White : Diseases of the Skin - Vascular Disorders

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Gary M. White & Neil H. Cox

Diseases of the Skin

15	Vascular Disorders

ANGIOMAS AND TUMORS

The types of angioma are outlined in Table 15.1, and the differential diagnosis of commoner vascular or angiomatous papules and nodules applicable to this section is presented in Table 15.2.

Congenital and infantile hemangioma

Etiology and pathogenesis

Most IHs appear after birth, grow rapidly, and regress slowly. They are found in 6–10% of white infants, and are more common in preterm infants and in girls (ratio 3:1). They are also found at increased frequency in children whose mothers had undergone chorionic villus sampling. There are rare kindreds in which hemangiomas are common, following an autosomal dominant inheritance pattern. Some of these kindreds have vascular malformations as well. It is presumed that there are genetic mutations in these families.

Some hemangiomas have a higher risk of internal associations and complications. Variants that should alert the clinician include the following.

•	Large facial hemangiomas—these may be part of the PHACE(S) syndrome, a neurocutaneous syndrome including posterior fossae brain abnormalities, hemangiomas, arterial anomalies, coarctation of the aorta and/or other cardiac anomalies, eye abnormalities, and sternal defects in some cases.
•	Segmental hemangiomas—the most common sites of internal abnormalities associated with segmental hemangiomas in one study were the liver, gastrointestinal tract, brain, mediastinum, and lung.
•	A plaque-like hemangioma that spans the lumbar midline—this may be associated with a tethered spinal cord (also with genitourinary abnormalities). Like other hemangiomas, the lumbar hemangioma will regress over time, so this entity must be recognized in infancy before serious neurologic damage occurs. MRI is useful in imaging an infant with a significant midline lesion.
•	Multiple small scattered angiomas—also termed neonatal hemangiomatosis, which is commonly associated with hepatic angiomatosis and is classically manifest as a triad of hepatomegaly, heart failure, and anemia (sometimes with low-grade thrombocytopenia but usually with normal liver enzyme tests). MRI is useful for diagnosis and monitoring, but there is a high mortality rate. In those who survive, the internal lesions regress.

Congenital hemangiomas, as the name implies, are present at birth. They have typically reached their maximum size at birth and do not have an accelerated postnatal growth phase. Under this category, two subsets have been described.

•	Rapidly involuting congenital hemangiomas (RICH), which typically involute by 12–24 months (sometimes regression even starts in utero).
•	Non-involuting congenital hemangiomas (NICH), which stay stable in size.

Both subtypes affect boys and girls equally.

Potential complications of larger hemangiomas include ulceration, bleeding, infection, and high-output cardiac failure. Hemangiomas overlying the anterior neck may be associated with airway involvement and obstruction. Ultrasound with color flow imaging and MRI are useful non-invasive imaging procedures. Arteriography is only rarely needed. Hemangiomas are quite common, but only those on the midline of the neck or back routinely require imaging.

The Kasabach–Merritt phenomenon has classically been linked to hemangiomas but is actually now felt to occur in kaposiform hemangioendothelioma or tufted angioma (indeed, the precursor skin lesion is clinically very minor in most cases); the condition consists of a consumptive coagulopathy with thrombocytopenia, and has a high mortality rate. A lymphatic component in such lesions has been implicated.

Clinical

At birth, a barely visible, white, anemic stain; a faint, telangiectatic lesion; a blue spot mimicking a bruise; or, rarely, a full-grown hemangioma may be present (Figs 15.13 and 15.14). Hemangiomas usually present within the first month of life. Generally, they may be separated into a superficial (bright red, arising from the dermis), a deep (blue, arising from subcutaneous tissue), and a mixed type. If untreated, resolution to normal skin, slight redness, telangiectases, wrinkling, or sagging occurs in 50% by 5 years and 70% by 7 years. Some hemangiomas develop in utero and present as congenital hemangiomas. Rarely, these tumors may be picked up on ultrasonography. Growth after delivery is usually not seen. Rapid involution may occur, although some have necessitated treatment with prednisone or excision.

Differential diagnosis

This falls into several main categories.

•	Early, flat, pale-pink lesions may resemble nevus flammeus or PWS.
•	Deep or large hemangiomas may be difficult to distinguish from vascular malformations, although this is clear in most cases by the fact that the lesion is proliferative, typically during the first 3–9 months and rarely beyond 18 months (Fig.15.14).
•	Other rarer congenital vascular lesions may resemble hemangiomas, for example kaposiform hemangioendothelioma, congenital-type tufted angioma, and infantile myofibroma.
•	Other nodules and tumors, for example nasal glioma (Ch.19) and rhabdomyosarcoma. The latter might be suspected in any hemangioma that seems excessively firm, and deserves careful evaluation and biopsy if necessary.
•	Non-vascular eruptions—multiple small hemangiomas could be confused with rarities such as blueberry muffin baby (Ch.19), but the hemangiomas in such cases are usually quite red in color compared with the dusky blue color in blueberry muffin baby.

Table 15.2 DIFFERENTIAL DIAGNOSIS OF VASCULAR PAPULONODULES (EXCLUDING NEONATAL ANGIOMATOSES)

Lesion	Main feature	Comments
Capillary hemangioma	Bright red, unless patient is cyanosed; usually multiple; may be associated ‘minute’ lesions	Rarely a diagnostic problem; tiny lesions may be confused with purpura or vasculitis, or with angiokeratomas
Congenital and infantile hemangiomas	Present at or soon after birth	Some are difficult to distinguish from malformations
Nodules within a capillary malformation (port wine stain)	May develop gradually over time, but pyogenic granulomas may appear suddenly	Usually multiple, cobblestoned; may need biopsy to confirm benign nature
Pyogenic granuloma	Usually acral or facial, often crusted and bleed easily, solitary (occasionally grouped ‘satellite’ esions), commonly in children or during pregnancy	May be confused with several malignant tumors; amelanotic melanoma is the most important
Glomus tumor (solitary or multiple forms)	Typically red and painful if solitary (especially subungual); multiple lesions are more blue, and tenderness is variable	Various tender skin lesions are in the differential (Table 15.2); the multiple form (glomangiomas) is very similar to blue rubber bleb nevus syndrome
Blue rubber bleb nevus syndrome	Multiple blue lesions	Closely resembles glomangiomas
Targetoid hemosiderotic hemangioma	Solitary, may have elevated central nodule and bruising around it	Solitary angiokeratoma, bleeding in or around other angiomas (or lymphangiomas, aneurysmal fibrous histiocytoma), large spider nevi
Venous lake	Blue, compressible; solitary (especially on the lip) or multiple; mainly head and neck	May be confused with angiokeratomas occasionally with melanocytic lesions
Angiokeratomas (solitary or multiple forms)	Typically dark blue–purple color; often lower leg, but specific variants at other sites (Fordyce type, Fabry disease; see text)	May be confused with melanocytic lesions, occasionally with vasculitis
Angioma serpiginosum	Clustered small lesions, may have midline cut-off	Main differentials are multiple minute capillary hemangiomas, Fabry disease, capillaritis, and purpura
Angina bullosa hemorrhagica	Intraoral, see Chapter 20; solitary; may be recurrent; dome-shaped and sharply defined	Could be confused with intraoral Kaposi sarcoma, but thelatter produces vague expanding macules or plaques
‘Blood blister’	Usually obvious preceding trauma, but not always	May resemble angioma (early lesions) or melanoma (older lesions)
Angiolymphoid hyperplasia with eosinophilia	Often head and neck, may have cobblestoned surface	May resemble various angiomas or basal cell carcinoma; in east Asian people, Kimura disease has some similarity but is more aggressive
Kaposi sarcoma	Mostly HIV-associated and multiple; see text, this chapter, and Chapters 12 and 33	Look in the mouth for palatal lesions, or for candidiasis
Angiosarcoma	Usually starts as a flat patch or just raised plaque, may develop nodules; usually head and neck, in older subjects	Main differential is sporadic type of Kaposi sarcoma or other neoplasms
Various neoplasms	A red vascular appearance is particularly likely in amelanotic melanoma, Merkel cell tumor, poorly differentiated squamous cell carcinoma, atypical fibroxanthoma, and metastatic renal cell carcinoma; local skin involvement or metastases from breast carcinoma may appear telangiectatic	Biopsy any pyogenic granuloma–like lesion if in doubt or if the site or age group is unusual
Vasculitis	May cause large blood and necrotic tissue–filled lesions	Usually acute onset and associated with lesions

Figure 15.13 Congenital and infantile hemangiomas (IHs). (a) A superficial variant of an IH. Note the slightly raised and irregular surface in contrast to a port wine stain. (b) If this periocular hemangioma were to grow to the point that it obstructed vision, treatment would be mandatory. Otherwise, permanent visual impairment could result. (c) Hemangioma in a premature infant girl.

Figure 15.14 (a,b) Capillary hemangiomas are distinguished from vascular malformations (e.g. port wine stain and arteriovenous malformations) by the fact that they proliferate, typically during the first 3–9 months of life. The first picture (a) shows a lesion at birth that could be either a port wine stain or a hemangioma. (b) The appearance of the same lesion several weeks later gives the answer.

Treatment

There is great pressure to act, but the majority of hemangiomas should be left alone. (Some have advocated intralesional corticosteroids regardless of the size or age of the patient.) To protect the area and promote healing when a lesion is located on an extremity, a self-adherent stretch bandage may be applied at home over a snug but not tight non-adherent dressing.

Ulceration may occur in approximately 5% of lesions, especially those of the lips and anogenital area. For these, routine cleansing, topical antibiotics, and possibly a dressing or oral antibiotics are indicated. Healing should occur within 2–3 weeks. Use of the pulsed dye laser for ulcerative hemangiomas has been recommended, but not proved in controlled studies. For ulcerated hemangiomas on the extremities, saline or Burow solution, followed by an antibiotic ointment, adherent pad, and a compressive wrap, has been recommended as being able to heal most ulcers within 2 weeks.

The so-called alarming hemangiomas require aggressive therapy. Hemangiomas are alarming if they are compromising, or threatening to compromise, vision, breathing, or eating, or are causing gastrointestinal bleeding, congestive heart failure, or extensive skin ulceration. For such lesions, a corticosteroid given either intralesionally or systemically (e.g. prednisone 2–4mg/kg per day for 3 weeks, then tapered over 2 weeks) is the first-line treatment. One should monitor for growth retardation, blood pressure elevation, and immunosuppression. The administration of live vaccines (e.g. polio vaccine) during treatment should be avoided. Ensure that the patient has not recently been exposed to varicella. Some combine prednisone and the pulsed tunable dye laser (PTDL). In one study, prednisone (5mg/kg per day divided four times daily and given for 2 weeks, then tapered) was excellent, and better than 3mg/kg per day. Side effects included moon facies and delayed growth in a few. Catch-up growth occurred in all those so affected.

The pulsed dye laser has definite limitations but can be helpful for small, superficial lesions and for some large, plaque-like lesions if treatment is started early enough. This laser can, at times, induce ulceration and, rarely, shallow scarring.

Interferon-alpha is effective in the treatment of hemangiomas but has been found to cause spastic diplegia in a small percentage of patients treated. The risk is highest in patients below 1 year of age, and thus it should be reserved for life-threatening conditions unresponsive to other therapies.

PRACTICE POINTS

•	Reassurance is the best treatment for most infantile hemangiomas.
•	Consider the possibility of associated internal lesions or other malformations in those with large facial hemangiomas, scattered small lesions, and segmental or midline trunk lesions.
•	The diagnosis of hemangioma should be reconsidered in cases where the lesion is abnormally firm. Rhabdomyosarcomas may masquerade as ‘firm hemangiomas'.

Capillary hemangiomas (cherry angiomas, Campbell de Morgan spots)

Etiology and pathogenesis

Capillary hemangiomas, also known as Campbell de Morgan spots, are vascular growths that affect almost every adult over 40. In one study of adults aged 30–39 years, 90% of the men and 65% of the women had at least one cherry angioma.

Clinical

Most adults over 40 have one or more red vascular papules on the trunk (Fig.15.15). Sometimes, they appear almost ‘petechial' as 1–2-mm red macules. These are also called minute Campbell de Morgan spots. Some angiomas, particularly those on the face, may have a significant arterial feeder vessel that gives them a surrounding flare (Fig.15.16), much like spider angiomas.

Figure 15.15 Capillary hemangiomas. (a) The red lesion on the left contains relatively more oxygenated blood, whereas the purple lesion on the right has more venous blood. (b) Multiple lesions, from papules to pinpoint petechia-like lesions, are present.

Differential diagnosis

Darker lesions, or those that transiently turn black due to intralesional bleeding from inadvertent trauma, have been confused with melanoma (if bruising is frequent, consider targetoid hemosiderotic hemangioma, which is discussed later).

The multiple minute form may resemble angioma serpiginosum (discussed later) if extensive, and occasionally give rise to concern about vasculitis, meningococcemia, etc., as they are too small to blanch with diascopy.

Less likely differentials for a larger solitary lesion include pyogenic granuloma, glomus tumor, and other vascular neoplasms, and for multiple lesions include Kaposi sarcoma or bacillary angiomatosis.

Treatment

No treatment is usually needed, although electrodesiccation is effective. Cryotherapy, especially with a probe to press blood from the lesion, may be tried.

Pyogenic granuloma

Etiology and pathogenesis

A pyogenic granuloma is a rapidly growing benign vascular tumor that histologically resembles vascular proliferation in healing tissue. They are more common in pregnancy. The vast majority occur in the skin, but they may occur in the oral mucosa (especially during pregnancy) and rarely in the gastrointestinal tract, a rare cause of gastrointestinal bleeding.

Figure 15.16 Angioma with flare of surrounding dilated vessels, in the beard area under the chin. Some angiomas of the face have a significant flare about them. An arterial vessel often feeds these lesions, similar to a spider angioma.

Figure 15.17 Pyogenic granuloma. (a) This is the classic appearance of a red, friable nodule growing rapidly on the finger. There is often a portion that extends under the skin laterally. (b) Pyogenic granuloma on the finger. This lesion is more dry and crusted. (c) Pyogenic granuloma on the chin of an adult. The fingers, lip, palms, soles, and face are typical sites. (d) Pyogenic granuloma of the eyebrow..

Figure 15.18 Pyogenic granuloma on the lip of a child.

Figure 15.19 Pyogenic granuloma. These may develop in a port wine stain as shown here.

Clinical

The sudden appearance of a vascular, friable papule that bleeds easily, on the finger, palm, sole, head, or neck, is characteristic of a pyogenic granuloma (Figs 15.17–15.19). An epidermal collarette may be prominent. The parents may apply layer on layer of bandages to control the bleeding, giving rise to the ‘bandage sign'.

Differential diagnosis

On rare occasions, a nodular melanoma may be mistaken for a pyogenic granuloma (Figs 15.20 and 15.21). Thus all specimens should be sent for histologic examination. Older lesions may be difficult to distinguish from other types of angioma or vascular neoplasms.

Treatment

Local anesthesia followed by shave biopsy, curettage, and electrocautery is usually curative. If the lesion is not fully curetted, control of bleeding may be difficult and recurrence common; if at a technically easy site, a formal elliptic excision may be preferred in the first instance for this reason. This procedure runs smoothly for the teenager or adult, but young children rarely cooperate. Use of the papoose (flat board with cloth wraps to hold the child still) is often needed. Lesions on the nger may benefit from a tourniquet to prevent bleeding. Wound care should consist of leaving the area open to dry. Keeping it moist may increase the likelihood of recurrence.

Patients or parents should always be told of the small risk of recurrence. If recurrence does occur, the same procedure may be tried again, or elliptic excision, including a small amount of dermis, may be done. Cryotherapy can be useful for some lesions or for recurrences but requires long freeze times and matching discomfort. Alternatively, one, two, or three treatments with the flash lamp-pumped pulsed dye laser were successful in 91% of children in one series. The site and age group need to be typical, and the diagnosis certain, if destructive therapies are to be used.

The eruption of multiple lesions after treatment of a single one (satellitosis) occurs rarely. In the case of a giant pyogenic granuloma with satellitosis, an oral steroid was successfully employed.

Figure 15.20 Pyogenic granuloma mimicking melanoma. The finger is a characteristic site of the pyogenic granuloma. Silver nitrate has been applied in a failed attempt to eradicate the lesion

Figure 15.21 Pyogenic granuloma. This pyogenic granuloma is less common, as it is large and does not have a friable, bleeding surface. A biopsy is mandatory to exclude an amelanotic melanoma (compare with Fig. 15.20).

PRACTICE POINTS

•	Remember that neoplasms, for example amelanotic melanoma, Merkel cell tumor, or cutaneous metastases, may appear vascular and in particular may mimic pyogenic granuloma. Always query the diagnosis of pyogenic granuloma if the site is unusual, and always get histologic confirmation.
•	A painful, red, subungual tumor is probably a glomus tumor.
•	A rapidly developing moist or crusted red tumor affecting the periungual skin or distal part of a finger is probably a pyogenic granuloma.

Figure 15.22 Solitary glomus tumor. This vascular lesion may be single or multiple. Lesions are often painful, and the subungual area is a common site.

Table 15.3 DIFFERENTIAL DIAGNOSIS OF PAINFUL SKIN TUMORS

Glomus tumor

Angiolipoma

Neurilemmoma (schwannoma)

Eccrine spiradenoma

Leiomyoma

Angioleiomyoma

Glomus tumor (solitary)

Etiology and pathogenesis

Glomus tumors are benign vascular lesions that arise from the neuromyoarterial apparatus. The glomus body from which they originate contains an afferent arteriole, a connecting vessel (Sucquet–Hoyer canal), a primary collecting vein, smooth muscle cells, and epithelial-type cells (glomus cells), surrounded by a fibrous capsule.

Clinical

A solitary blue-red vascular papulonodule is typical (Fig.15.22). It often occurs under the nail, where a bluish red discoloration overlying a subungual papule is characteristic. Pain may occur spontaneously, after contact, or after change to cooler temperature. Exact localization of the tumor may be difficult. Radiography may show bony erosion of the distal phalanx. Ultrasound and high-resolution MRI have been used.

Multiple glomus ‘tumors' (more correctly, GVMs) are rather different, as discussed previously.

Differential diagnosis

Other angiomas may be in the differential, and subungual melanoma may be considered but does not have the characteristic pain of a glomus tumor at this site. There are several causes of a painful tumor that should be considered in the differential of glomus tumor at other skin sites (Table 15.3).

Treatment

Excision is curative but usually involves removal of the nail for subungual lesions, which may be technically difficult to remove.

Targetoid hemosiderotic hemangioma

The targetoid hemosiderotic hemangioma (THH) is a solitary vascular tumor that clinically has a ‘targetoid' appearance (Fig.15.23). Specifically, there is a central violaceous papule with a surrounding ecchymotic or brown ring that can enlarge or disappear. The central papule may have a cobblestoned morphology that resembles a raspberry. It is postulated that both solitary angiokeratomas and THH are variants of the same process in which trauma induces a dilatation of vascular elements. THH, in general, is larger than solitary angiokeratoma. The differential diagnosis includes the following.

•	Solitary angiokeratoma.
•	Bleeding in and around other angiomas or small lymphangiomas, or occasionally around rarer lesions such as aneurysmal fibrous histiocytoma.
•	Large spider nevi may have a raised central nodule with a telangiectatic halo.

If there is any question of the possibility of an atypical pigmented lesion, a biopsy should be performed. Otherwise, no treatment is needed. Shave biopsy with cautery of the base or simple excision may be performed.

Figure 15.23 Targetoid hemosiderotic hemangioma. Note the central vascular papule with the surrounding ecchymosis. (Courtesy of Fred Fehl, M.D.)

Figure 15.24 Spindle cell hemangioendothelioma.

Spindle cell hemangioendothelioma

See Fig. 15.24.

Angioma serpiginosum

This benign vascular lesion (Fig. 15.25) usually has its onset in childhood. It usually progresses over several years and then remains stable. Most patients are female, and the lower extremity is preferred. From a distance, the lesion may appear as diffuse redness, but on close inspection, multiple pinpoint, angiomatous, red papules are seen. They do not blanch on pressure. Despite its name, there is no serpiginous component. The appearance of angioma serpiginosum may at times be similar to capillaritis, but the former is stable over time or slowly progressive, whereas capillaritis will either resolve or wax and wane over time. Unilateral nevoid telangiectasias may have a similar age of onset and be vascular and asymmetric in clinical presentation, but close inspection will show the individual lesions to be telangiectasias. No treatment is needed, but laser can reduce the appearance of the lesions.

Figure 15.25 Angioma serpiginosum. It is said that this childhood vascular lesion is more common in females and is most often found on the extremities. Note the presence of pinpoint red papules and the absence of a serpiginous component.

Kaposi sarcoma

Etiology and pathogenesis

Kaposi sarcoma is one of two cutaneous vascular proliferations derived from lymphatic endothelial cells (the other being angiosarcoma). Kaposi sarcoma is divided for clinical purposes into HIV-associated and classic, but both are associated with infection by the human herpesvirus 8.

Clinical

A reddish blue to purple papulonodule or plaque beginning on the toe or sole of a man of southern or eastern European descent is characteristic (Fig.15.26). Slow progression may occur, with lesions ascending the leg to all parts of the body. Internal involvement is most common in the gastrointestinal tract. Many other organs may be involved (e.g. bone) but, because of the slow progression of the disease, most patients die of unrelated causes.

Differential diagnosis

If the lesion is solitary, the differential is more broad (see Table 15.3). For multiple lesions, particularly on the lower extremities, the differential is more limited. One might consider an angiosarcoma (Fig.15.27) or possibly metastatic disease, as it can mimic a vascular lesion.

Treatment

HIV infection should be excluded. Cryotherapy, curettage and dilatation, or excision may be performed for small lesions. Radiation therapy is also effective. Intralesional interferon alpha-2a has been used. If classic Kaposi sarcoma develops on the legs of an elderly patient with some circulatory insufficiency and radiation therapy is used (at times repeatedly for recurrent disease with the potential for overlapping fields), stasis dermatitis or radiation dermatitis, with the potential for ulceration, may result.

Intralesional vinblastine may be used (vinblastine 0.2mg/mL, 0.1–0.3mL/lesion monthly, as needed).

Angiolymphoid hyperplasia with eosinophilia

Etiology and pathogenesis

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an unusual vascular proliferation that tends to occur in the head and neck, particularly about the ears, of adults. Although human herpesvirus 8 DNA has been reported in at least one case of ALHE, a larger series failed to show any connection.

Figure 15.26 Kaposi sarcoma, classic type. (a) A vascular lesion on the leg or foot of an older patient should raise the suspicion of classic Kaposi sarcoma. (b) Extensive lesions. (Courtesy of Michael O. Murphy, M.D.) .

Figure 15.27 Angiosarcoma.

Figure 15.28 Angiolymphoid hyperplasia with eosinophilia. This unusual benign, vascular proliferation is found most commonly on the ear and scalp. Dilated vessels and eosinophils are seen histologically. (See also Fig. 11.3.) (Courtesy of Duane Whitaker, M.D.)

Clinical

The ear and preauricular areas are most commonly affected by the red (less often, grayish or skin-colored) papulonodules of ALHE (Fig15.2 8). The head and neck may also be affected. Widespread papules mimicking prurigo nodularis have been reported. Peripheral eosinophilia is often seen. Ulceration and bleeding may occur. Work-up should include a complete blood count, a skin biopsy, and a lymph node examination.

Differential diagnosis

Kaposi sarcoma as well as angiosarcoma of the head and neck should be considered. Some lesions resemble basal cell carcinoma. Kimura disease must be considered, as it has a similar histologic picture. However, its lesions are typically larger, deeper nodules with normal overlying skin and often with lymphadenopathy. A biopsy is always necessary to establish the diagnosis.

Treatment

Excision, intralesional steroids, cryotherapy, electrodesiccation, or laser have been used. Mohs surgery is reported to be very effective, with the characteristic cells readily identified in frozen sections. Two cases related to elevated female hormones (birth control pill and pregnancy) resolved or improved after the exposure stopped (stopping ‘the pill' and after delivery, respectively). Multiple treatments with the pulsed dye laser have been helpful for superficial lesions. Radiation therapy was successful in one case without any side effects after 9 years of follow-up.