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