Characterization of mucous membrane pemphigoid in childhood: A multicentre study of 12 cases

Abstract

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease (AIBD) of the dermal–epidermal junction with predominant mucosal involvement and a tendency to scarring. MMP is rarely described and poorly understood in children.^{1, 2} Our study aimed to analyse clinical, histological and immunological features of the disease and its management.

A descriptive, retrospective, multicentre study was conducted. Children under 18 with a clinical diagnosis of MMP confirmed by histology, with or without immunological confirmation, were included. Other AIBDs were excluded.

Twelve patients were included; 11 were girls (Table 1). The median age of onset was 7 years and 8 months [4.5–14 years]. The time between diagnosis and histological or immunological confirmation was 4 months [0–12 months] and 6 months [0–31 months], respectively.

Mucosal involvement was predominantly genital (n = 7/12): erosive vulvitis (n = 5/7), clitoral blisters (n = 1/7), balanitis (n = 1/7). Other mucosal involvements included oral (erosive gingivitis n = 5/12, ENT blisters n = 1/12), nasal (crusting n = 2/12), ophthalmic (cicatrizing conjunctivitis n = 1/12) and pulmonary (bronchial stenosis n = 1/12) changes (Figure 1). Three children had multiple mucosal involvements. Three had skin bullae. Five had scarring involving genital and pulmonary localization.

This clinical suspicion was supported by a skin biopsy for histopathology, which revealed a subepidermal blister with mixed inflammatory cell infiltrates in the dermis in all patients (Table 1). The diagnosis was confirmed by positive direct immunofluorescence (10/12) and supported by ELISA (1/1) and immunoblotting (1/1) (Table 1). Two patients had negative DIF results. In one of these (Case 1), the diagnosis was supported by indirect immunofluorescence; in other (Case 3), immunological tests were all negative but clinicopathological correlation allowed us to retain the diagnosis of ‘most likely MMP’.

Regarding treatment, topical steroids (very potent) were used in 7 patients; they were effective as monotherapy in one patient with localized vulval involvement. Systemic treatment included dapsone (n = 8), doxycycline (n = 5), oral steroids (n = 3), rituximab (n = 2), intravenous immunoglobulin therapy (n = 1), omalizumab (n = 1), sulfasalazine (n = 1) and erythromycin (n = 1). After a median follow-up of 4 years, the patients had received an average of 4 treatments^1-6; remission was partial in 7 cases and complete in 5.

MMP is rare in childhood. The paediatric form affects children between ages 5 and 10,¹ predominantly females,³ as seen in our series. Diagnosis is difficult and often requires repeated skin biopsies.⁴ In one of our cases, the DIF had to be performed three times before being positive. Serum immunological confirmation is not always present, as in one of our patients, but this should not rule out the diagnosis or delay treatment. Genital involvement appears to be the most frequent in children, with a clinical presentation very similar to vulvar lichen sclerosis; in adults, oral localization is most frequent. Ophthalmological involvement is rarer than in adults.^{5, 6} Scarring is not always present, but early diagnosis and systematic screening of all mucous membranes is necessary to prevent scarring.¹

In mild/moderate cases, first-line treatment with dapsone or doxycycline was effective in improving or curing nine of our patients. Topical steroid treatment alone is rarely sufficient.^{7, 8} For more severe cases, rituximab must be considered on a case-by-case basis.⁹ We report the first case of paediatric bronchial involvement, which was particularly severe and resistant to treatment. This patient, who developed septicaemia, illustrates the iatrogenic effects of escalating therapy. Maintenance treatment is sometimes necessary as in six patients of this series, and regular monitoring is necessary to detect relapse as in three patients.

Our study provides a better characterization of this rare and clinically polymorphous disease, which is still misdiagnosed too frequently and whose treatment is unfortunately delayed, but which is potentially serious in children.

None.

None declared.

Reviewed and approved by the Assistance Publique - Hôpitaux (AP-HP) de Marseille and registered with PADS 24-T02 WMARVJ.

The parents/guardians of the patients cited in this manuscript have given their written informed consent to the publication of the relevant case details.

The data that support the findings of this study are available from the corresponding author upon reasonable request.