Radiology_May04 45 SA JOURNAL OF RADIOLOGY • May 2004 CASE REPORT Introduction The radiological detection of pul- monary air space consolidation opens up a broad differential diagnosis.1 In various pathological conditions alve- oli may be filled with fluid, pus, blood, tumour, gastric contents or a phos- pholipoproteinaceous material.1,2 The latter condition is known as pul- monary alveolar proteinosis.2 I report on a case of acquired pulmonary alve- olar proteinosis and give a short review of this fascinating disorder. Case report A 51-year-old caucasian male patient presented with a 2-year his- tory of progressive dyspnoea with a cough, productive of a yellow sputum. The patient had smoked 20 cigarettes a day for the past 30 years. One year ago the patient underwent a lung biopsy and a histological diagnosis of pneumonia was made. Both his occu- pational and recreational history did not reveal any risk factors for pul- monary disease. Clinical examination revealed cyanosis and bilateral inspi- ratory crackles. The chest radiograph demonstrat- ed extensive, bilateral alveolar consoli- dation. A high-resolution computed tomography (HRCT) scan confirmed widespread, bilateral air space consol- idation, with thickened interlobular septae, producing the so called ‘crazy paving’ pattern (Fig. 1). The patient was subjected to another thoraco- scopic lung biopsy and this time the histological examination revealed alveoli and terminal bronchioles filled with granular, eosinophilic, proteina- ceous material (Fig. 2) with preserva- tion of the alveolar architecture. The patient was treated by whole-lung lavage, followed by a 4-week trial of subcutaneous granulocyte-macro- phage colony-stimulating factor (GM-CSF). The trial of GM-CSF failed, however, and the patient is cur- rently being treated by monthly whole-lung lavages. Discussion Pulmonary alveolar proteinosis (PAP) is a rare syndrome that was first described by Rosen et al. in 1958.3 This disorder is characterised by abnormal intra-alveolar surfactant accumula- tion4 with a variable clinical course, ranging from respiratory failure to spontaneous resolution.5 Three distinct clinical forms of PAP can be distinguished:3-5 congeni- tal, secondary, and primary (idiopath- ic) pulmonary alveolar proteinosis. Congenital PAP is a heterogeneous group of disorders caused by muta- tions in surfactant proteins B or C, or the receptor for GM-CSF.3,6,7 Secondary PAP can develop in associ- ation with various conditions, such as immunodeficiency states, acute silico- sis and other inhalational syndromes, haematologic malignancies and myelodysplastic syndromes.4, 5 In all of these conditions there is a reduction in the number and/or functional impairment of alveolar macrophages.5 More than 90% of all cases of PAP occur as the primary (idiopathic) form.4 Recent studies have led to the current concept that primary PAP is an autoimmune disease, which pro- duces neutralising immunoglobulin G (IgG) antibodies against GM-CSF.8 Surfactant is normally cleared by uptake into alveolar macrophages and GM-CSF is critical for this process, as it is a cytokine stimulating the pro- duction of alveolar macrophages by Pulmonary alveolar proteinosis — a case report and review J Ker MB ChB, MMed (Internal Medicine) Department of Physiology University of Pretoria and Pretoria Heart Hospital Fig. 1. Widespread, bilateral areas of ground glass opacities with inter- and intralobular septal thick- ening leading to a ‘crazy paving’ pattern. Fig. 2. Alveoli filled with an eosinophilic, granular material, staining with periodic acid Schiff (PAS). Note the preservation of the alveolar architecture. REVIEW ARTICLE 46 SA JOURNAL OF RADIOLOGY • May 2004 the bone marrow. Therefore, all three forms of PAP share the feature of an impairment in the number and/or activity of alveolar macrophages lead- ing to the alveolar accumulation of surfactant.1-8 The most common symptoms are dyspnoea and cough, and because of the impaired alveolar macrophage function these patients are susceptible to pneumonia.2,4,5 Pulmonary func- tion tests usually reveal a restrictive defect with a reduction in lung vol- ume and diffusion capacity.2 The radiological feature is that of a non-specific pattern of air space con- solidation, which is usually bilateral and patchy and can be very extensive.2 It has been reported that in up to 50% of cases this patchy consolidation is peri-hilar, giving a ‘bat’s wing’ pat- tern.2 However, the consolidation may also be predominantly peripheral or basal in distribution.2 HRCT demon- strates patchy, ground-glass opacifica- tions with superimposed inter, and intralobular septal thickening, and this pattern is commonly referred to as ‘crazy paving’.5 Open-lung biopsy is the gold stan- dard for the diagnosis and reveals alveoli filled with granular, eosino- philic material that stains with period- ic acid Schiff (PAS)5 with preservation of the alveolar architecture.2 In secondary PAP treatment depends on the underlying cause. Successful lung transplantation has been reported in cases of congenital PAP.5 Whole-lung lavage remains the standard of care for primary PAP, although some patients may respond to subcutaneous GM-CSF at a dose of 5 µg/kg of body weight per day for 6 -12 weeks.5 The natural history of PAP can fol- low one of three pathways: sponta- neous improvement, stable with per- sistent symptoms, or progressive dete- rioration.5 References 1. Manheimer E. Chest roentgenography for car- diovascular evaluation. In: Walker HK, Hall WD, Hurst JW, eds. Clinical Methods. The History, Physical and Laboratory Examinations. New York: Butterworth, 1990: 188. 2. Shah PL, Hansell D, Lawson PR, Reid KBM, Morgan C. Pulmonary alveolar proteinosis: clin- ical aspects and current concepts on pathogene- sis. Thorax 2000; 55: 67-77. 3. Rosen SH, Castleman B, Liebow AA. Pulmonary alveolar proteinosis. N Engl J Med 1958; 258: 1123-1142. 4. Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis. Progress in the first 44 years. Am J Respir Crit Care Med 2002; 166: 215-235. 5. Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med 2003; 349: 2527-2539. 6. Teja K, Cooper PH, Squires JE, Schnatterly PT. Pulmonary alveolar proteinosis in four siblings. N Engl J Med 1981; 305: 1390-1392. 7. Nogee LM, deMello DE, Dehner LP, Colten HR. Deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. N Engl J Med 1993; 328: 406-410. 8. Kitamura T, Tanaka N, Watanabe J. Idiopathic pulmonary alveolar proteinosis as an autoim- mune disease with neutralizing antibody against granulocyte-macrophage colony-stimulating factor. J Exp Med 1999; 190: 875-880.