Abstract

Background: Lymphedema (LE) has been called the forgotten vascular disease, given such scant knowledge about LEassociated comorbidities or causes. Such knowledge of the comorbidities and treatment of LE may assist in diagnostic decisions and health care planning.

Methods: To determine the proportion of LE patients with various LE-associated comorbidities as well as the rate of associated treatment, deidentified Health Insurance Portability and Accountability Act-compliant commercial administrative claims from the Blue Health Intelligence (BHI) research database (165 million Blue Cross Blue Shield members) were queried. We analyzed a BHI study sample of 26,902 patients with LE who had been enrolled with continuous medical benefits for 12 months before and after the index date for the complete years 2012 through 2016. Patients were first identified by comorbidity and then grouped into those receiving no treatment for LE and those receiving any treatment for LE. Any treatment was defined as receiving manual lymphatic drainage, physical therapy, compression garments, or a pneumatic compression device. The purpose of this study was to determine the proportion of LE patients comorbid with various known LE-associated conditions and the treatment rates of LE patients with each comorbidity.

Results: Among the 84,579,269 BHI patients enrolled during the study window, 81,366 patients were identified with LE. From this LE group, our study focused on the 26,902 patients who were enrolled with continuous medical and pharmacy benefits for 12 months before and after the index date. Among these 26,902 LE patients, breast cancer was the most frequent comorbidity with LE (32.1%), and these patients almost universally received any treatment (94.2%); other cancer types, such as melanoma (2.1%) and prostate cancer (0.7%), were less frequent and received any treatment less often, 75% and 82% of the time, respectively. Venous leg ulcer was the most common non-cancer-linked comorbidity for LE (9.6%), but only 81.7% of venous leg ulcer patients received any treatment for LE.

Conclusions: To our knowledge, this is the largest study to date detailing the comorbidities associated with LE and LE treatment rates within each. Our findings suggest that a sizable proportion of cancer-related LE patients do not receive appropriate treatment. Furthermore, this study highlights the role of advanced venous disease as an LE comorbidity that is frequently untreated and its associated gap in treatment.

Main findings

• This analysis identified breast cancer as the leading comorbid condition associated with an LE diagnosis (32.1%). One of the major findings of this study is the previously underappreciated important role of phlebolymphedema as the second most common cause of LE (10.4%). Phlebolymphedema is a pathophysiologic consequence of venous hypertension and related lymphatic overload. Normally, excess interstitial fluid is effectively removed by lymphatic vasculature; but if the fluid load overwhelms the lymphatic capacity or if the lymphatics are defective through destruction of lymphatic vessels by episodes of cellulitis, interstitial fluid, macromolecules, and cytokines accumulate, which leads sequentially to edema, lipodermatosclerosis, and subsequent ulcer formation.
• Pelvic cancers were within the range of 0.6% to 1.9% of patients with LE. Melanoma and prostate cancer were less frequent at 2.1% and 0.7%, respectively. Similarly, however, these data may contain a referral and diagnosis bias, which can lead to under-reporting. Obesity, as an independent comorbidity for LE, was observed in 14.2% of patients, but this may be an underestimation of its true proportion because of the well-known unreliability of coding obesity in an administrative health care data set.
• There are multiple reasons for the existence of a treatment gap, which include physician-related, patient-related, and system-related causes. One major influential factor is that LE is a chronic disease; as such, there is no definitive cure, nor can the traditional acute care model of disease treatment be applied to the entire population of patients with LE.
• Currently, there are no universally accepted guidelines for the management of LE to assist physicians in the recommendation of treatment.
• To the authors knowledge this is the largest study to date of LE treatment rates and comorbid conditions. Our findings confirm the major role of cancer associated with LE among those who receive treatment. However, this study also highlights the role of advanced chronic venous diseasedand of VLU in particulardas a comorbidity for LE. Whereas LE associated with breast cancer commonly receives treatment, a sizable proportion of other cancerrelated LE patients do not receive appropriate treatment. Moreover, VLU, as a comorbidity, is associated with an 18% incidence of no treatment, further evidence of a treatment gap for LE.