A 34-year-old young lady was admitted to the Department of Rheumatology and Immunology of the 2nd affiliated hospital of Chongqing Medical University (CQMU), Chongqing, China, on May 6, 2021, due to "limb joint pain for more than one month" (Figure 1). More than a month before admission, the patient developed bilateral symmetrical pains in her wrists, elbows, knees, and ankles without obvious causes, along with tenderness. These symptoms were heavier in the morning with stiffness, and slight relieving at afternoon. The involved joints were intermittent swelling, without wandering or joint deformity. During the course of disease, she had no fever, cough, expectoration, abdominal pain, and diarrhea. This lady was with a height of 160cm, and a weight of 55kg (BMI 21.48kg/m2). She was a salesperson, working at a supermarket with central air conditioning. And a dog was raised at the lady's home. She had married without a child. She had no history of smoking or alcohol consumption. There was an allergic history to cephalosporin about 10 years ago. She was born and living in Chongqing for a long time, and she had not gone to other places for a recent year. Physical examination of her whole body showed no abnormal findings.
After admission, firstly, the lady's anti-Ro antibody was positive (++), Sjogren's syndrome was suspected. However, no abnormality was found in the parotid gland and bilateral submandibular glands. Therefore, lip mucosa biopsy was performed to further exclude the diagnosis of Sjogren's syndrome. At the same time, ultrasonography of muscle and bone showed that there was some effusion in the joint cavity of the right knee joint. Along with the symptoms of joint pain, rheumatoid arthritis should be considered. Next day, the negative results of anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) helped decrease the possibility of rheumatoid arthritis' diagnosis. Enhanced CT scanning of chest (Figure 2) unexpectedly showed bilateral pulmonary interstitial inflammation, with multiple lymphadenopathies, thus pneumonia was considered (Figure 2A and B). Although the patient had no typical symptoms like fever, cough, expectoration, or shortness of breath, levofloxacin was given empirically with elevated neutrophils (Figure 3A). At the same time, the relevant etiological examination was further arranged; however, these results were successively showed negative (Supplementary Table 2).
On the third day, the lady's joint pain was still obvious, so she underwent an intra-articular puncture, fluid extraction, and 1 mL of Diprospan injection into the intra-articular cavity for anti-inflammatory treatment. The pathological results of lip mucosa came back and showed that no lymphocyte aggregation was found. Till then, the diagnosis of Sjogren's syndrome was completely excluded. And the patient's joint pain relived. One week later, a re-examination of chest CT scanning showed that the inflammation of both lungs was smaller, but lymphadenopathies were basically the same as compared to before (Figure 2C and D). After consultation from the respiratory department, a transfer was recommended to clarify the nature of lymphadenopathy. Doppler ultrasonography of superficial lymph nodes detected several enlarged lymph nodes on the right clavicle, with clear boundaries, and the largest one was about 1.6 x 0.7cm.
On the eighth day, the patient underwent a bronchoscopy plus endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) operation under general anesthesia. During the operation, a small amount of purulent secretion was found in the patient's trachea and bilateral main bronchus, which was lavaged, washed out, and sent to culture. The lavage fluid in the lower left lobe was sent for exfoliative cytology and Xpert MTB/RIF detection. Microscopically, it can be seen that the bilateral bronchial mucosa of each leaf and segment of this patient was normal, the lumen was unobstructed. And no neoplasm, bleeding, or necrosis tissues were found. Then, the ultrasonic bronchoscope was replaced. EBUS-TBNA exploration showed that the lymph nodes in group N4, N7, R10, and L11 were swollen and fused. The lymph nodes in groups N4, N7, R10, and L11 were punctured with 21G puncture needles for 1, 3, 2, and 3 times, respectively. Necrotic chips and strip tissues were extracted and sent to exfoliated cytology, tNGS and pathological biopsy detection. The whole operation process was smooth.
The results of exfoliated cytology showed a few lymphocytes and neutrophils (Figure 3B-E). Pathologist reported squeezed lymphocytes and a few epithelial-like cells (Figure 3F and G). Immunohistochemistry analysis was CK (-), Vim (+), Ki-67 (+) 1%, CEA nidus (+), CK7 (-), and anti-acid staining (-). Xpert MTB/RIF was negative. However, tNGS reported 1225 reads of Legionella pneumophila in the samples of lymph node (Supplementary Table 3). Soon a multidisciplinary team (MDT) including experts in hematology, pathology, rheumatism immunity, respiration, and infection discussed the exact cause of this young lady's hospitalization. Finally, with all the information collected, especially the tNGS results, agreement was made that the patient's condition can be rationally explained by the infection of Legionella pneumophila. Thus, levofloxacin continued. By the 15th day, joint pain of the patient was completely relieved, so she was discharged from the hospital with the advice of another week's oral levofloxacin taking.
A month later, not only did the interstitial changes in both lungs were further improved by re-examination of chest CT scanning, but also the enlarged lymph nodes began to shrink (Figure 2E and F). On the 59th day, the patient was followed up at the outpatient department. The symptoms of joint pain did not recur, the interstitial changes of both lungs on chest CT were further improved, and the enlarged lymph nodes were further reduced (Figure 2G and H). During the last follow-up of 141th day, the joint pain still did not recur. The interstitial lesions in both lungs disappeared completely on chest CT, and the enlarged lymph nodes became much smaller (Figure 2I and J).
Enhanced chest CT scanning of the patient. Chest CT enhancement showed pneumonia of right lower lung disappeared under pulmonary window, and.