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CASE REPORT
Year : 2016  |  Volume : 7  |  Issue : 1  |  Page : 59-62

Ceelen-Gellerstedt syndrome in an elderly Indian man: Case report of an unusual case


1 Department of Radiodiagnosis, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India
2 Department of Chest Medicine, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India
3 Department of Pathology, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India
4 Department of Intensive Medicine, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India

Date of Web Publication21-Jan-2016

Correspondence Address:
Santosh Rai
Department of Radiodiagnosis, KMC Hospitals, Ambedkar Circle, Kasturba Medical College (Unit of Manipal university), Mangalore - 575 001, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0975-9727.174675

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  Abstract 

Ceelen-Gellerstedt syndrome, also known as idiopathic pulmonary hemosiderosis (IPH), is a rare disease characterized by recurrent pulmonary alveolar hemorrhages associated with a classical clinical triad of hemoptysis, unexplained iron deficiency anemia, and diffuse pulmonary infiltrates on imaging. We present a case report of Ceelen-Gellerstedt syndrome in an elderly 69-year-old Indian male patient, which is an unusual case as the condition is more common in children and young adults. Diagnosis was suspected on high-resolution computed tomography (HRCT) scan, which revealed diffuse areas of consolidation, ground glass opacities, and septal thickening with perihilar and basal predominance and further workup with bronchoscopy and bronchoalveolar lavage helped to confirm the diagnosis.

Keywords: Ceelen-Gellerstedt syndrome, diffuse pulmonary hemorrhage, hemoptysis, idiopathic pulmonary hemosiderosis (IPH), unexplained iron deficiency anemia


How to cite this article:
Prabhu S, Rai S, Acharya V, Lobo F, Hanaganahalli SB, Prabhu D. Ceelen-Gellerstedt syndrome in an elderly Indian man: Case report of an unusual case. Muller J Med Sci Res 2016;7:59-62

How to cite this URL:
Prabhu S, Rai S, Acharya V, Lobo F, Hanaganahalli SB, Prabhu D. Ceelen-Gellerstedt syndrome in an elderly Indian man: Case report of an unusual case. Muller J Med Sci Res [serial online] 2016 [cited 2022 Jan 21];7:59-62. Available from: https://www.mjmsr.net/text.asp?2016/7/1/59/174675


  Introduction Top


Ceelen-Gellerstedt syndrome, [1] also known as idiopathic pulmonary hemosiderosis (IPH), is a rare disease entity of unknown etiology characterized by recurrent pulmonary alveolar hemorrhages associated with a classical clinical triad of hemoptysis, unexplained iron deficiency anemia, and diffuse pulmonary infiltrates on imaging [chest radiograph/computed tomography (CT) scan]. We present a rare case report of Ceelen-Gellerstedt syndrome in an elderly patient, which is unusual considering that the condition is more common in children and young adults. [2],[3] The diagnosis was confirmed on pathological evaluation of the bronchoalvelolar lavage.


  Case Report Top


A 69-year-old Indian male had presented with severe breathlessness of 1-month duration to our emergency department. At admission, the patient gave a history of recurrent episodes of cough and progressive breathlessness for over 1 year with exertional dyspnea. There was no associated chest pain, palpitations, or abdominal pain. The patient was a chronic smoker and hypertensive on regular treatment. He had no relevant occupational history or past history of similar complaints. On examination, the patient had mild pallor and was afebrile with normal pulse and blood pressure. Tachypnea was present with respiratory rate of 30 breaths/min with 60% peripheral capillary oxygen saturation (SpO 2 ) at room air. Bronchial breath sounds were noted on auscultation with few crepitations; however, air entry was equal bilaterally. The rest of the systemic examination was unremarkable.

Arterial blood gas analysis showed respiratory alkalosis with hypoxia (FIO 2 -21%, pH-7.52, pCO 2 31 mmHg, pO 2 45.6 mmHg, ctHb 13.5 g/dL, SO 2 85.4%,). The chest radiograph [Figure 1]a showed bilateral, diffusely scattered, patchy infiltrates. The patient was admitted to the intensive care unit and put on bilevel positive airway pressure with oxygen by the nasal cannula. Blood investigations revealed elevated total counts (15,000 cells/mm 3 ) with normal hemoglobin (13.4 g/dL) and platelet count (5.63 lakhs/mm 3 ). Other tests such as renal and liver function tests, urine routine, and microscopy were within normal limits. Sputum acid-fast bacillus (AFB) smear and echocardiography were normal. The patient was later taken for a chest high-resolution computed tomography (HRCT) scan, which revealed diffuse areas of air space consolidation (with relatively dense Hounsfield units of about 60) with ground glass densities mainly in bilateral perihilar and basal predominance with smooth interlobular interstititial thickening [Figure 1]b-d. No significant lymphadenopathy or pleural effusion was present. Based on the HRCT findings, a diagnosis of diffuse pulmonary hemorrhage was suspected.
Figure 1: (a) Chest radiography reveals areas of dense consolidation and ground glass opacity in the right lung and left lower zone (b-d) HRCT chest axial section demonstrates diffuse areas of consolidation, ground glass densities, and interlobular septal thickening in bilateral lower lobes and the right middle lobe (e) (insert) showing haemorrhagic bronchoalveolar lavage fluid

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Brochoscopy with bronchoalveolar lavage was later performed. Bronchoscopy showed copious hemorrhagic secretions in the trachea, carina, and segmental bronchi. Bronchoalveolar lavage [Figure 1]e insert returns showed a sequential increase in hemorrhagic fluid density in the aspirated fluid during the bronchoscopic procedure. Bronchoalveolar lavage fluid (BAL) fluid microscopy later demonstrated hyperplastic clusters of endobronchial cells in clusters/singles with alveolar dust laden macrophages/siderophages [Figure 2]a. The background showed many acute and chronic inflammatory cells, red blood cells (RBCs), and eosinophils. Gram stain of BAL centrifuge showed polymorphonuclear lymphocytes. Perls stain was positive in alveolar hemosiderin laden macrophages/histiocytes [Figure 2]b. BAL cytology showed no malignant cells and culture sensitivity showed no growth. BAL fungal smear (KOH mount) was negative for fungal elements. BAL fluid was negative for AFB or pneumocystis carinii pneumonia.
Figure 2: (a) Bronchoalveolar lavage fluid: Cluster of bronchial epithelial cells with squamous cells and pigment laden macrophages. (Pap stain; 200x) (b) Perls stain showing hemosiderin laden alveolar macrophages (Perls stain; 400x)

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Blood antinuclear antibody (ANA), anti-glomerular basement membrane (anti-GBM), and antineutrophil cytoplasmic antibody (ANCA) were negative by immunoflorescence. Workups for rheumatologic diseases, hypersensitivity pneumonitis, granulomatous disorders, and bleeding disorders were negative. Hence, a diagnosis of IPH was considered. The patient was started on pulse therapy of parenteral steroids with parenteral broad-spectrum antibiotics and during the course of hospital stay; he had clinical improvement and was discharged on request. However, the patient presented with similar complaints a fortnight later and got readmitted. One month later after protracted course and clinical and radiological worsening, the patient expired.


  Discussion Top


Virchow in 1864 first described the pathological findings of IPH as "brown lung induration." However, detailed characterization of IPH was made much later in 1931 by Ceelen, who published the autopsy findings of two children who had large amounts of hemosiderin in their lungs. It was only in 1944 that first antemortem clinical and radiological diagnosis was described by Waldenstrom.[3]

Ceelen-Gellerstedt syndrome is more common in children with 80% of the cases occurring below the age of 10 years (usually 1-7 years) with pediatric incidence of 0.24-1.23 cases per million and a high mortality rate of 50%. [3],[4] No gender preference or racial propensity is known. [3],[5] Anemia and dyspnea are the most common clinical features in children (incidences of 64% and 68%, respectively) while hemoptysis occurred in only 50% of the patients as children frequently swallow their sputum. [6]

Only 20% of cases are adult-onset IPH, with incidence more common in young adults. Most reported cases have occurred before 30 years of age with a mild male predominance. [3] Only few cases are reported in middle-aged individuals and the elderly. Nine cases were reported in middle-aged men with a mean age of 56.1 ± 4.2 years by Ercan Kocakoc et al. in 2003. [5] The authors in the same article added that as there were few reports about collective cases in adults, the details are yet to be determined. In adult-onset IPH, sudden-onset dyspnea and hemoptysis are the presenting complaints and anemia is relatively uncommon. [7]

The clinical course may vary from being fatal in the early phase of the disease due to severe pulmonary hemorrhage or may progress to relapses and remissions leading to chronic pulmonary fibrosis, respiratory insufficiency, and death. [5] Long-term prognosis of IPH is poor. [6]

Radiological manifestations include diffuse dense acinar pattern characterized by air space consolidation and ground glass opacities with perihilar and basal predominance. During remission, consolidations usually resolve or progress to a reticular pattern. In the chronic phase, HRCT is valuable in evaluating fibrosis and septal thickening caused due to recurrent pulmonary hemorrhages. HRCT chest findings are relatively nonspecific as pulmonary edema, acute respiratory distress syndrome (ARDS), or other causes of alveolar hemorrhage will show similar CT findings. However, lymphadenopathy or pleural effusion is not common in IPH. [5]

Diagnosis of IPH in adults is by excluding other causes of diffuse alveolar hemorrhage. The differential diagnosis includes other causes of diffuse pulmonary hemorrhage such as immune complex-mediated and connective tissue disorders (Goodpasture syndrome, Wegener's granulomatosis, systemic lupus erythematosus), coagulation disorders, acute respiratory distress syndrome, and secondary pulmonary hemosiderosis due to cardiac conditions (mitral stenosis, etc.), lung malignancy, or following bone marrow transplantation. Bronchoscopy with alveolar lavage helps to diagnose IPH by demonstrating hemosiderin-laden macrophages (siderophage) using Prussian blue reaction (Perls reaction), which stains ferric iron contained in hemosiderin. The gold standard for confirmation is lung biopsy, which confirms the presence of numerous siderophages in the alveoli while excluding pulmonary vasculitis, granulomatous inflammation, or deposition of immunoglobulins. [3]

There is usually a long delay (4 months to 10 years) between the final diagnosis of IPH and the start of the symptoms [8] with delay being due to several factors such as insidious onset, lack of awareness about the condition, or the condition being mislabeled as iron deficiency anemia in children, especially if the respiratory signs are mild. [6] Once diagnosed the clinical course of IPH is also extremely variable, with some patients getting recurring pulmonary hemorrhage despite aggressive therapy. Therapeutic regimens in IPH are still controversial and corticosteroids have been thought to be effective in decreasing the frequency of hemorrhage, relapses, and pulmonary fibrosis progression, thus increasing the survival rate. [3],[8],[9] Treatments with prednisolone, azathioprine, and hydroxychloroquine have been shown effective in prolonging survival. [8],[9] Multiple blood transfusions for severe anemia may be required in IPH patients. [8]

The clinical course may vary from being fatal in the early phase of the disease due to severe pulmonary hemorrhage or may progress to relapses and remissions leading to chronic pulmonary fibrosis, respiratory insufficiency, and death. [5] Long-term prognosis of IPH is generally poor due to the development of severe pulmonary fibrosis. However, over the last decade with aggressive immunosuppressive therapy the 5-year survival has improved to 86% as reported by Saeed et al. {10} Another case study by Ercan Kocakoc et al. of nine middle-aged patients showed good prognosis in adult patients with no recurrence during the follow-up period of 45.2 ± 6.2 months.[7]

In children presenting with iron deficiency anemia with/without hemoptysis and bilateral chest infiltrates, a pediatrician needs to rule out IPH/Ceelen-Gellerstedt syndrome. In summary, even in an elderly patient presenting with unexplained dyspnea with/without frank hemoptysis and CT findings suggestive of diffuse alveolar involvement in the absence of mediastinal adenopathy or pleural effusion, the possibility of Ceelen-Gellerstedt syndrome needs to be suspected and further evaluation should be suggested by bronchoscopy and bronchoalveolar lavage to confirm the diagnosis.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.

 
  References Top

1.
Fendel A, Tremper J, Horger M. Idiopathic hemosiderosis of the lung, synonym is Ceelen-Gellerstedt syndrome. Rofo 2002;174:653-5.  Back to cited text no. 1
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2.
Pinto M, Correia J, Leal I, Reis A, Leão B, Carvalho S, et al. Hemossiderose pulmonar idiopática. Acta Med Port 1996;9:41-4.  Back to cited text no. 2
    
3.
Ioachimescu OC, Sieber S, Kotch A. Idiopathic pulmonary haemosiderosis revisited. Eur Respir J 2004;24: 162-70.  Back to cited text no. 3
    
4.
Saeed MM, Woo MS, MacLaughlin EF, Margetis MF, Keens TG. Prognosis in pediatric idiopathic pulmonary hemosiderosis. Chest 1999;116:721-5.  Back to cited text no. 4
    
5.
Kocakoc E, Kiris A, Sen Y, Bozgeyik Z. Pediatric idiopathic pulmonary hemosiderosis diagnosed by sputum analysis: Plain radiography and computed tomography findings. Med Princ Pract 2003;12:129-32.  Back to cited text no. 5
    
6.
Taytard J, Nathan N, de Blic J, Fayon M, Epaud R, Deschildre A, et al.; French RespiRare® group. New insights into pediatric idiopathic pulmonary hemosiderosis: The French RespiRare® cohort. Orphanet J Rare Dis 2013;8:161.   Back to cited text no. 6
    
7.
Miwa S, Imokawa S, Kato M, Ide K, Uchiyama H, Yokomura K, et al. Prognosis in adult patients with idiopathic pulmonary hemosiderosis. Intern Med 2011;50:1803-8.  Back to cited text no. 7
    
8.
Kiper N, Göçmen A, Ozçelik U, Dilber E, Anadol D. Long-term clinical course of patients with idiopathic pulmonary hemosiderosis (1979-1994): Prolonged survival with low-dose corticosteroid therapy. Pediatr Pulmonol 1999;27:180-4.  Back to cited text no. 8
    
9.
Kabra SK, Bhargava S, Lodha R, Satyavani A, Walia M. Idiopathic pulmonary hemosiderosis: Clinical profile and follow up of 26 children. Indian Pediatr 2007;44:333-8.  Back to cited text no. 9
    


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