Stressful Life Events as a Trigger for Autoimmune Disease? A Case Report on Mucous Membrane Pemphigoid

Presenting complaint

A 64-year-old male presented to the dental emergency department at the University Hospital, Wales, complaining of painful, ‘peeling’ and bleeding gums. He found that brushing his teeth made the gums develop blood-filled blisters, prior to bursting and leaving a painful ulcerated area that did not heal. The patient reported one single episode of a blister on the skin of his nose that had since healed, and reported no other cutaneous, genital or ocular symptoms.

History of presenting complaint

The patient had undergone heart surgery with the placement of cardiac stents 5 weeks earlier and noted the presence of blisters on his gums 7 days after the surgery. Initially, his cardiologist believed this to be an adverse reaction to the recently prescribed clopidogrel, which was immediately substituted for ticagrelor as an alternative antiplatelet therapy. Despite this, the painful bleeding gingivae had not alleviated and had, in fact, worsened. The patient then presented to his general medical practitioner who prescribed 0.2% chlorhexidine mouthwash, along with high-concentration sodium fluoride toothpaste, and advised attendance with his dentist.

Medical history,

The patient's medical history including medications, is shown in Table 1. Ticagrelor had been started 3 weeks previously; however, all other medications were long-standing (several years).

Clinical presentation

On examination, there was evidence of florid desquamative gingivitis: a marked erythematous appearance of the free and attached gingivae up to the mucogingival margin. Recently burst bullae resulting in extensive erosions were also present on the gingivae (Figure 1). Further examination showed that the other oral mucosal tissues were spared, and there was only mild erythema on the skin of the nose, where a previous blister was reported.

At this stage, MMP and pemphigus vulgaris (PV) were considered as the most likely diagnoses, with other blistering conditions such as linear IgA disease and erythema multiforme, or adverse drug reactions being considered as differential diagnoses.

Investigations

Following the clinical examination, serum was obtained for detection of circulating autoantibodies by indirect immunofluorescence (IIF) and assay of serum antibody titres by enzyme-linked immunosorbent assay (ELISA), and an oral mucosal biopsy was taken for direct immunofluorescence (DIF). Owing to the high clinical suspicion of a bullous disease, DIF was favoured over routine histopathology for gaining a definitive diagnosis, and therefore, a second biopsy specimen for routine histopathology was not obtained. The IIF results from the local immunology laboratory showed a weak positive result for pemphigus vulgaris; however, IIF and ELISA from a specialist immunodermatology laboratory were negative. DIF from the immunodermatology laboratory showed linear deposition of IgG (++), IgA (+), C3 (++) and fibrinogen (+) at the basement membrane zone, consistent with a definitive diagnosis of MMP.

Management and response

The patient was initially prescribed topical corticosteroids in the form of 500-μg betamethasone soluble tablets (made into a mouthwash, to be rinsed around for 2 minutes, up to four times daily) and 0.05% clobetasol cream (to be applied as a light smear to areas of sore oral mucosa, twice daily). This did not provide sufficient improvement in symptoms, and therefore systemic prednisolone was started at 40 mg/day with a tapering regimen, while awaiting biopsy results. Immediately following confirmation of the diagnosis from direct immunofluorescence, a second course of systemic prednisolone was started as symptom control was still poor, and mycophenolate mofetil (MMF) was introduced as a steroid-sparing immunosuppressant for long-term management. After 4 weeks of a therapeutic dose of MMF, there was resolution of the desquamative gingivitis and erosions. In the final week of the second course of systemic prednisolone (week 6), the patient developed bruising on his right forearm (Figure 2), suspected to be a side effect of prednisolone, particularly as he was also taking aspirin. Symptoms remained controlled after finishing the course of systemic prednisolone and continuing MMF.

The role of the general dental practitioner in MMP

The role of the general dental practitioner (GDP) should not be understated. Recognizing the oral manifestations, which may indicate bullous disease, and timely referral to oral medicine or oral and maxillofacial surgery, will have a significant effect on patient quality of life. Furthermore, undiagnosed or poorly controlled MMP can drastically reduce the ability of the patient to maintain good oral hygiene due to pain, and this may contribute to the onset or progression of periodontal disease. Therefore, the GDP also has a significant role in the long-term maintenance of oral health in MMP patients; these patients should receive relevant and personalized oral hygiene instruction and periodontal treatment where required (often under LA due to gingival soreness), recognizing that plaque accumulation will exacerbate gingival inflammation, in addition to that already caused by the bullous disease. For maximum symptom control, oral hygiene must, therefore, be excellent.

Both oral hygiene and disease control should be satisfactory before consideration is given to restoring edentulous spaces, and mucosa-borne prosthesis may be less favourable as they can traumatize the already fragile mucosa.

Medications to treat MMP can impact the oral cavity. Topical steroid use may cause oral candidosis, while immunosuppression can reduce healing and those on systemic steroids may require steroid cover for surgical procedures.