British Journal of Radiology (2003) 76, 838-840
© 2003 British Institute of Radiology
doi: 10.1259/bjr/33503694
Pulmonary involvement in an adult male affected by type B Niemann-Pick disease
E González-Reimers, MD
1
M J Sánchez-Pérez, MD
1
A Bonilla-Arjona, MD
2
M Rodríguez-Gaspar, MD
1
J L Carrasco-Juan, MD
3
H Alvarez-Argüelles, MD
3 and
F Santolaria-Fernández, MD
1
1 Departments of Internal Medicine, 2 Radiology and 3 Pathology, Hospital Universitario, Tenerife, Canary Islands, Spain
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Abstract
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We report the case of a 39-year-old male patient affected by type B Niemann-Pick disease, in whom pulmonary involvement became evident 15 years after the initial diagnosis. Pulmonary involvement was discovered incidentally during the evaluation of a dry cough and exertional dyspnoea which occurred in the context of an acute febrile, self-limiting illness. In this case, the pulmonary involvement is clinically mild, with minimal alteration of the diffusing capacity for carbon monoxide (DLCO), despite moderate fibrosis and widespread infiltration of both alveoli and interstitium by sea blue histiocytes.
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Introduction
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Type B Niemann-Pick disease is a rare heterogeneous disorder of lipid metabolism, defined by an accumulation of sphingomyelin and other sphingolipids in macrophages, due to a variable deficiency of sphingomyelinase. In most cases, macrophage lipids show a non-specific, intense blue staining with May-Grünwald Giemsa, so the term "sea blue histiocytosis" [1] has been employed to describe this feature. The prognosis of patients with type B Niemann-Pick disease is better than that of those affected by the other forms of this entity; however, in some cases, splenic rupture [2], bleeding tendency [3], liver failure [4] or pulmonary involvement may affect survival. Until now, only 34 cases of Niemann-Pick disease with pulmonary involvement have been described, most of them infants or children; the diagnosis of type B disease was definite in 19 cases, and probable in a further 6 [5]; very few were diagnosed in adulthood. We report the case of a 39-year-old man in whom pulmonary symptoms and radiological changes first appeared 15 years after the diagnosis of type B Niemann-Pick disease.
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Case report
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In 1984 a 22-year-old patient with abdominal pain and swelling, premature satiety, night sweats and rhinorrhoea, attended our hospital. Besides some data indicative of a trivial viral infection, physical examination revealed massive splenomegaly, which crossed the linea alba; laboratory evaluation showed moderate hypersplenism (platelet count, 58 000/mm3, total leucocyte count, 3900/mm3) as the only relevant abnormality. The patient underwent laparotomy and splenectomy; histological examination showed an intense sea blue histiocytosis in the spleen, liver and bone marrow. A low sphingomyelinase activity in fibrobast culture of a skin biopsy of the abdominal wall was consistent with the diagnosis of type B Niemann-Pick disease [6]. Plain-film of the thorax was normal at that time. The patient was discharged from the hospital 1 month later, and since then, had been followed up annually as an outpatient. For 15 years the patient remained well, with normal physical examination and laboratory evaluation, other than a slightly raised serum acid phosphatase concentration (17.9 U l-1 at the time of diagnosis, 6.9–7.4 U l-1 afterwards, normal range 0.1–6.5 U l-1; prostatic fraction 0.9 U l-1).
In December 1999 he complained of a dry cough, aqueous rhinorrhoea, slight fever and exertional dyspnoea when hunting in the central highlands of Tenerife (at an altitude of 2200 m above sea level). A thoracic radiograph examination revealed a diffuse reticulonodular bibasal infiltrate (Figures 1 and 2
); initially, the diagnosis of community acquired pneumonia, was considered. The patient was given a macrolide (azythromycin) antibiotic with no radiological benefit, although the fever, rhinorrhoea and exertional dyspnoea disappeared. Due to the lack of radiological improvement, a high resolution computed tomography (HRCT) of the thorax was performed, which confirmed a reticulonodular infiltrate (Figure 3). Physiological assessment of pulmonary function revealed normal lung volumes (forced expiratory volume in 1 s (FEV1)=3.50 l, 88% predicted; forced vital capacity (FVC)=4.59 l, 90% predicted) and slightly reduced diffusing capacity for carbon monoxide (DLCO)=22.24 ml CO/min/mm Hg, 75% predicted. Fibreoptic bronchoscopy and bronchoalveolar lavage was non-diagnostic, so a thoracoscopy-guided lung biopsy was performed. The biopsy specimen confirmed the diagnosis of pulmonary involvement secondary to Niemann-Pick disease (Figure 4). Both the alveoli and interstitium showed a dense infiltration by sea blue, CD 68 positive histiocytes (Figure 4 a,b), with moderate interstitial fibrosis (Figure 4c). Electronmicroscopy revealed swollen lysosomes containing lamellar spiral-like structures resembling myelin figures (Figure 4d).
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Figure 2. Detailed image of the reticulonodular infiltrate affecting the lower fields of the right lung.
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Figure 3. High resolution CT thoracic scan, with a ground glass pattern accompanied by septal and peribronchovascular interstitial thickening in the lung bases.
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Figure 4. Lung biopsy specimen, showing (a) massive infiltration of alveoli by foamy histiocytes (HE, x 40), (b) massive infiltration by histiocytes which stain sea-blue (arrows) with May-Grünwald Giemsa ( x 200), (c) moderate fibrosis (arrows) of alveolar walls and interlobular septae (Masson-Goldner, x 100) and (d) ultrastructural examination, showing (left) the sea blue histiocytes with numerous dense granules (arrows), which correspond to secondary lysosomes with abundant myelin figures (right).
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The patient is currently well without treatment; without dyspnoea, and normal laboratory evaluation, other than a slightly raised acid phosphatase (6.9 U l-1).
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Discussion
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The patient described was affected by the adult, non-neuropathic form of Niemann-Pick disease, consistent with type B disease, with low sphingomyelinase activity. He presented with an enlarged spleen, incidentally discovered during the evaluation of a mild, probably viral disease, a form of presentation shared by many other cases of type B Niemann-Pick disease. The exact incidence of lung involvement in Niemann-Pick disease is difficult to determine. As a rule, it is rare in adults and more common in the infantile forms of the disease. Indeed, in Minai's review [4], only 8 individuals out the 32 reported ones were older than 25 years, and only in 3 of these cases the diagnosis of type B Niemann-Pick disease was definite. In some cases, pulmonary involvement was probably already present many years before the age at report [3] and showed a mild course; in others, it was severe enough to lead to cor pulmonale [7], whereas other cases, as reported here showed initially, a normal chest X-ray film with pulmonary involvement appearing several years later [4, 8]. The few patients who underwent pulmonary function testing, had either mild to moderate alteration of the DLCO or a restrictive defect [4]. In this sense the pulmonary function tests performed in our patient were normal, other than a minimally impaired diffusing capacity. Also, both the radiological findings on the plain chest radiograph and the HRCT were in accordance with those reported in the medical literature [4, 8, 9, 11], although the ground glass opacity pattern was more marked in the lung bases than in the upper lung, in contrast to other reports [8]. Histological and ultrastructural features are also consistent with the diagnosis of Niemann-Pick disease [10], although our patient showed moderate lung fibrosis, a finding rarely reported in this entity.
In conclusion we report a case of an adult patient affected by type B Niemann-Pick disease, in whom pulmonary involvement became evident 15 years after the initial diagnosis. Pulmonary involvement is clinically mild, with minimal alteration of the DLCO, despite moderate fibrosis and widespread infiltration of both alveoli and interstitium by sea blue histiocytes.
Received for publication July 2, 2002.
Revision received October 14, 2002.
Accepted for publication March 6, 2003.
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References
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Abstract
Introduction
