History of present illness
A 53-year-old Caucasian male was admitted to the surgical ward due to bowel obstruction and suspected colon cancer. He underwent right hemicolectomy in one stage, with end-to-end anastomosis. The histological examination of the resected bowel showed no cancer but did show tissue inflammation with non-necrotizing granulomas and extensive involvement of the ileocecal valve and terminal ileum ( Fig. 11.1 ). Thus, the patient was diagnosed with terminal ileitis due to Crohn disease.
During hospitalization, a preoperative chest radiograph showed bilateral hazy opacities in the mid- and upper fields ( Fig. 11.2 ). He had no respiratory symptoms; thus, he was discharged, and an outpatient pulmonology visit was scheduled.
Past medical history
The patient was a plumber and a lifetime nonsmoker and had no allergies. He had a hiatal hernia and mild Helicobacter pylori– negative gastritis. Several years earlier, he underwent right saphenectomy and right meniscectomy. The patient did not routinely take drugs. No family members had respiratory diseases.
Physical examination and early clinical findings
At the pulmonology visit, the patient was afebrile, alert, and cooperative. He had no breathlessness at rest or during exertion. Oxygen saturation measured by pulse oximetry (SpO 2 ) was 97% on room air, heart rate was 76 beats/min, respiratory rate was 15 breaths/min, and blood pressure was 120/80 mmHg. The physical examination revealed normal respiratory sounds. No pallor, clubbing, or peripheral edema was observed. A chest computed tomography (CT) scan revealed several rounded ground-glass hyperdensities with centrilobular distribution. The central part of the lesions was less dense than the peripheral one (the atoll sign or reversed halo sign). They were mainly located in both the upper lobes and the apical segments of the lower lobes ( 
; Fig. 11.3 ). Calcific paratracheal and subcarinal lymph nodes were also found ( Fig. 11.4 ).
Clinical course
No clinical signs of rheumatic diseases were found. The search for antibodies against nuclear antigens (ANAs), extractable nuclear antigens (ENAs), and neutrophil cytoplasmic antigens (ANCAs) was negative.
The patient underwent bronchoscopy with BAL. No bronchial abnormalities were found on endoscopic exploration. Lymphocytes in the bronchoalveolar lavage fluid were 9% (normal values 7.5–12.5% for non-smokers, 3.5–7.5% for smokers). The CD4 + :CD8 + ratio was fairly increased (4.3; normal value < 2). Cultures for common pathogens and mycobacteria were negative. A nucleic acid amplification test (NAAT) for Mycobacterium tuberculosis was negative. No malignant tumor cells were found.
A PET/CT showed significant 18 F-fluorodeoxyglucose (FDG) uptake in the multiple lung parenchymal lesions, which was higher in their peripheral area (maximum standardized uptake value [SUV max ] 13.79). Several lymphadenopathies with increased FDG uptake were found in the right laterocervical area, in both pulmonary hila and the mediastinum (SUV max up to 19.33). An FDG uptake of abdominal lymph nodes was also found, in particular, in the lumboaortic and mesenteric area (SUV max 10.42) and at the right colonic flexure, near the recent hemicolectomy (SUV max 18.77).
The patient underwent an ultrasound-guided needle biopsy of a right supraclavicular lymph node. Histology confirmed chronic non-necrotizing granulomatous lymphadenitis, strengthening the hypothesis of a diagnosis of sarcoidosis.
However, the interferon-γ release assay (QuantiFERON-TB Gold) turned very positive (29.75 UI/mL, normal values < 0.20), thus documenting that the patient had exposure to M. tuberculosis . A PCR for the detection of M. tuberculosis complex on lymph node biopsy was positive. PCR for M. tuberculosis complex was also positive in bowel specimens that had been stored after right colectomy.
Recommended therapy and further indications
Both intestinal granulomas and those of the cervical lymph nodes were not attributed to sarcoidosis but rather to active TB. Glucocorticoid therapy was not initiated, and the patient was referred to the infectious disease department, where anti-TB therapy was set up with the four-drug regimen (rifampicin, isoniazid, pyrazinamide, and ethambutol) and concomitant administration of pyridoxine (vitamin B6 ). Monthly outpatient visits to the infectious disease clinic were scheduled. After a few weeks, cultures of lymph node specimens test turned positive for M. tuberculosis , and drug susceptibility testing did not show any drug resistance.
Follow-up and outcomes
The patient always remained afebrile and with poor respiratory symptoms. Chest radiographs performed 1 and 2 months after initiation of anti-TB therapy showed a progressive reduction of opacities. After 2 months, the therapeutic regimen was reduced to only rifampicin and isoniazid for a further 4 months, then stopped without signs of relapse. A chest CT scan after a total of 6 months of anti-TB therapy documented the disappearance of the pulmonary lesions.
Pulmonary granulomatosis includes a large and heterogeneous group of diseases characterized by different symptoms and evolutions ( Table 11.1 ).
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