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118:Two Sides of the Same Coin - A Genetic Mutation with Varying Oral Presentations[AAOM2020}
EP36009
Poster Title: 118:Two Sides of the Same Coin - A Genetic Mutation with Varying Oral Presentations[AAOM2020}
Submitted on 29 Mar 2021
Author(s): Krupali Patel1 (Registrar in Oral Medicine), Thomas Saunsbury 1(Specialty Dentist), Dr Timothy Hodgson1 (Consultant in Oral Medicine)
Affiliations: Unit of Oral Medicine, RNENT and Eastman Dental Hospital, UCLH Foundation NHS Trust, London, UK
This poster was presented at 2021 American Academy of Oral Medicine Virtual Conference
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Poster Information
Abstract: The Background

A 26 year old female previously under the care of the Oral Medicine department for the management of recurrent aphthous stomatitis was re-referred regarding an exponential increase in severity and frequency of oral ulceration, with widespread involvement of her lip and intra oral tissues. She reported increasing fatigue and lethargy, and had a nonspecific cutaneous rash. Three severe episodes occurred over a year. Her medical history was unremarkable and she was prescribed no medications. Her father was also under the care of Oral Medicine for management of limited systemic sclerosis and recurrent oral candidosis secondary to STAT1 mutation. Her sister had a long standing history of recurrent oral candidosis.

Clinically, multiple irregular poorly defined areas of sloughing mucosa and ulceration was noted affecting the soft palate, buccal mucosae and lower lip. A clinical diagnosis of a minor variant of erythema multiforme was made. Histopathological and direct immunofluorescence was negative for vesiculobullous disease. The features in this biopsy were those of hyperkeratosis, focal ulceration and candidal infection.

Her ulceration improved with systemic corticosteroid and antifungal therapy. Genetic analysis confirmed the presence of a STAT1 mutation resulting in an increase in phosphorylation of the STAT1 protein, increasing its function.

Conclusion

Gain-of-function mutations in the STAT1 gene (STAT1-GOF) are the most common genetic etiology for chronic mucocutaneous candidiasis, and may be demonstrated in families.

These mutations lead to excessive activation of the proinflammatory JAK-STAT pathway resulting in defective T helper cells (Th1 and Th17). Depending on the mutation, the mutation predisposes to infection, autoimmunity and carcinogenesis. Interestingly over activation of the same pathway is implicated in pathophysiology of scleroderma / systemic sclerosis (patient’s father’s phenotype).

These cases are unique and not previously described. We are managing two very different phenotypic presentations of the same genetic mutation
Summary: Gain-of-function mutations in the STAT1 gene (STAT1-GOF) are the most common genetic etiology for chronic mucocutaneous candidiasis, and may be demonstrated in families.

Ask the author questions about this poster:krupali.patel1@nhs.net
References: 1.Caproni M, Torchia D, Schincaglia E, et al. Expression of cytokines and
chemokine receptors in the cutaneous lesions of erythema multiforme and
Stevens-Johnson syndrome/toxic epidermal necrolysis. Br J Dermatol. 2006;155:
722-728. 7.
2. Higgins E, Al Shehri T, McAleer MA, et al. Use of ruxolitinib to successfully treat
chronic mucocutaneous candidiasis caused by gain-of-function signal transducer
and activator of transcription 1 (STAT1) mutation. J Allergy Clin Immunol.
2015;135: 551-553.
3. Damsky W, King BA. Idiopathic erythema multiforme: Evidence of underlying
Janus kinase–signal transducer and activator of transcription activation and
successful treatment with tofacitinib. JAAD case reports. 2016 Nov 1;2(6):502-4.
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