Clinical significance and epidemiological evolution of epitrochlear lymphadenopathy in pre- and post-highly active antiretroviral therapy era: A systematic review of the literature

Abstract

Epitrochlear lymphadenopathy is believed to be associated with distinct etiologies, however the evidence for the same is lacking. We systematically reviewed the reported causes of an enlarged epitrochlear lymph node and compared them over different time periods. Epitrochlear lymphadenopathy was encountered in a wide range of diseases, and we found no association with any particular disease.

INTRODUCTION

The site of enlarged lymph nodes has little relevance to the etiology. However, epitrochlear lymph nodes have been linked in the past with syphilis and recently to sarcoidosis and human immunodeficiency virus (HIV) infection.[1,2,3] Traditional teaching in clinical medicine emphasizes the importance of examining this node, considering the specific diseases it can diagnose. The scientific basis for such an assumption is lacking, and a comprehensive review on the various causes of epitrochlear lymphadenopathy is not available. Herein, we systematically review the literature to ascertain the various causes of epitrochlear lymphadenopathy and its possible association with a distinct etiology.

METHODS

We performed a search of the PubMed database from inception till 31^st August 2017 using the following free-text terms: “epitrochlear” OR “epitrochlear node” OR “epitrochlear adenopathy” OR “epitrochlear lymph node” OR “epitrochlear lymphadenopathy” OR “epitrochlear gland”. In addition, we reviewed the reference list of all the included articles and sifted our personal files.

Inclusion and exclusion criteria

We included articles meeting the following criteria: (a) palpable epitrochlear lymphadenopathy ≥1 cm in transverse diameter or the presence of hard immobile nodes and (b) cases reported to have definitive diagnosis proven by histology/cytology/microbiology or other ancillary tests. Articles were excluded if: (a) epitrochlear node enlargement was evident only on investigations like lymphoscintigraphy, (b) no specific etiology was identified, (c) animal studies, and (d) publications in language other than English.

A database was created from our search using the reference manager EndNote (version X8.1; Clarivate Analytics). Duplicate citations were discarded. Two authors (VM and RA) independently screened the database for relevant articles, and any discrepancy was resolved by discussion. After scrutiny, we reviewed the full text of the selected articles. The following information was then extracted: (a) details of publication (year, country and authors), (b) number of patients with enlarged epitrochlear node in each study, and (c) the final etiology of the enlarged epitrochlear node.

We compared the various causes of epitrochlear enlargement over the three-time periods: (a) pre-HIV (1983 and before), (b) pre-highly active antiretroviral therapy (HAART) (1984 till 1996), and (c) post-HAART era (1997 till 2017).

Data were represented as number (percentages) and the reported etiology was tabulated for the three different time periods.

RESULTS

We identified 144 articles, of which 79 (including 507 subjects) were found to be eligible for inclusion.[2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80] Infections (n = 356, 70.2%) and neoplasms (n = 116, 22.9%) were the most common reported causes of an enlarged epitrochlear node [Table 1].

Table 1.

Specific etiologies of epitrochlear lymph node enlargement reported in literature-compared between pre-human immunodeficiency virus, pre-highly active antiretroviral therapy, and post-highly active antiretroviral therapy era

Pre-human immunodeficiency virus era

Infections represented more than two-thirds of the reported causes, with leprosy being the most common (n = 68, 74.7%). Neoplasms (Hodgkin's lymphoma [HL], followed by non-Hodgkin's lymphoma [NHL] and melanoma) were the next common cause.

Pre-highly active antiretroviral therapy era

The most common cause in this era was infections (82.6%) of which HIV (with or without tuberculosis [TB]) infection constituted the majority (71.8%). Tuberculous epitrochlear lymphadenitis was either secondary to disseminated TB or synovial TB of the wrist.[19] Noninfectious causes such as rheumatoid arthritis and sarcoidosis were also diagnosed during this period; however, their proportion was small (5.5%). Lymphoma (NHL and HL) was the most commonly reported neoplasm in this era as well.

Post-highly active antiretroviral therapy era

Unlike the previous two-time periods, the proportion of infectious causes decreased to 50.4% [Figure 1]. Cat-scratch disease was the most common reported infectious cause (60%). Among the neoplastic causes, HL was the most common, apart from several other tumors (Kaposi's sarcoma, Merkel-cell carcinoma, and others). Kimura's disease and sarcoidosis were infrequently reported noninfectious causes.

Figure 1.

Comparison of the proportion of infectious, noninfectious and neoplastic causes of epitrochlear node enlargement reported in the pre-human immunodeficiency virus, pre- and post-highly active antiretroviral therapy era

DISCUSSION

The results of this systematic review suggest that the epidemiology of epitrochlear lymphadenopathy has evolved over the last few decades. There was a 3-fold increase in the rate of noninfectious causes (from 17.5% to 49.6%) over time [Figure 1]. The apparent increase in the noninfectious causes is probably due to a decreased burden of infectious illnesses in the post-HAART era. The “traditional” etiologies including syphilis and sarcoidosis were seldom encountered. This is because epitrochlear adenopathy results either from involvement of its drainage area by pathologic processes (analogous to other regional lymph nodes) or part of a systemic illness, rather than any particular etiology (syphilis, sarcoidosis, or HIV).

Our review has certain limitations. As most of the causes of an enlarged epitrochlear node were identified from case reports and series, it is not possible to estimate the true proportion of various etiologies. Nevertheless, it provides an overview of the various etiologies causing epitrochlear node enlargement in contemporary medicine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.