A 55-year-old Caucasian man, with a smoking history of about 40 pack years, being diagnosed with UC four months ago, presented to the emergency department with a week-long history of low-grade fever, dry cough, and gradually worsening shortness of breath resulted in severe hypoxemic respiratory failure. The patient was medicated with a daily dosage of 4 g of oral mesalazine. He was also initially treated with intravenous pulse doses of glucocorticoids with a subsequent tapering of prednisolone regimens for a three-month period. Specifically, glucocorticosteroids have been discontinued twenty days before hospital admission. The bowel symptoms remitted within the follow-up intervals. No history of intolerance to salicylates was noted. He had no history of chronic organic solvent or occupational exposures.
On admission, he was apyrexial, hemodynamically stable, tachypnoeic with nineteenth breaths per minute. Lung auscultation revealed non-musical rhonchi bilaterally, especially in middle and lower lung fields. The rest of the physical examination was unremarkable. The chest imaging disclosed a bilateral interstitial micro-nodular pattern (Fig. 1) not revealed in a previous chest X-ray four months ago. High-resolution computed tomography (HRCT) of the chest revealed a diffuse centrilobular ill-defined micronodular pattern (Fig. 2). Arterial blood gas studies performed in resting and breathing from room air showed respiratory insufficiency with pH, partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), HCO3 and oxygen saturation (SaO2) values of 7.46, 51 mmHg, 35 mmHg, 25.8 mmol/L and 85% respectively, while it was observed further deterioration on limited exertion (PO2: 40 mmHg, PCO2: 30 mmHg, SaO2: 81%). The white blood cell counted 19.103 per microliter, without peripheral eosinophilia or other increased inflammatory markers.
The differential diagnosis was broad and included miliary tuberculosis, opportunistic lung infections (such as fungal infections, Pneumocystis jiroveci pneumonia, and viral infections), HP, vasculitis, an extra-intestinal manifestation of UC and pulmonary complications caused by mesalazine. Initially, exclusion of infectious etiologies was mandatory, and for this reason, bacterial, fungal, viral and mycobacterial cultures were sent, yielded no isolation of an infectious agent. Bronchoscopy revealed normal airways and the BAL cellular analysis demonstrated a predominance of lymphocytes and an eosinophilia (recovery 60%, macrophages 54.3%, lymphocytes 39.6%, neutrophils 2.3% and eosinophils 3.8%. Lymphocyte CD4+/CD8+ ratio was 1.5. The transbronchial biopsy findings confirmed lymphocytic alveolitis (Fig. 3). Further workup for tuberculosis such as Mantoux test and blood T- SPOT Tuberculosis (T-SPOT TB) test were all negative as well as real-time reverse transcriptase polymerase chain reaction (RT-PCR) for Pneumocystis jirovecii, serology for viruses and cytologic exams. Furthermore, pulmonary function tests revealed an obstructive ventilatory pattern (Tiffeneau-Pinelli index: 57% of the expected value and forced expiratory volume in 1 second: 1.18ml, 34% of the expected value). Diffusion of carbon monoxide was not carried out owing to the strong dyspnea affecting the patient. Blood samples were sent for vasculitis screen which were normal. While ceftriaxone and azithromycin given intravenously failed to bring any clinical improvement, the mesalazine withdrawal was decided. After a two-day drug interruption, a surprisingly fast clinical recovery was noticed. Specifically, gas abnormalities remission with an elevation of PaO2 up to 73 mm Hg and forced expiratory volume-one second (FEV1) elevation up to 900ml was noticed (FEV1: 1.98ml, 60% of the expected value). In follow up intervals over a two year period the patient was asymptomatic. There was a gradual improvement of chest imaging (Fig. 4) and pulmonary function tests until full recovery within three months. Histopathologic findings obtained by lung biopsy before discontinuation of the drug establish the underlying lung disease process. Subacute HP typically presented with ill-defined nodular opacities in a centrilobular distribution (Fig. 2) that histologically reflect the presence of cellular bronchiolitis, poorly-formed noncaseating granulomas and bronchiolocentric interstitial pneumonitis with a predominance of lymphocytes (Fig. 3). However, in this Case, the lung biopsy was not necessary as the marked clinical and imaging improvement strongly established a relationship between the use of mesalazine and subsequent lung injury.