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Novel combination therapy of hydroxychloroquine and topical tacrolimus for chronic ulcerative stomatitis

topical tacrolimus for chronic ulcerative stomatitis Dear Editor, Chronic ulcerative stomatitis (CUS) is a rare immune-mediated mucosal disorder characterized by symptomatic chronic oral ulcers not typically associated with cutaneous lesions. Because of similar clinical presentation to other conditions, such as oral lichen planus (OLP), diagnosis of CUS is challenging and often delayed. CUS is most commonly observed in middle-aged Caucasian females with mean age of onset and diagnosis at 57 and 62 years, respectively. Etiopathogenesis is associated with binding of the immunoglobulin IgG to DNp63a, a nuclear protein located in the basal and parabasal layers of the stratified squamous epithelium, which results in separation of keratinocytes from each other and from the basement membrane. Clinical manifestations of CUS include Wickham’s striae, erythema, and ulceration which commonly affect the buccal mucosa and tongue. Gingival involvement demonstrates epithelial sloughing usually referred to as desquamative gingivitis. Histopathologic features of CUS closely resemble those in OLP, which is characterized by a predominantly lymphocytic lichenoid infiltrate, often resulting in atrophy and ulceration of the squamous epithelium. Direct immunofluorescence (DIF) analysis demonstrates a speckled pattern of IgG deposition in keratinocyte nuclei limited to the lower layers of the oral squamous epithelium distinguishing CUS from OLP. Presence of stratified epithelium-specific antinuclear antibodies (SESANAs), which are bound to IgG, on DIF is the diagnostic hallmark of CUS. Management of CUS is aimed at promoting healing, symptom relief, mitigating risk of secondary infection, and improving quality of life. Unlike most immune-mediated mucosal conditions, CUS typically does not respond favorably to corticosteroid therapy, however, it usually responds to antimalarials, such as hydroxychloroquine (HCQ), which is another distinguishing feature of this disease. A 53-year-old female complained of chronic symptomatic gingival and oral mucosal lesions of 6 months’ duration. Past medical history was significant for celiac disease and cervical radiculopathy. Clinical examination revealed diffuse oral ulcerations, Wickham’s striae, and severe desquamation of the maxillary anterior gingiva (Fig. 1a). Biopsy of the right buccal mucosa for routine histology revealed hyperkeratotic, acanthotic, stratified squamous epithelium exhibiting degeneration of the basal cell layer with a dense band-like infiltrate of lymphocytes immediately subjacent to the epithelium (Fig. 2a). DIF of perilesional tissue revealed intranuclear IgG deposition in the basal and parabasal nuclei without specific or significant staining seen with antibodies to IgA, IgM, C3, or fibrinogen (Fig. 2b). These cumulative findings were consistent with CUS. Prior to initiating therapy with HCQ, a baseline complete blood count