A rare case of pulmonary nocardiosis comorbid with Sjogren’s syndrome

Abstract Background Nocardia is an opportunistic pathogen, which occurs in patients with autoimmune diseases and immune dysfunction, and can cause bacteremia and other life‐threatening complications. The clinical manifestations of Nocardia pneumonia are similar to tuberculous and other clinical common bacterial pneumonia, but its antibacterial treatments are different and detection methods are unique, which may lead patients to suffer for many years due to clinical misdiagnosis and missed diagnosis. Methods Imaging and laboratory examinations were performed for preliminary diagnosis, and next‐generation sequencing was used to identify the exact species type of Nocardia in the bronchoalveolar lavage fluid (BALF) of the patient. Results Imaging and laboratory parameters preliminarily implied that the patient was infected with Nocardia with Sjogren's syndrome (SS), and NGS showed that the strain was N. terpenica. Conclusions Accurate etiological diagnosis and corresponding antibiotics are key to improve the prognosis of pulmonary nocardiosis in this case. Nocardia pneumonia is rare in clinical practice; it is of great medical significance to improve the understanding of pulmonary nocardiosis.

and tuberculosis, it often leads to misdiagnosis and missed diagnosis. 7 What is worse, than other bacteria, Nocardia grows slowly. 8 After 7 days of aerobic culture at 37 ℃, the wrinkled milky white colonies embedded in the culture medium can be observed. Therefore, it is easy to be missed in the laboratory diagnosis process. Diagnosis and treatment may be delayed due to the late results of pathogen identification. We describe a patient with pulmonary nocardiosis comorbid with SS with hemoptysis for more than 20 years.

| Clinical features
A 70-year-old male patient was admitted because of hemoptysis for more than 20 years without obvious inducement. The patient had a history of drinking and smoking for 50 years, about 500 ml of wine, and 20 cigarettes a day. He presented with bright red blood, cough and expectoration, no chest tightness, chest pain, shortness of breath, chills, or fever. Chest CT from the local hospital showed multiple nodules and bronchiectasis in both lungs. He did not have any treatment in the local hospital and came to Zhejiang Provincial People's Hospital (Zhejiang province, China) for further diagnosis.
Later, he was treated with pituitrin and tranexamic acid injection for hemostasis, ceftriaxone sodium for anti-infection, and ambroxol for resolving phlegm. His condition improved while he still had repeated intermittent hemoptysis for last 2 years, with small amount, bright red blood, cough and expectoration, dark brown sputum, and occasional active chest tightness.

| Imaging examination
High-resolution computed tomography (HRCT) showed that the nodules in the upper lobe of the left lung were newly found and could not currently completely exclude tumor lesions. There were multiple bronchiectasis and some bronchial mucus embolism in both lungs. Inflammatory foci were scattered in both lungs ( Figure 1). Therefore, doctors suggested improving laboratory examination to differentially diagnose between pulmonary tuberculosis and lung cancer. The patient was recommended to review and further examination such as acid-fast staining of sputum and tuberculin purified protein derivative (PPD) test after anti-inflammatory treatment.

| Immunologic examination
The main serological abnormalities were antinuclear antibody

| Hematologic examination
The increase in inflammatory indexes in peripheral blood suggested that there might be infection in the patient. The main abnormal results were increases in white blood cell count (13.01 × 10 9 /L), neutrophil proportion (86.6%), high sensitivity C-reactive protein (87.2 mg/L), and erythrocyte sedimentation rate (62 mm/h) and decreases in albumin (36.2 g/L). Therefore, the doctor gave the patient 100 ml levofloxacin injection containing 0.5 g levofloxacin and 0.9 g F I G U R E 1 High-resolution computed tomography (HRCT) of the thorax showed bronchiectasis and inflammation involving in both lungs. Patchy and nodular high-density shadows were scattered in both lungs, with unclear margin. Bilateral bronchiectasis and wall thickening were observed. Nodular high-density shadows were found in local lumen, especially in right lung. The right upper lobe (Se4, im69) showed nodular high-density shadow with unclear edge, about 9 mm in diameter. Small nodules and dense foci were seen in the right lung. In addition, small cystic areas without lung markings were found in both lungs, with clear edges sodium chloride every day for anti-infection treatment and suggested etiological examination for further diagnosis.

| Histopathology and cytology examination
Cytopathological examination showed that no cancer cells were found in brush biopsy of the middle lobe of the right lung. But the high proportion of neutrophils in BALF indicated that there might be acute inflammatory infection, and it was necessary to pay attention to the pile of radial rod-shaped bacteria ( Figure 2). were found and were highly suspected to be Nocardia ( Figure 3A,B). to obtain the number of sequences that could be matched to a certain pathogen. The results showed that it was N. terpenica with a sequence number of 306 and a 90.53% relative abundance. The patient's laboratory test results are shown in Tables 1 and 2.

| Treatment and prognosis
The doctor decided to stop levofloxacin intravenous drip QD (once a day), instead of isepamicin 0.4 g with sodium chloride 250 ml intravenous drip QD, continue to give cefmetazole sodium 2g intravenous drip BID (twice a day) for anti-infection, plus sulfamethoxazole tablets (SMZ) for treatment of Nocardia infection. Vitamin B6 10 mg oral QD, vitamin-B1 10 mg oral TID (three times a day), sodium bicarbonate 1 g oral TID for alkalization of urine, and compound sulfamethoxazole 1.44 g oral TID for anti-inflammatory. After a week of medication, the patient's cough and expectoration improved, no chest tightness, shortness of breath, no fever and chills, the breath sounds of both lungs were thick, no obvious rhonchus and moist rales were heard, the rhythm was regular, and no obvious pathological murmur was heard in the auscultation area of each valve. Experts agreed that the diagnosis of Nocardia infection was clear, and the treatment of the patient was effective.

| DISCUSS ION
The clinical manifestations of nocardiosis are similar to fungal, mycobacterium and bacterial infection, and lung adenocarcinoma.
Nocardia can cause granuloma, abscess, and pulmonary nodules.
The main respiratory symptoms are cough, expectoration, hemoptysis, chest pain, fever, dyspnea, fatigue, and empyema. Chest CT and other imaging findings are more than medium density of patchy infiltration, nodules, lung abscess, cavity, and hilar lymph node enlargement. Therefore, pulmonary nocardiosis is often mis-

| HIG HLIG HT
(1) Pulmonary nocardiosis comorbid with Sjogren's syndrome was rare in clinic, and its diagnosis is challenging. (2) NGS is more sensitive than 16S rDNA sequencing technique in the diagnosis of unspecified pathogens and can detect almost all kinds of pathogens F I G U R E 2 The results of cellular report of alveolar lavage fluid. There were many nucleated cells, mainly neutrophils, macrophages, lymphocytes, eosinophils, hemosiderin granules, radial rod-shaped bacteria, and no fungi or other special abnormal cells were found in alveolar lavage

CO N FLI C T O F I NTE R E S T S
The authors declare that they have no competing interests.

AUTH O R CO NTR I B UTI O N S
YMP collect the patient clinical information. YMP, XYD, YZZ, and HYL analyzed the data. YMP and YMG drawn the manuscript. All authors read and approved the final manuscript.

CO N S E NT FO R PU B LI C ATI O N
Written and informed consent was obtained from the patient for publication of this case report and any accompanying images.

DATA AVA I L A B I L I T Y S TAT E M E N T
The datasets used and/or analyzed during the current study are available from the corresponding author Yumei Ge on reasonable request.