Organizing pneumonia in Crohn's disease: a case report and literature review

Abstract

Organizing pneumonia (OP) is a rare pulmonary manifestation in patients with inflammatory bowel disease (IBD). Distinguishing between a primary extra-intestinal manifestation of Crohn's disease (CD) and mesalazine-induced lung injury remains a major clinical challenge, as both conditions are steroid-responsive. We report the case of a 31-year-old woman with CD who developed progressive dyspnea and migratory pulmonary infiltrates one month after initiating mesalazine. Laboratory findings revealed marked peripheral eosinophilia (1276/mm³) and a mixed eosinophilic bronchoalveolar lavage profile (30.8%). Histopathology confirmed OP with Masson bodies. Due to the diagnostic overlap, mesalazine was replaced by azathioprine, and systemic corticosteroid therapy (0.75 mg/kg) was initiated. Complete radiological resolution was achieved at 8 months. This case illustrates the diagnostic complexity of eosinophilic-rich OP in CD and emphasizes that while pathology confirms the pattern, the etiology often remains a dual hypothesis between systemic disease and drug toxicity.

Article Highlights

• •OP is a rare but severe complication of Crohn's disease.
• •Migratory CT infiltrates are a hallmark sign of organizing pneumonia.
• •Differentiating between IBD-related EIM and drug toxicity is essential.
• •A 12-month steroid taper achieved resolution without clinical relapse.
• •High BAL eosinophilia may be present in IBD-related organizing pneumonia.

1. Introduction

Crohn's disease (CD) is a systemic inflammatory disorder primarily affecting the gastrointestinal tract; however, extra-intestinal manifestations (EIMs) occur in up to 50% of patients [1]. Pulmonary involvement is relatively rare, estimated at 0.4% of cases, yet it encompasses a broad spectrum of diseases including bronchiectasis, interstitial lung disease, and organizing pneumonia (OP) [2,3]. The pathogenesis likely involves the 'lung–gut axis,' supported by the shared endodermal origin of the respiratory and gastrointestinal tracts [4]. While the respiratory system buds from the foregut and the colon originates from the midgut and hindgut, both organs share a common mucosal immune system [1,4,5].

Establishing a definitive diagnosis is often challenging due to the potential for drug-induced lung injury (DILI), particularly related to mesalazine. This drug-induced injury can radiologically and histologically mimic the pattern of OP, creating a significant diagnostic dilemma between a treatment complication and a primary EIM of the underlying disease [[6], [7], [8]]. Herein, we report the case of a patient with CD who developed OP shortly after initiating mesalazine therapy. Furthermore, we provide a comprehensive review of the literature to summarize the clinical features, diagnostic pitfalls, and management strategies for this rare complication.

2. Case presentation

A 31-year-old woman was diagnosed with CD in March 2025 and started on mesalazine (Pentasa) 4 g/day. One month after initiating treatment, she developed a persistent non-productive cough associated with prolonged evening fevers and night sweats. She was subsequently admitted to the Internal Medicine Department in April 2025 for further evaluation. She had no history of chronic respiratory disease, significant occupational or environmental exposures, or recent travel. She was a former electronic cigarette user, having discontinued vaping one month before admission. Laboratory investigations revealed marked systemic inflammation and eosinophilia, with a peripheral eosinophil count of 1276/mm³ and a C-reactive protein level of 152 mg/L. Procalcitonin level was within normal limits (<0.05 ng/mL). Renal function, liver enzymes, and creatine phosphokinase levels were within normal limits. An abdominal CT scan performed to exclude complications related to inflammatory bowel disease showed regular, circumferential, non-stenosing wall thickening of the right colon (approximately 100 mm) and rectum (approximately 50 mm), with mucosal enhancement and submucosal oedema. Homogeneously enhancing satellite lymph nodes were observed in the mesorectum, pericolic and mesenteric regions, with surrounding fat stranding. No small bowel involvement, intra-abdominal masses, significant lymphadenopathy, or intraperitoneal effusion was detected. Initial chest imaging demonstrated bilateral interstitial infiltrates with a left apical alveolar opacity (Fig. 1 A). Chest CT revealed bilateral peripheral parenchymal consolidations, predominantly in the upper lobes, associated with irregular septal thickening, intralobular reticulations, ground-glass opacities, and bronchiectasis. A lesion in the left upper lobe exhibited convex margins (Fig. 2A and B-C). Bronchoscopy with bronchoalveolar lavage demonstrated a mixed inflammatory cellular profile with macrophages 28.2%, lymphocytes 30.3%, neutrophils 10.7%, and eosinophils 30.8%, a CD4/CD8 ratio of 0.98, and absence of siderophages. Acid-fast bacilli testing on sputum and BAL was negative. Brucella serology (Wright agglutination) was negative. Serological tests for hepatitis B, hepatitis C, and HIV were negative, while cytomegalovirus and Epstein–Barr virus serologies were consistent with past infection. Tuberculin skin testing was negative. Transthoracic echocardiography showed preserved left ventricular systolic function, normal right-sided pressures, and no valvular abnormalities or evidence of infective endocarditis. The patient was discharged while awaiting the results of the investigations. She was readmitted in May 2025 to the pulmonology department for dyspnoea and fever. She denied having any diarrhea, constipation, or abdominal pain. On examination, BMI was 24.2 kg/m² and temperature 38.8°C. The patient was eupnoeic, with an oxygen saturation of 98% on room air, a heart rate of 70 beats per minute, and a blood pressure of 120/80 mmHg. No respiratory distress or peripheral lymphadenopathy was noted. The abdomen was soft, non-distended, and non-tender, with no palpable masses or organomegaly. Clinical examination was otherwise normal. Laboratory tests revealed WBC 11,410/mm³, haemoglobin 12.2 g/dL, and persistent eosinophilia of 722/mm³. CRP had decreased to 15 mg/L. Renal function, electrolytes, liver enzymes, and corrected serum calcium were normal. Repeat chest radiography demonstrated new bilateral peripheral opacities, predominating in the right lung (Fig. 1 B). Pulmonary CT angiography excluded pulmonary embolism and revealed migratory subpleural consolidations, predominantly in the right lung, with distorted air bronchograms, traction bronchiectasis, small bilateral pleural and fissural effusions, a thin pericardial effusion, and enlarged mediastinal, hilar, and interbronchial lymph nodes (Fig. 2D and E-F). Antineutrophil cytoplasmic antibodies (ANCA) were negative, ruling out vasculitis and parasitological stool examination was negative, ruling out helminthic causes of eosinophilia. Pulmonary function tests (PFTs) showed a restrictive ventilatory pattern. Baseline spirometry demonstrated a normal forced expiratory volume in 1 s/forced vital capacity ratio (FEV₁/FVC) of 90.8% (108% predicted), with reduced forced expiratory volume in 1 s (FEV₁: 2.22 L, 65% predicted) and forced vital capacity (FVC: 2.44 L, 60% predicted). Assessment of diffusing capacity of the lung for carbon monoxide (DLCO) revealed a moderate reduction, measured at 17.8 mL/min/mmHg (63% predicted; z-score −3.01), with a normal transfer coefficient for carbon monoxide (KCO; DLCO/alveolar volume [DLCO/VA]: 4.73 mL/min/mmHg/L, 86% predicted). Organizing pneumonia was strongly suspected based on clinical presentation, radiological findings, and BAL profile. However, in view of persistent fever, night sweats, eosinophilia, and mediastinal/hilar lymphadenopathy, lymphoma was considered and excluded by surgical lung and lymph node biopsies. Histopathology of the lung demonstrated patchy involvement of alveolar septa with mild lymphocytic infiltration. Intraluminal fibroblastic plugs were identified within alveolar sacs, ducts, and bronchiolar lumina, consisting of spindle-shaped fibroblasts embedded in loose collagenous stroma forming polypoid structures consistent with Masson bodies. No interstitial fibrosis, vasculitis, granulomatous inflammation, or malignancy was observed. Lymph node histology showed reactive changes without evidence of lymphoma (Fig. 3). Given the suspicion of mesalazine-induced lung injury, mesalazine was discontinued and replaced with azathioprine (150 mg/day; 50 mg three times daily) by the gastroenterology team. Systemic corticosteroid therapy was initiated with prednisone at 0.75 mg/kg/day (60 mg/day), together with potassium, calcium, and vitamin D supplementation, as well as gastric protection. The patient showed a rapid clinical response, with complete resolution of fever and progressive improvement of dyspnoea and cough, accompanied by complete resolution of chest radiographic abnormalities after two months of treatment (Fig. 1 C). She experienced corticosteroid-related adverse effects, including acne and weight gain. Prednisone was administered at 60 mg/day for two weeks, followed by gradual tapering to 30 mg/day for one month, 20 mg/day for two months, and 15 mg/day until the sixth month. Thereafter, the dose was reduced to 7.5 mg/day in April 2026 (10 months after treatment initiation), 5 mg/day in May, and 5 mg every other day in June. The planned total duration of corticosteroid therapy was 12 months. Owing to a persistent cough with tenacious sputum, inhaled budesonide/formoterol was added, resulting in further symptomatic improvement.

Fig. 1.

A. Initial chest radiograph showing bilateral interstitial infiltrates and a left apical alveolar opacity. B. Follow-up chest radiograph showing new bilateral peripheral opacities, predominating in the right lung. C. Follow-up chest radiograph obtained two months after treatment initiation, showing near-complete resolution of the previous peripheral pulmonary opacities, with only minimal postoperative changes at the right lung base corresponding to the surgical biopsy site.

Fig. 2.

A-B-C. Initial chest CT (April 2025): Bilateral parenchymal consolidations, predominantly peripheral and in the upper lobes, associated with irregular septal thickening, intralobular reticulations, ground-glass opacities, and bronchiectasis. A lesion in the left upper lobe showed convex margins. D-E-F. Follow-up chest CT (May 2025): Migratory subpleural consolidations with distorted air bronchograms and traction bronchiectasis. Enlarged mediastinal, hilar, and interbronchial lymph nodes. G-H-I. Follow-up chest CT at 8 months demonstrating complete resolution of parenchymal consolidations. A small, stable linear band is noted at the right lung base, corresponding to the surgical biopsy site (sequelae).

Fig. 3.

Histopathological features of organizing pneumonia. A–B. Haematoxylin–eosin staining showing patchy involvement of the lung parenchyma with mild inflammatory cell infiltration within the alveolar septa. C-D. Presence of fibroblastic plugs within alveolar sacs, alveolar ducts and bronchiolar lumina (White arrow). E–F. High-power views demonstrating polypoid Masson bodies composed of spindle-shaped fibroblasts embedded in a loose collagenous matrix.

A follow-up chest CT performed eight months after treatment initiation (Fig. 2G and H-I) demonstrated complete resolution of the bilateral parenchymal opacities, with only a small residual linear opacity at the right lung base, corresponding to the biopsy site. Pulmonary function tests performed at the same time showed normalization of spirometry (FEV₁/FVC ratio 87%, FEV₁ 90% predicted, z-score −0.86, with normal FVC) and marked improvement in gas transfer (corrected DLCO 83% predicted, z-score −1.39; KCO 83% predicted), indicating recovery of alveolar–capillary function.

3. Discussion

This case represents a rare EIM of inflammatory bowel disease (IBD): organizing pneumonia (OP) in a patient with CD. While EIMs are reported in up to 50% of patients with IBD [1], pulmonary involvement is exceptionally rare in CD, occurring in approximately 0.4% of cases—a frequency significantly lower than that observed in ulcerative colitis (UC) [2,3]. The pathogenesis likely involves the lung–gut axis, supported by the shared embryological derivation of the respiratory and gastrointestinal tracts from the primitive endoderm [4]. Although the respiratory tract branches from the foregut and the colon from the midgut/hindgut, they both derive from the endodermal layer and share an analogous mucosal immune system [1,4]. This common origin facilitates the migration of sensitized T-lymphocytes from the inflamed intestinal mucosa to the bronchus-associated lymphatic tissue (BALT) via specific chemokine receptors [1,9]. To better characterize this rare entity, we identified 28 reported cases of IBD-associated OP (18 CD and 10 UC), summarized in Table 1, Table 2.

Table 1.

Reported cases of Organizing Pneumonia in patients with Crohn's Disease (CD).

Author, Year	Patient (Age/Sex)	CD Duration/Treatment at Onset	Onset delay after drug start	Eosinophilia (Blood/BAL)	CT/Radiology Findings	OP Treatment (Drug management + Steroids)	Outcome/Follow-up
Camus, 1993 [10]	26 F	8 yrs/Sulfasalazine	NR	NR	Focal consolidation	IV Steroids	CR
Faller, 2000 [8]	38 F	3 yrs/Mesalazine	NR	900/mm3/30%	Migratory opacities	Stop Mesalazine + Prednisone	CR
Alrashid, 2001 [11]	66 F	1 yr/Mesalazine	NR	NR	Multiple nodules	Infliximab	CR
Casey, 2003 [12]	75 M	6 yrs/Mesalazine	NR	NR	Diffuse infiltrates	None	RI
Carratù, 2005 [3]	29 M	1 yr/Mesalazine	2 months	8.1%/< 4%	Peripheral opacities	Maintained Mesalazine + Steroids	CR
Krishnan, 2006 [13]	17 M	4 yrs/Mesalazine	NR	648/mm3/NR	Basal infiltrates	Infliximab	RI
Ananthakrishnan, 2007 [14]	71 M	1 yr/Azathioprine	NR	NR	Upper lobe GGO	Discontinue Aza + Steroids	CR
Gil-Simón, 2008 [15]	41 M	2 yrs (Remission)/None	N/A	Normal/5%	Migratory infiltrates	Prednisolone	RI
Pedersen, 2009 [16]	35 F	11 yrs/Aza + Steroids	N/A	NR	Peribronchial nodules	Infliximab	CR
Basseri, 2010 [17]	56 M	30 yrs/Mesalazine	NR	NR	Bilateral infiltrates	Prednisone	RI
Dinneen, 2014 [9]	64 M	10 yrs/Mesalazine	10 years	Normal/NR	Perihilar GGO	Maintained Mesalazine + Prednisone	CR
Tanida, 2016 [18]	64 M	34 yrs/Mesalazine + ADA	NR	NR	Patchy consolidation	Prednisolone	RI
Zaman, 2017 [5]	22 F	Years/None	N/A	NR	Bilateral nodules	Prednisone	NR
Zhou, 2017 [2]	66 M	8 mo/Azathioprine	1 month	2.8%/NR	Bronchovascular opacities	Oral Prednisone	CR
Cebrián García, 2018 [19]	31 M	New/None	N/A	NR	Right upper lobe consolidation	Prednisone + Azathioprine	RI
Santiago, 2025 [20]	45 F	Known/Infliximab + Aza	N/A	NR	Persistent pneumonia	High-dose steroids	RI
Present Case	31 F	Known/Mesalazine	1 month	1276/mm3/30.8%	Migratory consolidations	Stop Mesalazine (Switch to Aza) + Prednisone (12 mo taper)	CR (10-mo stability)

Table 2.

Reported cases of Organizing Pneumonia in patients with Ulcerative Colitis (UC).

Author, Year	Patient (Age/Sex)	UC Duration/Treatment at Onset	Onset delay after drug start	Eosinophilia (Blood/BAL)	CT/Radiology Findings	OP Treatment (Drug management + Steroids)	Outcome
Basseri, 2010 (C6) [17]	37 F	8 mo/Mesalazine	8 months	NR	Cavitary lesion	Prednisone	CR
Basseri, 2010 (C7) [17]	19 M	3 yrs/Mesalazine	NR	High/30.8%	Peripheral infiltrates	Stop Mesalazine + Prednisone	CR
Aydoğdu, 2012 [21]	57 M	32 yrs/Mesalazine	4 years	NR	Multifocal GGO, Pneumothorax	Stop Mesalazine + IV Steroids	CR
Jang, 2013 [22]	81 F	12 yrs/None	N/A	Normal/0%	Diffuse patchy densities	Prednisolone	RI
Talwar, 2013 [23]	25 M	Long/Mesalazine	NR	NR	Bilateral nodules	Prednisone	RI
Inoue, 2014 (C1) [7]	15 F	New/Mesalazine	4 weeks	1100/mm3/NR	Non-segmental consolidations	Stop Mesalazine	RI
Inoue, 2014 (C2) [7]	48 F	Known/Mesalazine	NR	9600/mm3/47.5%	Right-side consolidations	Stop Mesalazine	RI
Inoue, 2014 (C3) [7]	50 F	Known/Mesalazine	5 weeks	4300/mm3/NR	Upper lobe consolidations	Stop Mesalazine	CR
Moeser, 2015 [6]	20 M	6 mo/Mesalazine	6 months	984/mm3/20%	Subpleural consolidations	Stop Mesalazine + Prednisone	CR
Huang, 2020 [24]	75 F	2 yrs/Mesalazine	2.8 years	Normal/0%	Peribronchial consolidations	Stop Mesalazine + Prednisone	RI

Abbreviations: Aza: Azathioprine; ADA: Adalimumab; BAL: Bronchoalveolar Lavage; CR: Complete Resolution; GGO: Ground-Glass Opacities; NR: Not Reported; N/A: Not Applicable; RI: Rapid Improvement.

The primary manifestations are often non-specific, including fever, progressive dyspnea, and cough [2,14,24]. In our patient, the presence of persistent fever and mediastinal lymphadenopathy necessitated the exclusion of granulomatous infections (tuberculosis) and malignancies such as lymphoma, a challenge also noted in other reports where lung nodules were a predominant feature [5,23]. The "migratory" nature of the consolidations observed on CT imaging in our patient is a hallmark feature of OP, as also reported by Faller et al. [8] and Gil-Simón et al. [15].

A major diagnostic challenge in this case lies in distinguishing between a primary EIM of CD and mesalazine-induced lung injury, a known form of DILI [6,24]. Mesalazine is a recognized trigger for both OP and eosinophilic pneumonia [24]. In our patient, the onset of respiratory symptoms occurred only one month after initiating mesalazine therapy, a temporal relationship highly suggestive of drug toxicity, as described in the cases by Inoue et al. [7]. Unlike the case reported by Carratù et al., where mesalazine was maintained [3], our patient's treatment was switched to azathioprine (50 mg, 3 tablets/day) due to the strong suspicion of DILI. Since corticosteroids are the standard treatment for both IBD-related OP and DILI, the rapid clinical improvement confirms steroid sensitivity but prevents us from definitively excluding mesalazine as the primary etiology [6,9]. As noted by Moeser et al., a pragmatic approach—discontinuing the potentially toxic drug while initiating steroids—is often necessary when these two entities overlap [6].

The presence of marked peripheral (1276/mm³) and BAL (30.8%) eosinophilia in our patient is atypical for classic idiopathic OP, which usually presents with lymphocytic alveolitis [12,18]. This profile raises the differential diagnosis of Chronic Eosinophilic Pneumonia (CEP) or drug-induced eosinophilic pneumonia [24]. However, "eosinophilic-rich" variants of OP are well-described in IBD; Faller et al. reported a similar case of CD with migratory infiltrates and 30% eosinophils in the BAL [8]. The discrepancy between the high eosinophil count in the BAL and the predominantly fibroblastic plugs (Masson bodies) seen on histology can be attributed to the "patchy" nature of OP. While the surgical biopsy provides a specific architectural snapshot of the organization, the BAL reflects the broader inflammatory environment of the distal airspaces [12,23]. Furthermore, although the patient had a history of electronic cigarette use, E-cigarette or Vaping Product Use–Associated Lung Injury (EVALI) was considered unlikely given the classic migratory pattern and the clear temporal link with her CD flare and mesalazine initiation [5].

Histopathology remains the gold standard for establishing a definitive diagnosis, particularly in patients with atypical clinical features or mediastinal lymphadenopathy [8,19]. In our patient, the identification of Masson bodies (intraluminal fibroblastic plugs) on surgical lung biopsy was pivotal in confirming the diagnosis of organizing pneumonia and excluding alternative diagnoses, including tuberculosis and malignancy.

The published cases consistently demonstrate that organizing pneumonia is highly responsive to systemic corticosteroids [2,6,19]. However, given the substantial risk of relapse associated with premature corticosteroid withdrawal, we adopted a prolonged 12-month tapering regimen. At the time of writing (10 months after treatment initiation), the patient remains clinically stable while receiving prednisone 5 mg every other day. Follow-up chest CT performed eight months after treatment initiation demonstrated complete resolution of the pulmonary opacities, with only a minimal residual linear scar at the biopsy site, accompanied by normalization of spirometry and marked improvement in gas transfer.

This case highlights that organizing pneumonia should be considered in patients with Crohn's disease presenting with persistent respiratory symptoms and bilateral pulmonary infiltrates. Early multidisciplinary collaboration, thorough exclusion of alternative diagnoses, and prompt initiation of corticosteroid therapy were associated with sustained clinical, radiological, and functional recovery. Although the concomitant discontinuation of mesalazine precludes definitive distinction between Crohn's disease-related organizing pneumonia and mesalazine-induced lung injury, this diagnostic uncertainty did not alter the therapeutic approach.

4. Strengths and limitations

This case report has several strengths. Histopathological confirmation by surgical lung biopsy established the diagnosis of organizing pneumonia while excluding infectious, malignant, and granulomatous diseases. In addition, the accompanying literature review places our findings in the context of previously reported cases and highlights the diagnostic and therapeutic challenges associated with this rare extra-intestinal manifestation. Finally, the 10-month clinical, radiological, and functional follow-up provides valuable insight into the patient's long-term recovery.

However, several limitations should be acknowledged. As a single-case report, our findings cannot be generalized. Furthermore, because mesalazine was discontinued at the time corticosteroid therapy was initiated, it remains impossible to determine whether the pulmonary disease represented an extra-intestinal manifestation of Crohn's disease or mesalazine-induced lung injury. Finally, owing to the rarity of inflammatory bowel disease-associated organizing pneumonia, the optimal corticosteroid dose and tapering schedule remain undefined.

5. Conclusions

Organizing pneumonia is an uncommon but important pulmonary manifestation of Crohn's disease that should be considered in patients presenting with unexplained respiratory symptoms and bilateral pulmonary infiltrates. Because its clinical and radiological features may overlap with mesalazine-induced lung injury, establishing the diagnosis often requires a comprehensive evaluation, including histopathological examination when appropriate. Early recognition and timely immunosuppressive treatment are associated with favourable outcomes. Further studies are needed to better define the pathophysiological mechanisms underlying inflammatory bowel disease-associated organizing pneumonia and to establish evidence-based therapeutic strategies.

CRediT authorship contribution statement

Soumaya Debiche: Writing – review & editing, Writing – original draft, Visualization, Validation, Methodology, Formal analysis, Data curation, Conceptualization. Hela Cherif: Writing – review & editing, Writing – original draft, Validation, Supervision. Sarra Ben Rjeb: Supervision, Formal analysis, Data curation. Ferdaous Yangui: Writing – review & editing, Validation, Supervision. Salma Mokaddem: Writing – review & editing, Validation, Supervision. Mondher Briki: Validation, Supervision, Data curation. Mariem Triki: Validation, Supervision, Formal analysis, Data curation, Conceptualization. Mohamed Ridha Charfi: Writing – review & editing, Validation, Supervision.

Consent

The authors declare that written informed consent was obtained for the publication of this manuscript and accompanying images and attest that the form used to obtain consent from the patient(s) complies with the Journal requirements as outlined in the author guidelines.

Declaration of generative AI and AI-assisted technologies in the manuscript preparation process

During the preparation of this work the authors used Google AI Studio and ChatGPT to improve language readability and assist in the organization of the literature review tables. After using these tools, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.

Funding

This research did not receive any specific grant from funding agencies in the public and commercial sectors.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.