Chronic Ulcerative Stomatitis
What is Chronic Ulcerative Stomatitis?
Chronic Ulcerative Stomatitis (CUS) was first identified in 1990 as a rare auto-immune condition that presents as painful ulcers in the mouth, often coming and going for many years. Unlike other auto immune diseases that cause mouth blisters and ulcers, it does not respond well to corticosteroids.
(Stomatitis means a sore mouth).
Who gets Chronic Ulcerative Stomatitis?
CUS is rare with less than 100 cases so far reported.
It seems to almost exclusively affect white women in late middle age with an average age at onset of 60 years. There are rare reports of CUS affecting males or younger women.
Often the symptoms have been present many years before the diagnosis is made. It is associated with antibodies against keratinocyte nuclei of stratified squamous epithelium.
Clinical Features of Chronic Ulcerative Stomatitis
CUS presents as painful erosions (superficial ulcers) in the mouth which can resemble erosive lichen planus. It may mimic other auto-immune conditions that cause mouth ulcers or erosions including pemphigus vulgaris and cicatricial pemphigoid or resemble a desquamative gingivitis.
The ulcers can occur on the gums, inside the cheeks or on the tongue.
The condition lasts many years, sometimes coming and going.
Very rarely similar lesions have also been reported on the genital or conjunctival mucosa.
Skin lesions resembling oral lichen planus have been reported in some patients. It is not yet clear if CUS co-exists with oral lichen planus or is a variant of it.
The patient is otherwise well.
How is Chronic Ulcerative Stomatitis diagnosed?
CUS is diagnosed on the combination of clinical and pathological features.
Mucosal biopsies from the mouth show non-specific pathology features, most often resembling oral lichen planus. However, direct immuno-fluorescence (DIF) shows a speckled pattern of IgG (immunoglobulin G, a type of antibody) in the lower one third of the epithelium (basal & para-basal cell layers).
Indirect immuno-fluorescence (IIF) on a blood sample detects an IgG and / or IgA (another type of immunoglobulin / antibody) auto-antibody against keratinocyte nuclei in skin. This specific antibody is called Stratified Epithelium-Specific (SES)-Anti-Nuclear Antibody (ANA). The antigen recognised by these auto-antibodies is a 70 kilo Dalton epithelial nuclear protein and has been identified as Delta Np63 alpha (ΔNp63α).
An ELISA test assay has recently been developed to detect the specific auto-antibodies. The SES-ANA (Stratified Epithelium Specific-Anti-Nuclear Antibody) titre is usually high and persists despite clinical remission with treatment. Although the titre is often lower with treatment, it does not disappear completely. The titre does not appear to correlate with disease activity. However, the combination of both IgG and IgA auto-antibodies may indicate severe disease.
Diagnostic criteria have been proposed by Chorzelski et al (1998):
Major Criteria
• erosive or exfoliative lesions in the mouth
• characteristic indirect and direct immuno-fluorescence (I-IF & D-IF)
Minor Criteria
• chronic course with relapses
• female in the older age group
• response to hydroxychloroquine alone or combined with small doses of cortisone.
Treatment of Chronic Ulcerative Stomatitis
CUS typically does not respond to topical steroids or oral steroid treatment.
However there is usually an excellent initial response to oral hydroxychloroquine, 200 – 400mg / day. This may result in a long-lasting remission. However in the long term, hydroxychloroquine may not prevent relapses and low dose systemic corticosteroids & / or dapsone may be required in addition.