A 68-year-old Chinese female kindergarten teacher with a history of hypothyroidism after hyperthyroidism treatment was admitted to our hospital in September 2010 due to cough, expectoration and fever for 15 months and a rash for 1 month. At the end of May 2009, she first developed cough with expectoration accompanied by fever, and her highest body temperature was 39 C. Chest computed tomography (CT) revealed consolidation in the right lower lobe. The patient showed no obvious improvement after treatment at a local hospital. She was first hospitalized at our hospital in August 2009. Routine blood examination showed a white blood cell (WBC) count of 11 x109/L, a neutrophil count of 8.6x109/L and a hemoglobin concentration of 62 g/L. The C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) were 38.7 mg/L and 105 mm/h, respectively. Chest CT revealed pneumonia in the middle and lower lobes of the right lung, and Klebsiella pneumoniae was identified in the sputum. She was treated with antibiotics and was discharged after her symptoms improved. In October 2009, the patient experienced a recurrence of the above symptoms accompanied by herpes zoster on the right chest wall. Chest CT revealed progressive pulmonary lesions with new consolidation in the apicoposterius segment of the upper lobe of the right lung, and Candida albicans was identified in the sputum. Routine blood examination revealed a WBC count of 23.5x109/L, a neutrophil count of 19.8x109/L, and a hemoglobin concentration of 68 g/L. The CRP concentration and ESR were 91.3 mg/L and 69 mm/h, respectively. The patient was treated with clindamycin, cefoperazone sulbactam, fluconazole and ganciclovir as prescribed. Repeated chest CT revealed that the pulmonary lesions and pleural effusion were slightly absorbed, and the patient was discharged and returned to her local hospital for continuous treatment. In September 2010, the patient was admitted to our hospital for the third time due to fever, cough with expectoration and scattered herpes of various sizes on her limbs for one month. She had lost 15 kg since the onset of illness.
The physical examination after admission revealed a body temperature of 38 C; the presence of painful erythematous papules studded with white blisters on her palms, back of the hands, fingers, face and limbs (Figure 1); bilateral axillary and inguinal lymphadenopathy; and moist rales in the bilateral lungs. Routine blood examination revealed that her WBC count, neutrophil count, lymphocyte count and hemoglobin concentration were 24.24x109/L, 20.07x109/L, 2.16x109/L and 85 g/L, respectively. The concentrations of CRP, albumin, globulin, serum immunoglobulin (Ig) G, IgA and IgM were 182 mg/L, 26.2 g/L, 45.9 g/L, 24.53 g/L, 2.64 g/L and 1.38 g/L, respectively. The percentages of total T cells, CD4+ T cells and CD8+ T cells, and CD4/CD8 cells were 50.9%, 29.3%, 17.4% and 1.6, respectively. The levels of creatinine and urea nitrogen were 51 micromol/L and 2.4 mmol/L, respectively. In addition, her transaminase, tumor markers, rheumatoid factor, and anti-Streptococcus hemolysin O were all within normal ranges, and she was negative for plasma human immunodeficiency virus (HIV) antibodies. The results of bone marrow aspiration biopsy suggested iron deficiency anemia. Her lung function test revealed that her forced expiratory volume in the first second (FEV1) was 76.9%, her FEV1/forced vital capacity (FVC) was 78.13%, and her carbon monoxide transfer factor (TLCO) was 46.7%, suggesting mild restrictive ventilatory dysfunction and diffusion disorder. Chest CT showed consolidation and exudation in the apicoposterior segment of the upper lobe and in the posterior basal segment of the lower lobe of the left lung, and a large amount of pleural effusion was noted on the left side. Cytological and biochemical examination of the pleural effusion showed that her total cell count, percent of segmented cells, percent of lymphocytes, adenosine deaminase, and protein concentration were 140x106/L, 70%, 30%, 3.8 U/L, and 37 g/L, respectively. Her Rivalta test was positive, and the effusion was proven to be exudative. Histopathology of the rashes and the lymph node biopsy specimen obtained from the patient confirmed SS (Figure 2). Candida was repeatedly isolated from the sputum, while microbial cultures of the blood and alveolar lavage fluid were negative. In addition, there were no abnormal findings on bronchoscopy. Following treatment with vancomycin, moxifloxacin, cefoperazone, fluconazole and dexamethasone during hospitalization, the patient's symptoms improved, and the rash subsided. Repeated routine blood tests showed a WBC count of 12.4x109/L, a neutrophil count of 7.92x109/L and a hemoglobin concentration of 108 g/L. Chest CT showed absorption of the pulmonary lesions and pleural effusion. The patient was discharged from the hospital on October 20, 2010. She was continuously treated with oral prednisone and thalidomide outside the hospital, and her condition was stable However, the patient was admitted to the People's Hospital of Guangxi Zhuang Autonomous Region due to a pulmonary fungal infection and SS and was hospitalized from March 2011 to May 2011. Her specific process of diagnosis and treatment was unknown, and she was discharged after her condition improved.
On May 21, 2011, the patient was admitted to the Nanning Fourth People's Hospital due to cough with expectoration, subcutaneous abscesses on her left chest wall and several palpable soybean-sized lymph nodes on her neck bilaterally. She was diagnosed with bilateral pulmonary tuberculosis and a tuberculous abscess of the left chest wall based on chest CT and was administered anti-tuberculosis therapy for 3 months without clinical improvement. Her chest wall abscess continued to ulcerate and discharge pus and did not heal. Routine blood examination revealed a WBC count of 8.14x109/L, a neutrophil count of 6.07x109/L and a hemoglobin concentration of 75.20 g/L. On August 3, 2011, the culture results of the patient's sputum and chest wall pus were available, and the patient was confirmed to be positive for NTM (unclassified) culture. Based on the results of the antimicrobial susceptibility test (AST) (para-aminosalicylic acid, streptomycin, capreomycin, protionamide, amikacin: R; isoniazide: I; rifampicin, ethambutol, levofloxacin: S), she received combination treatment with isoniazid, rifapentine, ethambutol, and levofloxacin for more than 1 month. Her WBC count, neutrophil count and hemoglobin concentration were 7.58x109/L, 5.42x109/L and 88.7 g/L, respectively. She was discharged after her symptoms improved. She regularly took anti-NTM agents outside the hospital with regular follow-up, and her chest wall lesion had completely healed after 6 months. Repeated routine blood examination showed that her WBC count and hemoglobin concentration were 5.51x109/L and 113 g/L, respectively. The patient was maintained on anti-NTM therapy until December 1, 2012. On March 16, 2013, the patient was admitted to the hospital again due to cough, expectoration and anorexia. Routine blood examination after admission showed a WBC count of 8.98x109/L, a neutrophil count of 6.26x109/L and a hemoglobin concentration of 68.2 g/L. The albumin concentration and ESR were 27.9 g/L and 142 mm/h, respectively. Chest CT revealed exacerbation of her pulmonary lesions, with mottled and linear high-density shadows observed in both lungs. Due to a positive sputum smear for acid-fast bacilli, a recurrence of NTM infection was considered, and clarithromycin was added to the original regimen. The patient's condition improved again, and she was transferred to the outpatient department for treatment. Repeated laboratory tests on January 24, 2015 revealed that her WBC count, hemoglobin concentration, CD3+ T-cell count, CD4+ T-cell count, CD8+ T-cell count, albumin concentration and A/G were 7.20x109/L, 118 g/L, 1109 cells/muL, 686 cells/muL, 397 cells/muL and 1.17, respectively. Her liver and kidney functions were normal. Chest CT showed absorption of her pulmonary lesions, and she subsequently discontinued anti-NTM treatment.
In March 2016, 1 year after the discontinuation of anti-NTM therapy, the patient was readmitted to the hospital with a back abscess that had continued to ulcerate and discharge pus for 1 month. Physical examination after admission revealed cervical lymph node enlargement, a few moist rales in the left lower lobe and soft tissue swelling in the upper back. On the left side of the spinous processes of the C7-T1 vertebral bodies, a skin ulcer with a diameter of approximately 0.6 cm and a sinus tract with granulation tissue and purulent exudation (leading to the vicinity of the spinous process of the C7-T1 vertebral bodies, which was approximately 3.5 cm deep) were observed. Her WBC count, hemoglobin concentration, CRP concentration, ESR and A/G were 7.43x109/L, 114 g/L, 8.3 mg/L, 38 mm/h and 0.92, respectively. Serum AIGAs were determined by an enzyme-linked immunosorbent assay (ELISA) kit (Cloud-Clone Corp, Wuhan, China), and the AIGA titer was 79276.59 ng/mL (the cutoff value of the AIGA titers was 9583.21 ng/mL). Chest CT showed increased pulmonary lesions with multiple patchy exudations, fibrous proliferation and ground glass opacity in both lungs and bronchiectasis in the dorsal segment of the left lower lobe (Figure 3A). Bone CT revealed bony destruction in C7-T2 vertebral bodies with surrounding abscess formation (Figure 3B-D). NTM were cultured from the pus obtained from the patient's back abscess, and NTM were further identified as M. phlei using the indirect homologous gene method (gene chip). Given that her AST results were the same as before, the patient continued treatment with the original regimen. Furthermore, the patient underwent local sinus tract grabbing. Three months later, the bone destruction had gradually repaired, the surrounding abscess had disappeared, and the skin ulcer and sinus tract had healed. The patient was discharged and remained on treatment with the above regimen, showing gradual improvement. In July 2017, repeated chest CT showed that the pulmonary lesions were absorbed (Figure 3E). Repeated bone CT showed that the bone destruction had further repaired, and the surrounding abscess had disappeared (Figure 3F-H). No lymph node enlargement was found. Routine blood examination revealed a normal WBC count of 5.06x109/L and a normal hemoglobin concentration of 141 g/L. Her CRP concentration and ESR were within the normal range. In April 2018, the patient returned to the hospital for re-examination, and her clinical indicators showed normal results. The patient was cured after 2 years of regular anti-NTM therapy with no recurrence noted at present.