High titers of anti-interferon-γ autoantibodies (AIGAs) are an important factor leading to persistent, relapsed, and refractory infections in HIV-negative hosts infected with Talaromyces marneffei (TM). We report 5 patients treated with pulses of high-dose intravenous cyclophosphamide (IVCY) who were followed for 2 years. Before IVCY therapy, all patients had multiple relapses, with a median (interquartile range [IQR]) of 2 (1-3) instances of relapse. The median serum AIGA titers (IQR) were 58 753 (41 203-89 605) ng/mL at diagnosis, 48 189.4 (15 537-83 375) ng/mL before IVCY therapy, and 10 721.2 (5637-13 245) ng/mL at the end of IVCY therapy (P < .05). After 3 months of follow-up, the median AIGA titers (IQR) rose gradually to 21 232.6 (9896-45 626) ng/mL, and to 37 464.2 (19 872-58 321) ng/mL at 24 months (P < .05). Five patients discontinued antimicrobial therapy within 3-12 months after completion of IVCY therapy, but only 1 patient had a relapse. In conclusion, pulses of short-term and high-dose IVCY can effectively reduce AIGA titers.

BACKGROUND: Nontuberculous mycobacteria (NTM) usually invades vulnerable hosts. Disseminated NTM (dNTM) infection can affect nearly all organs and be easily misdiagnosed as metastatic carcinoma or other systemic diseases, especially in seemingly immunocompetent hosts. Identification of underlying immunodeficiency is critical for the diagnosis and treatment of dNTM. Adult-onset immunodeficiency (AOID) with anti-IFN-γ autoantibodies has recently been recognized as a crucial but frequently neglected risk factor for dNTM infection. Frequent relapses of infection are common in AOID patients despite appropriate anti-infective treatment and B-cell-depleting therapy has shown some promising results. Herein, we report a case of dNTM infection mimicking malignancy in an AOID patient who was successfully treated with rituximab.
METHODS: A middle-aged male presented with fever, productive cough, multifocal skin abscesses and multiple osteolytic lesions with pathological fractures. Chest CT revealed consolidation of the lingula while bronchoscopy showed a mass completely blocking the airway opening of the inferior lingual segment. Metagenomic next-generation sequencing and mycobacterial culture of skin pus and bronchoalveolar lavage fluid reported Mycobacterium Colombiense, confirming the diagnosis of dNTM infection. However, anti-NTM antibiotics alone failed to prevent disease relapse and progression. Further evaluation indicated undetectable serum IFN-γ concentration and high-titer autoantibodies against IFN-γ, suggesting that AOID was the underlying reason for dNTM. Rituximab was added to treatment and successfully controlled the infection without relapse at one-year follow-up.
CONCLUSIONS: We reported a rare case of disseminated Mycobacterium Colombiense infection manifested with pulmonary mass, pathological fracture and dermapostasis in a host with AOID. Our case demonstrated that AOID should be screened when patients get the episode of disseminated NTM infection particularly when other risk factors are excluded. Besides prolonged anti-NTM therapy, AOID-associated NTM infection should be treated with B-cell-depleting therapy to prevent recurrence.

UNASSIGNED: Disseminated nontuberculous mycobacterial (DNTM) infection can involve multiple organs, including the lungs, skin and soft tissues and lymph nodes. However, NTM infection leading to osteolysis has been rarely reported. Here, we analyzed the clinical features, osteolytic mechanisms, treatment and prognosis of patients with DNTM disease with osteolytic lesions.
UNASSIGNED: This retrospective study was conducted between January 1, 2011, and December 31, 2020, at the First Affiliated Hospital of Guangxi Medical University and the Fourth People\'s Hospital of Nanning City. Patients who had culture and/or histopathological proof of DNTM disease with osteolytic lesions were included.
UNASSIGNED: Ten HIV-negative patients with DNTM disease with osteolytic lesions were enrolled. Five of these patients had underlying diseases. Seven and three of the patients were positive and negative for anti-interferon-γ autoantibodies (AIGAs), respectively. The AIGA positivity rate was 70% (7/10). Ostealgia and anemia were the most common symptoms, followed by fever, emaciation, cough, expectoration, anorexia, subcutaneous abscesses and lymphadenopathy. Leukocyte and neutrophil counts were increased. The most common sites were the vertebrae, sternum, clavicle and ribs, although the femur, ilium, humerus, and scapula were also involved. Radiography and computed tomography (CT) showed moth-eaten or irregular destruction of bone, bone defects, pathological fracture, periosteal proliferation and surrounding abscesses. Emission CT (ECT) bone scans showed significantly increased uptake in many skeletal regions. Positron emission tomography(PET)/CT showed metabolic activity in multiple bones. All patients received anti-nontuberculous therapy, and five underwent surgery. Two died during treatment.
UNASSIGNED: DNTM infection of bone and leading to osteolysis usually occurs in patients with AIGA-positive antibodies. DNTM disease with osteolysis is characterized by increased leukocytes and neutrophil counts, focal suppurative granulomas, and multiple areas with moth-eaten or irregular destruction of bone with increased radioactive concentrations. Early diagnosis and timely, effective combination anti-NTM therapy can improve the prognosis.

BACKGROUND: Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China.
METHODS: Between January 2018 and September 2020, we enrolled patients with T. marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded.
RESULTS: Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy.
CONCLUSIONS: T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions.