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Oral Ulcers in Juvenile-Onset Systemic Lupus Erythematosus - A Review of The Literature
Oral Ulcers in Juvenile-Onset Systemic Lupus Erythematosus - A Review of The Literature
DOI 10.1007/s40257-017-0286-9
REVIEW ARTICLE
1 Introduction
classification criteria are now widely used in JSLE, and the JSLE patients are palatal erythematous ulcers, oral DLE
diagnosis requires at least four out of 17 criteria (including and aphthous ulcers [10, 11].
at least one clinical criterion and one immunological cri-
terion), or lupus nephritis with a presence of antinuclear
antibody (ANA) or anti-double-stranded DNA (anti-ds 3 Clinical Manifestations
DNA) antibodies [8, 9].
Mucocutaneous manifestations are common signs and Oral mucosa is normally characterized into three types:
symptoms in JSLE at diagnosis, and they are found in lining; masticatory and specialized mucosa [22, 23]. The
approximately 70–75% of JSLE populations worldwide lining mucosa is nonkeratinized epithelium covering buc-
[7, 10–14]. According to the ACR revised criteria, four cal mucosa, labial mucosa, alveolar mucosa, soft palate,
mucocutaneous features are included, one of which is oral ventral tongue and the floor of the mouth [24], whereas the
ulcers. The terminology of oral ulcers in these criteria is masticatory mucosa is keratinized mucosa covering gin-
usually ‘‘painless oral or nasopharyngeal ulceration giva, attached gingiva and hard palate. The dorsal surface
observed by a physician’’, yet these may be unclear, of the tongue is covered with specialized mucosa that
especially in children [15]. In the new SLICC group clas- consists of taste buds and epithelially derived structures
sification criteria, oral ulcers remain included. They are called papillae [22–24]. Understanding of these different
defined more specifically as oral ulcers at palate, buccal types of oral mucosa is important for making a diagnosis,
mucosa or tongue without other causes (e.g., vasculitis or as some lesions tend to affect one type of tissue more than
infection) [8]. In fact, there are several types of oral ulcers the others. The clinical manifestations of oral ulcers in
presented in JSLE patients. Moreover, some ulcers (e.g., JSLE patients are summarized in Table 1 [16, 25–30].
palatal erythematous ulcers and aphthous ulcers) occur
particularly when disease is active. However, other types of 3.1 Lupus Erythematosus (LE)-Specific Oral Ulcers
ulcers may appear without being related to disease activity
and severity [16, 17]. 3.1.1 Palatal Erythematous Ulcers
The mucocutaneous manifestations in JSLE are classi-
fied as lupus erythematosus (LE)-specific and LE-non- A palatal erythematous ulcer is the typical oral ulcer in the
specific skin diseases, according to the Gilliam ACR criteria, and it is described as a usually painless,
classification of skin lesions associated with LE [18]. single/multiple lesion(s) at masticatory or keratinized
Typical oral ulcers in the ACR criteria and SLICC group mucosa, especially the hard palate (Fig. 1a). It is an acute
classification criteria are LE-specific and most lesions are sign occurring when disease is active, and sometimes is the
categorized in chronic cutaneous lupus erythematosus first clue of JSLE without skin lesions [26]. The early
(CCLE), such as oral discoid lupus erythematosus (DLE), lesion may be hemorrhaging before developing into the
whilst others are LE-nonspecific (e.g., aphthous ulcers) ulcer [10]. If the ulcers are coalesced into a large erythe-
[10]. matous patch at the hard palate and extend to the soft
We searched for literature reviews and studies in the palate, the early onset of oral DLE should be considered.
PubMed database using the following key words: Palatal erythematous ulcers are sometimes characterized as
‘‘oral/mucosa/mucosal/mucocutaneous’’ and ‘‘lupus/LE/ acute cutaneous lupus erythematosus (ACLE) of LE-
SLE’’ and ‘‘juvenile/child/childhood/children’’ (until specific skin disease in some reports [16].
August 1, 2016). All published articles related to the
clinical manifestations of oral ulcers in JSLE patients were 3.1.2 Oral Discoid Lupus Erythematosus
reviewed.
Oral DLE is a well-defined, atrophic plaque with white
radiating keratotic striae and telangiectasia at lining
2 Epidemiology mucosa, especially buccal mucosa and the soft palate
(Fig. 1b) [16, 26]. JSLE patients often develop an erythe-
Oral ulcers are the second most common mucocutaneous matous lesion with painful telangiectasia, and keratotic
manifestation in JSLE patients after butterfly rash [11], and scaling occurs afterward. The lesion eventually transforms
they are the most common mucosal sign of JSLE [19]. The into an atrophic lesion with keratotic border [31]. The
incidence of oral ulcers in JSLE is approximately typical oral DLE is composed of (a) white papule/plaque,
11.4–37%, which is significantly higher than in adult SLE (b) central erythema, (c) a border zone of irradiating white
[4, 5, 20]. In adult patients, males have a lower rate of oral striae and (d) peripheral telangiectasia [27, 28]. Although
ulcers than females, but there are no reports of gender the lesion appears at lining mucosa, the masticatory
preference in children [21]. The common oral ulcers in mucosa may be involved without radiating striae (e.g., hard
Oral Ulcers in Juvenile-Onset Systemic Lupus Erythematosus
Table 1 Clinical manifestations of oral ulcers in juvenile-onset systemic lupus erythematosus (JSLE) [16, 25]
Classification Type of lesions Locations Key clinical features
LE-specific oral Palatal Masticatory mucosa (especially hard Painless, single/multiple erythematous ulcer(s)
ulcers erythematous palate)
ulcer
Oral discoid LE Lining mucosa (especially buccal mucosa Atrophic plaque with white radiating keratotic striae and
and soft palate) painful telangiectasia
Honeycomb Lining and masticatory mucosa Chronic, well-circumscribed erythematous plaque with
plaque white lacy hyperkeratosis
Verrucous LE Lining mucosa Raised, intense keratotic plaque
LE-nonspecific Aphthous ulcer Lining mucosa White to yellow painful ulcer(s) with erythematous halo
oral ulcers Lupus cheilitis Buccal lips (especially lower lip) Small or diffuse erythematous and edematous lips, or
crusty painful ulcer(s)
LE lupus erythematosus
palate) [28]. The dental alveolar process is another location presented with multiple lesions or in a group, and tends to
that should be carefully inspected, as oral DLE is easily involve primarily lining tissue: the soft palate, buccal and
overlooked. Of note, the radiating white striae sometimes labial mucosa. Aphthous ulcers are more common in JSLE
resemble the Wickham striae of oral lichen planus (OLP); patients than in adult SLE and usually occur when disease
therefore, a lesional biopsy should be performed if a defi- is active [36]. There are four types of aphthous ulcer,
nite diagnosis is required. Other locations of oral DLE are classified as (a) minor ulcers, smaller than 1 cm, usually
not common, such as vermilion borders of buccal lips and healing without scar; (b) major ulcers, larger than 1 cm,
specialized mucosa (tongue) [10, 31]. often healing with scar; (c) herpetiform ulcers, a group of
small ulcers (more than ten lesions); and (d) severe ulcers,
3.1.3 Honeycomb Plaques a continuous minor ulcer lasting months [37]. In our
observations, the most common type of aphthous ulcer in
A honeycomb plaque is described as a chronic, well-cir- JSLE patients is multiple minor ulcers and less than ten
cumscribed plaque with white lacy hyperkeratosis and lesions (Fig. 1d).
buccal erythema [16, 25, 32]. The lesion usually occurs at
both lining and masticatory tissues, but the lesion at the 3.2.2 Lupus Cheilitis
lining part (e.g., soft palate) is less hyperkeratotic [25].
Some reports suggest that this lesion is a morphological Lupus cheilitis is an inflammation of the buccal lips. The
variant or a late stage of oral DLE [18]. The incidence of typical lesion is small or diffuse, erythematous and ede-
honeycomb plaque in JSLE is very rare. matous, and may turn into crusty painful ulcers [29].
Cheilitis often involves the vermilion zone of the lower lip
3.1.4 Verrucous LE (typical lupus cheilitis) [30]. As the lesion is found in the
sun-exposed area, lupus cheilitis is usually associated with
Verrucous LE is a rare type of CCLE-specific oral ulcer photosensitivity in JSLE patients [25]. Extensive erosive
that has been reported in adult SLE and JSLE [16, 33–35]. lupus cheilitis that involves both upper and lower lips has
The lesion is a raised, intense keratotic plaque normally also been reported in JSLE patients and appears in active
found at lining mucosa, such as the buccal mucosa and lips. disease (Fig. 1e) [38].
However, the hard palate (e.g., alveolar ridge) may be
involved (Fig. 1c) [33]. 3.2.3 Other LE-Nonspecific Oral Lesions
3.2 LE-Nonspecific Oral Ulcers Bullous SLE is a rare clinical manifestation developed by
circulating antibodies against type VII collagen at the sub-
3.2.1 Aphthous Ulcers epidermis. It typically presents with multiple tense bullae
at the face, neck and trunk [39]. Bullous LE at buccal
An aphthous ulcer is described as a white to yellow painful mucosa has been reported in adult SLE and JSLE patients
ulcer with a surrounding red rim. The lesion is usually [40, 41].
P. Rodsaward et al.
Although clinical features are sufficient for making a herpes simplex virus (HSV) infection. A Tzanck smear,
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within 2 weeks [57]. Therefore, oral ulcers in JSLE should
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