British Journal of Dermatology 2001; 144: 1219±1223.

Systemic lupus erythematosus presenting with oral mucosal

lesions: easily missed?
C.H.ORTEU, J.A.G.BUCHANAN,* I.HUTCHISON,² I.M.LEIGH AND R.H.BULL
Departments of Dermatology, *Oral Medicine and ²Oral and Maxillofacial Surgery, The Royal London Hospital, Whitechapel,

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London E1 1BB, U.K.
Accepted for publication 17 January 2001

Summary Two caucasian patients are described in whom oral mucosal lesions were the first manifestation of
systemic lupus erythematosus. In both cases the diagnosis was delayed despite histological
examination of oral lesions. Treatment with antimalarials and azathioprine was of significant
benefit. In the absence of cutaneous or systemic features, distinguishing oral lupus erythematosus
from lichen planus and epidermal dysplasia can be difficult, both clinically and on histology, and
requires a high index of suspicion.
Key words: azathioprine, hydroxychloroquine, mepacrine, oral mucosal lesions, systemic lupus
erythematosus

A wide spectrum of oral mucosal lesions is found in
cutaneous and systemic forms of lupus erythematosus
(LE): cheilitis, erythematous patches, `honeycomb'
plaques, discoid lesions, lichen planus (LP)-like lesions
and discrete ulcers have been described (Table 1).1±4 In
established disease, reported prevalence rates range
from 9% to 45% of cases,3±7 although the true figure
may be nearer to 20%.8 The frequency with which
systemic LE (SLE) presents with oral mucosal lesions
remains uncertain as there are only a few cases
reported in the literature.1,9
We describe two caucasian patients presenting with
oral mucosal involvement, in whom the diagnosis of LE
was only made after other systemic or cutaneous signs
of LE appeared several months later. We believe that the
frequency with which SLE presents with oral lesions is
underestimated. These cases highlight the difficulties
that may be encountered in early diagnosis.2,3,10
Case reports
Patient 1
A 44-year-old male smoker presented to the
Department of Oral and Maxillofacial Surgery in June
1998 with a painful left buccal mucosal lesion of
Correspondence: Dr R.H.Bull.
Patient 1 was presented at the Royal Society of Medicine, Section of
Dermatology, on 17 June 1999.
2 months' duration, consisting of patchy white hyper-
keratosis and erythema. A biopsy showed parakeratosis,
basal layer crowding, hyperchromatic nuclei, and an
upper dermal predominantly lymphocytic infiltrate
(Fig. 1). A diagnosis of leucoplakia with mild to
moderate epithelial dysplasia was made, and when
he failed to respond to conservative measures the
lesion was excised.
He subsequently developed cheilitis, extensive typical
palatal `honeycomb' lesions (Figs 2 and 3) and buccal
mucosal ulceration. Nine months after the onset of
oral manifestations, he presented with an itchy
papulosquamous eruption, with associated scarring,
on the arms and trunk. Biopsy of a papule showed
acanthosis, vacuolar degeneration of the basal layer
and a lichenoid infiltrate in the upper dermis (Fig. 4).
Direct immunofluorescence (IMF) of lesional and
perilesional skin showed granular staining of the
basement membrane zone with IgM, IgG and C3.
Further investigations revealed a positive antinuclear
antibody (ANA; 1 : 640, speckled pattern) and anti-
nRNP, borderline C4 (0´2, normal 0´15±0´7) and
mildly impaired renal function (creatinine clearance
75 mL min21). Other autoantibodies were negative.
There was no evidence of myositis.
Despite treatment with hydroxychloroquine 200 mg
twice daily and oral prednisolone 30 mg daily, the oral
lesions remained active (Fig. 5). He also became
increasingly unwell with malaise, arthralgia and a

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1220 C.H.ORTEU et al.

Table 1. Clinical characteristics of oral

Type of lesion Appearance Commonest site
lesions seen in lupus erythematosus
Cheilitis Erythema and scaling Lower lip, vermilion border
Erythematous patches Poorly demarcated ^ Hard palate
telangiectasia and
oedema
`Honeycomb' plaques Well-circumscribed, Palatal mucosa
white lacy
hyperkeratosis and

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erythema
Discoid lesions Red atrophic centre and Buccal/labial mucosa and gingiva
peripheral radiating (often at sites of missing teeth)
white hyperkeratotic
striae and
telangiectasia
Lichen planus-like Reticulate Buccal mucosa
lesions leucokeratosis
Discrete ulcers Red/grey base and Palatal mucosa
hyperkeratotic borders

generalized livid reticulate scaly erythema, with nail-

fold erythema and ragged cuticles. The palms and soles
were erythematous, hyperkeratotic and painful. There
was a partial response to pulsed methylprednisolone
0´7 mg kg21 daily (three pulses), but remission was
only achieved 6±8 weeks after the addition of
azathioprine 100 mg daily. Three months later, oral,
systemic and cutaneous manifestations were controlled
on hydroxychloroquine and azathioprine.

Patient 2
A 19-year-old woman initially presented to a dental
hospital elsewhere in April 1997 with a sore mouth. A
diagnosis of LP was made on histology. Four months
later she developed urticated indurated erythematous

Figure 1. Histology of an oral lesion showing parakeratosis,

acanthosis, basal layer crowding, hyperchromatic nuclei and an
upper dermal lymphocytic infiltrate (patient 1: haematoxylin and Figure 2. Extensive typical honeycomb plaques on the hard palate
eosin; original magnification  400). (patient 1).

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Figure 3. Histology of an oral lesion showing more typical features,
with parakeratosis, alternating epithelial hyperplasia and atrophy,
vacuolar changes in the basal layer and a dense upper dermal
lymphocytic infiltrate (patient 1: haematoxylin and eosin; original
magnification  200).
plaques on the cheeks and temple, and had bilateral
erosions on the buccal mucosae. There were no genital
lesions or systemic features. Histology of a cutaneous
lesion showed a superficial and deep dermal peri-
vascular lymphohistiocytic infiltrate, pigmentary
incontinence, but a normal epidermis. Direct IMF of
lesional and perilesional normal skin showed moderate
granular staining with IgG at the basement membrane.
Further investigations revealed a positive ANA (1 : 640
rising to . 1 : 1000, speckled pattern), anti-Ro (SS-A)
and anti-La (SS-B), erythrocyte sedimentation rate
48 mm in the first hour, and borderline C4 (0´15).
Routine haematology, biochemistry and other auto-
antibodies, including double-stranded DNA were nega-
tive or normal. The cutaneous lesions initially
Figure 4. Histology of a cutaneous papule showing vacuolar
degeneration of the basal layer and a dense band-like lymphocytic
infiltrate in the upper dermis (patient 1: haematoxylin and eosin;
original magnification  200).
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ORAL LESIONS IN SLE 1221
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Figure 5. Discoid-type lesion in an unusual linear pattern on the left
buccal mucosa. There are peripheral white hyperkeratotic striae and
telangiectasia radiating from an erythematous atrophic base. A
discrete ulcer with a hyperkeratotic edge is seen more posteriorly
(patient 1).
responded to potent topical steroids; however, buccal
mucosal erosions persisted and there were new
reticular LP-like lesions. Her cutaneous lesions relapsed
after a skiing holiday and she also developed scalp
lesions with associated alopecia. Oral and cutaneous
lesions responded to mepacrine 100 mg daily.
Discussion
We have reported two patients who presented with
oral lesions that were not diagnosed initially as LE, but
who subsequently developed other features of SLE. It is
difficult to ascertain the true incidence with which SLE
presents with oral involvement because of a relative
lack of symptoms and different referral pathways. Oral
mucosal lesions are frequently chronic, with a mean
duration of 4´2 years for discoid lesions in one
study,2 and may be asymptomatic in 50±80% of
patients.4,11 Symptomatic patients may present early to
dentists, oral surgeons or physicians, whereas asymp-
tomatic patients may not present until much later,
when they develop cutaneous or systemic manifesta-
tions. Of patients seen by dermatologists, 15±36%
give a retrospective history of oral ulcers at the onset of
their disease, but it is not known what proportion
represent true lupus ulcers.3,12 In a prospective study of
66 patients with oral discoid lesions followed for 6 years
in a department of oral medicine, oral manifestations
were the first sign of disease in six of 15 (40%) patients
with SLE, and seven of 29 (24%) patients with
isolated oral lesions subsequently developed cutaneous
1222 C.H.ORTEU et al.
discoid LE (DLE).13 Interestingly, patients with con-
comitant oral and cutaneous discoid lesions and high
titres of circulating ANA may be at particular risk of
developing systemic disease, and warrant careful
monitoring.13,14
The main differential diagnoses are LP and oral
leucoplakia, but distinguishing between oral LE,
LP and leucoplakia can be difficult, both clinically
and histologically, even when established histopatho-
logical criteria are used.10,15±18 The histological
features of mucosal DLE lesions are more variable than
those of skin lesions and may show non-specific
changes.1,9,19 Light microscopic findings include
hyperkeratosis, alternating epithelial hyperplasia and
atrophy, disturbed epithelial maturation with reactive
cytological atypia, vacuolar degeneration of the basal
layer, and a predominantly lymphocytic dermal infil-
trate, which may be focal, interstitial, perivascular
or band-like.3,4,10,19,20 In difficult cases, direct IMF
studies may be helpful.4,14,20 Granular or homo-
geneous bands of immunoglobulin in the basement
membrane zone have been demonstrated in lesional
and non-lesional mucosa in SLE (100% and 71%,
respectively) and in lesional mucosa in DLE (73%),
but only rarely in LP (4%) or leucoplakia (3%).14
Deposits of IgG and IgA were the most specific for
oral discoid lesions, and deposits of IgM showed the
highest sensitivity.14 Routine use of histopathology
and direct IMF studies of lesional and normal oral
mucosa should, therefore, increase the diagnostic
yield in patients with mucosal lesions and early
disease.
Treatment is aimed at symptom control. We could
find no large or controlled studies in the literature
on the management of oral LE. The efficacy of metho-
trexate,21 dapsone22 and gold1 is described in isolated
cases and small series. Thalidomide should be of benefit
on theoretical grounds.23 At this centre we have
experience in the use of antimalarials (hydroxy-
chloroquine and mepacrine) and azathioprine in
patients with oral manifestations of LE, LP and lichen
sclerosus, and have found them to be of significant
benefit. Unfortunately, there are no current data
available to suggest whether certain patient character-
istics might favour a response to one or another
treatment modality.
These cases emphasize that LE should always be
considered as a diagnosis in patients presenting with
oral lesions, such as those in Table 1, and that the oral
mucosa should be examined in patients with suspected
LE. Biopsy and direct IMF studies are worthwhile in
q 2001 British Association of Dermatologists, British Journal of Dermatology, 144, 1219±1223
patients presenting with cutaneous or systemic
manifestations suggestive of LE.
References
1 Edwards MB, Gayford JJ. Oral lupus erythematosus. Oral Surg
1977; 31: 332±42.
2 Schiodt M, Halberg P, Hentzer B. A clinical study of 32 patients
Downloaded from https://academic.oup.com/bjd/article/144/6/1219/6691069 by University of Melbourne user on 19 May 2023
with oral discoid lupus erythematosus. Int J Oral Surg 1978; 7:
85±94.
3 Burge SM, Frith PA, Juniper RP, Wojnarowska F. Mucosal
involvement in systemic and chronic cutaneous lupus erythema-
tosus. Br J Dermatol 1989; 121: 727±41.
4 Jonsson R, Heyden G, Gunnar Westberg N, Nyberg G. Oral
mucosal lesions in systemic lupus erythematosus. A clinical,
histopathological and immunopathological study. J Rheumatol
1984; 11: 38±42.
5 Dubois EL, Tuffanelli DL. Clinical manifestations of SLE. Computer
analysis of 520 cases. JAMA 1964; 190: 104±11.
6 Grigor R, Edmonds J, Lewkonia R et al. Systemic lupus
erythematosus. A prospective analysis. Ann Rheum Dis 1978;
37: 121±8.
7 Pisitiner M, Wallace DJ, Nesim S et al. Lupus erythematosus in the
1980s: a survey of 570 patients. Semin Arthritis Rheum 1991; 21:
55±64.
8 Rowell NR, Goodfield MJD. The `connective tissue diseases'. In:
Textbook of Dermatology (Champion RH, Burton JL, Burns DA,
Breathnach SM, eds), 6th edn, Vol. 3. Oxford: Blackwell Science,
1998: 2478.
9 O'Neill SM, Thomson J, Strong AMM, Lang W. Systemic lupus
erythematosus presenting as a recurrent sore throat and oral
ulceration: a case report. Br J Dermatol 1977; 96: 211±13.
10 Schiodt M, Pindborg JJ. Oral discoid lupus erythematosus I. The
validity of previous histopathologic diagnostic criteria. Oral Surg
1984; 57: 46±51.
11 Urman JD, Lowenstein MB, Abeles M, Weinstein A. Oral mucosal
ulceration in systemic lupus erythematosus. Arthritis Rheum
1978; 21: 58±61.
12 Yell JA, Mbuagbaw J, Burge SM. Cutaneous manifestations of
systemic lupus erythematosus. Br J Dermatol 1996; 135: 355±
62.
13 Schiodt M. Oral discoid lupus erythematosus II. Skin lesions and
systemic lupus erythematosus in sixty-six patients with 6 year
follow-up. Oral Surg 1984; 57: 177±80.
14 Schiodt M, Holmstrup P, Dabelsteen E, Ullman S. Deposits of
immunoglobulins, complement, and fibrinogen in oral lupus
erythematosus, lichen planus, and leukoplakia. Oral Surg 1981;
51: 603±8.
15 Plotnick H, Burnham TK. Lichen planus and co-existing lupus
erythematosus versus lichen planus-like lupus erythematosus.
J Am Acad Dermatol 1986; 14: 931±8.
16 van der Horst JC, Cirkel PKS, Nieboer C. Mixed lichen planus-
lupus erythematosus disease: a distinct entity? Clinical, histo-
pathological and immunopathological studies in six patients. Clin
Exp Dermatol 1983; 8: 631±40.
17 Lever WF, Schaumburg-Lever G, eds. Histopathology of the Skin.
6th edn. Philadelphia: Lippincott, 1983: 446.
18 WHO Collaborating Centre for Oral Precancerous Lesions.
Definition of leukoplakia and related lesions. Oral Surg Oral Med
Oral Pathol 1978; 46: 518±39.
19 Karjalainen TK, Tomich CE. A histopathologic study of oral
 ORAL LESIONS IN SLE 1223

mucosal lupus erythematosus. Oral Surg Oral Med Oral Pathol
1989; 67: 547±54.
20 Jorizzo JL, Salisbury PL, Rogers RS et al. Oral lesions in systemic
lupus erythematosus. Do ulcerative lesions represent a necrotiz-
ing vasculitis? J Am Acad Dermatol 1992; 27: 389±94.
21 Bottomley WW, Goodfield M. Methotrexate for the treatment of
severe mucocutaneous lupus erythematosus. Br J Dermatol 1995;
133: 311±14.
22 Ruzicka T, Goerz G. Dapsone in the treatment of lupus
erythematosus. Br J Dermatol 1981; 104: 53±6.
23 Gardner-Medwin JM, Powell RJ. ThalidomideÐthe way forward.
Postgrad Med J 1994; 70: 860±2.

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