Clinical and Laboratory Investigations

Down syndrome: lip lesions (angular stomatitis and fissures)and Candida albicans

C . S C U L L Y , W . V A N B R U G G E N , P . D I Z D I O S , * B . C A S A L , * S . P O R T E R A N D

M - F . D A V I S O N †International Centre for Excellence in Dentistry, Eastman Dental Institute for Oral Health Care Sciences, University College London

(UCL), University of London, 256 Gray’s Inn Road, London WC1X 8LD, U.K.

*School of Medicine and Dentistry, University of Santiago de Compostela, Spain

†Horizon Trust, Radlett, Hertfordshire, U.K.

Accepted for publication 12 April 2001

Summary Background The incidence of angular cheilitis (angular stomatitis, perleche, commissural fissures)

appears to be increased in people with Down syndrome (DS). Lip fissures are also (in our clinical

impression) a fairly regular feature, yet this is scarcely mentioned in the literature.Objectives To establish the incidence of angular cheilitis and lip fissures in a substantial group of

patients with DS and to examine the relationship with Candida albicans.

Patients and methods The prevalence of orofacial soft tissue lesions was investigated in a group of77 DS patients. Swabs were taken from lip lesions, palate and tongue and inoculated on Sabou-

raud’s agar discs for the isolation of C. albicans, identified with commercially available kits.

Results Lip fissures were seen in at least one-quarter of DS patients. Angular cheilitis was alsofound in a similar percentage.

Conclusions C. albicans was isolated from a substantial proportion of lesions tested, and was present

more frequently than in those without lip lesions, but it is uncertain whether this represents causeor effect.

Key words: Candida, candidiasis, cheilitis, Down syndrome, lips, oral

In 1866 John Langdon Down described some of thecharacteristics of the syndrome that now bears his

name. Down syndrome (DS), also known as trisomy 21

or trisomy G,1 is one of the most common causes oflearning difficulties. One-third of the DS population is

severely mentally challenged and in the past 5–10%

were institutionalized.2 An increased susceptibility toinfection, including candidosis, may be related to

multiple immunological defects in DS,2–6 and persons

with DS also suffer from a multitude of other disorders,including orofacial anomalies and disease.2,7–11

The most obvious orofacial characteristic in DS is a

relatively enlarged and protruding tongue, with arecorded prevalence between 11 and 96%,12–14 and an

open mouth posture.12,15 Mouth breathing is

extremely common (60–96%) and may causedrooling.5 The incidence of angular cheilitis (angular

stomatitis, perleche, commissural fissures) also appearsincreased in people with DS.14,16–19

Apart from angular cheilitis, lip fissures, which are

sometimes termed cracked or fissured lips, are also (in ourclinical impression) a fairly regular feature seen in our

patients with DS, compared with other patients with

learning disability; however, this was scarcely mentionedin a recent review.20 We could find only a single publi-

cation documenting this observation in the English lan-

guage literature16 and one in the Spanish literature;14

neither report included more than about 35 DS patients.

The aims of this study were to establish the incidence

of lip fissures and angular cheilitis in a substantialgroup of patients with DS and to examine the

relationship with Candida albicans.

Patients and methods

In this observational, descriptive study, 77 patients (40

male, 37 female) with DS were examined. TheseCorrespondence: C.Scully.

E-mail: cscully@eastman.ucl.ac.uk

British Journal of Dermatology 2002; 147: 37–40.

� 2002 British Association of Dermatologists 37

included dental patients with DS, of all ages, bothgenders and all types of DS chromosomal abnormality,

and included institutionalized and community-based

persons from two different European countries. Thestudy group included 27 U.K. DS patients (20 from a

hospital, seven living at home) and 50 Spanish DS

patients (43 living at home, the remainder living incommunity care).

Orofacial examinations were performed by instructed

dentists under a strict protocol with the help of astandard registration form. The examination was made

simple and quick enough for persons with DS to tolerate.

Intra-oral examination took place with the patientsitting in a dental chair tilted 45� backwards, with the

use of a standard mouth mirror and dental lighting.

The dentist recorded the presence and location of lipfissures and angular cheilitis. Lip fissures were charac-

terized as fissures on the vermilion of the lips running

in a sagittal plane. The location of lip fissures wasrecorded as mid-line (level with the labial frenum) or

between the frenum and commissure. If a fissure was

present at a commissure this was regarded as angularcheilitis. Angular cheilitis was the term used when

inflammatory changes, including redness, soreness and

ulceration, appeared on either or both commissures.The lips were examined for evidence of scarring from

previous lip fissures or angular cheilitis.

Swabs were taken from the lip lesions (fissures orangular cheilitis) where present, and from the hard

palate and dorsum of tongue, of 50 patients, and were

inoculated on 4% Sabouraud’s dextrose agar discs(Sigma Ltd, Madrid, Spain) for the isolation of

C. albicans. C. albicans was identified with the use of

Candifast Unipath, and API 20C AUX commerciallyavailable kits (Biomeriuex, Madrid, Spain).

Results

Lip fissures and ⁄ or angular cheilitis, or evidence ofhealed lesions, were found in a significant minority of

persons with DS (Table 1). No patients showedevidence of perioral dermatitis or actinic cheili-

tis, and lip-licking was present in only a small

minority.Lip fissures were seen mainly in the lower lip (62%)

(Table 2). Lip fissures were present in 27% of the total

studied population and there was only a slight andnon-significant difference in the prevalence of lip

fissures between the sexes (30% in males and 24% in

females). They were slightly more common in Britishsubjects, in whom there was a slightly increased

prevalence in males and a later age of peak prevalence

(sixth vs. third decade).Angular cheilitis was present in 25% of the total

studied population of DS patients, with the same

prevalence in males and females. The sample size wastoo small to establish age-related trends, although

angular cheilitis was not common in the first decade.

Angular cheilitis was present in only 5% of theBritish DS patients but was present in 34% of

the Spanish DS patients with a higher prevalence

in the male population (41% in males vs. 29% infemales).

There was no correlation between the presence of the

two different types of lip lesions, fissures and angularcheilitis, nor between fissures and angular cheilitis and

lip-licking.

C. albicans was isolated from the mouths of 28 of50 (56Æ0%) patients with DS. The organism was

found both in angular cheilitis and in lip fissures.

C. albicans was detected in the majority (17 of 22;77Æ3%) of patients with lip lesions (Table 3), while

only 35Æ7% of those with no lip lesions carried

C. albicans.In patients under 20 years of age, lip fissures and ⁄ or

angular cheilitis were present in 40% of cases, and 90%

of them were positive for C. albicans isolates. In patientsover 20 years of age, lip fissures and ⁄ or angular

cheilitis were detected in 48% of cases, and 66Æ6% of

them were positive for C. albicans isolates.

Table 1. Incidence of lip fissures (fissures) and angular cheilitis (cheilitis) in Down syndrome

Age(decade) Gender 0–10 11–20 21–30 31–40 41–50 51–60 > 60

Total

populationaffected

Number 11 13 15 16 10 7 5 77

Fissures Male 3 ⁄ 8 (37%) 1 ⁄ 8 (13%) 2 ⁄ 8 (25%) 2 ⁄ 8 (25%) 1 ⁄ 2 (50%) 1 ⁄ 3 (33%) 2 ⁄ 3 (67%) 12 ⁄ 40 (30%)Fissures Female 0 ⁄ 3 (0%) 0 ⁄ 5 (0%) 2 ⁄ 7 (29%) 3 ⁄ 8 (38%) 1 ⁄ 8 (13%) 2 ⁄ 4 (50%) 1 ⁄ 2 (50%) 9 ⁄ 37 (24%)

Fissures Both sexes 3 ⁄ 11 (27%) 1 ⁄ 13 (8%) 4 ⁄ 15 (27%) 5 ⁄ 16 (31%) 2 ⁄ 10 (20%) 3 ⁄ 7 (43%) 3 ⁄ 5 (60%) 21 ⁄ 77 (27%)

Cheilitis Male 1 ⁄ 8 (13%) 2 ⁄ 8 (25%) 3 ⁄ 8 (38%) 3 ⁄ 8 (38%) 1 ⁄ 2 (50%) 0 ⁄ 3 (0%) 0 ⁄ 3 (0%) 10 ⁄ 40 (25%)

Cheilitis Female 1 ⁄ 3 (33%) 2 ⁄ 5 (40%) 2 ⁄ 7 (29%) 2 ⁄ 8 (25%) 2 ⁄ 8 (25%) 0 ⁄ 4 (0%) 0 ⁄ 2 (0%) 9 ⁄ 37 (24%)Cheilitis Both sexes 2 ⁄ 11 (18%) 4 ⁄ 13 (31%) 5 ⁄ 15 (33%) 5 ⁄ 16 (31%) 3 ⁄ 10 (30%) 0 ⁄ 7 (0%) 0 ⁄ 5 (0%) 19 ⁄ 77 (25%)

3 8 C . S C U L L Y et al.

� 2002 British Association of Dermatologists, British Journal of Dermatology, 147, 37–40

Discussion

In this study we investigated lip fissures in a substantialnumber of patients with DS. Lip fissures were observed

in over a quarter of the present group of DS patients.

Although no control group was included, the incidenceof lip fissures in the present DS group is very much

higher than the 0Æ6% recorded in a general popula-

tion.21,22 We are unaware of any similar study onpatients with other types of learning disability, which

might be regarded as an appropriate control group. Inthe present DS group there was a slight male predom-

inance, with the lower lip as the main location for lip

fissures. In contrast, in the general population gener-ally, lip fissures tend to be more common in men than

in women with a male ⁄ female ratio 4 : 1 and are more

prevalent in the age groups under 45 years than inthose above this age.21

The lip fissures of the present group of DS patients

tended to be on the vermilion of the lips with cracksrunning in a sagittal plane. The most common site in

the lower lip was the mid-line and in the upper lip

slightly lateral to the mid-line. As far as we know theonly prevalence survey of lip fissures in individuals

with DS in the English literature was reported in

1960,16 although a later Spanish study also identifiedlip fissures.14 The first study observed the highest

incidence of lip changes to be in the third decade,

as seen in our Spanish patients, and to be morecommon in male (76%) than female patients (59%).16

Butterworth et al. studied 19 biopsy specimens andconcluded that the fissuring was caused by trauma or

low-grade infection.16 The other (Spanish) study found

a prevalence of lip changes to be about 60%.14

The aetiology of lip fissures is still uncertain. One

study concluded that in the general population a

congenital decrease in the size and number of mucousglands in the lips or anatomically different lips might

predispose to lip fissures21,22 but we know of no

evidence for this in DS. Other suggestions for causes oflip fissures in the general population include weakness

in the fusion between the prenatal lateral segments of

the lower lip, mouth breathing, avitaminosis, outdooroccupations, smoking, and bacterial and mycotic

infections.22,23 Certainly, patients with DS often

breath through their mouths mainly because of lipincompetence, a protruding tongue, drooling, or the

high frequency of persistent rhinitis caused by a

narrow and partially obstructed air passage.24 It ispossible that the higher prevalence seen in the English

patients in the present study could be related to the

cooler more humid climate in Britain compared withSpain.

Patients with DS also have a tendency to orofacial

infections, especially with Candida sp.6 Indeed, wefound C. albicans was cultured from the patients with

DS who had labial lesions twice as frequently as in

those with no lip lesions.A high incidence of angular cheilitis was also found,

about one-quarter of patients with DS being affected,

consistent with previous reports.14,16–19 Identifiedpredisposing factors for angular cheilitis include

immune defects, and upper respiratory tract infec-

tions.6,18 The high incidence of angular cheilitis inpeople with DS found in the present study may be

caused by C. albicans; as we have shown here,

C. albicans was cultured from patients with DS twiceas frequently in those who had labial lesions than in

those with no lip lesions. In the present study, fissures

appeared related in the first decades, mainly toC. albicans and to mandibular prognathism and lip

eversion. An increased incidence of C. albicans has

previously been reported in the mouths of those withDS,6 and our results would lend support to the

Table 3. Oral isolation of Candida albicans and lip fissures in Down syndrome by age (n ¼ 50)

Age (decades) 0–10 11–20 21–30 31–40 41–50 Total

C. albicans isolated 11 ⁄ 13 (84Æ6%) 7 ⁄ 12 (58Æ3%) 4 ⁄ 8 (50%) 5 ⁄ 12 (41Æ6%) 1 ⁄ 5 (20%) 28 ⁄ 50 (56%)

Lip fissures 5 ⁄ 13 (38Æ4%) 5 ⁄ 12 (41Æ6%) 5 ⁄ 8 (62Æ5%) 5 ⁄ 12 (41Æ6%) 2 ⁄ 5 (40%) 22 ⁄ 50 (44%)

C. albicans ⁄ lesion 4 ⁄ 5 (80%) 5 ⁄ 5 (100%) 3 ⁄ 5 (60%) 4 ⁄ 5 (80%) 1 ⁄ 2 (50%) 17 ⁄ 22 (77%)

Table 2. Lip fissures (excluding angular cheilitis) and their location

in Down syndrome

Age (decade) Lip fissures Location of lip fissures

0–10 3 ⁄ 11 U ¼ 2, L ¼ 111–20 1 ⁄ 13 L ¼ 1

21–30 4 ⁄ 15 U + L ¼ 1, U ¼ 1, L ¼ 2

31–40 5 ⁄ 16 U ¼ 1, L ¼ 441–50 2 ⁄ 10 U ¼ 1, L ¼ 1

51–60 3 ⁄ 7 U ¼ 1, L ¼ 2

61+ 3 ⁄ 5 U ¼ 1, L ¼ 2

n ¼ 77 21 ⁄ 77 (27%) U + L ¼ 1 ⁄ 21 (5%),U ¼ 7 ⁄ 21 (33%),

L ¼ 13 ⁄ 21 (62%)

L, lower lip; U, upper lip; U + L, both lips.

D O W N S Y N D R O M E : L I P L E S I O N S A N D C A N D I D A 3 9

� 2002 British Association of Dermatologists, British Journal of Dermatology, 147, 37–40

hypothesis that the immune defect of DS predisposes tocandidosis and mucosal lesions.

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