Amyloidosis occurs when normally soluble proteins misfold into sticky, beta-sheet-rich structures that aggregate into insoluble fibrils. These fibrils accumulate in tissues, disrupting organ function as they build up. The disease is broadly divided into systemic forms, where deposits spread throughout the body, and localized forms, where they remain confined to a single organ or tissue. Pulmonary involvement is well documented in immunoglobulin light-chain amyloidosis, the most common type affecting the lungs. But transthyretin-related amyloidosis, known as ATTR, is a different story entirely: it rarely touches the lungs at all, and when it does, its clinical features remain poorly characterized because so few cases have been described.

ATTR itself comes in two flavors. Hereditary ATTR results from pathogenic mutations in the TTR gene and runs in families. Wild-type ATTR, by contrast, is primarily an age-related phenomenon in which the normal transthyretin protein, a carrier molecule that transports thyroxine and retinol-binding protein in the blood, becomes progressively prone to misfolding over decades. In both forms, the heart, peripheral nervous system, and eyes are the organs most frequently affected. The patient in this report had no family history of amyloidosis, and genetic analysis of her peripheral blood found no pathogenic TTR variants, pointing firmly toward the wild-type, age-related variety.

When the woman was referred emergently to the hospital, her oxygen saturation had dropped and a chest radiograph revealed a new infiltrative opacity in the left mid-to-lower lung field, layered on top of a nodular opacity that had been monitored for roughly a decade. Chest computed tomography added crucial detail: bilateral bronchial wall thickening, material retained inside the left main bronchus suggestive of blood clots, infiltrative opacities concentrated in the left upper lobe, and a calcified nodule. Notably, her white blood cell count and C-reactive protein were not elevated, biochemical and coagulation parameters were normal, and tests for tuberculosis and tumor markers all came back negative, narrowing the differential diagnosis considerably.

After initial stabilization with hemostatic agents, the clinical team turned to bronchoscopy, the procedure that would ultimately crack the case. The scope revealed irregular, bumpy mucosal lesions with a whitish-to-erythematous appearance extending from the trachea into both bronchi, while the peripheral airways showed diffuse wall thickening with luminal narrowing. A biopsy taken from the right upper lobe bronchial orifice, along with a bronchial aspirate, provided the tissue needed for definitive analysis. Under the microscope, pathologists found amorphous, pale eosinophilic material in the subepithelial region and around vascular walls, the classic histological signature of amyloid deposition.

Confirming the specific protein type required a sequence of staining techniques. Congo red staining, the gold-standard screen for amyloid, was positive, and the deposits resisted potassium permanganate treatment, a step that helps distinguish certain amyloid subtypes. Immunohistochemistry then delivered the decisive result: the deposits stained positive for transthyretin, establishing a diagnosis of ATTR amyloidosis. Without this layered pathological workup, the deposits could easily have been misclassified as the far more common light-chain variety, which would have sent the diagnostic workup in an entirely different direction.

Excluding systemic disease was the next painstaking task. Electrocardiography, echocardiography, and myocardial scintigraphy showed no evidence of cardiac amyloidosis, the most common and dangerous manifestation of ATTR. The patient had no sensory, motor, or autonomic nervous system symptoms, and orthopedic evaluation ruled out carpal tunnel syndrome and spinal stenosis, both frequent early signs of systemic ATTR. Ophthalmologic examination was unremarkable. To exclude multiple myeloma and other plasma cell disorders, hematologists assessed serum and urine monoclonal proteins and serum free light chains and performed a bone marrow biopsy, all of which were normal. Gastrointestinal biopsies obtained by endoscopy showed no amyloid deposition either. Collectively, these findings established that the disease was truly localized to the tracheobronchial tree, a phenotype the authors describe as exceptionally rare.

The story took one more twist when cultures of the bronchial aspirate grew Aspergillus fumigatus and Mycobacterium mucogenicum, two opportunistic organisms colonizing the damaged airway. Because both amyloid deposition and airway infection could have contributed to the hemoptysis, the team prescribed oral itraconazole for approximately one year and managed the mycobacterial infection conservatively. A CT scan performed a year later showed reduced endobronchial secretions and improved pulmonary opacities, even though the bronchial wall thickening persisted. The patient has experienced no recurrent bleeding, no progression of the airway lesions, and no emergence of systemic disease during follow-up, an encouraging outcome for a condition with no standardized treatment.

The case also carries broader lessons about how unexplained hemoptysis should be investigated. Dyspnea is the most common presenting symptom of pulmonary amyloidosis, followed by cough, weight loss, and chest pain; hemoptysis accounts for only about seven percent of presentations. Tracheobronchial amyloidosis can cause secondary infections and bleeding through mucosal fragility and bronchial stenosis driven by submucosal amyloid deposits. A prospective study of 606 patients with hemoptysis found diagnostic yields of 77.3 percent with CT, 48.7 percent with bronchoscopy, and 83.9 percent with a combined approach. In many cases, CT alone can identify the culprit, for instance when it reveals cavitary opacities strongly suggestive of tuberculosis alongside positive sputum testing. But when imaging and noninvasive tests fail to explain the bleeding, or when airway lesions are suspected, bronchoscopy can supply information nothing else can. In this patient, bronchoscopic biopsy delivered the pathological diagnosis of ATTR amyloidosis, and bronchial aspirate culture uncovered the concurrent infection that may have aggravated the bleeding, directly shaping the treatment strategy.

Treatment options for localized tracheobronchial amyloidosis remain frustratingly limited. Disease-modifying therapies for ATTR, including transthyretin stabilizers and gene-silencing agents, are approved in Japan for cardiac or neurologic involvement, but their efficacy in pulmonary disease is unknown. For airway-limited disease, interventional approaches such as bronchoscopic debulking, laser therapy, and radiotherapy have been reported, yet no standardized treatment has been established, and the evidence base rests on scattered case reports rather than controlled trials. Patients with progressive airway stenosis or recurrent hemoptysis may require such interventions, though this patient has so far been spared. The authors argue that their report demonstrates that tracheobronchial-localized ATTR can occur, however rarely, and that amyloidosis deserves a place in the differential diagnosis of hemoptysis. As wild-type ATTR becomes increasingly recognized in aging populations worldwide, clinicians evaluating unexplained airway disease may need to keep this vanishingly rare entity in mind, because the cost of missing it is measured in delayed diagnoses and unexplained bleeding that could otherwise be explained.

Subject of Research: Localized wild-type transthyretin amyloidosis of the tracheobronchial tree diagnosed after hemoptysis

Article Title: Localized Tracheobronchial Transthyretin Amyloidosis Diagnosed After Hemoptysis: A Case Report

Article References: Inoue, K., Tanaka, Y., Yanagi, M., Michimata, H., Nagahisa, Y., & Kondoh, S. (2026). Localized Tracheobronchial Transthyretin Amyloidosis Diagnosed After Hemoptysis: A Case Report. Respirology Case Reports, 14(10), Article e70781. https://doi.org/10.1002/rcr2.70781

Image Credits: AI Generated

DOI: 10.1002/rcr2.70781

Keywords: amyloidosis, transthyretin, ATTR, tracheobronchial amyloidosis, hemoptysis, bronchoscopy, Congo red staining, wild-type ATTR, pulmonary amyloidosis, airway disease, case report, respirology

Mesalazine, also known as 5-aminosalicylic acid or 5-ASA, has been a cornerstone of inflammatory bowel disease management for decades. It is prescribed to both quell active flares of ulcerative colitis and Crohn’s disease and to keep those diseases in remission over the long term. Because it is generally well tolerated, patients often take it for years with little thought. Yet the new report underscores that even this familiar molecule can provoke serious lung injury. Drug-induced eosinophilic pneumonia occurs when an offending medication triggers an influx of eosinophils into the alveolar air spaces and the interstitial tissue of the lungs, impairing oxygen exchange and producing cough, breathlessness, and infiltrates visible on chest imaging. Diagnosis typically rests on a compatible drug history, elevated eosinophils in peripheral blood or bronchoalveolar lavage fluid, characteristic imaging, and exclusion of infection and other causes.

What makes this case exceptional is timing. In the vast majority of reported instances, mesalazine-related lung injury emerges two to six months after treatment begins, a lag that can easily lull clinicians into overlooking the drug as a culprit. The literature contains only a handful of cases in which symptoms appeared within ten days of the first dose, and the present patient, whose cough began on day seven, now ranks among the earliest ever recorded. By the time she was referred to hospital on day 39, chest radiography showed worsening consolidation in the right upper lung field along with a pleural effusion. Computed tomography demonstrated diffuse consolidation concentrated in the right upper lobe. Her vital signs remained stable, with an oxygen saturation of 96 percent on room air, but her white cell differential told a striking story: eosinophils made up 37.8 percent of a total count of 9,700 cells per microliter, and her C-reactive protein was mildly elevated at 2.67 mg/dL.

To pin down the diagnosis, clinicians turned to bronchoscopy. Bronchoalveolar lavage returned fluid with a total cell count of 5.88 × 10⁶ per milliliter, of which an extraordinary 78.6 percent were eosinophils, a signature finding in eosinophilic lung disease. Transbronchial biopsy and transbronchial lung cryobiopsy, a technique that freezes a larger sample of lung tissue for histological analysis, revealed dense eosinophilic infiltration in both the alveolar spaces and the interstitium. Bacterial and mycobacterial cultures and cytology were all negative, ruling out infection and malignancy. With the drug withdrawn, the clinical course became its own confirmation: chest radiography began improving just two days after mesalazine was stopped, the patient’s cough resolved within a month, and pulmonary infiltrates and peripheral eosinophilia had normalized six weeks later, all without corticosteroid therapy. She was subsequently transitioned to vedolizumab, a gut-selective biologic, for her ulcerative colitis, and the pneumonia did not recur.

Behind this single patient stands a much larger body of evidence assembled by the reporting team. Searching MEDLINE and screening references from prior reviews, the authors identified 57 additional cases of mesalazine-induced lung injury, bringing the total analyzed to 58. The demographic picture is instructive: patients ranged from 14 to 84 years of age, with a median of 35 and a peak in the third decade of life, and women outnumbered men 34 to 24. Ulcerative colitis accounted for 84 percent of underlying diagnoses, with Crohn’s disease making up most of the remainder. Eosinophilic pneumonia was the most common pattern of injury, representing 43 percent of cases, followed by interstitial pneumonia at 27 percent and organizing pneumonia at 10 percent. Most patients, 67 percent, showed bilateral infiltrates, though unilateral disease, as in this case, does occur and can mislead clinicians toward an infectious diagnosis.

The timing data from that literature review are perhaps the most clinically valuable takeaway. While lung injury typically develops two to six weeks after initiation, roughly 10 percent of cases occur within the first two weeks, and only two cases on record, including this one, manifested within ten days. In a focused analysis of 18 well-documented eosinophilic pneumonia cases, symptom onset ranged from seven days to fourteen months, with 70 percent occurring within two months. The median cumulative dose at onset was 81 grams of mesalazine; the present patient had consumed only about 14 grams when her symptoms began. That discrepancy carries real mechanistic weight, because a reaction that ignores both the duration of exposure and the total dose ingested is the hallmark of hypersensitivity rather than toxicity.

That mechanistic distinction matters for how clinicians think about drug safety. Drug-induced lung injury generally arises through two principal pathways: direct cytotoxic damage to alveolar epithelial or endothelial cells, which tends to be dose-related, and immune-mediated inflammation, which can erupt unpredictably at any exposure level. The evidence points firmly toward the immune pathway for mesalazine. Researchers propose that the drug may skew immune signaling toward a Th2-dominant response, in which cytokines such as interleukin-5 drive the production, recruitment, and activation of eosinophils, ultimately seeding them in lung tissue. Pharmacokinetic data reinforce the plausibility of a hypersensitivity mechanism: approximately 20 to 30 percent of orally administered mesalazine and about 10 percent of rectal formulations are absorbed systemically, and eosinophilic pneumonia has been reported even after rectal administration, indicating that small systemic exposures can suffice to ignite the reaction.

The case also settles a long-standing question about the older drug sulfasalazine, a prodrug that is metabolized in the gut into mesalazine and sulfapyridine. When eosinophilic pneumonia occurred in patients taking sulfasalazine, toxicity was often attributed to the sulfapyridine moiety. But the accumulating reports of identical lung injury with mesalazine alone suggest that the 5-aminosalicylic acid molecule itself is capable of triggering the immune response. For the millions of patients with inflammatory bowel disease who take 5-ASA compounds worldwide, this reframing means that no formulation of the drug class can be considered free of pulmonary hypersensitivity risk, however rare that risk may be in absolute terms.

One intriguing wrinkle in the present case is the patient’s respiratory history. She had suspected bronchial asthma and used inhaled corticosteroids as needed, and her fractional exhaled nitric oxide, a noninvasive marker of eosinophilic airway inflammation, was elevated at 51 parts per billion. The authors caution that this reading may have reflected pre-existing asthmatic airway inflammation rather than pneumonia alone, and they note that only one previously reported mesalazine lung-injury patient had a history of bronchial asthma. Whether underlying allergic airway disease can accelerate the onset of drug-induced eosinophilic pneumonia remains uncertain, but the possibility offers a concrete hypothesis for future research and a reason for heightened vigilance in asthmatic patients starting the drug.

The practical message for clinicians and patients alike is one of awareness rather than alarm. Corticosteroids, the usual mainstay of eosinophilic pneumonia treatment, are not always necessary; simple drug withdrawal can be sufficient when respiratory status is stable, as this case demonstrates. Yet some patients have received prednisolone out of concern that stopping mesalazine might precipitate a relapse of their inflammatory bowel disease, illustrating the delicate balancing act physicians face. The authors’ conclusion is straightforward: eosinophilic pneumonia can develop early in the treatment course, and drug-induced lung injury should be considered whenever respiratory symptoms or pulmonary infiltrates appear during mesalazine therapy. For a drug taken daily by so many, recognizing that the lungs can protest within a single week of the first tablet may make the difference between a swift, uncomplicated recovery and a prolonged diagnostic odyssey.

Subject of Research: Rapid-onset mesalazine-induced eosinophilic pneumonia occurring seven days after drug initiation

Article Title: Rapid Onset of Mesalazine‐Induced Eosinophilic Pneumonia Manifesting 7 Days After Initiation: A Case Report

Article References: Inazaki, T., Takeda, K., Iwasaki, M., Tajima, H., Shionoya, Y., Hirama, R., Sato, S., Naito, A., Kawasaki, T., Ikari, J., Kageyama, S., Ikeda, J.-I., & Suzuki, T. (2026). Rapid Onset of Mesalazine‐Induced Eosinophilic Pneumonia Manifesting 7 Days After Initiation: A Case Report. Respirology Case Reports, 14(9), Article e70758. https://doi.org/10.1002/rcr2.70758

Image Credits: AI Generated

DOI: 10.1002/rcr2.70758

Keywords: mesalazine, eosinophilic pneumonia, ulcerative colitis, drug-induced lung injury, inflammatory bowel disease, bronchoalveolar lavage, hypersensitivity pneumonitis, 5-aminosalicylic acid, adverse drug reaction, respirology, eosinophils, case report

The story began in March 2022, when the previously healthy man developed fever and a dry cough. Empirical antibiotics for suspected pneumonia achieved nothing. By April he had been admitted to hospital, where computed tomography revealed consolidation studded with ground-glass opacities in his left lower lobe. His blood work painted a picture of vigorous inflammation: a white cell count of 17,600 per microlitre with neutrophils dominating, and a C-reactive protein level of 15.0 milligrams per decilitre. Crucially, he carried a long-standing diagnosis of oesophageal achalasia, a rare motility disorder first treated with balloon dilation at age 35. Over the preceding five years his ability to swallow had deteriorated relentlessly, with worsening dysphagia and vomiting despite medical therapy.

Diagnostic certainty proved elusive. A single sputum culture yielded Mycobacterium fortuitum, but subsequent cultures were negative, and the findings did not satisfy standard criteria for established nontuberculous mycobacterial disease. The team initially diagnosed aspiration pneumonia complicated by secondary organising pneumonia, treating him with antibiotics and corticosteroids. Neither touched the disease. Then came an observation that would eventually unlock the diagnosis: his respiratory symptoms rose and fell in eerie synchrony with his gastrointestinal ones, flaring during bouts of vomiting and easing when the vomiting subsided. That temporal coupling, the clinicians reasoned, pointed toward chronic microaspiration as the engine of the lung disease.

When symptoms escalated again in April 2024, bronchoscopy was repeated. Histopathological examination of biopsy specimens from the left lower lobe revealed non-caseating granulomas, the characteristic immune structures of mycobacterial infection, and Ziehl-Neelsen staining demonstrated acid-fast bacilli directly within the tissue. Combined with the earlier positive culture, these findings fulfilled the current Japanese diagnostic criteria for pulmonary nontuberculous mycobacterial disease attributable to M. fortuitum driven by chronic aspiration secondary to achalasia. The authors acknowledge that a two-year gap separated the microbiological and histopathological evidence, but they argue that persistent symptoms, repeated parallel exacerbations, and tissue demonstrating granulomas with acid-fast organisms made transient colonisation or contamination implausible.

The therapeutic decision was the radical part. Recognising that control of the underlying oesophageal disorder was essential, the team performed peroral endoscopic myotomy, known as POEM, in October 2024. POEM is a minimally invasive procedure in which an endoscope tunnels through the oesophageal wall to divide the muscular fibres of the lower oesophageal sphincter, restoring the passage of food into the stomach. The effect on the patient’s achalasia was dramatic; his swallowing difficulties and vomiting improved markedly. But the lung outcome was the real headline. Without ever initiating antimycobacterial therapy, his cough and fever resolved, and follow-up imaging showed marked radiological improvement. More than a year after the procedure, no recurrence of pneumonia or mycobacterial disease had been observed, though mild residual fibrosis remains.

To appreciate why this matters, one must understand both organisms and mechanism. Mycobacterium fortuitum belongs to Runyon group IV, the rapidly growing nontuberculous mycobacteria, and is ubiquitous in soil and water. It most often causes skin, soft-tissue, catheter-related and postoperative infections, with pulmonary disease being distinctly uncommon and usually a secondary affair in people with structural lung disease or chronic aspiration. Achalasia, characterised by impaired relaxation of the lower oesophageal sphincter and absent peristalsis, produces stasis of food within a dilating oesophagus. Nontuberculous mycobacteria are commonly ingested with food and can colonise the upper gastrointestinal tract; in achalasia patients, repeated microaspiration of these retained contents seeds the airways. The association between achalasia and pulmonary nontuberculous mycobacterial infection has been recognised for decades, with rapidly growing species frequently implicated.

The authors add a provocative mechanistic twist: the lipid-rich environment within retained oesophageal contents may itself potentiate the pathogenicity of rapidly growing mycobacteria. Previous work has suggested that lipid conditions can impair macrophage phagocytosis and promote mycobacterial growth, effectively disarming one of the lung’s first lines of cellular defence. In this patient, the team notes that dietary habits favouring high-fat intake may have facilitated bacterial persistence, though they concede this remains speculative. If confirmed, the idea would give clinicians yet another reason to view oesophageal stasis not as a mere inconvenience but as an active contributor to pulmonary immunopathology.

How does this case compare with the medical literature? The authors compiled eleven previously reported cases of pulmonary nontuberculous mycobacterial infection associated with achalasia, spanning organisms from M. fortuitum and M. abscessus to M. thermoresistibile and M. wolinskyi. Virtually every patient required prolonged multidrug antimycobacterial regimens, often involving combinations of amikacin, imipenem, clarithromycin, fluoroquinolones, linezolid or other agents, in addition to endoscopic or surgical correction of the oesophagus. In contrast, the present patient achieved sustained clinical and radiological improvement through POEM alone. To the authors’ knowledge, this is the first reported case in which treating achalasia alone successfully controlled an established pulmonary nontuberculous mycobacterial infection, implying that eliminating chronic aspiration can restore effective host defence mechanisms capable of containing the infection without pharmacological help.

The authors are appropriately cautious about the limits of a single observational report. Causality cannot be definitively established: spontaneous fluctuation of disease activity or delayed effects of earlier treatments cannot be entirely excluded, though the tight temporal relationship between POEM and sustained improvement supports the aspiration hypothesis. A further limitation is the absence of microbiological follow-up, because once his respiratory symptoms resolved the patient could no longer produce sputum, so eradication of the organism could not be confirmed in cultures. Still, the clinical message is unambiguous. Clinicians should consider oesophageal achalasia as an underlying cause of pulmonary nontuberculous mycobacterial infection, particularly when respiratory symptoms fluctuate in step with gastrointestinal ones. In such patients, addressing the underlying motility disorder may be as important as any antibiotic, and in rare cases may be enough on its own to conquer the infection and prevent recurrence.

Subject of Research: A case report of pulmonary Mycobacterium fortuitum infection associated with oesophageal achalasia that improved after peroral endoscopic myotomy without antimycobacterial therapy.

Article Title: Pulmonary Mycobacterium fortuitum Infection Associated With Achalasia Treated With Peroral Endoscopic Myotomy Alone: A Case Report

Article References: Masuda, H., Torii, R., Yamasaki, K., Shingu, T., Hata, R., & Yatera, K. (2026). Pulmonary Mycobacterium fortuitum Infection Associated With Achalasia Treated With Peroral Endoscopic Myotomy Alone: A Case Report. Respirology Case Reports, 14(9), Article e70718. https://doi.org/10.1002/rcr2.70718

Image Credits: AI Generated

DOI: 10.1002/rcr2.70718

Keywords: Mycobacterium fortuitum, nontuberculous mycobacteria, achalasia, peroral endoscopic myotomy, chronic aspiration, pulmonary infection, POEM, respirology, case report, oesophageal motility disorder, Pulmonary, Mycobacterium