Section 8. Disorders of Blood and Lymph Vessels

Insight

It is important to differentiate between the three most common vascular anomalies in newborns: capillary stains that self-resolve, port-wine stains that benefit from laser treatment, and hemangiomas, which spontaneously involute.

Capillary Stain (Salmon Patch)

The salmon patch is the most common benign vascular lesion seen in infants, typically on the forehead, glabella, or nape of neck that are most prominent during infancy, then self-resolve during childhood.

Synonyms Nevus simplex, telangiectatic nevus, “stork bite,” nuchal nevus, Unna’s nevus, evanescent macule, angel kiss, or aigrette.

Epidemiology

Age Present at birth, fades with time.

Gender M = F.

Incidence Occurs in 30% to 40% of newborns.

Etiology Thought to be a persistence of fetal circulation, gradually becomes less prominent.

History

Present at birth, these benign lesions fade with time. In lighter skin types, the patch may be more persistent or evident during episodes of crying or physical exertion. Fifty percent of salmon patches in the nuchal region persist for life. They are asymptomatic and benign.

Physical Examination

Skin Findings

Type Macular with telangiectasias.

Color Dull pink to red.

Distribution Head and neck.

Sites of Predilection Nape of neck (22%), glabella (20%) (Fig. 8-1A), and eyelids (5%).

Differential Diagnosis

Salmon patch is the most common vascular birthmark. Its classic locations and self-resolving tendencies should differentiate it from other vascular birthmarks such as capillary malformations and hemangiomas.

Laboratory Examinations

Histopathology Skin biopsy reveals dilated dermal capillaries.

Course and Prognosis

Facial salmon patches fade with time (Fig. 8-1B) and only become evident in lighter skin types with crying or physical exertion. Nuchal salmon patches can persist but are asymptomatic and not usually of cosmetic concern because they are covered by the posterior hairline.

Management

Unlike capillary malformations, facial salmon patches fade almost completely and usually do not require treatment. Persistent lesions can occur in the nuchal area, but these are typically covered with hair and not a cosmetic concern. Rare bothersome persistent lesions can be treated with laser ablation.

Capillary Malformations (Port-Wine Stain) and Associated Syndromes

The most common capillary malformation is a port-wine stain (PWS): a lesion comprising dilated capillaries, which are macular at onset, but become plaquelike with time as the capillaries dilated. The majority are present at birth, and unlike salmon patches, they persists for life. PWS are benign, but rarely may be associated with a complicated syndrome such as Sturge-Weber (see Table 8-1).

Synonyms Nevus flammeus, telangiectasia.

Epidemiology

Age Present at birth, persists throughout life.

Gender M = F.

Race Whites > Asians > blacks.

Etiology Mutation in vascular morphogenesis.

Pathophysiology

Given the occasional association of a PWS with Sturge-Weber or Klippel-Trenaunay syndromes (see Table 8-1), it is postulated that the PWS is caused by a mutation in the anterior neural crest or mesoderm during embryogenesis.

Physical Examination

Skin Lesions

Type Infancy: macular. Adulthood: nodular, plaquelike.

Color Infancy: pink. Adulthood: red, purple.

Shape Segmental. Large lesions follow a dermatomal distribution and rarely cross the midline (Fig. 8-2A).

Distribution Localized or diffuse. Most commonly involve the face (Fig. 8-2B) in a trigeminal nerve distribution (V1, V2, or V3).

Differential Diagnosis

The diagnosis of a PWS is made clinically. The differential diagnosis of a PWS includes a hemangioma, salmon patch, venous malformation, lymphatic malformation, or arteriovenous malformation. Doppler ultrasound, CT, MRI, or other imaging studies may be needed if the diagnosis is unclear.

Laboratory Examinations

Histopathology Dilated capillaries and increased ectasias in the deep reticular dermis.

Immunohistochemistry GLUT-1-negative differentiating PWS from hemangiomas.

Course and Prognosis

PWS do not regress spontaneously. The area of involvement tends to increase in proportion to the size of the child. In adulthood, PWS can turn darker red–purple in color and thicken, which leads to more severe cosmetic disfigurement. In some cases, the thickening is associated with hyperplastic skin changes and asymmetric overgrowth of the area underlying the PWS (face > trunk and limbs).

Management

Isolated PWS are benign but can be disfiguring and distressing to the patient. Multiple treatments with a pulsed dye laser are very effective and should be considered in childhood before the lesion progresses to a more severe nodular, disfiguring form. Alternatively, a PWS can be covered up with makeup.

The majority of PWS have no associated abnormalities. Infrequently, a midline PWS of the lumbosacral, back, or nape area may be a hallmark for spinal dysraphism especially if seen in conjunction with other skin signs (pit, dimple, sinus, fibroma, lipoma, or hypertrichosis). Dysraphism can be detected with ultrasound or MRI.

Rarely, PWS can be associated with Sturge-Weber syndrome or Klippel-Trenaunay syndrome (see Table 8-1). It is estimated that 10% to 15% of infants with a V1 PWS will develop the ocular glaucoma and neurologic seizures of Sturge-Weber syndrome. If suspected, internal imaging with radiography (calcifications), CT (pial brain lesions), MRI (myelination), SPECT (blood flow), or PET (glucose metabolism) may be helpful. Klippel-Trenaunay syndrome is the association of limb hypertrophy with an overlying PWS or capillary venous malformation. Again, Doppler ultrasound or MRI can better detect the extent of tissue involvement in these patients.

Hemangiomas and Associated Syndromes

Hemangiomas are benign, vascular proliferations that rapidly enlarge during the first year of life and slowly spontaneously involute by age 5 to 10 years. Superficial hemangiomas have a bright red, nodular surface and deeper lesions may be blue–purple in color. Rarely, they may be associated with systemic malformations (see Table 8-2).

Synonyms Infantile hemangioma, hemangioma of infancy, strawberry nevus, angioma cavernosum, capillary hemangioma.

Epidemiology

Age 10% to 12% have onset <1 years. Rarely present at birth.

Gender F > M, 5:1

Prevalence Seen more in premature infants (<30 weeks gestational age or birthweight <1500 g), infants of mothers status postchorionic villus sampling, infants of older mothers, and infants of multiple gestation.

Race More common in Caucasians.

Incidence Most common tumor of infancy. Seen in 2.6% of all newborns.

Etiology Abnormally increased vascular proliferation. Reports of familial cases (?AD inheritance).

Pathophysiology

Hemangiomas are localized proliferations of blood vessels. Extensive study is underway to understand the signaling mechanisms that cause this benign tumor to grow, plateau, and then spontaneously involute. Several proposed mechanisms for hemangioma formation include the following:

1. 1. A mutation in endothelial cells,

   2. A mutation in other cells influencing endothelial proliferation,

   3. Placental origin of proliferative cells, and/or

   4. Dysregulation of immature endothelial progenitor cells.

It seems that a combination of these mechanisms, multiple genes, and local effects all influence the development, growth, and involution of hemangiomas.

History

Lesions present soon after birth during the first few weeks of life. The lesions proliferate 6 to 18 months, and then spontaneously involute by age 9 years; 30% of lesions involute by age 3, 50% by age 5, 70% by age 7, and 90% by age 9. At the end of involution, most lesions are cosmetically undetectable, but a few can leave atrophic, fibrofatty, or telangiectatic markings. Rarely, a hemangioma can proliferate in utero, is present at birth and undergoes rapid spontaneous resolution (“rapidly involuting congenital hemangioma” or “RICH”) in the first year of life. Even more rare is a noninvoluting congenital hemangioma (“NICH”), which will not go away spontaneously. Both of these latter hemangioma variants are the exception rather than the rule.

Solitary hemangiomas are asymptomatic and benign and rarely bleed (see Fig. 8-3A). Possible complications include the following:

1. 1. Ulceration (seen in 10% of hemangiomas, see Fig. 8-3B) most common in lip, neck, or anogenital locations.

   2. Location near critical structures (periorbital, nasal tip, lip, pinna, breast, and anogenital area) causing obstruction.

   3. Associated with internal abnormalities (CNS, laryngeal obstruction, and spinal dysraphism).

Physical Examination

Skin Findings

Type Nodule, plaque, may ulcerated.

Color Superficial: pink, red; Deep: blue–purple. Involuting: white/gray.

Frequency 50% to 60% superficial, 25% to 35% combined, 15% deep.

Size Average 2 to 5 cm but can grow up to 20 cm in size.

Pattern Focal or segmental.

Palpation Superficial lesions are soft/compressible; deeper lesions are more firm.

Sites of Predilection Face, trunk, legs, oral, and genital mucous membranes.

Differential Diagnosis

Hemangiomas are sometimes confused with other vascular abnormalities such as capillary malformations, infantile myofibromatosis, or pyogenic granulomas. Deeper lesions can mimic dermal or subcutaneous masses such as fibrosarcoma, rhabdomyosarcoma, neuroblastoma, dermatofibrosarcoma protuberans, nasal glioma, lipoblastoma, venous, lymphatic, or AV malformations. The characteristic proliferative and involuting phase can clinically differentiate hemangiomas from other vascular lesions. Radiographic studies or histologic examination may be necessary in most difficult cases.

Laboratory Examinations

Histopathology Proliferating: endothelial cell hyperplasia, lobule formation, masts cells, and prominent basement membrane. Involuting: fibrofatty tissue, decreased mast cells.

Immunohistochemistry GLUT1-positive staining differentiating hemangiomas from all other vascular malformations.

Doppler Evaluation Can determine slow flow hemangiomas versus fast flow AV malformations.

CT Scan Uniformly enhancing soft tissue mass with dilated feeding and draining vessels.

MRI Soft tissue mass which is iso-or hypointense to muscle with flow voids.

Course and Prognosis

Hemangiomas spontaneously involute by age 5 to 9 years. The residual skin changes are barely detectable but can include: skin atrophy, fibrofatty tissue, telangiectasia, or depigmentation (Fig. 8-3C). Typical spontaneous involution leaves the best cosmetic results, and thus nonintervention in uncomplicated lesions is recommended.

Focal hemangiomas are typically small, arise from one locus and spontaneously involute without any complications. Larger segmental hemangiomas may be associated with systemic anomalies such as spinal dysraphism, GI, GU anomalies, or PHACES syndrome (see Table 8-2).

A midline hemangioma of the lumbosacral, back, or nape area may be a hallmark for spinal dysraphism especially if seen in conjunction with other skin signs (pit, dimple, sinus, fibroma, lipoma, or hypertrichosis) or other malformations (imperforate anus, GI fistulae, skeletal, and renal abnormalities). An MRI can detect these underlying defects.

Ten to twenty-five percent of patients will have multiple hemangiomas, and numerous hemangiomas can be a marker for internal involvement. A child with numerous cutaneous hemangiomas should be evaluated for the possibility of hemangiomas of the visceral organs, GI tract, liver, CNS, lungs, mucous membranes, or eyes. Complications include cardiac failure, GI bleeding, hydrocephalus, visceral hemorrhage, and ocular abnormalities. Radiologic evaluation (ultrasound, CT, or MRI) may be helpful in determining the extent of internal involvement.

Management

Treatment for the majority of simple hemangiomas is unnecessary because they are asymptomatic and self-resolve with a good cosmetic result.

Less than 2% of hemangiomas require intervention (for ulceration/bleeding, blocking facial structures or GI/GU tracts). Ulcerations can be managed with local wound care: saline soaks, topical antibiotics (mupirocin or metronidazole), and occlusive dressings. Pain with the ulcers can be alleviated with oral acetaminophen. Superinfected lesions may require a course of oral antibiotics (such as a first-generation cephalosporin).

Intralesional steroids can be used to treat small hemangiomas, but periocular injections can be complicated by ophthalmic artery occlusion and can lead to blindness. Topical steroids are safer, but their efficacy is unclear. Topical 5% imiquimod cream reportedly helps proliferating hemangiomas, but the cream can cause erosions as a complication.

Systemic steroids, such as prednisolone or prednisone, are the first-line treatment for life-threatening obstructive hemangiomas; 2–3 mg/kg/d is recommended until cessation of hemangioma growth or shrinking is achieved, then the steroids should be tapered. Adverse reactions to systemic steroid include cushingoid facies, irritability, GI symptoms, and decreased growth rate.

Systemic α-IFN (angiogenesis inhibitor) can be used for refractory, severe life-threatening hemangiomas at a dose of 1–3 million U/m/d injected subcutaneously. Adverse effects include spastic diplegia, fever, irritability, diarrhea, neutropenia, elevated LFTs, and skin necrosis. Systemic vincristine is a chemotherapy approach for resistant life-threatening hemangiomas, but its effectiveness is unclear. Adverse effects include peripheral neuropathy, jaw pain, anemia, and leukopenia.

Pulsed dye laser is effective in lightening the surface of proliferative red lesions; however, there was no change in clearance compared to un-lasered children by age 1 and the PDL-treated children were more likely to develop atrophy, hypopigmentation, ulceration, and scarring. Argon and Nd:YAG lasers are capable of treating deeper hemangiomas, but the risk of scarring is even higher with these lasers.

Surgical management (with or without embolization) is difficult, and should be reserved for proliferating hemangiomas in life-threatening locations. Otherwise the timing of surgical intervention might be most helpful after complete involution (for any residual fibrofatty component), for cosmetically it may leave a preferable cosmetic outcome to surgical scarring.

Spider Angioma

A spider angioma is a localized area of dilated capillaries, radiating from a central arteriole, occurring in healthy children.

Synonyms Nevus araneus, spider nevus, arterial spider, spider telangiectasia, vascular spider.

Epidemiology

Age Young childhood and early adulthood.

Gender F > M.

Incidence May occur in up to 15% of normal individuals.

Etiology Usually idiopathic dilated blood vessel. Maybe associated with hyperestrogen states such as pregnancy or estrogen therapy (e.g., oral contraceptive) or hepatocellular disease (such as subacute and chronic viral hepatitis and alcoholic cirrhosis).

Physical Examination

Skin Findings

Type Central papule at the site of the feeding arteriole with radiating telangiectatic vessels (legs).

Size 2 mm to 1.5 cm in diameter. Usually solitary (Fig. 8-4).

Color Red.

Shape Round to oval.

Palpation On diascopy, radiating telangiectasia blanches and central arteriole may pulsate.

Sites of Predilection Face, neck, upper trunk, arms, hands, fingers, and mucous membranes of lip or nose.

Differential Diagnosis

Spider angiomas can be confused with other vascular lesions such as cherry angiomas or telangiectasias.

Course and Prognosis

A few spider angiomas can regress spontaneously. However, the majority of lesions will persist. They are benign and asymptomatic, but often occur on the face and are cosmetically distressing to patients. Rarely, they may be associated with systemic diseases such as hereditary hemorrhagic telangiectasia, ataxia telangiectasia, progressive systemic sclerosis, and CREST syndrome.

Management

Spider angiomas are benign and thus do not require treatment. Lesions that are of cosmetic concern may be eradicated with electrodesiccation, electrocoagulation, or laser therapy. Patients should be forewarned that the lesions often recur.

Cherry Angioma

Cherry angiomas are benign, bright red, dome-shaped vascular lesions that usually occur on the trunk.

Synonym Campbell de Morgan spots, senile angioma, cherry hemangioma.

Epidemiology

Age Any age, more commonly seen in adults.

Gender M = F.

Incidence Common, seen in most adults by age 60 years.

Etiology Increased number in elderly and during pregnancy.

Physical Examination

Skin Findings

Type Small macule to dome-shaped papule (see Fig. 8-5).

Color Bright red to violaceous.

Size 1 to 8 mm in size.

Number Elderly adults may have 50 to 100.

Palpation Soft, compressible. Often blanches completely with pressure.

Sites of Predilection Trunk, proximal extremities.

Differential Diagnosis

The diagnosis of cherry angiomas is made clinically. They may sometimes be confused with petechiae. Larger lesions may look like a pyogenic granuloma or hemangioma.

Laboratory Examinations

Dermatopathology Numerous dilated, congested capillaries; stroma edematous with homogenization of collagen. Epidermis thinned.

Course and Prognosis

Cherry angiomas begin to appear in adolescence, becoming more numerous with advancing age. They are asymptomatic, but may bleed when traumatized. Rare cases of eruptive cherry angiomas can be associated with systemic disease.

Management

Cherry angiomas in children are benign and hence no treatment is necessary. Lesions that are of cosmetic concern can be treated with electrodesiccation, laser therapy, or surgical removal.

Angiokeratoma

An angiokeratoma is a benign skin lesion comprised dilated dermal capillaries with overlying epidermal hyperkeratosis. There are five variants:

1. 1. Solitary or multiple angiokeratomas: result from injury or irritation to the wall of a venule in the papillary dermis.

   2. Angiokeratomas or the scrotum or vulva (Fordyce): may be associated with thrombophlebitis, varicoceles, inguinal hernias, varicosities, hemorrhoids, OCPs, or increased venous pressure from pregnancy.

   3. Angiokeratoma corporis diffusum: clustered angiokeratoma on the trunk usually secondary to hereditary lysosomal storage diseases such as Fabry disease (α-galactosidase deficiency), α-1 fucosidase deficiency.

   4. Angiokeratoma of Mibelli: may be AD with lesions on the fingers and toes. This variant may be associated with chilblains or acrocyanosis.

   5. Angiokeratoma circumscriptum: a capillary–lymphangioma malformation that occurs on the trunk or extremities of children.

Epidemiology

Age Angioma circumscriptum can be seen at birth, in infancy, and in childhood. The other forms appear later in life.

Gender F > M: Angioma circumscriptum, angiokeratoma of Mibelli.

Prevalence Angiokeratoma of Fordyce is common. The other forms are uncommon.

Etiology Unclear. Solitary angiokeratomas are sometimes associated with trauma.

Genetics Mibelli may have AD inheritance with variable penetrance. Fabry’s disease: X-linked recessive.

Physical Examination

Skin Findings

Type Verrucous papules coalescing into plaques (Fig. 8-6).

Color Dark-red to black.

Size 1 mm to several centimeters.

Shape Round to stellate, can be in streaks or bands.

Palpation Soft.

Sites of Predilection

1. 1. Solitary or multiple angiokeratomas: Lower extremities.

   2. Angiokeratomas or the scrotum or vulva (Fordyce): Scrotum in males, labia in females.

   3. Angiokeratoma corporis diffusum: clustered angiokeratomas on the trunk (bathing suit distribution).

   4. Angiokeratoma of Mibelli: dorsa of hands, feet, fingers, toes, elbows, and knees.

   5. Angiokeratoma circumscriptum: trunk, arms, and legs.

Differential Diagnosis

Angiokeratomas are diagnosed and categorized by clinical presentation. Numerous angiokeratomas should alert one to check for more systemic disease.

Laboratory Examinations

Histopathology Dilated papillary dermal blood vessels with overlying acanthosis and hyperkeratosis of the epidermis. Angiokeratoma circumscriptum: capillary–lymphatic malformation. Fabry’s disease: glycolipid vacuoles (PAS- and Sudan black-positive staining) in endothelial cells and pericytes.

Course and Prognosis

Angiokeratomas are typically asymptomatic but persist for life and grow proportionately with the child. Occasionally, they may bleed or warrant removal for cosmetic reasons.

Angiokeratoma corporis diffusum has more widespread lesions and may be associated with hereditary lysosomal storage diseases such as Fabry disease (α-galactosidase deficiency), α-1 fucosidase deficiency.

Management

Angiokeratomas are benign and thus do not need treatment. They may, however, bleed or warrant removal for cosmetic reasons. They can be treated with surgical excision, electrodesiccation, or laser therapy.

Pyogenic Granuloma

Insight

Although the clinical diagnosis of pyogenic granuloma can often be readily made, because of the worrisome differential diagnosis, it is always reasonable to send the lesions for histologic confirmation.

A pyogenic granuloma is a rapidly developing, bright red papule or nodule usually occurring at a site of trauma.

Synonyms Granuloma telangiectaticum, granuloma pyogenicum, lobular capillary hemangioma, tumor of pregnancy, eruptive hemangioma.

Epidemiology

Age Usually children or young adults.

Gender M = F.

Etiology Reactive vascular proliferation. One-third seen posttraumatic injury. Can be seen with systemic retinoids, indinavir, anti-ECFR antibodies, PWS, and pregnancy.

History

Pyogenic granulomas are rapidly proliferating vascular nodules that typically arise at a site of minor trauma. They are benign but have a tendency to get traumatized easily and bleed copiously.

Physical Examination

Skin Lesions

Type Solitary vascular papule or nodule with smooth or warty surface (Fig. 8-7).

Color Bright red, dusky red, violaceous, and brown–black.

Size 5 mm to 2 cm. Usually < 1 cm.

Shape Usually lesion is pedunculated, base slightly constricted, or sessile.

Sites of Predilection Area of trauma: fingers, face, lips, face, tongue. Gingiva in pregnant women.

Differential Diagnosis

The diagnosis of a pyogenic granuloma is typically made on history and clinical examination. The differential diagnosis includes a hemangioma, amelanotic melanoma, metastatic carcinoma, glomus tumor, irritated nevus, or wart.

Dermatopathology

Histopathology Well-circumscribed, usually exophytic, proliferation of small capillaries in a fibromyxoid matrix surrounded by hyperplastic epithelial collarette.

Course and Prognosis

Pyogenic granulomas are benign, but have a tendency to get traumatized easily and bleed copiously. They are often precipitated by minor trauma and have a tendency to recur after (traumatic) removal or sprout new satellite lesions.

Management

Surgical shave excision with electrosurgery of the base under local anesthesia is recommended. Patients should be forewarned that the lesions can recur.

Some pyogenic granulomas have been treated with pulsed dye lasers successfully.

Livedo Reticularis

Livedo reticularis (LR) is common physiologic finding of a mottled bluish (livid) discoloration of the skin that occurs in a netlike pattern.

Synonyms Livedo racemosa, livedo annularis.

Classification

1. 1. LR with no systemic disease:

   • a. Phyisologic LR (cutis marmorata): normal LR response to cold in neonates, young children, some adults with chilblains, or acrocyanosis.
   • b. Benign idiopathic LR. Permanent bluish mottling from persistent vasospasm of arterioles for which no underlying disease is found.

   2. LR secondary to systemic disease:

   • a. Vasospasm: occurs with Raynaud’s and connective tissue disease.
   • b. Intravascular obstruction: cryoglobulins, cold agglutins, paraproteins, polycythemia vera, thrombocytosis, APS and protein C deficiency, protein S or antithrombin III deficiencies, emboli, heparin or warfarin necrosis. Stasis from paralysis, cardiac failure. Sneddon’s syndrome. Extensive LR, hypertension, cerebrovascular accidents, and transient ischemic attacks.
   • c. Vasculitis: polyarteritis nodosa, cryoglobulinemic vasculitis, rheumatoid vasculitis, lupus erythematosus, dermatomyositis, lymphoma, syphilis, tuberculosis, pancreatitis, calciphylaxis.
   • d. Others: drugs (such as amantadine [Fig. 8-8], norepinephrine, quinine, and quinidine), infections, or with neoplasms.

Epidemiology

Age Adolescence to adulthood.

Gender M = F.

Pathophysiology

Livedo pattern is caused by vasospasm of the arterioles in response to cold leading to hypoxia and dilation of the capillaries and venules. Decreased perfusion of the skin and/or decreased blood drainage leads to pooling of deoxygenated blood in the venous plexus creating the mottled cyanotic reticular pattern that persists after rewarming.

History

LRs appearance or worsening with cold exposure, sometimes with associated numbness and tingling.

Physical Examination

Skin Findings

Type Netlike, blotchy, or mottled macular cyanosis (see Fig. 8-8) Ulceration may occur.

Color Reddish-blue.

Palpation Skin feels cool.

Distribution

1. 1. Physiologic/benign idiopathic LR: Symmetrical, arms/legs; less commonly, body; lower legs.

   2. Secondary LR: Patchy, asymmetrical on extremities.

Differential Diagnosis

The differential diagnosis for LR includes other reticulated skin disorders such as erythema ab igne, erythema infectiosum, or poikiloderma.

Laboratory Examinations

Dermatopathology Can vary as causes for LR varies: arteriolar intimal proliferation with dilated numerous capillaries, thickening of walls of venules; and a lymphocytic perivascular infiltration.

Course and Prognosis

Physiologic or benign idiopathic LR recurs with cold exposure but rarely becomes permanent. Secondary LR is a precursor to more serious systemic sequelae.

Management

Physiologic or benign idiopathic LR:

1. 1. Keep extremities from cold temperature exposure.

   2. Low-dose aspirin (3–5 mg/kg/d po divided qid).

   3. Pentoxifylline (Trental) for severe refractory cases.

• Secondary LR: Treat associated disorder.

Cutis Marmorata Telangiectatica Congenita

Cutis marmorata telangiectatica congenita (CMTC) is a reticulated mottling of the skin that is more extensive and persistent than cutis marmorata. CMTC can lead to skin ulceration and atrophic scarring.

Synonym Congenital generalized phlebectasia.

Epidemiology

Age Onset at birth.

Gender M = F.

Prevalence Rare.

Etiology Unknown.

Genetics Autosomal dominant with low penetrance.

Pathophysiology

Ectasia of capillaries and veins may represent a mesodermal defect, which would explain CMTC’s association with other mesodermal congenital abnormalities.

Physical Examination

Skin Findings

Type Macular reticulated mottling. Ulceration may be present over the reticulated vascular pattern and may heal with depressed scars (Fig. 8-9).

Color Red to blue.

Size Dilated venous channels 3 to 4 mm in diameter.

Distribution Typically generalized. Localized forms have been seen confined to the trunk or one extremity.

General Findings

Generalized CMTC: can see neurologic, vascular, ocular, skeletal abnormalities. Localized CMTC: can see decreased limb girth.

Differential Diagnosis

CMTC needs to be differentiated from cutis marmorata, which has a more short-lived, transient course and does not scar. Both are diagnosed by clinical history and physical examination.

Laboratory Examinations

Histopathology Skin biopsy may show dilated capillaries and venules in all layers of the dermis and subcutaneous tissue. Histology may also be subtle and nondiagnostic.

Course and Prognosis

Typically mottled pattern is present at birth and improves but persists with age. Most cases are localized to one extremity possibly with hypoplasia of the affected limb, but no systemic abnormalities. fifty percent of CTMC cases can have other congenital abnormalities, particularly diffuse CMTC (vascular, skeletal, ocular, neurologic, or soft-tissue defects). Rarely, CMTC can be seen in infants with neonatal lupus.

Management

The skin lesions do not require therapy and the mottled vascular pigmentation usually improves. Reticulated scarring, however, is permanent. With localized CMTC, limb hypoplasia can develop. For generalized CMTC, ocular, skeletal, and neurologic issues may need to be addressed.

Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant condition that affects blood vessels, especially in the mucous membranes of the mouth and the GI tract. The disease often manifests itself by recurrent epistaxis that appears often in childhood. The telangiectasias of the skin and mucous membranes appears later in life and the clinical spectrum can range from cosmetic, asymptomatic lesions to severe pulmonary, GI, GU, and CNS hemorrhages.

Synonyms Osler-Weber-Rendu disease, Osler’s disease.

Epidemiology

Age Epistaxis may appear in childhood (average 8 to 10 years) but skin lesions begin after puberty, along with epistaxis.

Prevalence Rare.

Genetics Autosomal dominant. Mutations in ENG (endoglin gene) and ACVRL1 have been identified.

Pathophysiology

HHT blood vessels lack adequate perivascular support (pericytes, smooth muscle, and elastic fibers). Thus, the telangiectatic capillaries rupture easily and cause repeated nasal and GI hemorrhages.

History

The typical skin lesions (punctate red macules and papules) begin to appear after puberty but peak in the third or fourth decade. Bouts of recurrent epistaxis often begin in childhood; GI bleedings in HHT patients in adulthood. Thirty percent of HHT patients develop hepatic AVMs, 30% develop pulmonary AVMs, and 10% to 20% develop cerebral AMVs.

Physical Examination

Skin Findings

Type Macules or papules.

Size 1 to 3 mm in diameter.

Color Red.

Shape Punctate (most frequent; Fig. 8-10A), stellate, or linear.

Arrangement of Multiple Lesions Symmetrical and scattered, nonpatterned.

Distribution Upper half of the body; begin on the mucous membranes of the nose, later develop on the lips; (Fig. 8-10B), mouth (tongue), conjunctivae (Fig. 8-10C), trunk, upper extremities, palms, soles, hands, fingers, and toes.

Nails Nail beds of fingers and toes.

Mucous Membranes Telangiectases appear on nasal septum, on the tip and dorsum of the tongue, nasopharynx, and throughout the GI tract.

General Findings

Thirty percent have hepatic AVMs, 30% have pulmonary AVMs, and 10% to 20% have cerebral AMVs.

Laboratory Examinations

Hematology Anemia from chronic blood loss.

Dermatopathology Skin biopsy reveals dilated capillaries and venules located in the dermis, lined by flattened endothelial cells.

Imaging X-ray, CT, or MRI to rule out pulmonary AV fistulae.

Differential Diagnosis

Clinical diagnosis made if triad is present of (1) typical telangiectases on skin (fingers and palms) and mucous membranes (lips and tongue), (2) repeated GI hemorrhages, and (3) family history.

Management

In mild cases of HHT, treatment of the telangiectases is not necessary; however, iron supplementation for anemia is recommended. Troublesome or cosmetically unwanted telangiectases can be destroyed with laser therapy or cauterization.

In severe cases of HHT, there may be extensive systemic involvement. Pulmonary AVMs can lead to hypoxemia, hemorrhages, and cerebral events. Hepatic AVMs may cause liver fibrosis and cirrhosis, which leads to coagulation defects increasing the severity of hemorrhaging. Surgical resection or embolization of involved pulmonary and GI segments may be necessary.

Microcystic Lymphatic Malformation

A microcystic lymphatic malformation is a benign tumor of the lymphatic system characterized by groups of deep-seated vesicles that have been likened to “frog spawn.” Often there is a hemangiomatous component.

Synonym Hemangiolymphoma, lymphangioma circumscriptum.

Epidemiology

Age Present at birth or infancy.

Gender M = F.

Prevalence Uncommon.

Etiology Unclear.

History

Appear at birth or soon after; can remain stable or slowly grow with time.

Physical Examination

Skin Findings

Type Deep-seated, crops of vesicles coalescing into plaques (Fig. 8-11).

Color Clear or red–purple.

Size 2- to 4-mm vesicles.

Shape Grouped vesicles.

Sites of Predilection Proximal extremities, shoulder, neck, axillae, mouth (cheek, tongue, floor).

Laboratory Examinations

Dermatopathology Skin biopsy reveals dilated lymph vessels with associated blood vessel dilation in the upper dermis.

Differential Diagnosis

The diagnosis of microcystic lymphatic malformation can be made clinically, radiologically, or by biopsy. The differential diagnosis includes angiokeratoma, hemangioma, recurrent herpetic lesion, contact dermatitis, and molluscum contagiosum.

Course and Prognosis

Many microcystic lymphatic malformations are asymptomatic and so slow-growing that no systemic effects are seen. More extensive lesions can increase in size and if bleeding (from a hemangiomatous part) occurs, they can require intervention.

Management

Asymptomatic, stable microcystic lymphatic malformations do not need treatment. Lesions are often much more extensive than is clinically visible and have a tendency to recur, thus attempts at removal can sometimes worsen the outcome. Symptomatic (leaking lymph, inflammatory flares, or infections) lesions can be removed by surgical excision, fulguration, coagulation, or CO2 laser ablation. It may be more difficult to remove larger/deeper lesions, because they can be extensive and recurrent. Multiple surgical excisions may be necessary.

Macrocystic Lymphatic

Malformation

Macrocystic lymphatic malformations are interconnected, large, loculated lymphatic proliferations that are often detectable in utero. They are benign, but can become symptomatic with hemorrhaging and sudden swelling. They can also be associated with malformation syndromes or teratogenics.

Synonym Hygroma colli, cystic hygroma.

Epidemiology

Age May be present at birth or infancy.

Gender M = F.

Prevalence Rare.

History

Lesions appear later in life as subcutaneous swellings that involve large body surface areas. They can be quite deep and debilitating (Fig. 8-12).

Physical Examination

Skin Findings

Type Translucent nodular or cystic swellings.

Color Flesh colored to pink–red.

Size 1 to several centimeters in size.

Sites of Predilection Neck, axillae, lateral chest, groin, or popliteal fossa.

General Findings

Can be associated with karyotype abnormalities (Down syndrome, Turner syndrome, and Noonan syndrome).

Laboratory Examinations

Dermatopathology Histologic examination shows a uniloculated or multiloculated nodule of numerous dilated lymph channels lined with flat or cuboidal endothelial cells.

Radiologic Ultrasound, CT, or MRI reveal large, cystic spaces in the dermis, subcutis, or muscles.

Differential Diagnosis

The diagnosis of a macrocystic lymphatic malformation is made by history and clinical findings and can be confirmed by imaging studies and/or tissue diagnosis. The differential diagnosis includes a cavernous hemangioma, and soft-tissue proliferation.

Course and Prognosis

Macrocystic lymphatic malformations can involve large parts of the face, trunk, or extremities and can be very debilitating.

Management

Percutaneous sclerotherapy is the treatment of choice for macrocystic lymphatic malformations and multiple treatments may be necessary to induce inflammation and encourage scarred shrinkage of the cysts. Surgical removal is the second approach and may require split-thickness grafts and/or tissue expanders to fill in the wound. Severe, extensive macrocystic lesions may be untreatable.

Lymphedema

Lymphedema is diffuse soft-tissue swelling caused by poor lymphatic drainage. It may be a primary disease (congenital) or secondary (e.g., postsurgical) to pathologic obstruction of the lymph vessels.

Lymphedema may be (1) primary (manifesting at birth or childhood) or (2) secondary (acquired).

Epidemiology

Age Primary lymphedema: 13% congenital, age 9 to 25 years. Secondary lymphedema: any age.

Gender F > M.

Etiology

• Primary:

1. 1. Milroy disease: mutation in genes that encode vascular endothelial growth factor receptor 3.

   2. Meige lymphedema: mutation in genes that encode for forkhead family transcription factor C2.

• Secondary: Postsurgery, postinfection, filariasis.

Pathophysiology

The lymphatic drainage to an extremity is impaired either primarily (e.g., congenital lymphedema) or secondarily (e.g., postsurgical) and leads to swelling of the affected extremity.

History

Lymphedema of the involved area results in swelling that fluctuates in severity and gradually worsens with age. Milroy’s disease is an autosomal dominant disorder with an inherited tendency for lymphedema of the legs. The etiology is unclear.

Physical Examination

Skin Findings

Type Diffuse swelling (Fig. 8-13).

Palpation Firm with pitting under pressure.

Sites of Predilection Lower extremities, upper extremities.

Differential Diagnosis

The diagnosis of lymphedema is made by history and clinical examination. The differential diagnosis includes cellulitis and deep tissue infection.

Course and Prognosis

Lymphedema slowly progresses with age, and repeated swelling of the affected area leads to worsening of the disease.

Management

Maintenance therapy consists of the following:

1. 1. Rest and limb elevation.

   2. Compression with elastic support stockings, wraps, or pneumatic compression devices.

   3. Reducing sodium intake.

   4. Diuretics can also be helpful.

   5. Subcutaneous lymphangiectomy can be attempted, but scarring is extensive and unsightly.