PATHOLOGY OF VASCULAR SKIN LESIONS - PART 2 pdf

Table 1 Classification of Phakomatosis Pigmentovascularis I a,ba Nevus flammeus and nevus pigmentosus et verrucosus II a,b Nevus flammeus, mongolian spots, ± nevus anemicus III a,b Nev

P ATHOGENESIS

The most commonly accepted opinion is that phakomatosis pigmentovascularis resultsfrom developmental abnormalities of the vasomotor nerves derived from the neural crest

and melanocytes (30) It is thought that an alteration in the neural regulation of blood

vessels could lead to the development of the vascular abnormalities seen in this condition.This is probably the explanation for the coexistence of nevus flammeus and nevusanemicus characteristic of this disease The abnormal melanocytic component resultsfrom alterations during the migration of the neural crest-derived melanocytes, whichproduces lesions such as the nevus of Ota, nevus spilus, and mongolian spot

H ISTOPATHOLOGIC F EATURES

Histopathologically, there are an increased number of dilated thin-walled capillariesand venules in the upper part of the reticular dermis, although occasionally superficialareas of subcutaneous fat are also involved The melanocytic component consists ofspindled-shaped dendritic melanocytes loaded with abundant melanin in their cytoplasmscattered between the collagen bundles of the dermis (Fig 2) Sometimes, the number ofspindled melanocytes is sparse; thus lesions of phakomatosis pigmentovascularis may bemisinterpreted as nevus flammeus Immunohistochemical stains with S-100 protein orHMB-45 are helpful in highlighting the melanocytic component

Table 1 Classification of Phakomatosis Pigmentovascularis

I a,ba Nevus flammeus and nevus pigmentosus et verrucosus

II a,b Nevus flammeus, mongolian spots, ± nevus anemicus III a,b Nevus flammeus, nevus spilus, ± nevus anemicus

IV a,b Nevus flammeus, mongolian spots, nevus spilus, ± nevus anemicus

a

a, cutaneous involvement only; b, cutaneous and systemic involvement.

Fig 1 Clinical features of phakomatosis pigmentovascularis (A) The anterior abdomen and the

right thigh of this newborn show a combination of erythematous areas of nevus flammeus with

bluish areas of dermal melanocytosis (B)The buttocks and the posterior thighs of the same baby

show a combination of similar features.

It is important to remember that lesions of nevus flammeus associated withphakomatosis pigmentovascularis are indistinguishable from port wine stain not associ-ated with melanocytic abnormalities Ultrastructural studies indicate that nevus flammeusassociated with phakomatosis pigmentovascularis is surrounded by perivascular nerve

fibers, which are not present in isolated nevus flammeus (31).

T REATMENT

The vascular component of phakomatosis pigmentovascularis may cause cal trauma to the patient, especially when it involves the face In that case cosmeticcamouflage may be indicated Laser therapy is also capable of producing good results in

psychologi-treating nevus flammeus of phakomatosis pigmentovascularis (32).

There is no description of a melanoma originating in the melanocytic component ofphakomatosis pigmentovascularis

References

1 Ota M, Kawanura T, Ito N Phacomatosis pigmentovascularis (Ota) Jpn J Dermatol 1947;52:1–3.

2 Hasegawa Y, Yashura M Phakomatosis pigmentovascularis type IVa Arch Dermatol 1985;121:651–5.

3 Guillaume JC, Evenou P, Charpentier P, Avril MF Phacomatose pigmento-vasculaire type IIa Ann Dermatol Venereol 1988;115:1113–5.

4 Mahroughan M, Mehregan AH, Mehregan DA Phakomatosis pigmentovascularis Report of a case Pediatr Dermatol 1996;13:36–8.

5 Stadhouders-Keet SA, Glastra A, Van Vloten WA Phakomatosis pigmentovascularis (type IIIa) Ned Tijdschr Geneeskd 1999;143:1337.

6 Cincinnati P, Carucci T, Rutiloni C La facomatosi pigmento-vascolare Minerva Pediatr 1996;48:225–8.

7 Murdoch SR, Keefe M Phakomatosis pigmentovascularis type IIA in a Caucasian child Pediatr Dermatol 2000;17:157.

8 Toda K A new type of phacomatosis pigmentovascularis (Ota) Jpn J Dermatol 1966;76:47–51.

9 Hasegawa Y, Yasuhara M A variant of phakomatosis pigmentovascularis Sin Res (Osaka) 1979;21:178–86.

10 Hasegawa Y, Yasuhara M Phakomatosis pigmentovascularis type IVa Arch Dermatol 1985;121:651–5.

11 Noriega Sanchez A, Markand ON, Herndon JH Oculocutaneous melanosis associated with the Weber syndrome Neurology 1972;22:256–62.

Sturge-12 Furukawa T, Igata A, Toyokura Y, et al Sturge-Weber and Klippel-Trenaunay syndrome with nevus of Ota and Ito Arch Dermatol 1970;102:640–5.

Fig 2 Histopathologic features of phakomatosis pigmentovascularis (A) Low-power tion shows dilated vascular structures at different levels of the dermis (B) Higher magnification

magnifica-shows the dilated and congestive capillary blood vessels and scattered spindle, dendritic cytes with abundant melanin interstitially arranged between collagen bundles of the dermis.

melano-13 Sigg C, Pelloni F Oligosymptomatic form of Klippel-Trenaunay-Weber syndrome associated with giant nevus spilus Arch Dermatol 1989;125:1284–5.

14 Peyron N, Dereure O, Bessis D, Guilhou JJ, Guillot B La phacomatose pigmento-vasculaire A propos

de 2 cas associés à une angiodysplasie J Mal Vasc 1993;18:336–9.

15 Teekhasaenee C, Ritch R Glaucoma in phakomatosis pigmentovascularis Ophthalmology 1997; 104:150–7.

16 Hagiwara K, Uezato H, Nonaka S Phacomatosis pigmentovascularis type IIb associated with Weber syndrome and pyogenic granuloma J Dermatol 1998;25:721–9.

Sturge-17 Uysal G, Guven A, Ozhan B, Ozturk MH, Mutluay AH, Tulunay O Phakomatosis pigmentovascularis with Sturge-Weber syndrome: a case report J Dermatol 2000;27:467–70.

18 Guiglia MC, Prendiville JS Multiple granular cell tumors associated with giant speckled lentiginous nevus and nevus flammeus in a child J Am Acad Dermatol 1991;24:359–63.

19 Kikuchi I, Okazaki M Congenital temporal alopecia in phakomatosis pigmentovascularis J Dermatol 1982;9:485–7.

20 Kim HJ, Park KB, Yang JM, Park SH, Lee ES Congenital triangular alopecia in phakomatosis pigmentovascularis: report of 3 cases Acta Derm Venereol 2000;80:215–6.

21 Zahorcsek Z, Schmelas A, Schneider I Progrediente zirkumskripte Lentiginose Phakomatosis pigmentovascularis III/A Hautarzt 1988;39:519–23.

22 Gilliam AC, Ragge NK, Perez MI, Bolognia JL Phakomatosis pigmentovascularis type IIb with iris mammillations Arch Dermatol 1993;129:340–2.

23 Van Gysel D, Oranje AP, Stroink H, Simonsz HJ Phakomatosis pigmentovascularis Pediatr Dermatol 1996;13:33–5.

24 Di Landro A, Tadini GL, Marchesi L, Cainelli T Phakomatosis pigmentovascularis: a new case with renal angiomas and some considerations about the classification Pediatr Dermatol 1999;16:25–30.

25 Tsuruta D, Fukai K, Seto M, et al Phakomatosis pigmentovascularis type IIIb associated with moyamoya disease Pediatr Dermatol 1999;16:35–8.

26 Joshi A, Garg VK, Agrawal S, Agarwalla A, Thakur A Port-wine stain (nevus flammeus), congenital Becker’s nevus, café-au-lait-macule and lentiginides: phakomatosis pigmentovascularis type Ia—a new combination J Dermatol 1999;26:834–6.

27 Huang C, Lee P Phakomatosis pigmentovascularis IIb with renal anomaly Clin Exp Dermatol 2000;25:51–4.

28 Cho S, Choi JH, Sung KJ, Moon KC, Koh JK Phakomatosis pigmentovascularis type IIB with logic abnormalities Pediatr Dermatol 2001;18:263.

neuro-29 Bielsa I, Paradelo C, Ribera M, Ferrandiz C Generalized nevus spilus and nevus anemicus in a patient with a primary lymphedema: a new type of phakomatosis pigmentovascularis? Pediatr Dermatol 1998;15:293–5.

30 Libow LF Phakomatosis pigmentovascularis type IIIb J Am Acad Dermatol 1993;29:305–7.

31 Smoller BR, Rosen S Port wine stains: a disease of altered neural modulation of blood vessels? Arch Dermatol 1986;122:177–9.

32 Ono I, Tateshita T Phacomatosis pigmentovascularis type IIa successfully treated with two types of laser therapy Br J Dermatol 2000;142:358–61.

2 ECCRINE ANGIOMATOUS HAMARTOMA

Eccrine angiomatous hamartoma (EAH) refers to a cutaneous hamartoma that bines a proliferation of both eccrine glands and thin-walled blood vessels, usually of a

com-capillary nature So far, 45 examples of EAH have been reported in the literature (1–35), although some of the reported cases may be variations of normal skin (36) or simply

vascular malformations located in volar skin, where eccrine glands are normally abundant

EAH was initially reported in 1859 by Lotzbeck (1), who described a lesion of

angi-omatous appearance on the cheek of a child Histopathologically, the lesion was posed of numerous clusters of eccrine glands within a stroma containing prominent blood

com-vessels In 1895 (2), Beier used the term sudoriparous angioma to describe a painful sudoriparous skin lesion of an angiomatous nature In 1968, Hyman et al (3) coined the term eccrine angiomatous hamartoma for this lesion and published a literature review on

the subject They noted that similar lesions were previously described under several

designations, including secreting sudoriparous angiomatous hamartoma (4), functioning sudoriparous angiomatous hamartoma (5), nevus of sweat glands with angioma (6), and cavernous angiomatosis of the sweat ducts (7).

C LINICAL F EATURES

Clinically, most lesions of EAH present as solitary, erythematous nodules with an

angiomatous appearance, although multiple lesions have also been described (4,7–10,34).

They usually appear at birth or during early childhood, and several congenital examples

have been described (8,11,12) In an isolated case, the lesion developed after therapy (21) The most commonly affected areas are the acral zones, in particular the

radio-palms and soles (Fig 3), although lesions on the face, neck, and trunk have also beenreported One patient with multiple lesions of EAH on the extensor surface of the wrists

also had lesions on the knuckle pads (34).

Biologically, the lesions are generally slow growing and asymptomatic, but pain andhyperhidrosis may be an occasional feature of this lesion The pain is probably owing to

nerve involvement (14,15) and the hyperhidrosis presumably results from stimulation of

the eccrine component owing to a local increase in temperature caused in turn by the

angiomatous component (8,10,14,16).

Fig 3 Clinical features of eccrine angiomatous hamartoma (A) Nodular lesion involving the dorsum of the right toe in a newborn (B) Nodular lesion involving the tip of the fifth finger.

Although the lesions tend to grow slowly, as mentioned before, there are cases thatincrease rapidly in size In one reported case the increase in the size of the lesion was notedduring pregnancy, indicating a possible hormonal influence In this particular case, par-

tial amputation of the involved finger was necessary because of severe pain (13).

H ISTOPATHOLOGIC F EATURES

The characteristic histopathologic features of EAH include lobules of mature eccrineglands and ducts closely associated with thin-walled blood vessels, usually of a capillary

nature (Fig 4), although large venous channels have also been reported (12) In addition

to these two components that define the lesion, the presence of other structures including

fatty tissue (17,27,30), hair follicles (18,19), apocrine glands (10), neurovascular glomic-like bodies (27), and occasional epidermal hyperplasia (32) has been described

and lends further support to the hamartomatous nature of the EAH cal studies have demonstrated that antigens commonly found in eccrine glands, such ascarcinoembryonic antigen (CEA) and S-100 protein were qualitatively diminished in the

Immunohistochemi-eccrine component of the EAH, whereas endothelial markers such as Ulex europaeus,

CD34, CD44, and factor VIII-related antigen were expressed by endothelial cells of the

vascular component (10,16) Immunoreactivity for gross cystic disease fluid protein-15 was detected in the eccrine gland component of one case (33).

T REATMENT

Although it is benign and slow growing, EAH is often painful and may require surgicalexcision There have been reports, however, of troublesome lesions in which the pain

spontaneously resolved after some time (15).

Fig 4 Histopathologic features of eccrine angiomatous hamartoma (A) Scanning magnification shows numerous dilated vascular structures involving both the upper and deeper dermis (B)

Higher magnification demonstrates an abundant number of eccrine units intermingled with dilated thin-walled vascular structures.

5 Issa O Hamartoma angiomatoso sudoriparo funcionante Actas Dermosifiliogr 1964;55:361–5.

6 Söltz-Szötz K Berich über Fall von Schweissdrüsen naevus Kombiniert mit einem Angiom Z Hautkr 1958;24:189–92.

7 Archer BWC Multiple cavernous angiomata of the sweat ducts associated with hemiplegia Lancet 1927;2:595–6.

8 Domonkos AN, Suarez LS Sudoriparous angioma Arch Dermatol 1967;96:552–3.

9 Aloi F, Tomasini C, Pippione M Eccrine angiomatous hamartoma: a multiple variant Dermatology 1992;184:219–22.

10 Sulica RL, Kao GF, Sulica VJ, Penneys NS Eccrine angiomatous hamartoma (nevus): tochemical findings and review of the literature J Cutan Pathol 1994;21:71–5.

immunohis-11 Kikuchi J, Kukari Y, Inoves S Painful eccrine angiomatous nevus on the sole J Dermatol 1982;9:329–32.

12 Sanmartin O, Botella R, Alegre V, Martinez A, Aliaga A Congenital eccrine angiomatous hamartoma.

18 Zeller DJ Goldman RL Eccrine-pilar angiomatous hamartoma Dermatologica 1971;143:100–4.

19 Velasco, JA, Almeida V Eccrine-pilar angiomatous nevus Dermatologica 1988;177:317–22.

20 Aloi FG, Molinero A, Ronco A, Pippione M Nevo eccrino-angiomatoso G Ital Dermatol Venereol 1989;124:235–6.

21 Dallot A, Chemaly P, Kemeny JL, et al Hamartome angio-eccrine chez un adulte après radiothérapie Ann Dermatol Venereol 1992;119:903–4.

22 Diaz-Landaeta L, Kerdel FA Hyperhidrotic, painful lesion Eccrine angiomatous hamartoma Arch Dermatol 1993;129:107.

23 Torres JE, Martin RF, Sanchez JL Eccrine angiomatous hamartoma PR Health Sci J 1994;13:159–60.

24 Nair LV, Kurien AM Eccrine angiomatous hamartoma Int J Dermatol 1994;33:650–1.

25 Nakayama H, Mihara M, Hattori K, Mishima E, Shimao S Eccrine angiomatous hamartoma of the sacral region Acta Derm Venereol 1994;74:477.

26 Calderone DC, Glass LF, Seleznick M, Fenske NA Eccrine angiomatous hamartoma J Dermatol Surg Oncol 1994;20:837–8.

27 Damiani S, Riccioni L Palmar cutaneous hamartoma Am J Dermatopathol 1998;20:65–8.

28 Michel JL, Secchi T, Balme B, Barrut D, Thomas L, Moulin G Hamartome angio-eccrine congenital Ann Dermatol Venereol 1997;124:623–5.

29 Kwon OC, Oh ST, Kim SW, Park GS, Cho BK Eccrine angiomatous hamartoma Int J Dermatol 1998;37:787–9.

30 Cebreiro C, Sanchez Aguilar D, Gomez Centeno P, Fernandez Redondo V, Toribio J Eccrine tous hamartoma: report of seven cases Clin Exp Dermatol 1998;23:267–70.

angioma-31 Nakatsui TC, Schloss E, Krol A, Lin AN Eccrine angiomatous hamartoma: report of a case and literature review J Am Acad Dermatol 1999;41:109–11.

32 Tsuji T, Sawada H Eccrine angiomatous hamartoma with verrucous features Br J Dermatol 1999;141:167–9.

33 Tanaka M, Shimizu S, Miyakawa S Hypertrophic eccrine glands in eccrine angiomatous hamartoma produce gross cystic disease fluid protein 15 Dermatology 2000;200:336–7.

34 Morell DS, Ghali FE, Stahr BJ, McCauliffe DP Eccrine angiomatous hamartoma: a report of symmetric and painful lesions of the wrists Pediatr Dermatol 2001;18:117–9.

35 Lee SY, Chang SE, Choi JH, Sung KJ, Moon KC, Koh JK Congenital eccrine angiomatous hamartoma: report of two patients J Dermatol 2001;28:338–40.

36 Laeng RH, Heilbrunner J, Itin PH Late-onset eccrine angiomatous hamartoma: clinical, histological and imaging findings Dermatology 2001;203:70–4.

5 Cutaneous Vascular Malformations

SUPERFICIAL CUTANEOUS LYMPHATIC MALFORMATIONS

CYSTIC LYMPHATIC MALFORMATIONS (CYSTIC HYGROMAS)

LYMPHANGIOMATOSIS

Malformation denotes an abnormal structure that results from an aberration inembryologic development Although the term malformation is conventionally used as asynonym for hamartoma, the two are different, because hamartoma refers to a potpourri oftissue elements normally present at a particular site Vascular malformations can be eitherfunctional or anatomic In the case of functional abnormalities, the changes are relatedmostly to physiologic changes, as is the case for nevus anemicus In contrast, anatomicvascular malformations exhibit evident morphologic abnormalities of the involved vessels.Anatomic vascular malformations are subdivided into the following groups: capillary,venous, arterial, lymphatic, and combined anomalies (Table 1) Clinically, it is important

to separate the vascular malformations into those of low flow and high flow Low-flow

27

Table 1 Cutaneous Vascular Malformations

FunctionalNevus anemicusAnatomicalCapillaryCutis marmorata telangiectatica congenitaNevus flammeus (port wine stain)

Hyperkeratotic vascular stainsVenous and arterial

LymphaticSuperficial lymphaticDeep (cystic) lymphaticLymphangiomatosisCombined vascular malformations

abnormalities include malformations of capillary, venous, lymphatic, or combination,

whereas high-flow abnormalities include arteriovenous malformations (1).

References

1 Mulliken JB Classification of vascular birthmarks In: Mulliken JB, Young AE, eds Vascular marks Hemangiomas and Malformations Philadelphia, WB Saunders, 1988;24–37.

Birth-1 NEVUS ANEMICUS

C LINICAL F EATURES

Nevus anemicus is an uncommon congenital vascular malformation observed morefrequently in women than in men Clinically, the lesion consists of a localized circum-scribed, pale macule with irregular margins occasionally surrounded by satellite macules

(1–14) Although the upper chest is the most commonly affected site (Fig 1), it may occur

in any part of the body Under diascopic pressure, the lesion becomes indistinguishablefrom the blanched surrounding skin Wood’s lamp examination does not accentuate thelesion, and the application of friction, cold, or heat does not induce erythema in theinvolved areas All these maneuvers are helpful in distinguishing nevus anemicus fromvitiligo, hypochromic nevus, and other hypomelanosis Nevus anemicus can be an addi-

tional feature in types II, III, and IV of phakomatosis pigmentovascularis (5,9,12,14).

The presence of persistent, localized areas of livid erythema, caused by an increase inthe vasoconstrictor tone of the thermoregulatory vessels of the involved skin and leading

to relative stasis in the superficial nutritional vasculature, is considered a clinical variant

Fig 1 Clinical features of a nevus anemicus involving the anterior chest of an adult woman (A) Hypochromic macule on the right anterior chest (B) Rubbing of the lesion results in peripheral

erythema secondary to vasodilation in adjacent noninvolved skin, whereas the lesion of nevus anemicus remains a whitish color.

of nevus anemicus (8) The term nevus oligemicus has been proposed for this clinical

variant of nevus anemicus Another variant of nevus anemicus was described by Miura

et al (15) This lesion is characterized by multiple anemic macules on the arms; however, other authors (16) consider this lesion to be an expression of an exaggerated physiologic

speckled mottling of the limbs caused by transient changes in the vascular tone of thecutaneous vessels, but not a true variant of nevus anemicus

H ISTOPATHOLOGIC F EATURES

Since nevus anemicus is a functional anomaly rather than an anatomic one, logic and ultrastructural examination of these lesions demonstrates that vascular struc-

histopatho-tures are essentially normal (1) Intralesional injections of bradykinin, pilocarpine,

acetylcholine, 5-hydroxytryptamine, nicotine, or histamine fail to produce vasodilation

of the affected areas (1) However, erythema develops after an axillary sympathetic block

or the intralesional injection of an α-adrenergic blocking agent (2,3) A disturbance in the

regulation of vascular intramural adrenergic receptors may be demonstrated by means of

autoradiography, resulting in persistent vascular constriction (6,7) Furthermore, it has

been demonstrated that the blood vessels in nevus anemicus do not respond normally toproinflammatory cytokines, at least at the level of E-selectin expression Additionally, ifcontact dermatitis affects the area of nevus anemicus, the keratinocytes overlying the area

do not express intercellular adhesion molecule-1 and HLA-DR, probably because of the

absence of infiltrating lymphocytes (11) All these findings support the conclusion that

nevus anemicus results from locally increased vascular reactivity to catecholamines.Autograft transplant shows donor site dominance, lending further support to the idea thatthe cause of nevus anemicus is either an increased sensitivity to stimulation by vasocon-

strictors or inhibition of vasodilator influences (2) The presence of vascular twin nevi,

i.e., telangiectatic nevus and nevus anemicus occurring together and adjacent to each

other, can be explained as twin spots resulting from allelism of somatic mutations (10).

3 Mountcastle EA, Diestelmeier RM, Lupton GP Nevus anemicus J Am Acad Dermatol 1986;14:628–32.

4 Fleischer TL, Zeligman I Nevus anemicus Arch Dermatol 1969;100:750–5.

5 Ratz JL, Roenigk HH Jr Multiple vascular anomalies: report of a case J Dermatol Surg Oncol 1978;4:684–6.

6 Raff M Die Bedeutung adrenerger Rezeptoren fur die Entstehung des naevus flammeus und des Naevus anaemicus Wien Klin Wochenschr 1981;129(suppl):1–14.

7 Dupre A, Bonafe JL, Jouas H Naevus anemique generalisé acquis Dermatologica 1981;163:276–81.

8 Davies MG, Greaves MW, Coutss A, Black AK Nevus oligemicus A variant of nevus anemicus Arch Dermatol 1981;117:111–3.

9 Hidano A, Arai Y Hémihypertrophie congénitale associée à des anomalies cutanées vasculaires, cérébrales, viscèrales et squelettiques Ann Dermatol Venereol 1987;114:665–9.

pigmento-10 Happle R Allelic somatic mutations may explain vascular twin nevi Hum Genet 1991;86:321–3.

11 Mizutani H, Ohyanagi S, Umeda Y, Shimizu M, Kupper TS Loss of cutaneous delayed hypersensitivity reactions in nevus anemicus Evidence for close concordance of cutaneous delayed hypersensitivity and endothelial E-selectin expression Arch Dermatol 1997;133:617–20.

12 Di Landro A, Tadini GL, Marchesi L, Cainelli T Phakomatosis pigmentovascularis: a new case with renal angiomas and some considerations about the classification Pediatr Dermatol 1999;16:25–30.

13 Ahkami RN, Schwartz RA Nevus anemicus Dermatology 1999;198:327–9.

14 Hasegawa Y, Yasuhara M Phakomatosis pigmentovascularis type IVa Arch Dermatol 1985;121:651–5.

15 Miura Y, Tajima S, Ishibashi A, Hata Y Multiple anemic macules on the arms: a variant form of nevus anemicus? Dermatology 2000;201:180–3.

16 Plantin P, Schoenlaub P Multiple anemic macules on the arms: not a variant form of nevus anemicus Dermatology 2001;202:271–2.

2 CUTIS MARMORATA TELANGIECTATICA CONGENITA

Cutis marmorata telangiectatica congenita (CMTC) is usually present at birth and ischaracterized by the presence of a reticulated cutaneous vascular network of a blue-violet

color These lesions may be either localized or generalized Van Lohuizen originally (1)

described CMTC in 1922 and coined the term CMTC should be distinguished from cutismarmorata, which is a physiologic response to cold and is prominent in neonates Toemphasize the distinction, some authors have used the term reticulated vascular nevus for

CMTC (2) Although some familial cases have been reported (3–6), no recognizable

pattern of inheritance has been demonstrated by this disease In about 50% of patients,

CMTC is associated with various other congenital anomalies (5), suggesting that CMTC

is the principal cutaneous manifestation of a complex syndrome (3).

C LINICAL F EATURES

Clinically CMTC can be either localized (7) or generalized (8–10); when the lesions

are localized, the distribution is usually segmental, with a sharp midline demarcation.However, the lesions occasionally involve the upper right limb and the lower left limb,

in a crossed limb dimelia distribution (11) The areas of involved skin show either a flat

or a reticulated erythema, producing a marbled appearance (Fig 2) Telangiectasias aregenerally visible within the reticulated lines, and the red-purple hue of the lesions maybecome more prominent after crying, vigorous movements, or decrease in the ambienttemperature The skin in the affected areas may be atrophic, and ulceration may be a

prominent feature (12) The lesions of CMTC show gradual spontaneous improvement

Fig 2 Clinical features of cutis marmorata telangiectatica congenita (A) Lesions involving the lower left extremity (B) Close-up view of the lesions involving the anterior aspect of the left leg.

with time and in some patients disappear entirely (8–10) In others, however, little or no

significant change occurs, and the lesions remain unmodified throughout life

When the face is involved, there is either a diffuse erythema or nevus flammeus that

affects the upper lip and philtrum (12–16) Patients with facial lesions are at risk of congenital glaucoma (17–22), which may be bilateral if the involvement is diffuse, especially in those cases affected by nevus flammeus (12,13) However, congenital glau-

coma may also be present in patients with facial involvement of CMTC in the absence

of nevus flammeus (12,23) Other associated anomalies include hemiatrophy or pertrophy of the body (15,16), atrophy (2,5,6,14,15,24) or hypertrophy (5,14) of the involved limb, macrocephaly (14,16,25–33), mental retardation (13,15,26,28), hydro- cephalus (16,26,28,32), neuronal migrations defects (31), hearing loss (16), strabismus (16), persistent ducts arteriosus (13) and other cardiovascular abnormalities (16), cardiac arrhytmia (33), sudden infant death (33), internal arteriovenous malformations (28), hypothyroidism (16), nevus anemicus (16), hemangiomas (13,16,29,32), congenital melanocytic nevus (12), café-au-lait spots (16), asymmetric skull (13,34,35), microg- nathia (13), triangular face (13), scaphoid scapulae (13), elevation of the hemidiaphragm (16), lipomas (16), dystrophic teeth (13,31), anomalies of the growth of hair (31), high- arched palate (13), cleft palate (14), syndactyly of the fingers or toes (13,15,16,28,32), short fingers (13), polydactyly (32), acral cyanosis (13), simian lines on the palms (14), anal atresia (16,36), rectovaginal and urethrovaginal fistulas (36), absent clitoris (36), hypospadias (37), short stature (13), diffuse demineralization of bones (14), lipoatrophy (34), weakness of the long extensor muscles of both thumbs (14), dislocated hips (31), joint laxity (32), hypoplasia of a lumbar vertebra (35), stridor (31), Adams- Oliver syndrome (aplasia cutis congenita with terminal transverse limb defects) (38–43), spina bifida (44), neonatal ascites (45), congenital generalized fibromatosis (46), porencephaly (46), soft tissue herniations on the lower legs (47), and bilateral retinal detachment (48,49), tendinitis stenosans and bowing of the lower legs (50), congenital hypothyroidism (51), double aortic arch (52), hypoplasia of the iliac and femoral veins (53), moyamoya-like vascular abnormalities with factor V Leiden mutation resulting in congenital hypercoagulable disorder (54), and elevated maternal serum human chorionic gonadotrophin level with transitory isolated fetal ascites (55) Despite these numerous

hemihy-anomalies associated with CMTC, most of the cases of this disease present as a solitaryabnormality

H ISTOPATHOLOGIC F EATURES

There is still some debate about the nature of the vascular lesions in CMTC Althoughmost authors believe that there is true anatomic malformation, others believe that CMTC

is a functional malformation Most of the skin biopsies exhibit dilated capillaries and

veins throughout the entire dermis and subcutaneous fat (1,3) whereas in a few cases (13),

no vascular abnormalities have been detected Histopathologic examination of the lesions

in a patient with painful lesions of CMTC demonstrated an increased number of nerve

fibers (56) Ultrastructural studies have demonstrated an increased number of perithelial cells, as well as atypical endothelium with a discontinuous basal lamina (5).

Colored echo-Doppler and phlebography studies have shown dilated deep venous

tracts with reflux to the superficial veins (57) Laser Doppler fluxmetry of the involved

skin has shown evidence of functional disturbance, which may be the expression of an

α-adrenergic innervation deficit of the cutaneous terminal blood vessels (58).

The differential diagnosis of CMTC is with Bockenheimer’s syndrome or diffuse

genuine phlebectasia (12,59,60) Bockenheimer’s syndrome appears in childhood and

shows a progressive development of multiple large and painful venous ectasias involving

a single limb Cutaneous lesions similar to those of CMTC may be also seen in newborns

with neonatal lupus erythematosus (61,62).

T REATMENT

The cutaneous lesions of CMTC tend to fade with time, and there is no need to treatthese lesions during the first years of life For persistent cutaneous lesions, treatment withargon or dye laser may be helpful The discovery of this malformation in the skin of aninfant, however, should prompt a diligent search for an associated congenital anomaly byneuropediatric, ophthalmologic, and orthopedic explorations, in addition to dermato-

logic examination (63).

References

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