Summary of Etiology of ADL. Although the literature on the etiology of ADL episodes is vast, the results, study methods, and outcome definitions are varied. To understand the etiology of ADL episodes, an ideal study would randomly expose lymphedema patients to a variety of bacterial and fungal pathogens. These patients would then be followed up for ADL episodes. Those pathogens whose exposure resulted in an episode would then be prime candidates for being the causative agent in ADL morbidity. If more than one pathogen exposure resulted in ADL episodes among the patients, then perhaps a multiple agents are involved in the etiology. This type of study is unethical and therefore not feasible to conduct. The studies done to date exploring the etiology of ADL have used a variety of techniques: comparing lymphedema patients with ADL to non-ADL lymphedema controls, comparing lymphedema patients with ADL to healthy controls without lymphedema, comparing two time points (an ADL and convalescent time point) among both lymphedema patients with ADL and lymphedema patients without ADL. They have also explored a variety of pathogens using a variety of laboratory indicator tests. Although many studies have found higher levels of both Streptococcus antibody and Streptococcus bacterial cultures among patients experiencing an ADL, most of the earlier work was descriptive; no analytical hypothesis tests were performed. Furthermore, some studies have specifically looked at the outcome of ADL defined by redness, swelling, and systemic symptoms, while others have used such vague outcomes as acute filarial disease or acute filarial fever. These differences make studies difficult to compare. Two other study design issues arise in trying to identify the cause of ADL episodes among lymphedema patients. First, understanding the temporal order of pathogen exposure and the occurrence of ADL cannot be underestimated when attempting to determine the etiology of ADL. Most of the literature on the etiology of ADL consists of cross-sectional studies with data from only one time point. Although one can show higher antibody levels to a certain pathogen among lymphedema patients with ADL compared to non-ADL controls, temporality cannot be established without multiple time points. If a study collects serologic samples during the ADL episode (acute period) and during a convalescent period following the episode, one can assess the change in antibody response and potentially implicate a specific pathogen or set of pathogens...
