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Clinical Meetings at RH Year 2001

2001 - A Lady with Cough

Dr. Veronica Chan, Dr KS Chan, Pulmonary Unit, Heaven of Hope Hospital

Case Report
Ms HHY is an 80-year-old housewife. She presented to our hospital for intractable cough. She was known to have type-2 diabetes mellitus and cataract. Her condition was stable and enjoyed an active lifestyle.

She began to develop subacute onset of dry cough about a month before admission. The cough was worse on lying down and was associated with progressive shortness of breath. She was admitted to our hospital on 24 March 2001. Physical examination showed a febrile lady with intractable cough, frequently interrupting her speech. Her vital signs were stable, with room air SaO2 of 96%. There was mild inspiratory and expiratory stridor. Crepitations were noted over her right lower lung field. Examination of all other systems was unremarkable.

Investigations revealed leukocytosis (WBC = 28.4, with neutrophil predominance). The ESR was elevated to 82mm/hr. The renal and liver function tests were normal. Sputum culture only showed growth of commensals. Her blood culture revealed Gram negative cocci in cluster from the anaerobic broth. Her CXR (Figure 1) showed collapse and consolidation of her right middle lobe. She was treated as right middle lobe lobar pneumonia with septicaemia. Intravenous Augmentin@ was given. Her fever had favorable response but she remained dyspnoeic with intractable cough. Major airway obstruction was suspected in view of her remarkable cough pattern. Urgent bronchoscopy was performed. The supraglottic region was normal. Her vocal cord was smooth and mobile. Yellowish nodular mucosal growths were observed from the lower third of the lower trachea all the way down to the carina, with dynamic collapse of her major airway during the expiratory phase. The right upper and middle lobe bronchus was completely obliterated by the abnormal mucosal growth, with easy contact bleeding. Biopsy was not attempted due to significant desaturation during the procedure. Bronchial trap for AFB, cytology and culture were negative.



Urgent CT thorax (Figure 2) showed nodular growth projecting from the carina, obliteration of the proximal part of the right main bronchus, with collapse of right upper and middle lobe. There was a moderate amount of right pleural effusion. No parenchymal lung lesion or lymphadenopathy was detected. Liver, spleen and adrenal glands were normal; intra-abdominal lymph nodes were not enlarged.



Right pleural tap only revealed transudative fluid, which was negative for AFB, cytology and culture. Pleural biopsy did not show any evidence of granuloma or malignancy.

The infiltration of the tracheobronchial wall resulting in increased main airway compliance and dynamic collapse during expiration is better known as tracheobronchial malacia. The differential diagnosis for tracheobronchial malacia [1] is shown in Table 1.

Dexamethasone was then prescribed aiming to reduce airway edema. She had a partial response with reduced cough and dyspnoea. Second bronchoscopy with bronchial biopsy over the right main bronchus showed that the subepithelial tissue was almost completely replaced by deposition of amyloid tissue. Specific stain confirmed AL type amyloid. There were no inflammatory reaction, nor malignancy. The features were compatible with tracheobronchial amyloidosis (Figure 3).



The patient later deteriorated with fever and worsening shortness of breath. Chest X-ray showed cavitatory lesions over right middle lobe and left upper lobe, which were compatible with post-obstruction lung abscess. She responded well to a course of intravenous antibiotic with Cloxacillin and Gentamycin.

A series of investigations was done to look for myeloma or monoclonal gammopathy. Urine did not reveal any Bence Jones protein, and serum protein electrophoresis did not show any monoclonal band. Immunoglobulin pattern only revealed marginally low IgG level, with normal IgA and IgM. Echocardiogram did not have the pathognomonic sparkling echogenicity. Ultrasound kidney was normal and 24-hour urine only revealed proteinuria of 0.5 g/day, which was mostly accountable by her diabetes. Finally, pyrophosphate scan showed some increased uptake in the pericardium and liver (Figure 4). We concluded that the patient was suffering from AL type tracheobronchial amyloidosis, probably with some systemic involvement.



Discussion
Amyloidosis of the respiratory tract is a rare clinical condition [1]. It can be further subdivided into the following types: I.Laryngeal amyloidosis, which mainly involves the supraglottic larynx, causing hoarseness of voice and stridor. 2. Parenchymal amyloidosis, also called amyloidoma, is mostly asymptomatic with a benign course. Mediastinal and hilar amyloidosis, is mostly associated with systemic amyloid deposits. 4. Tracheobronchial amyloidosis, which is characterized by nodular or diffuse infiltrative deposits over the tracheobronchial tree. In most situations, respiratory amyloidosis is of the AL type.

Tracheobronchial amyloidosis is an extremely rare condition. Less than 100 cases had been reported in the literature [2,3]. It typically presents in the fifth decade, with no sex difference.The main presenting symptoms include dyspnoea, cough, haemoptysis, hoarseness of voice and wheezing. Narrowing of the airways can also cause distal atelectasis or recurrent pneumonia. Pulmonary function test does not have any consistent pattern. CT scan often demonstrates multiple nodules protruding from the wall of trachea and/or large bronchi, causing diffuse rigid narrowing of long tracheal segment. The gold standard for diagnosis is made by bronchoscopy with biopsy.

During bronchoscopy, the appearance of amyloid deposits ranges from circumscribed, superficial yellow lesions to erythematous, raised, cobblestone infiltration of airway mucosa. They tend to bleed very readily on biopsy.

Histologically, amyloid deposits in the bronchial biopsy specimen stain with Congo red and give the pathognomonic apple-green birefringence under crossed-polarized light (4). The Congo red histology should be followed by immunochemical stain to determine the amyloid type. In most of the reported cases of tracheobronchial amyloidosis, search for systemic amyloidosis failed to reveal any association with systemic amyloid involvement (2-3).

New scintigraphic examination using iodine-123 lablelled serum amyloid P component (SAP) has been developed with much higher sensitivity and specificity to look for systemic amyloid involvement. SAP is a co-deposition substance present in all amyloid deposits. It carries important role in fibrillogenesis and protection from degradation. The iodine-labelled SAP can rapidly and specifically localize the amyloid deposits, proportional to the quantity of amyoid present [5-6]. It is also the only method for serial monitoring of the progress of amyloidosis.

However, SAP scintigraphy in not widely available. Some has documented the use of Tc-99m pyrophosphate or HDP/HMDP whole body imaging bone scan as an alternative method. Although it is quite sensitive, there is non-specific uptake of the pyrophosphate isotope in the liver, spleen, heart and major airway (7).

Treatment of tracheobronchial amyloidosis depends on the degree of airway compromise. Spontaneous regression of diffuse tracheobronchial amyloidosis had been reported with simple observation. But most patients have progressive or recurrent disease. Tracheostomy is often required for upper airway involvement. Many patients rely on repeated sessions of bronchoscopic debulking, dilatation and stenting. This carries considerable risks of significant bleeding. YAG laser resection had also been reported with efficacy, but it is limited to trachea and the proximal bronchi only (8). External beam radiation could also be considered as a treatment option (9). Chemotherapy had been used for primary systemic amyloidosis, but experience on localised tracheobronchial amyloidosis is still inconsistent.

Despite the new treatment modalities, outcome for tracheobronchial amyloidosis is still poor [2,3]. In the 10 patients of the Boston series, 6 had recurrent symptoms, 4 required tracheostomy and 3 died, (2 from respiratory insufficiency and 1 from pneumonia). In 17 patients of the Mayo Clinic series, 6 had recurrent symptoms, 4 required tracheostomy, and 5 died, (2 from amyloid involvement and 3 from unrelated disease).

Conclusion
We presented a case of tracheobronchial amyloidosis. It is a rare clinical condition. The clinical presentation, investigation, treatment and clinical outcome were reviewed in detail.

References
  1. 1 Case records of the Massachusetts General Hospital: weekly clinicopathological exercise. New England Journal of Medicine 1999; 341(17):1292-1299.
  2. Gillmore JD, Hawkins PN. Amyloidosis and the respiratory tract. Thorax 1999; 54:444-4451.
  3. Capizzi SA, Betancourt E, et al. Tracheobronchial amyloidosis. Mayo Clinic Proceedings 2000; 75(11):1148-1152.
  4. O'Regan A, Fenlon HM, et al. Tracheobronchial amyloidosis: The Boston University experience from 1984 to 1999. Medicine (Baltimore) 2000; 79(2):69-79.
  5. Pepys MB. Amyloidosis. In: Weatherall DJ, Ledingham JGG, Warrell DA, eds. Oxford textbook of medicine. 3rded. Oxford: Oxford University Press, 1995:1512-1524.
  6. Hawkins PN, Myers MJ, et al. Diagnostic radionuclide imaging of amyloid: biological targeting by circulating human serum amyloid P component. Lancet 1998; 1(8600): 1413-1418.
  7. Hawkins PN, Lavender JP, et al. Evaluation of systemic amyloidosis by scintigraphy with l23I-labeled serum amyloid P components. New England Journal of Medicine 1990; 323(8):542-543.
  8. Yamamoto T, Maeda M, et al. Primary diffuse tracheobronchial amyloidosis: radiologic findings. Thoracic Imaging 2001; 16(3):177-180.
  9. Herman DP, et al. The treatment of tracheobronchial amyloidosis using a bronchial laser. Apropos of a series of 13 cases. Revue des Maladies Respiratories 1985; 2(1): 19-23.
  10. Kurrus JA, et al. Radiation therapy for tracheobronchial amyloidosis. Chest 1998; 114(5): 1489-1492.
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