A 24-year-old male was referred to our hospital with symptoms of abdominal pain and diarrhea without hematochezia. The patient had previously been treated with antibiotics in a local hospital with poor treatment outcomes. Then, he had a colonoscopy that indicated colitis (tuberculosis could not be excluded). Pathology showed chronic inflammation with granulomas (Figure 1A and B). The T-SPOT test for tuberculosis infection was positive. The patient was diagnosed with intestinal tuberculosis and was treated with isoniazid, rifampicin, pyrazinamide, and ethambutol. However, his symptoms did not improve, and he came to our hospital for further treatment. The patient had no underlying disease or overt immunodeficiency. After admission, physical examination revealed fever (38.5 C). Abdominal examination showed slight tenderness under the xiphoid and the left epigastric, periumbilical and right epigastric. Abdominal auscultation showed reduced bowel sounds. A chest CT scan revealed a nodular lesion in the right main bronchus (Figure 2A). An abdominal CT scan revealed a mass in the right lower abdomen (Figure 2B). Bronchoscopy was performed, which revealed mucosal infiltrate and blockage of the upper left and lower right bronchus (Figure 2C). Puncture revealed granulomatous inflammation in the left cervical lymph nodes and acid-fast staining was positive (Figure 1C and D). Pathological examination of the bronchial biopsy sample revealed many acid-fast stain positive bacteria (Figure 1E and F). Biochip system can be used for species identification of mycobacterium by detecting the difference of 16S rRNA sequence. After sample preparation, chip hybridization, washing, data acquisition and analysis, the biopsy specimen was identified as Mycobacterium intracellulare by the Biochip system.
Whole-exome sequencing (WES) is a useful tool for identifying new disease-causing genes. In this method, blood samples are used to prepare the library, and then DNA is captured and enriched by chip, and finally, mutations are detected through a high-throughput sequencing platform. WES revealed that the patient carried compound heterozygous mutations c.3083A>G/c.2590C>T (p.N1028S/p. R864C) in TYK2 (Figure 3A). We also investigated the TYK2 gene of the patient's parents by Sanger sequencing. Both parents were heterozygous and healthy (Figure 3B). The mutation c.2590C>T (p. R864C) was found in his mother and the mutation c.3083A>G (p.N1028S) was carried by his father. The mutation c.2590C>T (p. R864C) was inherited maternally and c.3083A>G (p.N1028S) was inherited paternally.
The patient was finally diagnosed with Mycobacterium intracellulare infection. Nontuberculous mycobacteria had invaded the intestine, lymph nodes and bronchi. The patient had impaired liver function, we started therapy with iproniazid, ethambutol, moxifloxacin, and linezolid, and replaced iproniazid with meropenem after diagnosis. His clinical condition showed significant improvement. The patient was discharged when his temperature became normal and the abdominal pain disappeared. Treatment with moxifloxacin, linezolid, ethambutol and faropenem was continued after discharge from hospital, which was effective and with no obvious side effects. After five months of treatment, bronchoscopy showed a narrowing of the nodule in the right bronchus (Figure 2D). The patient recovered after two years of anti-mycobacterial treatment and no relapse is observed so far.