A 53-year-old female patient, who was a native of Guangxi and resided in China, was admitted to hospital in October 2017 due to the incidental discovery of a mass in the right supraclavicular fossa. The laboratory test revealed elevated erythrocyte sedimentation rate (ESR) and immunoglobulin G (IgG) levels, with values of 107.0 mm/h and 34.0 g/L, respectively. Additionally, positive results were obtained for antinuclear antibody (ANA, 1:320), anti-SSA, and anti-RO52 antibodies, while showing negative result for anti-HIV antibody (Table 1). Chest computed tomography (CT) suggested enlarged lymph nodes (right supraclavicular fossa, bilateral neck, bilateral axilla and mediastinum) (Fig. 1A). Pathological examination of the right supraclavicular lymph nodes suggested granulomatous inflammation. After empirical antituberculosis therapy with isoniazid, rifapentine, ethambutol, and pyrazinamide, the patient subsequently developed recurrent low-grade fever. With a suspect of primary Sjogren's syndrome complicated with lymphoma, biopsies were performed on lymph node and labial gland. The biopsy of lymph node revealed chronic inflammation and excluded lymphoma, and the biopsy of labial gland biopsy did not support the diagnosis of Sjogren's syndrome. Emission computer tomography of salivary gland is normal. Meanwhile, when asked about the patient's medical history, she reported an absence of symptoms such as dryness in gustatory and ocular sensations. In summary, there is insufficient evidence for the diagnosis of SS or lymphoma. During the hospitalization, T. marneffei was detected in both blood and lymph node tissue cultures, confirming a diagnosis of TM infection. Following antifungal treatment with voriconazole (VRC) 0.2 g twice daily, the patient’s symptoms improved.
Table 1
Laboratory data and pathological condition during patient 1’s previous hospitalization
Time | Laboratory data | Pathological condition |
| WBC (× 109/L) | CRP (g/L) | ESR (mm/h) | IgG (g/L) | |
2017.10 | 4.67 | 24.7 | 107.0 | 34.0 | Revelation of T. marneffei infection |
2018.8 | 9.07 | 31.1 | 99.0 | 25.1 | Revelation of A.flavus and M. intracellulare infection |
2021.9 | 7.74 | 87.8 | 113.0 | 34.5 | Infection recurred after discontinuation of medication |
2021.12 | 4.97 | 4.7 | 73.0 | 27.6 | Ocular pathologies |
2022.2 | 7.55 | < 0.80 | 41 | 17.8 | After treatment of ocular pathologies |
WBC: white blood cell;CRP: C-reactive protein༛ESR: erythrocyte sedimentation rate༛IgG༚immunoglobulin G |
In August 2018, she was admitted to hospital due to exacerbation of cough and progressive changes on lung CT scan (Fig. 1B). Aspergillus flavus (A.flavus) was found on sputum and lung tissue cultures, and Mycobacterium intracellulare (M. intracellulare) was cultured from the lung tissue. During hospitalization, the patient was initiated on a course of anti-NTM therapy consisting of azithromycin (AZM), ethambutol (ETM), and amikacin (AMK). Following discharge, the regimen was adjusted to AZM and ETM, while maintaining antifungal treatment with VRC. Because of the improvement of condition, she stopped the anti-NTM regimen and reduced the dose of VRC in May 2021.
However, the patient experienced a recurrence of fever in September 2021. The laboratory workup showed increased levels of C-reactive protein (CRP, 87.8 mg/L), ESR (113.0 mm/h) and lgG (34.5 g/L) (Table 1). The T-cell count was 638 /L (1185–1,901 /L), and CD4 + T-cell count was 245 /L (561–1,137 /L). A serum sample was collected for testing the titer of AIGAs. Serum AIGAs were measured by Enzyme-Linked Immunosorbent Assay method and yielded a positive result at 1:2500. The chest CT showed patchy exudation in the left upper lobe (Fig. 1C). Biological examination of sputum and bronchoalveolar lavage fluid (BALF) revealed no pathogenic organisms. However, considering the patient's current high-titer of AIGA, history of refractory infection with TM, A.flavus and M.intracellulare, as well as elevated inflammatory markers and evidence of pulmonary infection on imaging at admission, we considered the possibility of recurrent infection.
After nearly 3-month of anti-NTM treatment with AZM and ETM, as well as antifungal treatment with VRC, the inflammatory markers turned to normal levels and the lung lesions were absorbed (Fig. 1D). However, she complained of experiencing ocular symptoms (Fig. 2A) accompanied with elevated immune indexes (ESR:73.0 mm/h, IgG: 27.6 g/L, high-titer AGIAs: 1:2500) and normal inflammatory markers (CRP: 4.7 mg/L) in December 2021 (Table 1). The ophthalmic examination revealed congestion in both conjunctiva, dry corneal epithelium with patchy fluorescein staining, and small grayish keratic precipitate behind the cornea of both eyes (Fig. 2B). Combined with her medical history and the result of physical and laboratory examinations, we suspected that the ocular manifestations observed, including uveitis and conjunctival fibrosis in the anterior segments of both eyes, were likely attributed to an immune response mediated by anti-IFN-γ autoantibodies. The ophthalmologist recommended treatment with tacrolimus. After 2-month treatment with tacrolimus, her ocular symptoms significantly improved (Fig. 2A), and the laboratory revealed reductions in ESR levels (41 mm/h), IgG concentrations (17.8 g/L), and AIGA titers (1: 500) (Table 1). Overall, AZM and ETM were administered for 16months, and VRC was for 17months. No relapse of either intracellular infection or ocular pathologies had been observed during 27-month follow-up.