Radiology Abstract Löffler’s syndrome was initially described as a disorder characterised by transient pulmonary infiltrates accompanied by peripheral blood eosinophilia in asymptomatic or mildly ill patients. Abnormal chest radiographic findings are said to occur in 95% of patients but there are no descriptions of CT findings. There are many causes of this syndrome, but in developing countries the most common presentation remains sec- ondary to the migratory larvae of common intestinal helminths. We present the clinical and radiological features of a boy with clearly defined Löffler's syndrome due to larval migration. Introduction Löffler’s syndrome was initially described by the Swiss internist Wilhelm Löffler (1887 - 1972) as a clinical disorder characterised by tran- sient pulmonary infiltrates accom- panied by peripheral blood eosino- philia in asymptomatic or mildly ill patients. Migratory pulmonary infil- trates are recognised in many lung diseases1 and the term Löffler’s syn- drome is used interchangeably with a myriad of other different names; these include, ‘simple pulmonary eosinophilia’, ‘cryptogenic eosino- philic pneumonia’, ‘larval pneumoni- tis’, ‘pulmonary infiltrates with eosinophilia (PIE)’, and ‘Löffler’s pneumonia’. Dr Wilhelm Löffler also described a condition of fibroplastic parietal endocarditis with eosinophil- ia which further complicates the cor- rect use of terminology. Eosinophilic pulmonary reactions are typical of the immediate Type I allergic response,1 which may be induced by differing factors includ- ing allergic bronchopulmonary mycoses, parasitic infestations, drug reactions, eosinophilia-myalgia syn- drome, Löffler’s syndrome, chronic eosinophilic pneumonia, allergic granulomatosis of Churg and Strauss, hypereosinophilic syndrome, and acute eosinophilic pneumonia.2 Non- infectious causes include drug reac- tions (to penicillin, the sulphonamides, aminosalicylic acid, nitrofurantoin),3 smoke and dust inhalation (mouldy hay, zinc chloride, beryllium, nickel), collagen vascular diseases (polyarteri- tis nodosa, rheumatoid arthritis, sys- temic lupus erythematosis) and neo- plastic disorders (Hodgkin’s disease). Infectious causes of Löffler’s syn- drome include protozoa, fungi, bacte- ria and helminths.1 In developing countries with high parasitic loads, helminthic causes predominate. The majority of worms implicated are nematodes, including Strongyloides stercoralis, Ascaris lumbricoides, Toxo- cara canis, Schistosoma mansoni, Paragonimus westermani, Wuchereria bancrofti, Dirofilaria immitis, Trichuris trichiura and Fasciola hepat- ica.1 This case study and brief review will concern itself only with Löffler’s syndrome occurring as a consequence of larval migration through the lung. A spectrum of disease severity may result as a consequence of this phase in the nematode life cycle involving one or more of the following: cough with or without sputum, haemopty- sis, prolonged expiration and wheez- ing, dyspnoea, chest pain, occasional rales, and pleural and pericardial effu- sion. Abnormal chest radiographic findings are said to occur in 95% of CASE REPORT 27 SA JOURNAL OF RADIOLOGY • February 2005 Imaging findings in a patient with eosinophilic pneumonia (Löffler’s syndrome) S Andronikou MB BCh, FCRad (Diag) (SA), FRCR (Lond) Department of Paediatric Radiology Red Cross Children’s Hospital and University of Cape Town G du Toit MB BCh, DCH, MMed, FCP, FRCPCH D Allergy Department of Paediatric Allergy and Immunology Imperial College at St Mary’s Hospital London M Carrighal MB ChB, DCH, FC Paeds A Argent MB BCh, FC Paeds, MMed (Paed), DCH Department of Paediatrics Red Cross Children’s Hospital and University of Cape Town Radiology 2/24/05 4:50 PM Page 27 patients. We present the clinical and radiological findings of a young child who experienced severe respiratory compromise due to larval-induced pulmonary eosinophilia. To the best of our knowledge high-resolution computed tomography (HRCT) find- ings have not been described previ- ously for Löffler’s syndrome as a con- sequence of larval migration. Case report A previously well 26-month-old boy presented with fever and acute severe respiratory distress, for which he required intubation and ventilato- ry support. Initial investigations revealed a microcytic hypochromic anaemia (Hb 10.1 g/dl, MCV 73 fl), with an elevated WCC of 23.1 × 109/l and peripheral blood eosinophilia of 26%. Erythrocyte sedimentation rate was 39 mm/hour. Bronchoalveolar lavage revealed 57% eosinophilia. Further investigations revealed positive Toxocara canis serology (immunoglobin G enzyme-linked immunosorbent assay > 100 units; normal < 0 units) and Ascaris lumbri- coides adults and ova were present in his stool. Serial chest radiography demon- strated flitting bilateral patchy opacifi- cation. A HRCT was performed in the subacute phase of the disease. This demonstrated bilateral, asymmetrical, patchy, peripheral, upper and lower zone areas of interlobular septal thick- ening with associated areas of air- space disease in the central rather than peripheral dependent areas of the lungs (Figs 1a and b). There was rela- tive sparing of the anterior or non- dependent areas of the lungs. The sep- tal thickening outlining the secondary pulmonary lobules was smooth, as was the thickening around the bron- chovascular bundles. No ground glass attenuation was noted, but the HRCT was performed during the subacute phase of the illness at which time clin- ical and radiological resolution was occurring. The patient responded rapidly to corticosteroid and anti- helminthic therapy, and at follow-up was asymptomatic with a clear chest radiograph. Discussion We report the case of a young boy who presented with life-threatening Löffler’s syndrome secondary to para- sitic infestation. Although our patient met many of the diagnostic criteria for acute eosinophilic pneumonia4 (Table I), a parasitic cause was unequivocally established. In making a diagnosis of Löffler’s syndrome, heavy reliance is frequently placed on radiological fea- tures. Chest radiographs obtained during the migratory phase classically demonstrate fine miliary nodules or diffuse, reticulonodular interstitial areas of increased opacity. With the development of heavier infestation, bilateral, patchy air-space / alveolar areas of increased opacity and seg- mental or even lobar areas of opacifi- cation may develop. Serial radi- ographs may show migration of areas of increased opacity. Such findings are associated with several pulmonary processes, but the presence of filari- form larvae in the sputum, bronchial washings, or lung biopsy specimens is diagnostic. Striking sputum and peripheral blood eosinophilia is often associated. The presence of eggs of the causative nematode, except in early infestation or with a population of purely male worms, further strength- ens the diagnosis of Löffler’s syn- drome secondary to migratory larvae. The HRCT findings of helminth- associated pulmonary eosinophilic pneumonitis (Löffler’s syndrome) have not been reported. HRCT is gen- erally more useful than plain radi- ographs in defining severity and extent of diffuse lung disease.5 HRCT findings have, however, been reported for drug-induced pulmonary eosino- philia and include bilateral, non-seg- mental, peripheral areas of ground- glass attenuation or consolidation, indistinguishable from those seen in organising pneumonia, typically involving the upper lobes.3,6,7 The find- ings may be difficult to distinguish from adult respiratory distress syn- drome, overhydration pulmonary 28 SA JOURNAL OF RADIOLOGY • February 2005 CASE REPORT Fig. 1a. Figs .1a and b. High resolution CT scan findings of the chest. (a) Upper zone patchy areas of interlobular septal thickening, right worse than left, with associated areas of air-space disease. Fig. 1b. (b) Mid/ lower zone scan demonstrating patchy, predominantly peripheral and basal inter- lobular septal thickening outlining the secondary pulmonary lobules. There are associated central and dependent areas of dense air-space disease. The anterior portions of the lung are relatively spared. Radiology 2/24/05 4:50 PM Page 28 CASE REPORT 29 SA JOURNAL OF RADIOLOGY • February 2005 oedema or atypical bacterial or viral pneumonia.8,9 Our HRCT findings correspond with the histological reports of pulmonary eosinophilia and Löffler’s disease, which demon- strate thick alveolar walls and intersti- tial infiltration by eosinophils, lym- phocytes and plasma cells.1,3 Alveolar spaces contain aggregates of histio- cytes and numerous eosinophils.1 In contradistinction to Wegner’s dis- ease, which also has pulmonary eosinophilic infiltrates, eosinophilic pneumonia preserves the lung archi- tecture.1 True hypersensitivity pneu- monitis (usually caused in children by exposure to numerous bird antigens) shows ground-glass attenuation, but has centrilobular nodules.6,10 HRCT findings have been report- ed for numerous diffuse lung diseases in children including bronchiolitis obliterans, hypersensitivity pneu- monitis, recurrent aspiration, Langer- hans cell histiocytosis, idiopathic pul- monary haemosiderosis, pulmonary alveolar proteinosis, lymphangioleio- myomatosis, congenital lymphangiec- tasia, alveolar microlithiasis, pul- monary vein atresia, capillary heman- giomatosis, Gaucher’s disease, Nieman- Pick disease, as well as for the idio- pathic pneumonitides (desquamative interstitial pneumonitis (DIP), nor- mal interstitial pneumonitis (NIP), lymphocytic interstitial pneumonitis (LIP), and chronic organising pneumonitis (COP)/ bronchiolitis obstructive organising pneumonitis (BOOP).5-7,10 The HRCT findings in our patient correspond with those reported for drug-induced pul- monary eosinophilic pneumonia, except for the absence of ground-glass attenuation. Ground-glass attenua- tion is a nonspecific finding in many diffuse lung diseases of childhood, usually indicating reversible or poten- tially reversible disease.6 The absence of this finding in our patient is proba- bly due to the scan being performed during the subacute period of the dis- ease when acute alveolitis may have resolved spontaneously or on treat- ment. Follow-up HRCT may be use- ful in identifying chronic interstitial changes and possible fibrosis and as suggested by the HRCT findings in the sub-acute period, may also demonstrate improvement by demon- strating resolution of ground-glass attenuation. References 1. Bedrossian CW, Greenberg SD, Williams LJ jun. Ultrastructure of the lung in Loeffler’s pneumonia. Am J Med 1975; 58: 438-443. 2. Tazelaar HD, Linz LJ, Colby TV, Myers JL, Limper AH. Acute eosinophilic pneumonia: histopathologic findings in nine patients. Am J Respir Crit Care Med 1997; 155: 296-302. 3. Cleverley JR, Screaton NJ, Hiorns MP, Flint JD, Muller NL. Drug induced lung disease: high- resolution CT and histological findings. Clin Radiol 2002; 57: 292-299. 4. Badesch DB, King TE jun, Schwarz MI. Acute eosinophilic pneumonia: a hypersensitivity phenomenon? Am Rev Respir Dis 1989; 145: 716-718. 5. Copley SJ, Coren M, Nicholson AG, Rubens MB, Bush A, Hansell DN. Diagnostic accuracy of thin-section CT and chest radiography of pediatric interstitial lung disease. Am J Roentgenol 2000; 174: 549-554. 6. Lynch DA, Hay T, Newell JD jun, Divgi VD, Fan LL. Pediatric diffuse lung disease: diagnosis and classification using high resolution CT. Am J Roentgenol 1999; 173: 713-718. 7. Erasmus JJ, McAdams HP, Rossi SE. High-reso- lution CT of drug-induced lung disease. Radiol Clin North Am 2002; 40(1):61-72. 8. King MA, Pope-Harman AL, Allen JN, Christoforidis GA, Christoforidis AJ. Acute eosinophilic pneumonia: radiologic and clinical features. Radiology 1997; 203(3):715-719. 9. Cheon JE, Lee KS, Jung GS, Chung MH, Cho YD. Acute eosinophilic pneumonia: radi- ographic and CT findings in six patients. Am J Roentgenol 1996; 167: 1195-1199. 10. Kuhn JP, Brody AS. High resolution CT of pedi- atric lung disease. Radiol Clin North Am 2002; 40(1): 89-110. Table I. Proposed diagnosxtic criteria for acute eosinophilic pneumonia2 Acute febrile illness (days, rarely weeks in duration) Hypoxaemic respiratory failure Diffuse alveolar/mixed alveolar interstitial radiographic changes Bronchoalveolar lavage — eosinophils > 25%, or biopsy confirmation of eosinophilic lung infiltrates* No identifiable infection Prompt and complete response to steroids Failure to relapse after discontinuation of steroids *Biopsy evidence of acute and/or organising diffuse alveolar damage with eosinophils is the most characteristic feature, but marked tissue eosinophilic infiltrate with clinical confirmation of the history is also sufficient. Radiology 2/24/05 4:50 PM Page 29