Transcript Chapter 35 Cutaneous Vascular Diseases
Cutaneous Vascular Diseases
Michael Hohnadel, DO 10/11/05
Cutaneous small-vessel vasculitis (leukocytoclastic vasculitis)
Presentation: Palpable purpura ranging in size from a pinpoint to several centimeters Early on lesion may not be palpable Papulonodular, vascular, bullous, pustular or ulcerated forms may develop Predominate on the ankles and lower legs dependent areas Mild pruritis, fever, malaise, arthralgia and/or myalgia may occur. Renal, GI
Cutaneous small-vessel vasculitis (leukocytoclastic vasculitis)
Course: Typically resolve in 3 to 4 weeks with postinflammatory hyperpigmentation May recur or become chronic.
Histology: Angiocentric segmental inflammation, endothelial cell swelling, fibrinoid necrosis of blood vessel walls and a cellular infiltrate composed of neutrophils showing fragmentation of nuclei.
Cutaneous small-vessel vasculitis (leukocytoclastic vasculitis)
Etilology Many forms of small-vessel vasculitis are felt to be caused by circulating immune complexes. These lodge in vessel walls and activate compliment Infections - bacterial and viral, Drugs, autoimmune disease, lymphoproliferative disorders and solid tumors.
Cutaneous small-vessel vasculitis (leukocytoclastic vasculitis)
Workup: CBC, strep throat culture or ASO titer, Hep B & C serologies and ANA are a reasonable initial screen.
Cutaneous small-vessel vasculitis
Treatment Initial treatment should be nonaggressive Rest and elevation of the legs Analgesics, a good diet, and avoidance of trauma or cold Any identified antigen or drug should be eliminated
Cutaneous small-vessel vasculitis
Treatment: A variety of systemic treatments may be required for severe, intractable or recurrent disease For disease limited to the skin NSAIDs, antihistamines, colchicine and dapsone.
Systemic corticosteroids for those with systemic manifestations or necrotic lesions Immunosuppressive agents for rapidly progressive course and severe systemic involvement
LCV
LCV A. classical purpuric papules & papules on lower leg B. CSVV evolving to form confluent hemorrhagic plaque on posteroir ankle C. lesions in various stages of evolution
Subtypes of Small Vessel Vasculitis
Henoch-Schönlein Purpura (HSP) (anaphylactoid purpura)
Presentation: Characterized by intermittent purpura, arthralgia, abdominal pain, and renal disease 40 % preceded by mild fever, headache, joint symptoms, and abdominal pain for up to 2 weeks Typically purpura appears on the extensor surfaces of the extremities Become hemorrhagic within a day and fades in 5 days New crops appear over a few weeks
Henoch-Schönlein purpura
Primarily occurs in male children Peak age 4-8 years Adults may be affected.
Etiology: Viral infection or streptococcal pharyngitis are the usual triggering event. May be related to a medications.
Complications: Pulmonary hemorrhage, Abdominal pain and GI bleeding. Renal manifestations may occur in 25% or more Hematuria Good Prognosis but should be monitored long term for IgA nephropathy
Henoch-Schönlein purpura
Treatment : Supportive Duration of illness is typically 6 to 16 weeks 5 and 10 % of patients will have persistent or recurrent disease Antispasmodics, antibiotics, and antiinflammatory drugs, including systemic corticosteroids Plamaphoresis in severe cases
Henoch Schönlein purpura
Henoch-Schönlein purpura
Henoch-Schönlein purpura
Acute Hemorrhagic edema of infancy
Presentation: Child under the age of 2 with a recent history of an upper respiratory illness (75%) , a course of antibiotics of both.
Abrupt onset of large cockade, annular, or targetoid purpuric lesions involving the face, ears, and extremities Early in the course there may first be acral edema, may be nontender and asymmetrical Low-grade fever is common.
No extracutaneous involvement. Children are often nontoxic in appearance.
Acute Hemorrhagic edema of infancy Etiology: Considered a variant of leukocytoclastic vasculitis with many similarities to HSP Routine lab tests are nondiagnostic DDX: meningococcemia, HSP, erythema multiforme, urticaria and Kawasaki’s disease Clinically most urgent to exclude meningococcemia Course: Spontaneously resolves with 1 3 weeks
Acute Hemorrhagic edema of infancy Multiple erythematous, nummular & targetoid plaques on an infant’s thighs
Urticarial vasculitis
1.
2.
3.
Three clinical features distinguish the skin lesions of urticarial vasculitis from urticaria Lesion are usually painful rather than pruritic Lesions last longer than 24 hours On healing there is postinflammatory hyperpigmentation Systemic symptoms.
Assoc with hypocomplementemia (in some cases), arthritis, angioedemia, abdominal/chest pain.
Urticarial vasculitis
Several erythematous urticarial plaques on the foot & ankle
Urticarial vasculitis
Many disease associations: gammopathies, SLE, viral (hepatitis, EBV).
Treatment: Pts with hypocomplementemic type respond to oral corticosteroids Hydroxychloroquine sulfate, colchicine, dapsone, NSAIDs or pentoxifylline Some pts require a combination of therapies with antihistamines
Familial Mediterranean fever
A periodic fever syndrome reported to affect Sephardic Jews, Armenians, and individuals of Arabian descent.
Presentation: Cutaneous findings consist of erysipelas-like erythema showing a sharp border.
Erysipelas-like erythema occurs in less than half of patients Affects the lower extremities on the dorsa of the feet , over the ankles, and sometimes the knees Arthralgias, peritonitis, and constipation may occur No lymphadenopathy
Familial Mediterranean fever
Onset: Usually under 10 years Biopsy: leukocytoclastic vasculitis Tx - colchicine
Erythema elevatum diutinum
A rare condition considered to be a chronic fibrosing leukocytoclastic vasculitis Presentation: Multiple yellow papules develop over the joints, particularly the elbows, knees, hands, and feet Initially nodules are soft & mobile then take on a doughy to firm consistency and develop red to purple.
Face & ears usually affected Lesions may be painful or asymptomatic Course: Variable, lasting 5-35 yrs.
Assoc: HIV. Gammopathies.
TOC: Dapsone
Top: multiple symmetric red brown nodules & plaques on extensor surface of digits Bottom: red brown palques & nodules of concha, antihelix & of the ear
Erythema elevatum diutinum
Early stage: dense perivascular infiltrate of neutrophils admixed with lymphs & histiocytes Late-stage: minimal inflammatory infiltrate & marked perivascular fibrous thickening
Granuloma Faciale
Presentation: Brownish-red, infiltrated papules, plaques, and nodules typically on the face esp nose. (head or neck) Typically healthy, middle aged, white men Pathology: Identical to EED. Mixed vasculitis with less prominent fibrosis.
Treatment Often resistant to TX.
Intralesional corticosteroids (first line non scarring option) Also: Cryotherapy, dermabrasion, electrosurgery, many others.
Granuloma faciale
Note prominent follicular openings
Granuloma faciale
Left: dense, diffuse dermal infiltrate with a Grenz zone Right: high power of polymorphous infiltrate of lymphocytes, eos, neuts & plasma cells
Polyarteritis Nodosa
Characterized by necrotizing vasculitis affecting the small and medium-sized muscular arteries 1.
2.
Two major forms: Systemic Microscopic polyangiitis Benign cutaneous
Polyarteritis nodosa
Systemic PAN
Cutaneous findings (40 %) 15% of pts have 5 - 10 mm subcutaneous nodules occurring singly or in groups distributed along the course of blood vessels.
Skin above is normal or slightly erythematous Often painful, may pulsate or ulcerate
PAN Top: petechiae & multiple purpuric papules with central necrosis on plantar surface Bottom: confluent hemorrhagic plaques on the medial & plantar aspect of the foot
Polyarteritis nodosa
Systemic PAN
Internal manifestations: May involve the vessels throughout the entire body.
Hypertension, tachycardia, fever, edema glomerulosclerosis and weight loss are the cardinal signs of the disease Mononeuritis multiplex, most often manifested as foot drop, is the hallmark of PAN
Polyarteritis nodosa
Systemic PAN
Laboratory findings: Leukocytosis as high as 40,000 may occur with neutrophilia to 80% Thrombocytosis and progressive normocytic anemia, elevated sed rate.
Urinary abnormalities seen in 70% May have elevated
C
-ANCA (consult Dr. Berrett)
Polyarteritis nodosa
Microscopic Polyangiitis
Considered by many to be a subset of systemic PAN. May be related to Wegner’s and Churg Strauss. Segmental, necrotizing and crescentic glomerulonephritis associated with extrarenal vasculitis involving small-size vessels without granulomas or asthma Positive
P
-ANCA
Polyarteritis nodosa epidemiology
Systemic PAN
4 X more common in men than women. Mean age 45 yrs.
Assoc with: IV drug abusers, SLE, inflammatory bowel disease, hairy cell leukemia, and familial Mediterranean fever. Also: Hep-B and Hep-C. (check ck for during work-up)
Polyarteritis nodosa
Systemic PAN
Histology: An inflammatory necrotizing and obliterative panarteritis that attacks the small and medium-sized arteries.
Biopsy is mainstay of diagnosis.
Polyarteritis nodosa
Systemic PAN
Course: Untreated classic PAN has a 5 year survival rate of 13%.
Death from renal failure, cardiovascular or GI complications Treatment: High-dose corticosteroids with slow taper to DC. Cytotoxic agents such as may be added like cyclophosphamide with taper to DC.
Polyarteritis nodosa
Cutaneous PAN
Absence of visceral involvement Presentation: Recurrent skin, joint, and muscle involvement without involvement of vital organs Cutaneous findings similar to those described for the systemic form Assoc: Hep B,C. Crohn’s & others.
Most patient respond well to aspirin, prednisone, methotrexate, alone or in combination
Wegener’s Granulomatosis
1.
2.
3.
Syndrome consisting of: Necrotizing granulomas of the upper and lower respiratory tract.
Generalized necrotizing angiitis affecting the medium-sized blood vessels. Focal necrotizing glomerulitis.
Wegener’s granulomatosis
Presentation: Rhinorrhea, severe sinusitis, and nasal mucosa ulcerations. One or several nodules in the nose, larynx, trachea, or bronchi.
Fever, weight loss and malaise m:f = 1.3 : 1 Age 40 to 50 years.
“strawberry gums” = hypertrophic gingivitis Focal necrotizing glomerulitis occurs in 85% of patients Cutaneous findings (45% of patients) Nodules may appear in crops, especially along the extensor surface of the extremities Firm,slightly tender, flesh-colored or violaceous nodules may later ulcerate
Wegener’s granulomatosis
LAB: (+)
C
– ANCA Histology: Cutaneous lesions may demonstrate a leukocytoclastic vasculitis with or without granulomatous inflammation.
Wegener’s granulomatosis
Nodules on extensor surfaces
Wegener’s granulomatosis
Left: purpuric plaques on the distal fingers Right: ulceration of the tongue
Wegener’s granulomatosis
Prognosis and treatment: Untreated the mean survival time is 5 months and a 90% mortality over 2 years.
Improves when corticosteroids are combined with cytotoxic drugs: 75% remission rate, 87% survival rate in pts between 6 months & 24 yrs
Churg-Strauss Syndrome
Presentation: 1.
3 clinical phases occur: Prodrome: asthma , allergic rhinitis, peripheral blood eosinoiphilis & eosinophilic infiltrative dx 2 – 12 years of prodrome. 2.
3.
Vasculitis, characterized by arthritis, & myositis with cardiac, pulmonary, nervous system, GI, renal, ocular or genitourinary dx. Post-vasculitic phase-dominated by allergic rhinitis, asthma, HTN & peripheral nerve damage
Churg-Strauss Syndrome
Cutaneous lesions Most common features of the vasculitic phase (70%) Most common skin findings are purpura & infiltrated nodules on extensor surfaces.
Less common are: necrotizing livedo reticularis, migratory erythema, new onset Raynaud’s phenomenon & digital ischemia.
Extracutaneous manifestations: wt loss, myalgias, arthralgias, mononeuritis multiplwex, GI symptoms, & cardiomyopathy
Churg-Strauss Syndrome
Lab Peripheral eosinophilia and (+) P-ANCA (less frequently for C-ANCA) Correlate with disease severity Histopathology: Sm. vessel vasculitis with eosinophils.
Etiology: Several drugs have been implicated: Zafirlukast, Azithromycin, freebase cocaine.
TX: prednisone alone clinical remission in >90% of pts
Churg-Strauss Syndrome
Crusted, firm papules of the elbow
Giant-cell arteritis
Systemic disease of people over the age of 50 Presentation: Unilateral headache and exquisite tenderness in the scalp over the temporal arteries which may be enlarged and firm.
Erythema and scalp gangrene can occur.
Fever, anemia, and a high sed rate are usually present.
Histology: Characterized by a necrotizing panarteritis with granulomas and giant cells
Giant-cell arteritis
Polymyalgia rheumatica has a significant clinical association Diagnosis: Temporal artery biopsy is diagnostic MRI may be of value TX: Prednisone until all symptoms have resolved, then taper to a low dose. May require 1-2 years. Complete remission is the norm.
Giant-cell arteritis
Takayasu’s arteritis
AKA: aortic arch syndrome and pulseless disease.
Pathology: Thromboobliterative process of the great vessels stemming from the aortic arch. Generally occurs in young women Radial and carotid pulses are typically obliterated Skin changes are due to disturbed circulation. Hair Loss, ulceration.
Takayasu’s arteritis
Treatment: Corticosteroids Methotrexate With active medical and surgical intervention the aggressive course of this disease can be modified
Takayasu’s arteritis
Malignant atrophic papulosis (Degos’ disease)
Cutaneous presentation: Crops of small 2-5 mm erythematous papules on trunk or extremities. Over a 2-4 week interval develop central depressions & ultimately a porcelain white scar, often a rim of telangiectasias Typically precede systemic manifestations Systemic presentation: Anemic infarcts involve the intestines Death is usually due to fulminating peritonitis caused by multiple perforations of the intestine
Malignant atrophic papulosis (Degos’ disease)
Porcelain white scaring
Malignant atrophic papulosis
Histology: Wedge-shaped necrosis brought on by the occlusion of arterioles and small arteries Etiology: Unknown. Inherited forms have been reported No proven Treatment – some cases respond to Acetyl salicylic acid with or without pentoxifylline
Thromboangiitis obliterans (Buerger’s disease)
An obliterative vascular disease affecting the medium and small sized arteries, especially those of the feet and hands Most often seen in men 20 to 40 who smoke heavily Presentation: Early cases may be transitory or persistent, producing blanching, cyanosis, burning, and tingling of extremities. Pain is a constant symptom. At first after exercise then constant.
Instep claudication is the classic complaint
Thromboangiitis obliterans (Buerger’s disease)
Thromboangiitis obliterans (Buerger’s disease)
Studies: A characteristic tapering of the arteries with “corkscrew” collateral circulation is found in Buerger’s disease on arteriogram.
Treatment: Cessation of smoking Serial amputations are often necessary
Arteriosclerosis obliterans
Occlusive arterial disease most prominently affecting the abdominal aorta and the small an medium sized arteries of the lower extremities Presentation: Intermittent claudication Diabetes and smoking play a role in the progression of the disease.
Treatment: Bypass of the affected artery or sympathectomy or both
Mucocutaneous lymph node syndrome (Kawasaki’s disease) Presentation: Irritable, febrile infant/child with erythema multiforme - like, scarlatiniform, or morbilliform skin lesions accompanied by stomatitis, cheilitis, edema of the hands and feet, conjunctival congestion and cervical lymphadenitis An early finding is the appearance of an erythematous , desquamating perianal eruption, usually within the first week of symptoms Peak age at 6 months
Mucocutaneous lymph node syndrome (Kawasaki’s disease) To make the diagnosis: Fever above 38.3 C for 5 days AND 4 of the 5 following criteria: 1.
2.
3.
4.
5.
Peripheral extremity changes (edema, erythema, desquamation) Polymorphous exanthem Nonpurulent, bilateral conjunctival injection Changes in the lips and oral cavity (erythema, strawberry tongue) Acute, nonpurulent cervical adenopathy
Mucocutaneous lymph node syndrome (Kawasaki’s disease) Pathology: Coronary artery disease and aneurysms and thrombocythemia.
Course: Disease last 10 to 20 days the subsides.
Vessel occlusion may occur and the subsequent MI, which occur as the child is recovering from the acute illness 1 to 2% may die from MI Treatment: IVIG is the cornerstone of treatment Antiplatelet therapy with aspirin is recommended
Mucocutaneous lymph node syndrome (Kawasaki’s disease) -Lips, Tongue and desquamating rash on hands
Mucocutaneous lymph node syndrome (Kawasaki’s disease) Diffuse erythematous macules & papules on trunk & confluent erythematous of axilla
Generalized Essential Telangiectasia
Characterized by the dilation of veins and capillaries over a large segment of the body without preceding or coexisting skin lesions Develops most frequently in women in their 40’s and 50’s. Not felt to be estrogen dependent.
Initial onset is on the lower legs with spread to the upper legs, abdomen, and arms Cause is unknown
Generalized Essential Telangiectasia
Unilateral nevoid telangiectasia
Presentation: Fine threadlike telangiectasia develop in a unilateral, sometimes dermatomal distribution Rare. Can occur in men Tends to be assoc with increased levels of estrogen.
Cirrhosis, pregnancy, Has been assoc with Hep C. The most commonly accepted theory is an increased level of estrogen receptors in involved skin
Hereditary hemorrhagic telangiectasia (Osler’s-Weber-Rendu disease) Presentation: Small tufts of dilated capillaries scattered over the mucous membranes and the skin. Develop mostly on the lips, tongue, palate, nasal mucosa, ear, palms, fingertips, nailbeds and soles.
Earliest location is under tongue and floor of mouth in puberty. More prominent symptoms in middle age.
Frequent nose bleeds and melena are experienced. GI bleeding is the presenting sign in up to 25% of cases Epistaxis is the most frequent and persistent sign
Hereditary hemorrhagic telangiectasia (Osler’s-Weber-Rendu disease) The disease is inherited as an autosomal dominant trait May have AV malfomations with direct connections. Treatment: Epistaxis has been reduced by estrogen therapy Dermoplasty of the bleeding nasal septum Aminocaproic acid for bleeding episodes id severe
Hereditary hemorrhagic telangiectasia (Osler’s-Weber-Rendu disease)
Hereditary hemorrhagic telang.
Bloom syndrome
A recessive trait in Jews of eastern Europe.
Presentation: Telangiectatic erythema in the butterfly area of the face, photosensitivity and dwarfism.
Exacerbation in summer months The stunted growth is characterized by normal body proportions, no endocrine abnormalities, and low birth weight at full term.
Bloom syndrome
About ¼ patients under age 20 develop a neoplasm.
TX: Regular use of sunscreen is recommended Monitor for neoplasia.
Bloom syndrome
Telangiectatic erythema in the butterfly area of the face
Poikiloderma congenitale
AKA Rothmund-Thomson syndrome Autosomal recessive, F>>M, rare.
Presentation: Begins at 3 to 6 months of age with tense, pink, edematous patches on the cheeks, hands, feet, and buttocks Short stature, small hands, absence or sparseness of eyebrows and eyelashes, alopecia of the scalp, and congenital bone defects are frequently observed Sensitivity to sunlight SCC and BCC of the skin occasionally occur, and osteosarcoma of bone has been reported Etiology: Abnormal DNA helicase.
Venous diseases of the extremities
Stasis dermatitis
Presentation: A blotchy red mottling and a yellowish or light brown pigmentation of the lower 1/3 of the lower legs due to venous insufficiency Frequent finding in the elderly Often associated with obesity and other disease states
Stasis dermatitis
Stasis dermatitis
Treatment: Two goals: 1.
2.
Relief of symptoms (steroids, emoliants) Treatment of the underlying cause (leg elevation, compression stocking diuretics ect.)
Venous ulcer
AKA varicose ulcer, stasis ulcer Etiology: Chronic venous insufficiency in the deep veins of the legs leads to shunting the venous return into the superficial veins, in which pressure, oxygen content, and flow rate are increased which result in dermatitis.
Edema and fibrosis develop as well as ulceration with minor trauma
Venous ulcer
Venous ulcer
Presentation: Venous ulcers usually occur on the lower medial aspect of the leg May be weepy or dry, scaling or lichenified.
Usually there is a preceding stasis dermatitis with lipodermatosclerosis.
Nearly always hyperpigmentation.
Varicosites are present but need not appear severe.
Diagnosis: clinically, venous rheography, biopsy if unclear etiology (neoplasia)
Venous ulcer
Treatment: Primarily to improve venous return Elevation of leg above heart Elastic support and exercise to improve calf muscle strength are recommended Compression therapy is the mainstay of tx Closure of ulcer Occlusive permeable biosynthetic wound dressing Cultured epidermal allografts, skin substitutes Metronidazole may reduce contmination/odor Culture and chronic oral antibiotics may be required
Venous ulcer
Treatment (cont) Risk factors that predict failure to heal within 24 weeks of limb-compression therapy: large wound area history of venous ligation or stripping history of hip or knee replacement Ankle brachial index of less than 0.80 fibrin on 50% or more of the wounds surface presence of the ulcer for an extended time May consider other tx for these pts like: Aspirin, Oral zinc sulfate, Stanazol, grafting
Ischemic ulcer
Presentation: Mostly located on the lateral surface of the ankle or digits Initial red, painful plaques breaks down into painful superficial ulcer with a surrounding zone of purpuric erythema Patients at risk are those with long standing hypertension or other signs and risk factors of arteiosclerotic disease
Ischemic ulcer
Ischemic ulcer
Diagnosis: Signs of arterial disease: dependency Thinning of the skin, absence of the hair, decreased or absent pulses, pallor on elevation, coolness of the extremity, dependent rubor, claudication on exercise, and pain on elevation relieved on Exam of pulses in the legs If ABI is less than 0.75 arterial insufficiency exists, less than 0.5 = substantial insuff.
Ischemic ulcer
Treatment: Topical abx, protection from injury, avoidance or cold, smoking and tight socks.
Consult vascular surgeon Prevent infection Hyberbaric oxygen
Lymphedema
Swelling of soft tissues in which an excess amount of lymph has accumulated Chronic lymphedema is characterized by long-standing nonpitting edema Causes: Most prevalent worldwide cause is filariasis In US most common cause is postsurgical
Lymphedema
Lymphedema praecox
Develops in females between 9 and 25 Presentation: Unilateral puffiness appears around the ankles and then extends upwards.
Leg becomes painful, with a dull, heavy sensation Etiology: A primary lymphedema caused by a defect in the lymphatic system Lymphangiography demonstrates hypoplastic lymphatics in 87%, aplasia in 5% and hyperplasia with varicose dilation in 8%.
Lymphedema distichiasis syndrome – late onset lymphedema and double row of eyelashes.
Lymphedema praecox
Hereditary lymphedema (Nonne-Milroy-Meige Syndrome)
Presentation: Unilateral or bilateral lymphedema present at birth and inherited as an autosomal dominant trait Edema is painless and pits on pressure Persists throughout life Most frequently is unilateral If long-standing a verrucous appearance to the affected extremity develops
Primary lymphedema associated with yellow nails and pleural effusion (Yellow Nail Syndrome) Primary lymphedema is confined mostly to the ankles, although other areas my be involved Nails show a distinct yellowish discoloration and thickening Recurrent pleural effusion requiring thoracocentesis may by a feature
Secondary lymphedema
In some malignant diseases involvement of the lymph nodes will produce blockage and lymphedema Frequently seen after mastectomy and the removal of axillary nodes
Secondary lymphedema
Post Mastectomy
Postmastectomy lymphangiosarcoma (Stewart-Treves syndrome)
Chronic postmastectomy lymphedema Presentation: Bluish or reddish nodules arising on the arms 2-20 years after mastectomy.
Pulmonary metastasis is frequent Prognosis is extremely poor
Stewart-Treves syndrome
Note tumor mass behind the ear & widespread purple discoloration elsewhere
Stewart-Treves syndrome
Grouped papules on the edematous arm of a woman with Stewart Treves syndrome
Stewart-Treves syndrome
Infiltration of the dermis by ill-defined vascular spaces & hyperchromatic, atypical endothelial cells
Isolated limb perfusion
Melphalan when used for treatment of malignancies with isolated limb perfusion has been reported to result in an increased chance of developing regional toxicity and lymphedema
Inflammatory lymphedema
Etiology: Recurrent bouts of acute cellulitis and lymphangitis Chills, fever, and swelling and redness of the involved extremity are severe and may last for as long as 3 to 4 days Recurrent attacks of streptococcal infections increases the likelihood of lymphedema
Factitial lymphedema
AKA hysterical edema Lymphedema can be produced by wrapping an elastic bandage, cord, or shirt around an extremity and/or holding the extremity in a dependent and immobile state Self-inflicted causes are usually difficult to prove
Treatment
Compression therapy, physical therapy, pneumatic pumps, and compressive garments Volume reducing surgery and lymphatic microsurgery are rarely performed