnosis of pulmonary alveolar proteinosis, is not available in South Africa. A transbronchial biopsy sample showed alveolar lumina filled with eosinophilic proteinaceous material that stained pink with Periodic Acid Schiff stain, consistent with pulmonary alveolar proteinosis. There were no infective organisms or granulomata. We treated the patient with whole lung lavage. At last follow-up in April, 2014, she was asymptomatic and repeat chest radiograph was normal. She has been followed up three monthly and might need repeat lung lavage if she becomes symptomatic. Pulmonary alveolar proteinosis is a rare pulmonary disease with specific features caused by alveolar
Figure: Pulmonary alveolar proteinosis Chest radiographs showing diffuse bilateral reticulonodular infiltrate with thickened septae, typical of the crazy-paving pattern.
714
accumulation of surfactant, composed of proteins and lipids, due to dysfunctional alveolar macrophages. It has an estimated annual prevalence of 3·7 cases per million population.1 There are three main categories of pulmonary alveolar proteinosis: congenital, secondary, and acquired.2 Autoimmune disease, an acquired form associated with anti-GM-CSF antibodies,1,2 accounts for almost 90% of cases of pulmonary alveolar proteinosis. The clinical presentation of pulmonary alveolar proteinosis is non-specific. Examination findings include inspiratory crackles (50% of patients), cyanosis (25%), and digital clubbing in a small percentage.2 Radiological signs are specific, however, with HRCT showing patchy, ground-glass opacifications with superimposed interlobular and intralobular septal thickening that gives rise to the so-called crazy-paving pattern.2 Whole lung lavage is the current standard treatment of choice. Other treatment options are inhaled aerosol GM-CSF, subcutaneous injected GM-CSF, plasmapheresis, and rituximab, a monoclonal antibody directed against the CD20 antigen on B lymphocytes.4,5 The natural history of pulmonary alveolar proteinosis falls into one of three types: spontaneous resolution, persistent symptoms, or progressive deterioration.2,3 Cough and dyspnoea are common symptoms seen by medical practitioners. It is sometimes difficult to distinguish between patients needing minimal investigation and conservative treatment, and those needing extensive evaluation and aggressive treatment. In our patient, despite the lack of remarkable findings on chest examination, the hypoxaemia and central cyanosis could not be ignored, and the impressive radiological findings demanded further invasive investigation. LDH is commonly elevated in pulmonary alveolar proteinosis and may be a useful marker of severity.2 Bilateral diffuse lung infiltrates can be caused by infection, inflammation, or malignancy. When a patient’s condition does not improve despite appropriate therapy, the clinician must critically appraise the original diagnosis. Contributors SE cared for the patient. PS and NJR wrote the report. Written consent to publish was obtained. References 1 Borie R, Danel C, Debray MP, et al. Pulmonary alveolar proteinosis. Eur Respir Rev 2011; 20: 98–107. 2 Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med 2003; 349: 2527–39. 3 Mazzone P, Thomassen MJ, Kavuru M. Our new understanding of pulmonary alveoloar proteinosis: what an internist needs to know. Cleve Clin J Med 2001; 68: 977–93. 4 Campo I, Kadija Z, Zorzetto M, et al. Novel treatment options for autoimmune pulmonary alveolar proteinosis. EMJ Respir 2013; 1: 122–28. 5 Campo I, Kadija Z, Mariani F, et al. Pulmonary alveolar proteinosis: diagnostic and therapeutic challenges. Multidiscip Respir Med 2012; 7: 4.
www.thelancet.com Vol 384 August 23, 2014
