Amyloidosis are a group of heterogeneous diseases due to protein misfolding and amyloid deposition in various organs and tissues, resulting in a wide range of clinical manifestations depending upon their chemical composition, location, and amount. The most frequent types of amyloidosis are the immunoglobulin light chain (AL) amyloidosis and the serum amyloid A, an acute phase reactant (AA) amyloidosis. The former is associated with plasma cell dyscrasia, while the latter results from longstanding chronic inflammatory/infectious diseases.1 Reports about amyloid involvement of the respiratory tract are scarce.

We report the case of a 52-year-old female with type 2 diabetes mellitus and arterial hypertension who was admitted due to a 6-month history of anorexia, non-bloody diarrhea and weight loss. Upper gastrointestinal endoscopy revealed numerous lymphangiectasias in duodenum mucosa. Histological staining of duodenum biopsy samples showed macrophages containing bacilliform structures positive for periodic acid-Schiff (PAS) staining. The classic diagnosis of Whipple disease (WD) is based on positive PAS staining of duodenal biopsies, but PAS staining can be positive in other circumstances, such as Mycobacterium infection.2 Real time PCR assays for M. avium and M. intracelulare were negative, and fungal structures were not identified in the biopsy specimen.

Despite the negative PCR for Tropheryma whipplei, the suggestive histological findings (but not entirely diagnostic) and the endoscopic characteristic observation, WD was assumed and the patient was treated accordingly. She completed 15 days of intravenous ceftriaxone 2g/od followed by oral cotrimoxazole (CTX) 960mg/bid with clinical improvement. One month later, she presented with acute kidney disease – creatinine 3.54mg/dL [normal range (NR), 0.5–0.9mg/dL], urea 180mg/dL (NR, 10–50mg/dL), hypoalbuminemia 17.5g/L (NR, 38–51g/L) proteinuria 194g/24h (NR, <0.1g/24h) and CTX was changed to doxycycline 100mg bid and hydroxychloroquine 200mg bid was initiated. A kidney biopsy revealed serum amyloid A (AA) amyloidosis. Due to effort dyspnea, an echocardiogram was performed and showed a normal cardiac function (left ventricular ejection fraction 67%) and signs suggestive of infiltrative cardiomyopathy. During a 2-year follow-up, there was a stabilization of renal function with conservative measures (creatinine 3–3.5mg/dL) and no recurrence of gastrointestinal symptoms. Surveillance endoscopies disclosed persistence of lesions suggestive of WD.

After this period, a decrease in breath sounds was noted over the right lung base. The patient was asymptomatic, afebrile, without peripheral edema. A chest radiograph revealed a mild right pleural effusion. A diagnostic thoracocentesis showed a clear light yellow fluid, exudate, glucose 118mg/dL and normal ADA. Cytological analysis showed a mononuclear predominance. Pleural fluid study was negative for malignancy or infection (T. whipplei PCR was negative). Thoracic CT scan revealed unilateral pleural effusion without parenchymal or mediastinal abnormalities. Two percutaneous Abrams needle biopsies of the pleura (with 3 weeks of interval) were negative for malignancy and infection, only demonstrating nonspecific fibrous thickening of the pleura. The thoracoscopy showed hyperaemia and thickening of the costal pleura, and small whitish nodular lesions, that were biopsied (Fig. 1). An apple-green birefringence was noted on Congo-red staining under polarized light, compatible with pleural amyloidosis, mostly with a perivascular pattern (Fig. 2).

Figure 1.

Thoracoscopy reveals small whitish nodular lesions at the costal pleura (circle, arrow).

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Figure 2.

Parietal pleura at polarized light, there is an apple green refringence, confirming the deposition of amyloid substance (magnification ×400).

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Eight months after the thoracoscopy, the pleural effusion recurred. This time, it was bilateral with a moderate volume and a transudate. Despite initiating treatment for WD few months after the beginning of symptoms, the inflammatory process evolved to systemic amyloidosis, which was the major factor contributing to the progressive deterioration of our patient, with cardiac and renal failure. The patient died due to multiple organ failure, after 3 years of follow-up.

Although a definitive diagnosis of WD could not be made, the endoscopic characteristic findings and the response to the antibiotic therapy suggest it as the precursor of the AA amyloidosis.

Pulmonary amyloidosis may present as tracheobronchial infiltration, parenchymal nodules, persistent pleural effusions, and pulmonary hypertension.3,4 Pleural involvement is very rarely reported, and it is usually associated with AL amyloidosis, which accounts for up to 80% of pulmonary amyloidosis.5,6 Typical aspects of thoracoscopy consist of hyperaemia of the pleural surface, inflammation with nodular lesions or brown nodules of the parietal pleura.5,7 Persistent pleural effusions occur in 1–2% of patients with systemic amyloidosis and are usually associated with poor prognosis and often refractory to treatment. Pleurodesis has been effective in some cases.7,8

This case illustrates the difficulty in diagnosing pleural amyloidosis, after two failed needle pleural biopsies. This is probably due to the fact that amyloid deposition is not uniform over the pleural surface. The pleural effusion in our patient may derive from increased fluid production induced by inflammation, interruption of lymphatic drainage caused by amyloid infiltration of the pleura, decreased resorption of fluid from the pleural space due to vascular deposition of amyloid and in the bilateral pleural effusion from congestive heart failure secondary to amyloid infiltration in the heart.5,7

Although in this case the previous diagnosis of amyloidosis supported and incited to actively search for amyloidosis, it should be always kept in mind, as pleural effusion is a rare manifestation of pulmonary involvement but could be the presenting manifestation of amyloidosis.