Mucous membrane pemphigoid of the larynx: A rare threat to vocal and airway integrity

Dear Editor,

A 28-year-old woman presented with a history of oral ulcers, blisters on skin, and redness of the left eye redness with visual impairment of two years duration, followed by a year of dysphonia and dyspnoea. Oral and topical steroids administered for a short duration offered only modest relief. Examination of the oral cavity revealed ulcers on the lateral and ventral aspect of the tongue, hard palate, soft palate, and buccal mucosa [Figure 1a]. Crusted erosions with scarring and post-inflammatory hyperpigmentation were noted on the lower back and buttocks [Figure 1b]. Ophthalmologist documented symblepharon in the upper and lower lids of the left eye, and conjunctivalisation of the cornea from 12 to 6 o'clock. [Figure 1c]. Video laryngoscopy revealed laryngeal erythema, a fibrotically curled epiglottis, ulcers on the left aryepiglottic fold, and true vocal cords, with subglottic stenosis [Figure 1d]. Her Voice Handicap Index (VHI) was 35, and the grade, roughness, breathiness, asthenia, and strain (GRBAS) score was 22111. Systemic examination and routine investigations were all within normal limits.

Close

Figure 1a:

Multiple ulcers on the hard palate and the lateral aspect of the tongue.

Export to PPT

Close

Figure 1b:

Discrete and confluent crusted erosions, scarring, and post-inflammatory hyperpigmentation on the lower back, buttocks, and intergluteal cleft.

Export to PPT

Close

Figure 1c:

Symblepharon affecting both upper and lower eyelids and conjunctival tissue covering the cornea from the 12 o'clock to the 6 o'clock position of the left eye.

Export to PPT

Close

Figure 1d:

A pre-treatment laryngoscopy showing diffuse laryngeal erythema and subglottic stenosis, featuring a curled-up epiglottis due to fibrosis (green arrow), an ulcer on the left aryepiglottic fold (black arrow), and another ulcer across the posterior two-thirds of the left true vocal cord (yellow arrow). (Non-polarised mode, 20×)

Export to PPT

Histopathology from a plaque on the buttock showed a subepidermal bulla with haemorrhagic exudate and infiltration by neutrophils and lymphocytes [Figure 2a]. Direct immunofluorescence displayed linear immunoglobulin (Ig)G (3+) and C1q(2+) deposition at the dermo-epidermal junction [Figure 2b]. Indirect immunofluorescence (IIF) on salt-split normal human skin as a substrate, using serum diluted at 1:10 and stained with IgG, demonstrated a linear band of IgG along the floor of the split. IIF performed on antigen-deficient skin substrates from dystrophic epidermolysis bullosa, lacking collagen VII, and junctional epidermolysis bullosa, lacking laminin 332, revealed negative reactions on collagen VII-deficient skin and a positive band on laminin 332-deficient skin [Figures 2c–e].

Close

Figure 2a:

Subepidermal bulla containing proteinaceous fluid and inflammatory cells (asterisk) and surrounding dermis with chronic inflammation. (Haematoxyin & eosin, 100x).

Export to PPT

Close

Figure 2b:

Direct immunofluorescence showing IgG antibody with a linear band along the dermo-epidermal junction (white arrows). (Fluorescein isothiocyanate, 200x).

Export to PPT

Close

Figure 2c:

Indirect immunofluorescence showing IgG staining to the floor of salt-spilt normal human skin. ( Fluorescein isothiocyanate (FITC)–labelled anti-human IgG antibody, 100x).

Export to PPT

Close

Figure 2d:

Modified indirect immunofluorescence showing negative IgG staining on collagen VII deficient skin (400x). ( Fluorescein isothiocyanate (FITC)–labelled anti-human IgG antibody).

Export to PPT

Close

Figure 2e:

Modified indirect immunofluorescence showing positive IgG staining on Laminin 332 deficient skin (400x). (Fluorescein isothiocyanate (FITC)–labelled anti-human IgG antibody).

Export to PPT

A diagnosis of mucous membrane pemphigoid (MMP) with laryngeal involvement and autoantibodies targeting type VII collagen was established.

In view of the aggressive disease phenotype and completion of childbearing, the patient was initiated on oral prednisolone at a dose of 1?mg/kg/day, oral cyclophosphamide (50?mg) daily, lubricants, and antibiotic eye drops. At the 3-month follow-up, oral and cutaneous ulcers had partially healed, conjunctival inflammation subsided, and laryngoscopy showed a healed aryepiglottic ulcer with a small residual ulcer in the left pyriform fossa [Figures 3a–d]. VHI and GRBAS scores improved significantly post-treatment, to 10 and 11110, respectively. A structured tapering protocol for corticosteroids is planned, with the aim of maintaining the patient on low-dose prednisolone and cyclophosphamide for one year to achieve durable remission while minimising long-term toxicity. Ocular reconstruction with symblepharon release and amniotic membrane grafting is planned for a later stage.

Close

Figure 3a:

Healing of oral ulcers on the tongue and palate after three months of immunosuppressive therapy.

Export to PPT

Close

Figure 3b:

Post-treatment healing of erosions with residual pigmentation on the buttocks.

Export to PPT

Close

Figure 3c:

Marked improvement in conjunctival inflammation in the left eye following therapy.

Export to PPT

Close

Figure 3d:

Post-treatment laryngoscopy after three months shows a curled epiglottis due to fibrosis (green arrow), resolution of the previous ulcer with healthy mucosa on the left aryepiglottic fold (black arrow), and a residual ulcer in the left pyriform fossa (yellow arrow). (Non-polarised mode, 20×).

Export to PPT

MMP is a rare autoimmune blistering disorder mainly affecting mucosal sites, oral cavity (85%), eyes (65%), nose/pharynx (20–40%), anogenital region (20%), oesophagus (5–15%), larynx (5–10%), with skin involvement seen in 25–30%. It shows linear IgG, IgA, and/or C3 deposition along the epithelial basement membrane, with autoantibodies against BP180 (75%), laminin 332 (10–20%), BP230 (10–30%), and type VII collagen (4%).^1–2 Table 1 summarises the literature on laryngeal MMP, associated antibodies, and their outcomes.

The 2021 S3 European guidelines now classify mucosal-dominant cases with type VII collagen autoantibodies as MMP, not epidermolysis bullosa acquisita (EBA). Collagen VII antibodies in MMP are detected by enzyme-linked immunosorbent assay (ELISA), immunoblotting, or IIF using NC1-expressing cells or collagen VII-deficient skin.²

Type VII collagen autoantibodies, although classically linked to epidermolysis bullosa acquisita (EBA), may also be present in mucosal-dominant MMP and in bullous systemic lupus erythematosus (BSLE). Their recognition with DIF/IIF and knock-out substrates is critical. EBA typically causes trauma-induced skin fragility, heals with scarring, and is treatment-refractory, whereas MMP presents with mucosal scarring but responds better to prolonged immunosuppression. In BSLE, the vesiculobullous lesions usually respond promptly when systemic lupus activity is controlled.^1–3

Laryngeal involvement in MMP occurs in only 5% to 15% of cases, and at the population level, it remains exceedingly rare, with an estimated prevalence of one in 10 million. It often leads to irreversible scarring, causing severe complications like airway obstruction, aphagia, and even death if not treated promptly.⁴ VHI (score range 0–120) was assessed using the validated 30-item questionnaire, which has 10 questions each on functional, physical, and emotional aspects, capturing the patient's perceived impact of voice problems. The GRBAS scale (scores 0–3) was applied by an experienced otolaryngologist using speech samples to reflect clinician-rated voice quality.⁵

Management is stratified by disease severity: low-risk cases (oral or cutaneous involvement) usually respond to topical corticosteroids, whereas high-risk disease (ocular, nasal, pharyngeal, oesophageal, anogenital or laryngeal sites) requires systemic corticosteroids and immunosuppressants, such as cyclophosphamide, azathioprine or mycophenolate mofetil. Refractory cases may benefit from rituximab or intravenous immunoglobulin.²

Although laryngeal involvement (5–10%) and type VII collagen autoantibodies (4%) occur in MMP, their co-occurrence in the present case appears distinctly uncommon. Dermatologists should be alert for symptoms such as hoarseness, sore throat, or breathing difficulty, which warrant urgent referral to an otolaryngologist. Early diagnosis and aggressive management of laryngeal MMP is critical to secure a safe airway, thereby minimising the need for surgical interventions.