Medical Care
Treatment for Klippel-Trenaunay-Weber syndrome (KTWS) is conservative and symptomatic. Compression garments are indicated for chronic venous insufficiency, lymphedema, recurrent cellulitis, and recurrent bleeding from capillary or venous malformations of the extremity. The compression garment may also protect the limb from trauma. Intermittent pneumatic compression pumps may also provide benefit. However, in some patients with absent or hypoplastic deep venous systems, elastic compression may increase venous stasis and cause discomfort. Pain management can be a very important aspect of caring for patients with KTWS. Referral to a pain clinic and/or a multidisciplinary team including a pain management specialist is recommended. [37]
Cellulitis and thrombophlebitis can be managed with analgesics, elevation, antibiotics, and corticosteroids. In patients with a history of recurrent cellulitis, intermittent or prophylactic antibiotics may be considered. Anticoagulant therapy is indicated in acute thrombosis and prophylactically prior to surgical procedures. Given the risk of thrombotic events, women with KTWS should avoid using oral contraceptive pills. There remains a question as to which patients would benefit from prophylactic treatment with director oral anticoagulants to prevent serious thromboembolic events and/or reduce pain. [38]
Regarding limb hypertrophy, heel inserts are generally sufficient for limb discrepancies of 1.5 cm or less. For greater discrepancies, orthopedic surgery may be considered. Possible orthopedic procedures include osteotomy, epiphysiodesis, or epiphyseal stapling. Rarely, amputation is required due to recurrent infections, nonhealing ulcers, or recurrent bleeding.
Gain-of-function mutations in the gene encoding the catalytic alpha-subunit of phosphatidylinositol-3 kinase (PIK3CA) lead to activation of PI3K-alpha and Akt-signaling cellular transformation. Many, but not all patients with KTS have been found to have PIK3CA gene mutations. [39]
Alpelisib (Vijoice) is the first drug approved for patients aged 2 years and older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy. US Food and Drug Administration (FDA) approval of alpelisib was supported by real world evidence from the open-label EPIK-P1 trial. A retrospective chart review showed patients treated with alpelisib had reduced target lesion volume and improvement in PROS-related symptoms and manifestations. After 24 weeks, 27% of patients (10/37) achieved a confirmed response to treatment, defined as 20% or greater reduction in the sum of PROS target lesion volume. Also, 23 or 31 patients (74%) showed some reduction in target lesion. [40]
Women with KTWS have been reported to have normal pregnancies. These patients should be monitored carefully with serial ultrasounds because previously asymptomatic arteriovenous malformations within the uterine wall may become pronounced with the additional blood flow to the uterus during pregnancy. [41, 42] Late puerperal hemorrhage has been described. [34]
Surgical Care
In Klippel-Trenaunay-Weber syndrome (KTWS), laser treatment of the hemangioma can be effective in lightening the color of the port-wine stain. Currently, the flashlamp-pumped pulsed dye laser is the treatment of choice in vascular lesions. Laser treatment is also indicated in the case of ulceration. Ulceration of hemangiomas can be painful and can impair functional abilities. When treated with laser, ulcers often heal more quickly. Laser treatment is most effective when performed early, as it can improve the long-term appearance of the port-wine stain and thereby also improve function. Typically, many treatments are required to achieve the desired effect. Laser treatment only helps with the superficial component of the hemangioma. [43]
Surgical intervention in the treatment of varicosities and venous malformations is controversial. One might consider surgery for either significant cosmetic deformity or the symptoms of pain, heaviness of the leg, bleeding, or infectious complications. Venous stripping, ligation, excision, or sclerotherapy are contraindicated unless the surgery involves the superficial system and the underlying deep system is normal or demonstrates only mild-to-moderate reflux. Lymphaticovenular anastomosis may represent a desirable approach. [44]
Inadequate evaluation prior to excision increases surgical complications. Symptomatic superficial varicosities can be removed without harm and with benefit to the patient when an adequate preoperative examination is performed. Although Baskerville et al demonstrated that some 90% of treated varicosities redevelop, treatment can provide lasting improvement for years. [8] Successful treatment of incompetent valves in the femoral vein of the affected limb with contralateral saphenous vein transplant has been reported.
Debulking procedures have limited use and may damage venous and lymphatic structures, leading to increased edema in the affected limb. The potential risks and benefits must be carefully weighed before attempting surgical intervention.
Radiotherapy has been reported to be of help in some cases of KTWS. The radiation may help to induce regression of hemangiomas; however, the results can be slow to develop. [45]
Endovenous laser therapy of the greater saphenous vein is gaining support for the management of varicosities in the general public and in patients with KTWS. [46] This therapy has been used alone and in combination with other surgical interventions. It is a novel and minimally invasive approach for the management of some varicosities. Vesical and uterine involvement may be treated by endoscopic and endovascular routes. [33]
Endovenous mechanochemical ablation for varicoses veins in pediatric KTWS patients appears safe and effective. [47]
Complications
Complications of hemangiomas include skin breakdown and ulceration, bleeding, and secondary infection.
Complications due to varicosities include paresthesia, stasis ulcers, pulmonary emboli, thrombophlebitis, stasis dermatitis, hemorrhage, and cellulitis.
Hypertrophy of a limb may lead to subsequent vertebral scoliosis, gait abnormalities, and compromise of function.
Klippel-Trenaunay-Weber syndrome (KTWS) patients tend to develop degenerative joint disease at an early age. [27]
KTWS has been described as associated with radial artery coronary graft spasm, although its linkage should be regarded as speculative. [28]
A 72-year-old man with longstanding KTWS and chronic penile and scrotal edema had a low-grade angiosarcoma arising in the setting of the chronic lymphedema, but he died from massive hemorrhage due to traumatic rupture of malformed leg vessels. [29]
Long-Term Monitoring
Patients with Klippel-Trenaunay-Weber syndrome (KTWS) should be monitored at least annually and more often if clinically indicated.
Stable disease can be followed clinically. KTWS is not always a static disease process. If progression of the disease arises, imaging studies should be performed. Medical or surgical intervention should be pursued if indicated.
-
Klippel-Trenaunay syndrome in a young person. Note the port-wine stain extending to the buttocks. These lesions can be associated with venous malformations involving the rectum and bladder.
