Correspondence
Case 3-2007: A Boy with Respiratory Insufficiency
N Engl J Med 2007; 356:2329-2330May 31, 2007
- Article
To the Editor:
In the Case Record of a patient with respiratory insufficiency, presented by Boyer et al. (Jan. 25 issue),1 the discussants do not mention a condition known to be associated with idiopathic pulmonary hemosiderosis and to have implications for its management: celiac disease. The association is referred to as the Lane–Hamilton syndrome.2 It is important to recognize this condition, since treatment of celiac disease with a gluten-free diet could lead to the remission of idiopathic pulmonary hemosiderosis.3 Although both celiac disease and idiopathic pulmonary hemosiderosis are believed to be immunologically mediated, the pathogenetic link between them is not clear. A recent systematic review identified 20 patients with the Lane–Hamilton syndrome.4 Of these, 16 had been prescribed a gluten-free diet, with improvement documented in 12.
Patients with idiopathic pulmonary hemosiderosis should be screened for celiac disease, even in the absence of gastrointestinal symptoms, by means of serologic testing for antiendomysial antibodies. If the test is positive, an intestinal biopsy should be carried out to confirm the disease, because a gluten-free diet is very effective for the regression of both celiac disease and idiopathic pulmonary hemosiderosis.
4 ReferencesRitesh Agarwal, M.D.
Ashutosh N. Aggarwal, M.D.
Dheeraj Gupta, M.D.
Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
ritesh@indiachest.org 1
Case Records of the Massachusetts General Hospital (Case 3-2007). N Engl J Med 2007;356:398-407
Full Text | Web of Science | Medline2
Lane DJ ,Hamilton WS . Idiopathic steatorrhoea and idiopathic pulmonary haemosiderosis. Br Med J 1971;2:89-90
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Malhotra P ,Aggarwal R ,Aggarwal AN ,Jindal SK ,Awasthi A ,Radotra BD . Coeliac disease as a cause of unusually severe anaemia in a young man with idiopathic pulmonary haemosiderosis. Respir Med 2005;99:451-453
CrossRef | Web of Science | Medline4
Agarwal R ,Aggarwal AN ,Gupta D . Lane-Hamilton syndrome: simultaneous occurrence of coeliac disease and idiopathic pulmonary haemosiderosis. Intern Med J 2007;37:65-67
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To the Editor:
Boyer et al. do not mention Behçet's disease among the possible causes of pulmonary hemorrhage. Pulmonary vascular problems, either pulmonary-artery aneurysms or involvement of the small vessels, are the main pulmonary disorders in Behçet's disease. Immunopathological findings indicate that the underlying pathogenesis is pulmonary vasculitis, which may result in thrombosis, aneurysms, infarction, and hemorrhage.1 Moreover, the patient described in the case report was found on esophagoscopy to have a proximal esophageal ulcer. As Dr. Kinane states, idiopathic pulmonary hemosiderosis is likely to be a heterogeneous condition, and an immunologic disorder may ultimately develop from it. It would therefore be interesting to assess the patient's HLA status (the presence or absence of the B51 allele) and perform a pathergy test to better investigate a possible association between Behçet's disease and idiopathic pulmonary hemosiderosis.
1 ReferencesGabriele Rossi, M.D.
Via Como 17, 20095 Cusano Milanino, Italy
gab.rossi@tiscali. it 1
Uzun O ,Akpolat T ,Erkan L . Pulmonary vasculitis in Behcet disease: a cumulative analysis. Chest 2005;127:2243-2253
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To the Editor:
The child with idiopathic pulmonary hemosiderosis described by Boyer et al. fortunately had a response to treatment with hydroxychloroquine and oral corticosteroids. However, some children with idiopathic pulmonary hemosiderosis continue to have episodes of intrapulmonary hemorrhage, despite immunosuppressive therapy. In our unit, an 11-year-old girl with idiopathic pulmonary hemosiderosis had 11 episodes of intrapulmonary hemorrhage over an 18-month period, despite treatment with oral prednisolone (20 to 40 mg once a day), azathioprine (75 mg once a day), and hydroxychloroquine (100 mg twice a day). Since free iron from blood may increase lung-tissue injury mediated by free radicals,1 we measured oxidative stress, using a urinary biomarker (8-oxo-7,8-dihydro-2'-deoxyguanosine)2 over a 6-month period. We found increased levels of oxidative stress during two additional episodes of intrapulmonary hemorrhage (Figure 1Figure 1
Results of Enzyme-Linked Immunosorbent Assay of Urinary 8-Oxo-7,8-Dihydro-2′-Deoxyguanosine, a Marker of Oxidative Stress, in a Patient with Idiopathic Pulmonary Hemosiderosis.). Treatment with the glutathione prodrug acetylcysteine3 (300 mg twice a day) was then started, and 6 months later, the patient remains clinically well while receiving a reduced dose of oral prednisolone (10 mg per day on alternate days). We conclude that the therapeutic potential of antioxidant therapy in children with idiopathic pulmonary hemosiderosis merits further study.3 ReferencesJonathan Grigg, M.D.
Queen Mary University, London E12AT, United Kingdom
j.grigg@qmul. ac. uk Marcus S. Cooke, Ph.D.
Jayachandran R. Panickar, M.D.
University of Leicester, Leicester LE27LZ, United Kingdom1
Halliwell B ,Gutteridge JM . Biologically relevant metal ion-dependent hydroxyl radical generation: an update. FEBS Lett 1992;307:108-112
CrossRef | Web of Science | Medline2
Cooke MS ,Lunec J ,Evans MD . Progress in the analysis of urinary oxidative DNA damage. Free Radic Biol Med 2002;33:1601-1614
CrossRef | Web of Science | Medline3
Tirouvanziam R ,Conrad CK ,Bottiglieri T ,Herzenberg LA ,Moss RB ,Herzenberg LA . High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis. Proc Natl Acad Sci U S A 2006;103:4628-4633
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Author/Editor Response
Agarwal et al. illustrate the important association between idiopathic pulmonary hemosiderosis and celiac disease. Our patient was screened for celiac disease at another hospital and was found to be negative for the disease. We routinely screen similar patients for celiac disease by monitoring for antibodies against transglutaminase.
We agree with Rossi that vasculitis is an important consideration. In our discussion, we emphasize that it is important to rule out vasculitis in cases of idiopathic pulmonary hemosiderosis, and we report that there was no evidence of vasculitis on pathological examination in this case; thus, Behçet's disease was ruled out. It is not listed as a cause of pulmonary hemorrhage in Table 2 of our article because it is exceedingly rare in this group of patients.
We agree with Grigg et al. that free radicals generated by pulmonary hemorrhage may be central to the induction of lung-tissue injury. We do not believe that the cited case proves that acetylcysteine is an effective therapy. We know that patients with idiopathic pulmonary hemosiderosis have long remissions, and the patient described by Grigg et al. could be in one of these remissions.
T. Bernard Kinane, M.D.
Massachusetts General Hospital, Boston, MA 02114James R. Stone, M.D., Ph.D.
Massachusetts General Hospital, Boston, MA 02114Debra Boyer, M.D.
Children's Hospital, Boston, MA 02115- Citing Articles (2)
Citing Articles
1
V. Sanz Santiago, A. López Neyra, M. Castro Codesal, J. Sevilla Navarro, A. García Salido, J.R. Villa Asensi. (2011) Anemia aguda grave recidivante como manifestación principal de una hemosiderosis pulmonar idiopática. Anales de Pediatría 75:1, 75-77
CrossRef2
Gulshan R. Sethi, Kamal K. Singhal, Amarender S. Puri, Mukta Mantan. (2011) Benefit of gluten-free diet in idiopathic pulmonary hemosiderosis in association with celiac disease. Pediatric Pulmonology 46:3, 302-305
CrossRef
