At 3-week follow-up, a trial of narrowband UVB therapy was recommended for control of pruritus. Two weeks later, a modified wet-wrap regimen using clobetasol ointment 0.5% twice daily covered with wet gauze followed by a self-adherent dressing was initiated only on the right arm for comparison purposes. This treatment was not successful. A biopsy taken from the left arm showed lymphedema with perivascular fibroplasia and epidermal hyperplasia consistent with ENV (Figure 2).
Two months after her initial presentation, we instituted treatment with tazarotene gel 0.1% twice daily to the arms as well as a water-based topical emulsion to the finger ulcerations and a healing ointment to the hands. A month later, the patient reported no benefit with tazarotene. She desired more flexibility in her arms and hands; therefore, after a discussion with her rheumatologist, biweekly psoralen plus UVA (PUVA) therapy was initiated. Five months after presentation, methotrexate (MTX) 15 mg once weekly with folic acid 1 mg once daily was added. The PUVA therapy and MTX were stopped 3 months later due to lack of treatment benefit.
The patient was referred to vascular medicine for possible compression therapy. It was determined that her vasculature was intact, but compression therapy was contraindicated due to underlying systemic sclerosis. She was subsequently prescribed mycophenolate mofetil 1000 mg twice daily by her rheumatologist. The options of serial excisions or laser resurfacing were presented, but she declined.
Elephantiasis nostras verrucosa is differentiated from elephantiasis tropica, which is caused by a filarial infection of the lymphatic system. The chronic obstructive lymphedema characteristic of ENV can present as a result of various primary or secondary etiologies including trauma, malignancy, venous stasis, inflammation, or infection.3 In systemic sclerosis, extravascular fibrosis theoretically can lead to lymphatic obstruction and subsequent lymphatic stasis. In turn, the pathophysiology of dermal and subcutaneous fibrosis likely reflects autoantibodies (eg, anticardiolipin antibodies) that can damage lymphatic and nonlymphatic vessels.4,5 With prolonged lymphostasis, excess protein-rich interstitial fluid accumulates, inducing fibroblast proliferation and inhibiting the local immune response.1
As the underlying mechanism of ENV, fibrosis of lymphatic vessels in systemic sclerosis is not well documented. Characteristic features of systemic sclerosis include extensive fibrosis, fibroproliferative vasculopathy, and inflammation, which are all possible mechanisms for the internal lymphatic obstruction resulting in the skin changes observed in ENV.6 It seemed unusual that the fibrotic changes of lymphatic vessels in our patient were extensive enough to cause ENV of the upper extremities; lower extremity involvement is the more common presentation because of the greater likelihood of lymphedema manifesting in the legs and feet. Lower extremity ENV has been reported in association with scleroderma.7,8
Regarding therapeutic options, Boyd et al9 reported a good response in a patient with ENV of the abdomen who was treated with topical tazarotene. Additionally, PUVA and MTX have been reported to be beneficial for the progressive skin changes of systemic sclerosis.10 Mycophenolate mofetil has been used in patients who fail MTX therapy because of its antifibrotic properties without the side-effect profiles of other immunosuppressives, such as imatinib.10,11 In our patient, skin lesions persisted following these varied approaches, and compression therapy was not advised due to the underlying sclerosis.
Because options for medical treatment of severe ENV are limited, surgical debridement of the affected limb often remains the only viable option in advanced cases.12 A PubMed search of articles indexed for MEDLINE using the terms elephantiasis (MeSH terms) or elephantiasis (all fields) and scleroderma, systemic (MeSH terms) or scleroderma (all fields) and systemic (all fields) or systemic scleroderma (all fields) or scleroderma (all fields) or scleroderma, localized (MeSH terms) or scleroderma (all fields) and localized (all fields) or localized scleroderma (all fields) yielded only 1 other case report of lower extremity ENV in a patient with systemic sclerosis who ultimately required bilateral leg amputation.8 When possible, avoiding lymphostasis through compression and control of any underlying infections is important in the treatment and prevention of ENV.3