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Idiopathic Pulmonary Hemosiderosis in a 9-Year-Old Girl

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Idiopathic Pulmonary Hemosiderosis in a 9-Year-Old Girl 112 EUROPEAN JOURNAL OF MEDICAL RESEARCH December 7, 2009 Eur J Med Res (2009) 14(Suppl. IV): 112-115 © I. Holzapfel Publishers 2009 IDIOPATHIC PULMONARY HEMOSIDEROSIS IN A 9-YEAR-OLD GIRL E. Kamienska1, T. Urasinski1, A. Gawlikowska-Sroka2, B. Glura1, A. Pogorzelski2 1Clinic of Pediatrics, Hematology and Oncology, and 2Department of Normal and Clinical Anatomy, Pomeranian Medical University, Szczecin, Poland; 3Institute of Tuberculosis and Lung Diseases, Rabka, Poland Abstract drugs. However, in most of cases this is ineffective Diffuse alveolar hemorrhage (DAH) is a rare and life- [12, 13, 14]. threatening condition characterized by hemoptysis, The estimated incidence of IPH in children is 0.24- dyspnoea, alveolar infiltrates on chest radiograph and 1.23 cases per million, with a mortality rate as high as various degrees of anemia. It may occur either as a 50% [2, 3]. Only about 500 cases of this disease have primary disease of the lungs or a secondary condition been described in medical literature, including 16 cases due to cardiac, systemic vascular, collagen or renal dis- reported in Polish medical journals [9, 10]. The rarity eases. Idiopathic pulmonary hemosiderosis (IPH) is a of this disease and the variable clinical course results separate form of DAH of unknown origin, associated in many diagnostic as well as therapeutic problems and in some cases with celiac disease. The estimated inci- pitfalls. The aim of this paper is to present our obser- dence of IPH in children is 0.24-1.23 cases per mil- vations relating to the diagnosis and treatment of IPH lion, with a mortality rate as high as 50%. Only about in a 9-year-old girl. 500 cases of this disease have been described in med- ical literature. We present a case of a 9-year-old girl di- CASE REPORT agnosed with IPH, which was confirmed by the pres- ence of many hemosiderin-laden macrophages in A 9-year-old, previously healthy girl, at the age of 5 bronchoalveolar lavage obtained by broncho fibero- developed weakness, fatigue, a chronic cough, tran- scopy. Therapy with glucocorticoids was initiated with sient dyspnea, recurrent respiratory tract infections a partial and transient response. Azathioprine and a and anemia. Physical examination at that time revealed gluten-free diet were subsequently introduced. Howev- profound skin and mucous membrane pallor and er, the girl still suffers from recurrent episodes of he- tachycardia with a silent systolic murmur. Laboratory moptysis, dyspnea and anemia. investigations showed anemia with hemoglobin (Hb) level of 5.8 g/dL, hematocrit value (Hct) - 0.22, red Key words: diffuse alveolar, hemoptysis, hemorrhage, blood cells (RBC) - 3.4 T/L, microcytosis, hypochro- hemosiderosis, idiopathic pulmonary mia and poikilocytosis with anulocytosis. The values of mean corpuscular haemoglobin (MCH) mean corpus- INTRODUCTION cular volume (MCV), mean cell haemoglobin concen- tration (MCHC), levels of serum iron and transferritin Diffuse alveolar haemorrhage (DAH) is a rare and life were decreased, and the reticulocyte rate was elevated threatening condition characterized by hemoptysis, (9%). The total iron-binding capacity was also elevat- dyspnea, and alveolar infiltrates on chest radiograph ed. The patient received a red cell transfusion followed and various degrees of anemia [1, 2, 3]. It may occur by prolonged oral iron supplementation. Despite of a either as a primary disease of the lungs or a secondary routine clinical work-up, the cause of the iron defi- condition due to cardiac, systemic vascular, collagen, ciency was not established. Chest X-ray was normal. or renal diseases. Pulmonary hemosiderosis is a very After a few days’ observation, the symptoms subsided rare entity, possibly of the immunologic mechanism, with no specific treatment. Several months later, the causing a defect in the basement membrane of the patient developed episodes of recurrent hemoptysis. pulmonary capillary [4], or of toxic origin [5]. Idio- Purpura, laryngeal disorders, esophagitis and bleeding pathic pulmonary hemosiderosis (IPH) is a diagnosis from the gastrointestinal tract, and congenital heart made by the exclusion of other causes. It should be disease, were excluded. Kidney function tests were confirmed by the presence of many hemosiderin- normal. Chest X-ray revealed no lesions. Due to he- laden macrophages in bronchoalveolar lavage fluid ob- moptysis, the patient was referred to the Institute of tained by bronchofiberoscopy [6]. It occurs in both Tuberculosis and Lung Diseases in Rabka, where adults and children. IPH is in some cases associated bronchofiberoscopy was performed. This showed in- with celiac disease, so patients with idiopathic pul- creased vascularization of the bronchial mucosa, most monary hemosiderosis should routinely be tested for prominent in the middle lobar bronchus (Fig. 1). gluten intolerance. Recently, other concomitant food There was no active bleeding; however, the broncho- allergies have been reported [8]. Treatment is based on scopic picture was typical of diffuse alveolar hemor- glucocorticoids and/or other immunosuppressant rhage. Microscopic examination of the bronchoalveo- December 7, 2009 EUROPEAN JOURNAL OF MEDICAL RESEARCH 113 Fig. 1. Broncho fibero - scopy showing in- creased vasculariza- tion of bronchial mu- cosa. However, antigliadin IgA, IgG and antiendomysial an- tibodies IgGEmA were positive, thus a gluten-free diet was introduced. This treatment modification did not result in a significant improvement. Moreover, due to prolonged glucocorticoid therapy the patient has be- came progressively cushingoid. Glucocorticoids were tapered off and substituted with azathioprine, given at the dose of 5 mg/kg/day. At present, the girl remains on a gluten-free diet and oral azathioprine. However, the treatment result is unsatisfactory. Episodes of alveolar hemorrhage occur at least every 2-3 months, most of them being trig- gered by viral infections of the upper respiratory tract. They are manifested by a cough, hemoptysis and dysp- nea associated with rapid falls in the hemoglobin level and erythrocyte count. Auscultation signs include rales and crepitations. Chest X-ray taken at relapse is usually nonspecific, demonstrating bilateral reticular and nodular opacities (Fig. 2). Up to now these episodes have responded to intravenous administration of methylprednisolone in a dose of 20 mg/kg/day for 5- 7 days. Even if better controlled, the disease is still ac- tive, thus the prognosis remains at least doubtful. DISCUSSION Idiopathic pulmonary hemosiderosis is a condition seen more frequently in children than in adults. Only 20% are adult-onset patients. Moreover, it is suspected Fig. 2. Posteroanterior chest radiography demonstrating pul- that a substantial proportion of this age group is undi- monary infiltrations during an acute phase of Idiopathic pul- agnosed childhood-onset cases. It is probably due to monary hemosiderosis. the fact that iron deficiency anemia may be the first and the only manifestation of IPH, preceding other symptoms and signs by several months [2]. Iron defi- lar lavage fluid revealed the presence of many hemo- ciency anemia is the most common haematologic dis- siderin-laden macrophages. Lung function tests were order seen in childhood. In infants and toddlers it re- within the normal range. Other causes of secondary sults from poor dietary intake of iron and does not re- pulmonary hemosiderosis, including glomerular and quire any additional work-up. However, every child hemolytic syndromes, hemorrhagic purpura, and car- older than 24 months presenting with iron deficiency diac, vascular, rheumatoid, and immunologic disorders anemia should be suspected and evaluated for chronic were excluded. The diagnosis of IPH was made and blood loss. Our patient, when seen for the first time, therapy with glucocorticoids was initiated with partial presented with deep microcytic and hypochromic ane- and transient response. In order to exclude celiac dis- mia and unspecific symptoms and signs from the res- ease serum markers of this condition were also inves- piratory tract, which subsided spontaneously after sev- tigated. Antiendomysial serum IgAEmA was negative. eral days. The patient was routinely evaluated for 114 EUROPEAN JOURNAL OF MEDICAL RESEARCH December 7, 2009 blood loss with a negative result. Hemoptysis, which dren results in several side effects with a potential im- occurred several months later, drew our attention to a pact on growth and development. This could also be pulmonary hemorrhage. observed in our patient, who subsequently developed Pulmonary hemorrhage and hemoptysis are uncom- Cushing’s syndrome. Prednisone was substituted with mon in children. They may be a manifestation of cys- azathioprine, which is a ‘second line’ immunosuppres- tic fibrosis or congenital heart disease, but these caus- sant agent recommended in IPH [2]. The prognosis es, as well as purpura, laryngeal disorders, oesophagitis for patients with IPH seems to improve over time. and bleeding from the gastrointestinal tract were ex- While two decades ago the mean survival was 3 years cluded in our patient. As discussed by Godfrey in his from diagnosis, recent data indicate a 5-year survival review [15], other causes of hemoptysis in children, rate in 86% of cases [2]. Our knowledge about IPH is including diffuse alveolar hemorrhage, are far less still very poor, and there is an urgent need for large common. registries and prospective studies on IPH. However, Gomez-Roman [13] classified diffuse alveolar hem- due
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