Hemangiomas of Infancy Clinical Characteristics, Morphologic Subtypes, and Their Relationship to Race, Ethnicity, and Sex Katarina G. Chiller, MD, MPH; Douglas Passaro, MD, MPH; Ilona J. Frieden, MD Background: Hemangiomas of infancy vary widely in appearance, size, and depth of cutaneous involvement, There is currently no standard classification system for these lesions. While they occur in any race, an in- creased incidence occurs in girls, light-skinned whites, and premature infants, especially those weighing less than 1500 g, Other epidemiologic and demographic factors have not been well characterized. Objectives To determine any correlations between he- mangioma subtype and anatomic location with demo- ‘graphic factors, complications, and other associated anomalies, Design: Retrospective chart review of 327 patients with hemangioma of infancy seen between 1997 and 2000 in an ambulatory referral center. Main Outcomes Measures: Demographic and gesta- tional information, lesion size, associated anomalies, complications, treatments, and outcomes were ana- lyzed together with classification of hemangiomas into 4 groups: localized, segmental, indeterminate, and multi- focal. Subtypes were correlated with race and ethnicity, the Incidence of complications, and overall outcome. Results: 01 472 hemangiomas (327 patients),359 (72%) were localized, 84 (18%) were segmental, 37 (8%) were indeterminate, and 12 (3%) were multifocal (8 or more noncontiguous lesions). Segmental lesions were larger and were more frequently associated with developmen- talabnormalities. They also requited more intensive and prolonged therapy and were associated with more com- plications and a poorer overall outcome (P<.001). Le- sions on Hispanic patients were more likely to involve mucous membranes, to be segmental (P<.004), to be as- sociated with abnormalities (P=.05), especially PHACE syndrome (P=.05), and to have more complications (P=.01). Increased incidence of segmental hemangio- mas was the only factor in Hispanic infants associated with complications, more extensive treatment, oF ass0- ciated anomalies, Conelusions: Hemangiomas of infancy can usually be classified as localized, segmental, indeterminate, and raul- Lifocal, based on clinical features. Segmental lesions have a higher frequency of complications and associated abnormalities, and this type of hemangioma seems to present with increased frequency in Hispanic infants Arch Dermatol, 2002;138:1567-1576 EMANGIOMAS OF infancy are the most common be- righ tumors in children. Theircharacteristic naus- ral history, with a prolif ing in a tumor with abluish cast or normal skin color. Combined superficial and deep hemangiomas, often referred to as mixed hemangiomas, involve the dermis and sub- cutis and demonstrate clinical features of From the Departments of Dermatology (Drs Chiller and Frieden) ad Pediatrics (Dr Frieden), University of California, San Francisco; andthe Department of Epidemiology, University of lino, Chicago (Dr Pasar) Dr Chillers now with the Department of Dermatology Emory University, Atlanta, Ga (aepRny Teo) SRCHDERVATOLNOLT, DECHO erative phase in early infancy followed by an involutional phase, has been well de- scribed.'* Epidemiologic observations in- clude a marked female predominance, a propensity for light skin types, anda higher Incidence in premature infants, espe- cially those weighing less than 1500 g,? The clinical appearance of eutane- ous hemangiomas depends on the lev- el(s) of the skin affected. Superficial hem- angiomas involve the superficial dermis and appear as bright red “strawberry” l sions, whereas deep hemangiomas in- volve the deep dermis and subeutis result (©2002 American Med both types. The degree of superficial in- volvement and other morphologic char- acteristics such as plaques and nodules have been reported toallect long-term ou come. In addition to size and lesional mor- phologic characteristics, some hemangio- ‘mas involve a broad anatomic region or a recognized developmental unit (such as the entire ear oF tip ofthe nose), wher others, including small plaques and large and small nodules, are discrete and well localized.” More than half of hemangiomas in- volve the head and neck, and the distr 1 Association, All rights reserved.5. aca a Renal er pd acd a Sea a ibgattos He exe Shout Fes eine Hh Fert aan eos ‘Figure 1. Diagram of numerical aptoi laations usd ta lary hamanloras by ste The paral ist pat appli wo prs Aand Bo tis gue and Poses he urbered anatomielocatons ta aud not be Husted (adequs})on te dara, bbution seems to favor certain sites, possibly related oem viewed. Demographic information regarding race, ex, bith, byologi ision ince and facaldevclopmentalmetameres® andgesation was obained(eportd full-term births were t= The importance of anatomic location swellrecoghized as 92 as being of 40 weeks gestation). Pictures of individual aimajor factor in determining whether complications such _ {sions and written descriptions were used to determine size, ts visual ats occlusion, airway involvement, ulceration, eatlon, and subype or permanent disfigurement may occur! . We undertook this retrospective study to under- INCLUSION CRITERIA standin more detail the clinical correlations between vart- Each patent hs study was examined by 1of2 pediatric de- foushemangioma subtypes, locations, rates of complica~ atlas. Only hemangiomas f infancy were included, us tions, and need for treatment(s).n addition, inclusion ing elutealand (when neces) radiobogic cen of sex, race, and ethnicity in our database allowed us to Correlate clinical observations with these laciors. LESION LOCATION AND SIZE otras ofa lestons of writen dexcplons wee ESC ERS anatomic location ofthe lesion was converted to a numerical DATA GATHERING value according to the diagrams shown in Figure ¥. Mucous membrane involvement was defined as any lesions that af- Using the University of California, San Francisco, computer fected sites 7, 8, 38, 39, 64, 67. 71, 73, 74, and 73 from ized medical record database, we compiled list of patients22_—_ Figure years or younger diagnosed with hemangioma (International ‘When patients presented with more than 1 lesion, each {Clasifcation of Diseases, Ninth Revision code 228.01) and seen lesion was mapped individually except inthe case of multlo- in the University of California, San Francisco, Pediatric Der-_cal (8 or more noncontiguous) lesions. A specific numerical matology practice over a 4-year period between January 1997 site was asigned regardless ofthe proportion of involvement and December 2000. allavailable charts were retrieved and re- ofthat anatomic site. The degree of involvement of the site was (aepnayTeD) TECH DERNATOL OTT DEC HE —W (©2002 American Medical Association, All rights reserved. ‘Downloaded From: https:/jamanetwork.com/ on 03/13/2023Figure 2. Localized nodular-od amangoma on tha chest (te 42 ram Figure 1) of G-montold white gi ascertained by a parallel analysis of individual surface area. The surface area of individval lesions was caleulated by multiply ing the width by the length, LESION TYPE Lesions were clase, based on unblinded agreement of ofus (K.G.C. and 1}. F), nto # groups: localized, segmental, nde- terminate, and muifocal Lesions were then subtyped a: n- Alicated belo Localized lesions demonstrated clear spatial containment, usually with involvement of only 1or2 mapped site (Figure 1). Insome case, lager lesions were classified aslocalizedbe- cause they were either focal Ge appearing tare from | cen- tral focus of growih) or lacked evidence of linea or gemet- te pattern that might associate them with a specific area of developmental growth, Localized lesions were further subdi- ‘ded Into nodules (rounded surface) or plaques (ator pla- teaulke surface), Nodular lesions were denied ax super lal, deep, or mixed. Paque-iype hemangiomas were subdivided by thickness and surfce characterise, Thus, here were 9 sub- Sper oflocaized lesions: (1) nodular-euperiial ats (2) nod Inrsuperiil prominent (having an exophytic or pedunci lsted appearance): 3) sodulr-mised (Figure 2 (3) nodlr- dleep, (5) plaque-thin (Mat-topped with a thickness of Spprosimatly 2m) (Figure 316) plage sick (>2 mm) G) plaque-telangictatic (mostly composed of telangleci- sia) (8) plaque papular (composed of sters of papules) and (9) localzed-superiial not thervise speci ‘Segmental esos demonstrated linear and/or geographic localization over a spcile cutaneous territory and were st ally associated witha least some plaqucike atures. They were often unilateral and usualy sharply demarcated st the mid- line, but there were exceptions, particularly nasal and lip le sions, although some of these segments were dermatomal in Alstribution, many involved areas that didnot correspond 19 Specific cutaneous dermatomes Some seemed to correspond to developmental facial metameres Sl others were of uncer tain developmental origins Segmental lesions were divided into 5 sublypes: (1) segmental-superticialtlangectatc; (2) seg tnentak superficial papular; ©) segmentat-superticial thin (Figure 4 snd Figure 5) (4) sepmenta-miperiil thick (aepnnyteD) SECT DERNATOLTVOLT, DEC (©2002 American Med Figure 3. Localzed plaque hamangoma an the scalp ee 24 frm Figure th of'a2ear-o white gt (Figure 6); and (5) segmental-mixed (Hgure 7). The actal dimensions of many segmental lesions were no recorded ov ing to ther large size. While most involved broader anatomic ‘tess than localized lesions, relatively small segmental lesions rere alo observed. The most noble examples were nasal p Hemangiomas wich, when fully involving the nasal ip, were Considered segmental rather than focal Beate they were judged tocorresponded tothe embryologc developmental unt known, asthe natal placode, mal “satelie" hemanglomas in he same Cutaneous teritry a5 segmental lesion wee not considered separate enties "The category of indeterminate lesions was needed because there were some hemangiomas that we could not confident categorize acter localized or segmental. Large deep lesions, for instance, were often nce inthis category beste was frequently dificult to determine whether they were seginen- tal Indeterminate lesions were subcategorized se supetfical (Figure 8). mised or deep Temangiomas were considered mulhocal fhe infant had 8 or more individual noncontiguous lesions of any morpho- logic characterise In thse patients, the individual heman- fomas were nol mapped, hut the numberof individual le Sons was documented and used to calculate the mean number of lesions per patent. HEMANGIOMA-RELATED COMPLICATIONS Complications included lesional ulceration, bleeding, pain infection, high-output cardise failure, postural oF functional difficulties (such as inability to turn the head in nuchal lesions), airway compromise, severe scaring, eating dificult, auditory canal occlusion, ophthalmologic problems (inelud- ing astigmatism and amblyopia), and “wortisome rapid growth.” The latter was generally growth thought to be eas- ing a risk toa vital struct like the eye or judged to have sig- nificant possiblity of causing permanent disfigirement ASSOCIATED ABNORMALITIES Associated abnormalities included anomalies characteristic of| PHACE syndrome (posterior fossa brain malformations, hem- angiomas, arterial anomalies, coarctation of the aorta and ear- diac defects, and eye abnormalities), urogenital abnormal ties,” spinal involvement (such as tethered spinal cord oF hemangioma tissue radiologically involving the deep paraspi- nal tissue)."* and mediastinal hemangiomas. They also in- cluded other abnormalities such as cardiac defects without 1 Association, All rights reserved.Toe ip: Cena al areas ae tc. Figure 9. Smal spmeta supra thin hanangoa inving bath sides th ver tp ad th ong (cts Band 7 rom Pure) on Pveskalé te gt other evidence of PHACE syndrome and other structural of developmental abnormalities such as limb hypertrophy oF left palate, Hemangiomas of the parotid gland or airway'*" ‘were nol included in this eategory. Parotid involvement was not routinely assessed oF dacumented in the records, while airway involvement was considered a complication rather than an anomaly. We did not diagnose any cases of associ- ated hypothyroidism, but no routine monitoring for hypo- thyroidism was performed because this potential complica- tion was not widely appreciated during the period of the study." ‘TREATMENT Treatments, either alone of in combination, included sys- temic therapies sch as oral prednisone and subcutaneous in- (aepRavTeD) SECEDE jamanetwork.comy on 03/13/2023 Figure 4, Lateral vi of ra fc sogmanal-upeflltlngetatthin hamangoma invlng ses 4 tough 0 17,19 trough 21,29, and 0 tom Figure ton 24¥+monthll whe gi. 8, Hea-on view of tho sama sen shoving wewmantol ha eolumal and extension bayond the midine oth ght Figure 0. Large ail sogmena-sypertil ick herangioma vith some grain sgn of voluton) involing sts 13,1 trough 2,27, and 28 Figure ton 2a Hipane gl Noe the randetmatoaldtibuon {nd tesla of thee terferon as well as localized therapies such as intralestonal ste roids, topical steroids, topical medicaments other than steroids (eg, topical antibacterial agents and colloidal dressings), oral antibiotics, eye patching, laser eatments, and embolization.‘Figur 7. Smal sogmenta-bad hemangioma a tes & hough tom que 1 on aZ-mont-oldHspanic gi. This lesion shows ears ofthe stealed Cyrano nose as wo as columa involve, (Detailed analyses of specific treatments and their results are not reported herein) OUTCOMES For the purposes of this study, the outcome of each lesion was defined by its status a the last recorded patient visit. Out- ‘comes were classified as (1) good ifthe final note indicated that the lesion was stable or improving and only as-needed fol- low-up was required: (2) lotto follow-up; (3) requiring sur- sical referral; and (4) poor or indeterminate ifthe lesion was Sl in the process of being regularly observed by a dermatolo- Bist at the conclusion of the study STATISTICAL ANALYSIS, Dichotomous variables were compared using the Mantl- Racnsseltest-To asses the reatvecontbution of etnc= iy and lesion type to complistion snd clini outcome, o- sg ieregrenion craps were performed Sex proportions ec nalyzelby assuming thatthe catchment population was 30% femal and using the binomial test for propertons: Contin cus and integer variables were compared ining the Kruskal ‘Wallis2-sampl est (Stata, College Staton, Tex). All Pal ues were tiled: P= 05 was considered significant and no ‘djustncats ware unde for nut eomperons —_—_ i id! ‘Our data were drawn from the records of 327 patients ‘with a total of 472 lesions; 44 other patients whose le- sions could not be clearly diagnosed or for whom insul- ficient information was available were excluded. There ‘were 257 girls (79%) and 70 boys (21%) (P<.001). Of 129 patients whose charts revealed information about ges- tational age, 47 (36%) were born at 37 weeks or earlier, and the overall mean gestational age for these patients was 36.8 weeks (median, 39; range, 26-41.5 weeks) (table 1). ‘A otal of 36% of patients had lesions at birth, while 40% developed lesions within the first month of ie. The mean age at first visit was 11.8 months (median age, 4.5; range, 0.2-158.3 months). Excluding 161 patients who ‘were seen in our clinic only once (generally because they were referred to us for one-time consultation), the mean (apna TED) SECHDERNATOL NOL TECH (©2002 American Med Figure 8. Ingeteminate-supericia amangoma invling the ih poe ip (stus 6 and on gue 1) ona21-morth-ol white gil Notte sharp marcato and leat nau, which suggest hat this could bea forme frst ofa sepmental tomangam duration of follow-up was 16.1 months (median, 8.1; range, 0.2-123.6 months) Information regarding birth weight was available for 31 patients. Their mean birth weight was 2.7 kg (me- dian weight, 2.7; range, 0.0-4.5 kg). Of 36 patients whose chart contained information about multiple gestations, 19 patients were of multiple-gestation pregnancies, with 17 win and 2 triplet pregnancies. A positive family hi tory of vascular birthmarks was documented in 32 pa- tients (10%), The most commonly involved anatomic segment (6% of the lesions) was the anterior cheek (site 18), followed inorder of decreasing Irequency by the forehead (site 11) and the preauricular area (site 20) (Figure 1). Mucous membranes were involved in 48 lesions (10%), exclud- ing the multifocal group. Sixty-six lesions (14%) under- went ancillary studies to assist in their diagnosis and/or management. These methods included radiography, mag- netic resonance imaging, magnetic resonance angiogra- phy, ultrasound, echocardiography, computed to- mogrpahy, and bronchoscopy The mean surface area of 355 lesions with docu ‘mentation of size was 8.6 cm (median, 3.6; range, 0.01- 108 em’). Forty percent ofthe lesions had some type of complication (Table 2). Ulceration was observed in 75 lesions (219) along with bleeding (usually minor) in 27, cutaneous infections in 14, and significant pain in 12 Other complications included high-output cardise fail ture without structural heart anomalies (n= 1); airway com- promise (n=5); severe scarring (n=32); worrisome rapid growth (growth that threatened a vital structure or held a significant possibility of causing permanent disfigure- ment) (n= 100); inability to turn the head in neck I sions (n=3); difficulty with oral intake (n=4); auditory canal occlusion (n=5); and ophthalmologic impair- ‘ment, including visual axis obstruction, astigmatism, and, amblyopia (n=27). A total of 174 lesions in 140 pa- tients received some form of treatment (Table 3 and Table 4). systemic therapy was used either alone or in conjunction with topical medications to treat 83 lesions, (18%) in 67 patients (20%). Four infants were treated with interferon alfa; all had received prior systemic cor- ticosteroid therapy. By the end of our study, 397 lesions, 1 Association, All rights reserved.‘Table 1. Patient Characteristics by Race/Ethnicity and Sex e(%=) _Mo-ofLesions —statonal ih Weight i. (2) ot Patots Folowsp, seer otPatels per alien Age" (a) Wg (0) __witnGesatioal Complications mo Females Fecalebicy White 20864) 19 385(7 $6250) 2110) 166 2 Hpac 5818) 23 wien 74336) 743) 175 4 Asan 258) 14 m5() © $3240) 5119) 133 6 Black 943) ar aug) 3816) 2) 72 7% Middle Eas 3 (1) 10 aq) a o a a Ober 230) 1“ 3) 838710) 343) a3 7 Sax Feral 25170) 19 gr) san 08) 21g) 175 se oan 2 870 57250) 5) 103 va a2 14 sea(ia) 58261) 3512) 161 8 Ot paso that arcu eiriciyace or sx ‘Plkindestes nt apple, Sisal sigan. ‘Table 2. Distribution of Hemangloma-Associated Complications To. no (ot tesons no. ot 1. ofCompleatons Lesions th completions compatons persion Faclanny Whe 32 120,38) 185 06 Hispanic 74 sn oat Asian 6 15102) 2 a7 Back 4 63) 10 a7 Nil aster 3 113) 1 03 Oar s 113) 7 05 Sex Femae an 1514) 208 o7 le 101 arn) 57 06 Lesion ype Lead 320 14st) ‘Ma out Saget ct cairn) orf tat Indteriat a 2150) 2 og Natit! 2 4133) 6 05 ‘iat a a8 40) 03 06 Wie nora Fl Bat) 0 16 RACE 5 11073) Ey a Urogenital 2 2100) 4 20 Spal 7 74100) 1 16 Ober 1 (a2) 1 10 PHACE nites association of poster osa bran malormations,hanangonas, ara aaa, coréaion lth ata and cara eet, rd aye stngralitie {Sinisa sigan. (8496) had a good outcome (follow-up as needed); 30 (89%) were referred for surgieal intervention, 21 (4%) were lost to follow-up, and 15 (3%) had poor/indeter- minate outcome (Je, still in treatment and/or requiring regular follow-up). LESIONS WITH ASSOCIATED ABNORMALITIES Twenty-two patients (79) had 31 lesions (7°) with as- sociated abnormalities (Table § and Table 6). Two px- tients, 1 with 1 lesion, and 1 with 3 lesions, had more than I associated anomaly. There were 11 patients with 4a total of 15 hemangiomas who had PHACE syndrom 2 with urogenital abnormalities, 7 with spinal involve ‘ment (4 with a tethered spinal cord, 3 with spinal hem- (aepnnyteD) SECT DERNATOLTVOLT, DEC (©2002 American Medical As jamanetwork.comy on 03/13/2023 angiomas extending deeper than the subcutaneous suc), and 11 had associated deep structural abnormalities G skeletal, 3 mediastinal hemangiomas, and 5 cardiac anomalies without other elements of PHACE syndrome). Two patients, 1 with urogenital and 1 with mediastinal involvement, also had spinal involvement. The most com- monly involved anatomic sites of hemangiomas asso ated with anomalies were the nonmucosal lower lip (site 30), the mandibular area (site 29), the preauricular area (ite 20), and the lateral cheek (site 19) (Figure 1). Of6 infants with sacral lestons (site 61), 3 (50%) had an as- sociated tethered spinal cord. Of 84 segmental lesions, 83% (n = 70) were facial, whereas only 54% (n = 203) of nonsegmental lesions were facial (P<001). OF the 70 facial segmental lesions, 14 (20%) were associated with lation, All rights reserved.‘Table 3. Lesion Characteristics by Race/Ethnicity and Sex Lesion ype We te.¢3) tenons ottsnans Wo.ot test, 1 wo.) tot Teatea“Tealed wth PI Laslont_sizeen?_Loealzed _sapmental_Indelerinalo_ulttocal_Alnormaltiet Lesions systemlaly* Follow-up Faclanny ‘hte mm 81 m0 Ey 8 166) 11438) raat) 288,88) Hispanic 7% gy 9 3 sc) 288) zor S88 Paian % 1 7 7 2 0 1) 18(@0) 8167) 31 85) ack “63 13 0 1 1M) 64s) 2) 867) Midileessem 33538 0 0 0 ie) 0 3100) Ott mms 2 2 0 50) 1183) 668) 2) Sex Feat mm 39 wo 2 9 26) tae) gr) 3128) ale mi 78% 10 3 9) 355) Tad) 5 BH va a eT 2 sii?) aTaG7) as ts) 87188) *Parcertage gens tom weted lesions on {Rinne as eed {Sinisa sigan. ‘Table 4, Hemanglomas Characterized by Speciic Lesion Type no. (2a 1.) Ne.) No.8) ti. 4) sons Moot Lesion of Lesions wot Anctary of Lesions ofLesonsMeatad_ wih PRN Lesion Te Lesions _sltem® __“‘Aiormaitet Evaluations Tealad”——-Sytomialy Followup Tesla 0 ert oo Bm 9508) 2520) 733 (8) Noda suprtiial hin cn oor 0 “ 41 Nodular supercil prominent 72 a4 3 a a Nodiar mae & 16 5 rr 0 Noda 4 a9 a € 8 Paget a 30 3 “ 6 Prague thick 2 ao 1 9 * Prague teangicatic 5 136 0 a 5 Prague ppl 5 102, 0 1 5 SupertialNOS 5 oor 0 o 4 Segment eat zea 22123) 5667) 209 ST 6a Talia 4 ma 0 1 3 Poplar 1 ma 0 o 1 Prague tin 1 ma 2 9 4 Prague thick 8 ooo 9 2 0 Nea a m6 7 4 2 Indtrmint 3 2s 508) tog 196 13168) 2a) Supertial 172 1 7 ‘ ea a 26 0 5 7 esp 23 9 7 8 utes 2 ma ° 502) 4193) 2160) 978) ‘a a a6 a0 oid) maar) 25/48) 07 (28) “PAW inate as oad: WA rt aplcable and NOS, et herve spt tindeses tattealy pian PHACE syndrome. One other patient with several fea- tures of PHACE syndrome, including sternal raphe and ‘congenital heart disease, hada segmental trunk and arm, hemangioma rather than factal. No visceral involve- ment was documented in patients with multifocal hem- angiomas during the study period." Lesions without associated anomalies had mean surface area of 8.2 em’ (median, 3.2; range, 0.01-90 cm’) Those with | associated anomaly had a mean surface area ‘of 13-4 em? (median, 2.25; range, 0.0199 em), and those With 2 associated anomalies were even larger, with amean surface area of 40.1 em* (median, 6.3; range, 6-108 em’) (©2002 American Medical As jamanetwork.comy on 03/13/2023 In addition, some segmental lesions too large to be exs- ‘measured had associated abnormalities (Table 4) ETHNIC AND RACIAL DIFFERENCES There were no significant differences in sex ratios and only minor differences in gestational age and birth weight between ethnic groups (Table 1), although Hispanic pa- dents had slightly higher gestational age and birth weight than non-Hispanics, Hispanies were also more likely to hhave segmental lesions than whites (30% vs 16%; P=.00: and all other ethnic groups combined (30% vs 15%; lation, All rights reserved.‘Table 5, Distribution of 31 Hemangiomas With Concomitant Abnormalities by Type Ne, on Lesion Np tie, ottmansiomae enters ‘Acsoctaied win ABpormaties [acai segmental determinate ut morales Paaces 6 ote T 7 Urgent 2 0 2 0 0 Sia spline thre cod) if 1 3 3 0 (tha (tal anaes, mail twohement cardiac anomalies) 1 5 2 4 0 stngraltie {itl hemangiomas that ad muliple associations. {siaisticay sean “PHACE indiates association of porter osea rain malormaion,Fvangomas areal ararals, cara ofthe aorta ad ead ‘Table 6, Distribution of 2 Patients With Concomitant Abnor malities by Race/Ethncly Wole_tapaie_ Asian ances Urgent Spiral (pal invent thre cod) (thar (ttl anaes, mail twohement cardiac anomalies) 1 5 & 0 0 0 1 1 2 200 0 0 9 9 2 st 2 2 09 1 0 9 4 et Bot 1 0 0 ft 2 snore {One patent tad bth tnarmates {siaistiay sigan. “PHACE indies association of porter osa rain maormation,bangomas anal anarals, carta ol th anta and ea tects and ‘Table 7. Characteristics ofthe Patients by Lesion Type No.of No.of Gesaional Bien Welght Wo. (%)ofLesions unin Falw-ap, Wa. () of Lesions Fo Lsionype__Lsslons _Fatiens* _agetwxn)__ Ig (a) —_Gasfallonalamplicaions mo Mulipe-Ostaton Pregnancy Tneaind wo a7) «RBI 3010) 1S 2) Sogmentl me TE 72021158 11113) 22h 308) Indesminse 3734 5.46) ‘() 5113) 17 aa) tos 2 2 256) 43) 1) 82 0 ‘a 719) 5725 UGE (tt) 164 31165) “Tey our pata several ype oasis otpatents wh he pac sins {Sia sigiean. P<.004) (Table 3). They had a marginally higher inci- dence than non-Hispanies of mucous membrane invol ment compared with all other lesions combined (10/55 lestons [18%] for Hispanics vs 26/260 lesions [10%] non-Hispanics; P=.08). Lesions in Hispanics were o slightly more likely to occur concomitantly with abn malities than in non-Hispanics, but they were spec cally and significantly more lik PHACE syndrome ( dence of complication per lesion was significantly hig! © systemic medications (P=.02) LESIONAL TYPES There were 339 localized (729%), 84 segmental (18%), Indeterminate (8%), and 12 multifocal lesions (3%) (Tal (©2002 American Medi jamanetwork.comy on 03/13/2023 to be associated with (05) (Tables 5 and 6). The inci- 01) in Hispanic patients (Table 2), and lesions of His- panic patients were treated significanily more often with 4). Age distribution with respect to age of onset was simi- lar between types. Segmental and indeterminate lesions were associated with aslightly higher rate (13% for both) of gestational complications than other hemangioma types (able 7). Segmental lesions occurred on patients of older gestational age and higher birth weight (P<.001 for ges- {ational age and birth weight), whereas multiple lesions ‘occurred on patients witha significantly lower birth weight compared with other lesions (P=.04) (Table 4). Segmen- tal lesions received longer follow-up (P<.001) than all other lesions combined, whereas localized lesions ré ceived shorter follow-up (P<.001) and had fewer ancil- lary evaluations (P<.001) than other lesions (Table 4), Segmental lesions were significantly larger than other lesions (P<.001) (Table 4) and were more often assoc ated with urogenital anomalies (P=.002) and PHACE syn- drome (P<.001) (Table 5). They were more likely to d velop in Hispanic patients (P<.004) (Table 3) and had a for ly lie her ble 1 Association, All rights reserved.higher rate of complications (P<.001)(Table 2). Twenty ‘segmental lesions (24%) were ulcerated compared with, 5 nonsegmental lesions (14%) (P=2.03). When com- pared with all types combined, segmental lesions were treated more frequently and more often with systemic therapy (P<001 for both). Segmental lesions had a higher frequency of poor or indeterminate outcomes (32% for ‘segmental vs 12% for nonsegmental lesions; P<.001) and, surgical referral (19% for segmental vs 6% for nonseg- mental) at the end of our study. SEX DIFFERENCES Segmental lesions were somewhat more likely to occur in female than male infants (10% in girls vs 12% in boys; P=.08), but sex difference was most striking in PHACE syndrome, where 14 of 15 cases occurred in girls. There ‘were no additional differences in sex with respect to age ‘of onset, gestational age, number of gestational compli- cations, duration of follow-up, number of lesions per pa- tient, lesion size, frequency of mucous membrane in- volvement, frequency of associated anomalies, number ‘of complications, frequency of treatment, oF frequency of as-needed follow-up (Tables 1-3) MULTIVARIABLE ANALYSIS Logistic regression analysis was performed to assess ‘which factors were most associated with lesion severity, defined as (1) presence of concurrent abnormalities, (2) occurrence of hemangioma-related complication, and G) poor overall outcome. Hispanic ethnicity was not in- dependently predictive of abnormalities (odds ratio [OR], 0.6; 05% confidence interval [Cl],0.07-+.7;P=.60), com- plications (OR, 1.1; 95% Cl, 0.06-2.00; P=.80), oF poor ‘outcome (OR, 0.8; 95% Cl, 0.3-2.4; P=.70). In contrast, ‘segmental lesions had associated anomalies (OR, 9.5; 95% Cl, 4.23; P<.001), complications (OR, 4.6; 05% Cl, 26- ‘8.3; P<.001), and poor or indeterminate outcome (OR, (0.3; 95% CI, 0.1-0.6; P=.002) independent of ethnicity ee OOS ‘Our study, which retrospectively gathered information fon 327 infants with 472 hemangiomas, allirms previ- ously reported information regarding sex, age of onset, gestational age, and birth weight distribution," but extends and adds to those observations. specifically, ‘we found increased morbidity, associated anomalies, and less favorable outcome with segmental hemangio- tas than with localized lesions, as well as an increased incidence of segmental hemangiomas in Hispanic infants The categorization of hemangiomas into localized and segmental types was valuable for prognosis. Segmen- tal hemangiomas had significantly higher rates of com plications and higher incidence of developmental anoma- Tes; therapeutic interventions, ancillary evaluations, surgical releral, use of systemic therapies, and poor out- ‘come. Segmental hemangiomas occurred in children bora atalater gestational age and with higher bith weight than (aepRay ED) ARCH DERVATOUNOLT DEC (©2002 American Med in patients with other types of hemangiomas. This find- ing isthe inverse of the known association of hemangio- mas with prematurity, again raising the possibility that there may be developmental differences beween seg- mental and localized hemangiomas, Indeterminate hemangiomas were those that we were unable to confidently categorize as being either segmen- talorlocalized. Their complication rateand need for teat- between those of localized and segmental sions, suggesting that some may be formes [rustes of segmental hemangiomas. Multifocal lesions had a greater rate of ancillary ra diologic evaluations to exclude visceral involvement. Al though patients with this type of lesion had as many as 30 individual lesions, rates of complications and need for \yeatment were comparable to those ofthe localized type, and no significant extrseutaneous hemangiomas were dis covered, The complication rates and associated anomalies in our study were relatively high, undoubtedly owing atleast {in part to the referral nature of our practice, and there fore are not necessarily representative of all hemangio- mas of infancy. PHACE syndrome was identified in 11 patients and tethered spinal cord in 3. All of these pa- Udents had segmental hemangiomas with the exeeption of 1 infant with an indeterminate lesion and tethered s} nal cord, Despite the potential referral bias in our practice, ‘most patients did not have associated anomalies, and more than three quarters of the lesions had a good outcome (as-needed follow-up). While some might return for later reevaluation and treatment of scarring or other compl cations, this study reinforces the good overall prognosis of hemangiomas as an aggregate, The contrast between the overall good prognosis and the large number of com- plications further emphasizes the need for increased vigi- lance at sites and in lesional types that are at higher risk for complications and/or adverse outcome Among the patients with PHACE syndrome, there was a male infant with a large segmental truncal and arm hemangioma, multiple cardiac defects, and midline con- genital xyphoid scar as well as a supraumbilical raphe. Although he did not have a facial hemangioma, which is defining characteristic of PHACE syndrome, he had rmul- Uiple other characteristic anomalies and thus was diag- nosed as having a variant of PHACE syndrome. His case adds weight to the concept that segmental hemangio- ‘mas at any anatomic site may have associated structural defects. The presence of extracutaneous hemangiomas in association with large segmental facial hemangiomas also deserves comment. Although we did not look for them systematically, large mediastinal hemangiomas were found in 3 patients, « finding that has been reported in several previous cases." With improved imaging techniques, we may discover that this occurrence is more common than previously realized. Although not ob- served in our series, large facial hemangiomas have also been associated with extensive gastrointestinal tact in- volverent.>2* Although several patients with segmental heman- sgiomas had parotid involvement, this was not included 1 Association, All rights reserved.as an associated anomaly because itis a common find- ing in large preauricular hemangiomas and was not sys- tematically recorded. Similarly, airway hemangiomas (present in 5 patients) were included only as complica- tons, not as anomalies. Itshould be noted that, because of the exclusion of airway and parotid involvement as, anomalies, and because imaging studies were per- formed only when clinically indicated, the overall asso- ‘lation between anomalies and segmental lesions repre- ‘Although racial differences have been previously reported,? to our knowledge, our data are the first to demonstrate thal Hispanic patients have greater mor- bidity and more complex hemangiomas than all other racial and ethnic groups. Furthermore, we demon- strated that this is associated with a striking prevalence ‘of segmental lesions among Hispanics, The eause of the increased tisk for segmental-type hemangiomas in His- panics is not known. Other birth defects, such as neural tube defects, are more common in Hispanic infants.*?** Moreover, another vascular anomaly, so-called cerebro- cutaneous angiomatosis, is more common in Hispan- ies. The higher incidence among Hispanics may hav cither a genclic or an environmental basis and deserves further study. While referral bias (ie, preferential refer- ral of segmental hemangiomas over localized heman- ‘glomas) cannot be excluded, the magnitude of the dif- ference is large. In conclusion, hemangiomas of infancy are very common tumors, but only a minority cause clinically significant problems. The challenge to clinicians is to recognize which hemangiomas need vigilant observa- tion and/or intervention. Our study shows that lesional type is a significant prognostic factor, and that segmen- tal hemangiomas have a higher rate of complications, more associated anomalies, and poorer outcomes. Moreover, in the population studied, Hispanic infants had a disproportionate number of segmental hemangio- mas, We hope that our observations will provide the ba- sis for prospective studies looking at lesional types and issues of race and ethnicity. Further refinement of the classification schema may also come out of these stud- les, particularly if data regarding pregnancy history, family history, gestational age, and birth weight are gathered systematically. Such studies could help shed more light on the origins of this common, but poorly understood, tumor of infancy Accepted for publication May'9, 2002. This study was presented at the 14th International Workshop on Vascular Anomalies, Nijmegen, the Nether- lands, June 28, 2002 We thank Mark A. Jacobson, MD, and Mary L. Wil- liams, MD, for their review of the manuscript Corresponding author: Mona J. Frieden, MD, 1701 Divisadero St, Third Floor, San Francisco, CA 94113 (e-mail: ifrieden@orca.uesfedu. (aepRaNTeD) TECH DERNATOL NOL TR DECHO kz” 1. Fin MC, Gonack Mulan J. Congenital asc lon: cic pea fan fnew eleifend Sor 199-18 0-00, 2. More. Long-rmelln-up themangonas incon, Wine Ho ‘Symgosum a Vasu Maton ard Menon esr. StLous Me: CV Mos 195-182-171 Arar, Maze A, Keer Rt Stauber hemangioma npr ints Pada Daal 1985-31-20, oink Cuaneous mangas inpemature its. Ata PaaS, toss.aes7057, 5. Prat AG Brearain inns, Ach Demat! 19535790206. 6 NlayanaH Cnc nd slog ste ofthe csfeaton athe na raeuse ofthe seanbcy mark J emt 19818277201 7 Met MY, Dowd CF, ara A, atl The many es of HACE yom, 2 Per 200 120187123 8 Waner Mt er Nort Petal. destin fo dine! pet haman- (ons, bet resin a 3 trio Wesaho on Vase oor es My 200; Montel usb 0. ty OW, Heber AA. Benign cutaneous acu uners of itn when to ‘ory htt do Arb Dermatol 2000136 65-21 (azar, Faden Hemangionas when wor Pedi Aan, 20002058- a. Ede BM, GPM, Sie Fe Vasc ip nagement. hemaniomas— tent f try. Pt Reco Surg T9970 1860173, Hak 8, Karol ZA, Goon A, a. Copia harangira atari per ‘cul umangona). Su Opa. 00438-00426 Fishman Mullion 8. 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