Incorrect diagnoses in patients with neutralizing anti-interferon-gamma-autoantibodies

Abstract

Disseminated non-tuberculous mycobacterial infections Incorrect diagnosesNeutralizing anti-interferon-gammaautoantibodies TB metastatic carcinoma a b s t r a c t Objectives: Early diagnosis of adult-onset immunodeficiency associated with neutralizing antiinterferon-gamma autoantibodies (anti-IFNg Abs) remains difficult given the lack of a distinctive phenotype and a routine test. This study aimed to investigate the determinants of incorrect tentative diagnoses and useful clues for early disease recognition. Methods: This study enrolled adult patients who had unexplained opportunistic infections diagnosed at six hospitals and identified those having neutralizing anti-IFNg Abs (cases). Demographics, medical history, initial presentations and laboratory data, causative pathogens, tentative diagnoses, and treatment were analysed and compared among individuals having neutralizing anti-IFNg Abs (cases) and those without (controls). Results: Among the 154 patients enrolled, neutralizing anti-IFN-g Abs were detected in 50 (71%) of 70 patients with disseminated non-tuberculous mycobacterial infection (dNTM) but not in 84 patients without dNTM. The median time from disease onset to the recognition of dNTM associated with neutralizing anti-IFNg Abs was 1.6 years (range, 0.25e19 years). Incorrect tentative diagnoses resulted in the administration of anti-tuberculosis regimens (60%, 30/50), immunosuppressants (48%, 24/50), and systemic chemotherapy (2%, 10/50) to the 50 cases. Multivariate analysis revealed that case patients were more likely than controls to present with multiple bone lesions (adjusted odds ratio (OR), 27.16; 95% confidence interval (CI), 1.21e609.59) and leukocytosis (adjusted OR, 1.48; 95% CI, 1.12e1.95); however, the controls had a higher rate of mycobacterial bloodstream infection (adjusted OR, 0.05; 95% CI 0.00 e0.66). Conclusions: The high rate of incorrect tentative diagnoses led to frequent inappropriate management in patients with neutralizing anti-IFNg Abs, and highlighted the need for increased awareness among clinicians. U.-I.

Characteristic clinical features and plasma cytokine profiles in patients infected with nontuberculous mycobacteria and Talaromyces marneffei due to anti–interferon-gamma autoantibodies

“…Although all patients enrolled in our study presented with NTM and/or T. marneffei infection, signi cantly different clinical manifestations were observed between patients in the ABP and ABN groups. The BMI levels of patients with anti-IFN-γ Abs were lower, and the probabilities of disseminated infection, fever, weight loss, and lymphadenopathy were higher than those in patients without anti-IFN-γ Abs, which was also found in previous studies [15,17]. In a study in Guangxi province, more than 70% of patients with anti-IFN-γ Abs showed symptoms of fever, weight loss, or lymphadenopathy [17], suggesting that these symptoms could be characteristic in distinguishing patients who are more likely to have anti-IFN-γ Abs.…”

“…Although previous studies have described the typical clinical manifestations and laboratory ndings of patients with anti-IFN-γ Abs, early disease diagnosis remains di cult in areas with low incidence [15]. Therefore, we conducted a case-control study in a large tertiary hospital in Shanghai to investigate the positive rate of anti-IFN-γ Abs in patients infected with NTM or T. marneffei and to provide guidance for early identi cation of such patients.…”

“…Therefore, we conducted a case-control study in a large tertiary hospital in Shanghai to investigate the positive rate of anti-IFN-γ Abs in patients infected with NTM or T. marneffei and to provide guidance for early identi cation of such patients. In addition, previous studies have revealed high levels of in ammatory markers, such as C-reactive protein (CRP), in patients with anti-IFN-γ Abs [15]. However, little is known regarding the expression of pro-and anti-in ammatory cytokines in these patients.…”

Pathological humerus fracture due to anti-interferon-gamma autoantibodies: A case report

“…However, an acute and accurate diagnosis of musculoskeletal NTM infection is often difficult because of the indolent clinical course and difficulty in isolating pathogens[ 8 ]. A recent prospective case-control study in Taiwan[ 9 ] reported an average 1.6 year delay in the diagnosis of nAIGA-related dNTM due to protean manifestations mimicking other systemic illnesses, including mycobacterial tuberculosis, malignancy, and connective tissue diseases. Multivariate analysis revealed that slow-growing NTM species ( i.e., Mycobacterium intracellulare ) in nAIGA cases were associated with multiple bone involvement.…”

Clinicopathological Manifestations and Immune Phenotypes in Adult-Onset Immunodeficiency with Anti-Interferon-γ Autoantibodies

“…Besides direct infections, reactive conditions such as skin manifestation were frequent, with reactive skin disorders, mostly neutrophilic dermatoses, reported in 82% of the patients [6]. Early diagnosis of the disease is di cult owing to the protean manifestations in apparently immunocompetent hosts and the absence of standard laboratory assays [7,8]. Patients may require long-term antimycobacterial therapy because of chronic infections and high recurrence rates, even after remission [9,10].…”