How Would You Diagnose This Patient’s Lower Extremity Edema?

Adam D. Perry, MD
John E. Jackson, MD
Joanna Bolton, MD
Volume 55 - Issue 9 - September 2015

A 67-year-old morbidly obese male with diabetes and chronic renal insufficiency presented for evaluation of long-standing lower extremity edema.

History

The patient has had multiple decade history of bilateral lower extremity swelling, but noticed an increase in the late 1990s associated with verrucous and mossy changes. He previously tested positive for a purified protein derivative reactor in 1985 and was treated for latent tuberculosis.

In 2012, the patient was evaluated at a tropical medicine institute in the Philippines and treated with diethylcarbamazine and doxycycline for presumed filarial infection. The following year after the treatment, he reported continued swelling as well as the development of skin breakdown and maggot infestation. He eventually returned to the United States for further care.

Elephantiasis nostras verrucosa

Laboratory Tests

Upon arriving to the United States, the patient was found to be nonambulatory and placed in an inpatient status to expedite the workup of his condition. Current blood smears and 2 punch biopsies were obtained and showed no evidence for ongoing filariasis or subcutaneous infections.

The patient was given twice a day bleach baths and was initiated for cutaneous decolonization due to 2+ Morganella morganii and 1+ Proteus mirabilis found on cutaneous bacterial swabs.

Upon workup for potential causes of lymphatic obstruction, CT and positron emission tomography scans found liver cirrhosis, lung nodules, and diffuse lymphadenopathy; the latter was due to sequelae of prior granulomatous disease versus chronic lymphatic destruction from an unkonwn cause. Current tuberculosis was ruled out via quantiferon testing.

(Answer, discussion, and podcast on next page)

Answer: Elephantiasis nostras verrucosa

Diagnosis

Elephantiasis nostras verrucosa (ENV) is a complication of chronic lymphedema resulting in massive enlargement of the affected area along with hyperkeratosis and fibrosis (Figure 1). Upper as well as lower extremities are at risk for developing ENV, but the abdomen, genitals, and lower extremities are more frequently affected due to the dependent nature of lymphatic flow. Larger lesions can have significant social impact and lead to permanent disability in extreme cases. Infections as well as malignancies must be considered and appropriately evaluated during the initial patient evaluations. Chronic venous insufficiency (CVI) and obesity both appear to play a role in more rapid progression of the disease.1 The importance of management continues to be placed on early intervention at improving lymphatic flow. 

Treatment

A multidisciplinary team evaluated the patient and provided treatment recommendations. Gastroenterologists upon workup of liver cirrhosis found the patient to be positive for anti-smooth muscle antibodies and a large gap between total protein and albumin suggestive of autoimmune hepatitis. However, due to the patient’s multiple comorbidities, a liver biopsy was not recommended to confirm suspicions. Infectious disease was initially concerned for infection by chromoblastomycosis or mycetoma.  However, upon tissue examination and lab testing an infectious etiology for the swelling could not be elucidated. Infectious disease, gastroenterology, dermatology, and internal medicine physicians agreed the best treatment at that point was to optimize his chronic kidney disease, diabetes (HgbA1c at admission was 8.1%), and edema by use of compression stockings, elevation, massage and physical therapy to attempt to return patient to ambulatory status. Surgical services were not utilized at this point due to the poorly managed medical conditions and high morbidity/mortality risks with only minimal data to suggest improvement in condition. Surgical debulking, however, was considered as a potential future treatment.

Discussion

ENV is a rare late finding in the setting of chronic lymphedema. While early disease of the lymphatics can be caused by either infectious or noninfectious lymphatic obstruction, late changes seen in the dermis and epidermis are results of fibroblast proliferation and hyperkeratosis as well as chronic lymphatic dilation.2 ENV is often separated from other causes of lymphedema by its verrucous appearance and plainly visible hyperkeratotic changes (Figure 2). Histologically, the epidermis shows pseudoepitheliomatous hyperplasia while the dermis shows extensive fibrous tissue hyperplasia and dilated lymph channels.3 The bilateral and chronically progressive nature of ENV is distinctive.

Lymphedema as a whole is a common occurrence throughout the world. A 2008 study combining data from 17 wound care centers showed lymphedema was present in 74% of its morbidly obese patients, suggesting that obesity itself may cause risk for developing lymphedema and eventually ENV.4 However, the differential diagnosis varies widely from infectious, noninfectious, malignancy, surgical, or traumatic disruptions of the lymphatics and medical. The large variation in causes of underlying lymphedema is why history and tissue biopsy is important in diagnosis in order to rule out treatable or life-threatening causes.5

Differential diagnosis for ENV specifically often includes chromoblastomycosis, filariasis, papillomatosis cutis carcinoides, and Stewart-Treves syndrome, among others.5,6 His bilateral symmetric involvement (Figure 3) was a clinical clue to indicate that his findings were related to chronic lymphatic involvement more likely than an infectious or malignant cause. However, all potential causes must be ruled out as misdiagnosis can lead to further irreparable damage.

Primary treatment for ENV is geared toward mechanical improvement in lymphatic flow. Mechanical massage, compression stockings, and improving underlying conditions that may cause lymphedema can decrease worsening of the disease and improve function. Medical management has yet to prove completely efficacious in reversing the disease process, but success has been shown with oral retinoids and tazarotene in isolated cases.7,8 Other topical agents, such as keratolytics, may be considered to improve normal continuity of the epidermis. Reduction of lymphedema with laser treatment in post-mastectomy patients showed promise, but the use of lasers to reduce lymphedema prior to or post-development of ENV has not been studied, yet may eventually lead to new treatments.9

While surgical debulking can improve patient outcome for patients with severe disability,10,11 there has not been a significant amount of research indicating early surgical intervention can improve long-term patient outcome. Furthermore, it would seem that patients with CVI or chronic lymphedema are at higher risk for wound infections. Therefore, surgical intervention as a treatment option must be weighed heavily.

Outcome of the Case

Since the time of initial presentation, the patient has relocated to be closer to family. Further follow-up at this time is not possible.

The author explains the case in this podcast:

References:

  1. Dean SM, Zirwas MJ, Horst AV. Elephantiasis nostras verrucosa: An institutional analysis of 21 cases. J Am Acad Dermatol. 2011;64(6):1104-1110.
  2. Smoller BR, Rongioletti F. Clinical and Pathological Aspects of Skin Diseases in Endocrine, Metabolic, Nutritional and Deposition Diseases. New York, NY: Springer; 2010: 77-78.
  3. Weedon D. Weedon’s Skin Pathology. 3rd ed. London, United Kingdom: Churchill Livingstone Elsevier; 2010: 843.
  4. Fife CE, Carter MJ. Lymphedema in the morbidly obese patient: unique challenges in a unique population. Ostomy Wound Manage. 2008;54(1):44-56.
  5. Sisto K, Khachemoune A. Elephantiasis nostras verrucosa: a review. Am J Clin Dermatol. 2008;9(3):141-146.
  6. Liaw FY, Huang CF, Wu YC, Wu BY. Elephantiasis nostras verrucosa: swelling with verrucose appearance of lower limbs. Can Fam Physician. 2012;58(10):e551-e553.
  7. Zouboulis CC, Biczó S, Gollnick H, et al. Elephantiasis nostras verrucosa: beneficial effect of oral etretinate therapy. Br J Dermatol. 1992;127(4):411-416.
  8. Boyd J, Sloan S, Meffert J. Elephantiasis nostrum verrucosa of the abdomen: clinical results with tazarotene. J Drugs Dermatol. 2004;3(4):446-448.
  9. Kozanoglu E, Basaran S, Paydas S, Sarpel T. Efficacy of pneumatic compression and low-level laser therapy in the treatment of postmastectomy lymphoedema: a randomized controlled trial. Clin Rehabil. 2009;23(2):117-124.
  10. Wollina U, Heinig B, Schönlebe J, Nowak A. Debulking surgery for elephantiasis nostras with large ectatic podoplanin-negative lymphatic vessels in patients with lipo-lymphedema. Eplasty. 2014;14:e11.
  11. Gacto-Sánchez P, Fernandez-Ortega P, Pereyra-Rodríguez JJ. Elephantiasis nostras verrucosa: successful surgical treatment in a gross deformity. Indian J Dermatol. 2009;54(2):189-190.