Epidemiology of tuberculous lymphadenitis in Denmark: A nationwide register-based study

Abstract

Background Tuberculous lymphadenitis (TBLA) is the most common extrapulmonary manifestation of tuberculosis (TB), often claimed to be reactivation. We aimed to describe the epidemiology of TBLA in Denmark, as it has not previously been investigated specifically although extrapulmonary TB has been associated with an increased long-term mortality and delays in the diagnosis. Methods Register-based study of all patients notified with TBLA in Denmark from 2007 through 2016 utilizing six different nationwide registers. Patients were identified through the national TB surveillance register, and the diagnosis evaluated based on microbiology, pathology and/or clinical assessment. Results In total, 13.5% ( n = 489) of all TB patients in Denmark had TBLA with annual proportions from 9.4 to 15.7%. Most patients were immigrants between 25–44 years. Incidence rates ranged from as high as 1,014/100,000 for Nepalese citizens to as a low as 0.06/100,000 for Danes. Danes had a significant higher median age and significant more risk factors and comorbidities, as well as an increased overall mortality, compared with immigrants ( p <0.05). A significant and much higher proportion of unique MIRU-VNTR genotypes were seen among TBLA patients compared to other TB manifestations. Conclusion In Denmark, TBLA is a common manifestation of TB, especially in young immigrants from high-incidence countries. In Danes, it is a rare disease manifestation and associated with higher morbidity and mortality. To our knowledge, this is the first study suggesting that TBLA is predominantly associated with reactivation of latent TB infection based on genotyping although this remains to be clarified.

Clinical features of tuberculous lymphadenitis in a low-incidence country

“…PUR was rare and mainly seen among young migrant females. In accordance with a previous study, the majority of patients were young migrants with the majority being of Somalian origin (Mathiasen et al, 2019a), most likely reflecting the substantial migration from Somalia to Denmark and the enormous burden of TB seen in this population group (Lillebaek et al, 2002). Physicians should be aware of the higher a priori risk of TB, HIV and other communicable diseases in migrants such as refugees and asylum seekers (Alberer et al, 2018;Deen et al, 2018).…”

“…Physicians should be aware of the higher a priori risk of TB, HIV and other communicable diseases in migrants such as refugees and asylum seekers (Alberer et al, 2018;Deen et al, 2018). As previously discussed (Mathiasen et al, 2019a), many of the TBLA cases have unique MIRU-VNTR genotypes and are likely to be reactivation of previously acquired infection, as most TB among migrants in Denmark is estimated to be imported infection Figure 2. Treatment outcome defined according to the World Health Organization (WHO) criteria (Anon, 2015).…”

“…Based on a recent nationwide analysis of TBLA in Denmark, hospital records from all TBLA patients in the Central Region from 2007-2016 were retrieved and analysed (Mathiasen et al, 2019a). The Central Region is one of five regions in Denmark with a population size of approximately 1.2 million, with around 100,000-130,000 migrants, including descendants (Anon, 2020).…”

“…One-fourth of the world's population is presumed to be latently infected with Mycobacterium tuberculosis (M. tuberculosis) (Cohen et al, 2019). The most common extrapulmonary manifestation of tuberculosis (TB) is tuberculous lymphadenitis (TBLA) (Holden et al, 2019a), which is often attributed to reactivation of latent infection (Fontanilla et al, 2011;Mathiasen et al, 2019a). The diagnosis may be difficult in countries with a low incidence of TB, as the disease is rare, which may delay appropriate treatment (Mathiasen et al, 2019b).…”

“…In Denmark, TBLA is seen in as many as 15.7% of TB patients annually, most often in young migrants (Mathiasen et al, 2019a). However, the clinical features of these patients have never been systematically studied in this setting.…”