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Jacobs Journal of Clinical Case Reports

Non-Filarial Elephantiasis, a Case Report with Review of the LiteratureManuel Lora Gonzalez1*, James Bush1, Michael Wilkins1, Douglas McGregor1*

1The University of Kansas, USA

*Corresponding author: Manuel Lora Gonzalez, Pathology Resident, The University of Kansas Medical Center, USA,

Email: mlora2@kumc.edu

Douglas McGregor, Professor, Kansas City VA Medical Center, USA, Email: douglas.mcgregor@va.org

Received: 06-04-2018

Accepted: 06-21-2018

Published: 06-25-2018

Copyright: © 2018 Manuel Lora Gonzalez

Keywords: Non-Filarial Lymphedema; Elephantiasis Nostras Verrucosa; Verrucous

Case Report

Cite this article: Manuel Lora Gonzalez. Non-Filarial Elephantiasis, a Case Report with Review of the Literature. J J Clini Case Rep. 2018, 5(2): 032

Case Report

A 67 year old male presented to the wound clinic for evalu-ation of non-healing ulcers and massive edema of the lower extremities. He was an obese male with a history of quadriple-gia secondary to septic embolus to the spinal cord. His course had been complicated by recurrent episodes of sepsis, includ-ing urosepsis. He routinely followed up at wound clinic for his lower extremity edema and recalcitrant ulcers over a period of years. Five years after his initial spinal cord injury, verru-cous plaques began to develop on his inner thighs. The lesions demonstrated a fine scale and were darker than the surround-ing tissue. They began as plaques bilaterally and spread slowly over time with formation of satellite lesions followed by co-alescence. These lesions appeared to favor areas with pro-longed exposure to moisture - remaining on the inner thighs bilaterally and extending to the groin. The primary treatment strategy was moisture reduction with wicking pads changed daily. The lesions did not respond to therapy, and recalcitrant ulcers and osteomyelitis of the left lower leg eventually led to a left above the knee amputation. This did lead to improvement in the verrucous lesions with a moderate reduction in the size of the lesions - presumably related to improved dryness of the area.

Biopsy of the plaque demonstrated two pedunculated lesions, confluent at their base, with dermal expansion by fibrocystic cells. There were increased and widened vascular and lym-phatic vessels throughout the dermis, but particularly in the superficial dermis. The stroma was variably collagenized and

edematous with many stromal cells staining positively for factor XIIIa and CD163. Inflammation was sparse with a mild infiltrate of perivascular lymphocytes. The epidermis was hy-perplastic with focal verrucous changes bordering on pseudo-epitheliomatous hyperplasia. The changes were considered consistent with verrucous lymphedema.

ENV is a condition characterized by woody fibrosis and often widespread verrucous change of the skin in an area affected by chronic lymphedema. Lymphedema can be categorized as primary (congenital) and secondary (acquired). Worldwide, secondary lymphedema is most often caused by filariasis - however this is not common in Western countries. The term elephantiasis nostras verrucosa was first used in 1969 by Cas-tellani to describe a condition which resulted from recurrent lymphatic blockage related to bacterial infection while other acquired causes of lymphatic obstruction (mycotic, neoplas-tic, etc.) were termed elephantiasis symptomatica [1]. Subse-quently, other authors have included all acquired, non-filarial, non-congenital causes of lymphatic obstruction in the defini-tion of ENV [2-4].

While filariasis is the most common cause of lymphedema worldwide, in Western countries common etiologies include repeated streptococcal lymphangitis/erysipelas, malignan-cy, trauma, surgery, radiation therapy, chronic venous stasis, scleroderma, and obesity. The blockage or damage of lymphat-ic channels leads to accumulation of protein-rich fluid in the interstitium. This causes a chronic inflammatory state with subsequent proliferation of fibroblasts, vasculature, and kera-

tinocytes. These changes lead to the firm, cobblestone appear-ance observed clinically [4-5].

ENV typically includes bilateral involvement of the feet and calves, occasionally extending to the thighs and groin. Al-though lower extremities are the classic site, ENV can develop the condition wherever chronic lymphedema occurs.

Jacobs Publishers 2All patients demonstrate non-pitting edema with “cobble-stone-like” plaques and papules with hyperkeratosis. Larger nodules, ulceration, and changes of chronic venous insufficien-cy often are identified within the affected area as well. As the condition progresses, the skin becomes more verrucous and increasingly firm [5].

Diagnosis Clinical presentation Histopathology/Diagnosis Lymphatic filariasis Travel to endemic areas. Possible

history of preceding lymphangitis. Frequently involves scrotum. (14) Developed lesions indistinguishable from ENV.

Filarial infection can be documented by identifying the parasite in tissue biopsies or peripheral blood smears or by antigen testing. (14) Histologically similar to ENV.

Localized lymphedema A single papillomatous, pendulous, or polypoid mass typically in the anogenital region or thigh (occasionally head and neck). (9)

Histologically similar to ENV.

Certain deep fungal infections Lesions begin as a solitary papule which expands to a verrucous nodule or plaque. (15)

Pseudoepitheliomatous hyperplasia with a mixed dermal inflammatory infiltrate. Microabscesses are common in the dermis and downgrowths of the epidermis. Granulomas often present. Organisms can be identified primarily within macrophages. Chromomycosis and blastomycosis are most common sources of this clinical and histologic picture. (16)

Lipodermatosclerosis Sequelae of venous stasis and ischemia. May be unilateral or bilateral. Woody induration from the foot to lower calf (appear as inverted champagne bottles). (15)

Septal fibrosis and sclerosis with foci of membranocystic change. Overlying dermis often with evidence of stasis change (vascular proliferation, hemosiderin, dermal fibrosis) Lobular panniculitis in early lesions with prominent plasma cells. (15, 16)

Pretibial myxedema Hyperthyroidism leads to bilateral cutaneous deposition of mucin. May appear as nodules or plaques, nonpitting edema, or elephantiasis-like thickening. W

Extensive dermal mucin often with hyperkeratosis. (16)

Venous stasis dermatitis Erythematous, light-brown discoloration of lower legs often with scaling. (15)

Vascular proliferation, hemosiderin deposition, mild spongiosis and dermal fibrosis. (16)

Multiple eruptive angiofibromas

Associated with tuberous sclerosis or MEN 1. Multiple angiofibromas appear over several years – reported on the face or trunk. (17)

Discrete papules with fibrosis of the dermis and increased dermal blood vessels with an unremarkable epidermis. (17)

Table. 1

Histologically, the condition is characterized by hyperkera-tosis and papillomatosis and often pseudoepitheliomatous hyperplasia. In early stages, there are dilated lymphatics and widened tissue spaces reflecting tissue edema. In later stages, there is extensive fibrosis of the dermis and subcutaneous tis-sue. Inflammation is sparse to absent with cases occasionally demonstrating a patchy dermal or subcutaneous lymphohis-tiocytic infiltrate. While hyperkeratosis, dilated lymphatics, and fibrosis are the histologic hallmarks of ENV, all three may not be present in a given biopsy due to the progressive nature of the disease [4, 6].

The clinical differential diagnosis of ENV includes lymphatic fil-ariasis, localized lymphedema, certain deep fungal infections; lipodermatosclerosis, pretibial myxedema, and venous stasis dermatitis (see Table 1). A possible additional consideration includes multiple eruptive angiofibromas – previously report-ed on the face and trunk. See table 1 for additional discussion. Diagnosis is often clinical with tissue biopsy used in difficult cases although in a review of ENV, Sisto and Khachemoune rec-ommended biopsy of all cases for diagnostic purposes as well as to rule out Stewart-Treves syndrome (angiosarcoma arising in a chronically lymphedematous area) [4,7].

The pathologic findings in our specimen included vasculature proliferation, verrucous epidermal hyperplasia, and a variably edematous and fibrotic dermis. The pathologic differential diagnosis included ENV, localized lymphedema, and multiple eruptive angiofibromas, among others. In our case, serious consideration of multiple eruptive angiofibromas was enter-tained, however the lesions were coalesced plaques rather than discrete papules and the increase in blood vessels was not dramatic. See table 1 for a complete discussion of the dif-ferential diagnosis.

Localized lymphedema is an entity first described in 1995 by Farshid and Weiss [8].

It arises as a single papillomatous plaque, polypoid tumor, or pendulous swelling typically in the ano-genital region or thigh. It is due to localized lymphatic obstruction, often due to obesi-ty, but with reported etiologies identical to ENV. Since the pro-cess remains localized, surgical therapy is often curative [9]. The dividing line between ENV and localized lymphedema is blurry as they represent varying degrees of the same process. Our case demonstrated large, coalescing plaques present bilat-erally. Although the calf was spared which is unusual in ENV, this remains the most appropriate diagnosis.

ENV is a progressive disease with enlargement and deformity of the involved area over the course of several years. As the tissue expands and becomes increasingly fibrotic, ulcers com-monly develop and enlarge and the area becomes colonized with microorganisms. This often leads to morbid infections including osteomyelitis and septic arthritis which may require

amputation. As mentioned previously, Stewart-Treves syn-drome is an uncommon development but is associated with a poor prognosis [4, 10].

Initial treatments include massage, compression stockings, and pneumatic compression pumps [11]. Oral retinoids have been used with moderate success and antimicrobial therapy is often required [4, 12]. If medical and compression therapies are not effective, amputation or debridement of the affected area can be performed [13]. The disease is difficult to treat with occasional positive outcomes using each of the therapy strategies. Currently however, there is no reproducibly effec-tive treatment option.

Figure 1. Lower extremity photograph showing generalized edema, coalescent verrucous plaques with dark pigmentation (A) and focal yellow crust (B).

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5. Dean SM, Zirwas MJ, Horst AV. Elephantiasis nostras verru-cosa: an institutional analysis of 21 cases. J Am Acad Dermatol. 2011, 64(6): 1104-1110.

6. Yang YS, Ahn JJ, Haw S, Shin MK, Haw CR. A case of elephan-tiasis nostras verrucosa. Ann Dermatol. 2009, 21(3): 326-329.

7. Liaw FY, Huang CF, Wu YC, Wu BY. Elephantiasis nostras ver-rucosa: swelling with verrucose appearance of lower limbs. Can Fam Physician. 2012, 58(10): e551-e553.

8. Farshid G, Weiss SW. Massive localized lymphedema in the morbidly obese: a histologically distinct reactive lesion sim-ulating liposarcoma. Am J Surg Pathol. 1998, 22(10): 1277-1283.

9. Lu S, Tran TA, Jones DM, Meyer DR, Ross JS et al. localized lymphedema (elephantiasis): a case series and review of the literature. J Cutan Pathol. 2009, 36(1): 1-20.

10. Sanders LJ, Slomsky JM, Burger-caplan C. Elephantiasis nostras: an eight-year observation of progressive nonfilarial elephantiasis of the lower extremity. Cutis. 1988, 42(5): 406-411.

11. Beninson J, Redmond MJ. Mossy leg--an unusual therapeu-tic success. Angiology. 1986, 37(9): 642-646.

12. Iwao F, Sato-Matsumura KC, Sawamura D, Shimizu H. El-ephantiasis nostras verrucosa treated with surgical debride-ment. Dermatol Surg. 2004, 30(6): 939-941.

13. J Boyd, S Sloan, J Meffert. Elephantiasis nostrum verrucosa of the abdomen: clinical results with tazarotene. J Drugs Der-matol. 2004, 3(4): 446–448.

14. CDC - National Center for Health Statistics – Parasites – Lymphatic filariasis. 2015.

15. James WD, Elston DM, Berger TG. Andrews’ Diseases of the Skin, Clinical Dermatology. Saunders. 2011.

16. Weedon D. Weedon’s Skin Pathology, Expert Consult - On-line and Print. Elsevier Health Sciences. 2009.

17. Schön MP, Ruzicka T, Wienecke R, Fackler I, Lehmann P. Multiple eruptive angiofibromas of the trunk: case report of a new entity?. Arch Dermatol. 2001, 137(11): 1533-1535.

Figure 2. Hematoxylin and Eosin stained sections showed hyperkera-tosis, papillomatosis, pseudoepitheliomatous hyperplasia, fibrosis of the dermis and vascular proliferation with sparse perivascular and interstitial inflammation.

References

1. Castellani A. Researches on elephantiasis nostras and ele-phantiasis tropica with regard to their initial stage of recur-ring lymphangitis (lymphangitis recurrens elephantogenica). J Trop Med Hyg. 1969, 72(89): 89-96.

2. Rowley MJ, Rapini RP. Elephantiasis nostras. Cutis. 1992, 49(2): 91-96.

3. Schissel DJ, Hivnor C, Elston DM. Elephantiasis nostras ver-rucosa. Cutis. 1998, 62(2): 77–80.

4. Sisto K, Khachemoune A. Elephantiasis nostras verrucosa: a review. Am J Clin Dermatol. 2008, 9(3): 141–146.

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