C A S E R E P O R T
Oral mucous membrane pemphigoid in a 6-year-old boy:
diagnosis, treatment and 4 years follow-up
MOSTAFA I. MOSTAFA1, NEHAL F. HASSIB1& AMANY H. NEMAT2
1Human Genetics and Genome Research Division, Department of Oro-dental Genetics, and2Medical Division, Oro-dental Research Department, National Research Center, Cairo, Egypt
International Journal of Paediatric Dentistry 2010; 20: 76–79 Background. Childhood oral pemphigoid is extre- mely rare and usually takes the form of desqua- mative gingivitis.
Case report. We describe a 6-year-old boy who presented with gingival bleeding, pain, eating difficulty, and peeling of the gums. Clinical examination revealed desquamative gingivitis with no extra-oral involvement. The diagnosis was established as oral pemphigoid based on
the clinical, histological, and immunofluores- cence findings. Symptoms resolved on treat- ment with occlusive topical corticosteroids. The patient was a carrier of the HLA-DQB1*0301 allele.
Conclusion. Mucous membrane pemphigoid should be considered in the differential diagnosis of chronic desquamative gingivitis in childhood.
Occlusive therapy with topical fluocinonide may alleviate the symptoms.
Introduction
Mucous membrane pemphigoid (MMP) is a chronic immune-mediated subepithelial vesi- culobullous disease of adults. Children are rarely affected. The term oral pemphigoid (OP) is used when lesions are confined to the mouth. Oral lesions usually take the form of desquamative gingivitis1–3. There is an associ- ation between MMP and HLA-DQB1*03014,5.
Case report
A 6-year-old boy with gingival bleeding, pain, eating difficulty, and peeling of the gums was referred to the Oro-Dental Genetics Depart- ment, National Research Center in Cairo. His parents had first noted redness of the gums at the age of 3 with the symptoms that led to the referral developing at the age of 5. Seven months prior to referral to our department, a diagnosis of chronic periodontitis was made but he did not respond to the treatment.
Clinical examination revealed generalized redness of the gingiva in both upper and lower jaws (Fig. 1a,b). Application of gentle lateral pressure on the gingiva using a piece of cotton caused peeling of the gums, indicat- ing a positive Nikolsky’s sign. Desquamative gingivitis was suspected. Histological findings showed separation of the epithelium from the underlying connective tissue (Fig. 1c).
Direct immunofluorescence showed linear deposition of IgG and C3 at the mucosal–sub- mucosal junction (Fig. 1d). No extra-oral abnormalities were detected. The diagnosis was established as OP based on the clinical, histological, and immunofluoroscence find- ings. The patient had the genotype HLA- DQB1*0501⁄ 0301, 0309, 0313.
Occlusive topical steroid therapy (5 mg betamethasone cream b.d.) was commenced.
Upper and lower vacuum-formed trays with spacers at the gingival portion were con- structed to retain the cream. An artificial space was designed in the trays to allow the eruption of the permanent incisors (Fig. 1e).
A 0.2% chlorhexidine mouth wash was pre- scribed twice daily 1 week of the 4 weeks to avoid candidosis and calculus formation, which may aggravate the condition. The
Correspondence to:
M. I. Mostafa, Human Genetics and Genome Research Division, Department of Oro-dental Genetics, National Research Center, 33, Dokki St, Cairo, Egypt.
E-mail: mostafanrc@yahoo.com
ª 2009 The Authors
76 Journal compilationª 2009 BSPD, IAPD and Blackwell Publishing Ltd
DOI: 10.1111/j.1365-263X.2009.01002.x
parents were instructed to avoid giving the child highly acidic foods and hard foods. Scal- ing and oral hygiene measures were per- formed. After 2 weeks a small improvement was noted. The treatment was modified, continuing betamethasone for the lower jaw but changing to 0.05% fluocinonide ointment for the upper one jaw. Five weeks later, the patient complained of bleeding, pain, and
peeling of the gums of the lower jaw only and clinical examination confirmed that there was a greater improvement in the upper gin- gival mucosa (Fig. 2a). Fluocinonide was con- tinued for upper and lower jaws for another 5 weeks. After that period (12 weeks), the signs and symptoms had resolved except for the redness of the gingiva (Fig. 2b). The patient was reviewed monthly and signs and
(a) (b)
(c) (d) (e)
Fig. 1. (a) Desquamation of palatal gingival margin related to left primary first molar and right permanent central incisor.
(b) Gingival redness with desquamated bloody areas in both upper and lower jaws. (c) Histological (H&E) findings show separation of the epithelium from the underlying connective tissue with lymphocytic infiltrate (original magnification·40).
(d) Direct immunofluorescence shows linear deposition of IgG at the mucosal–submucosal junction. (e) Vacuum-formed trays with artificial space.
(a) (b)
(c) (d)
Fig. 2. (a) Seven weeks after starting treatment: the upper gingival mucosa has improved, and bleeding and desquamation present in the lower gingival mucosa. (b) Twelve weeks after starting treatment: signs have disappeared except for the gingival redness. (c) Recurrence of signs about 30 months from starting treatment. (d) Appearance at most recent follow-up, off treatment: gingival mucosa appears normal.
Childhood oral pemphigoid: management of a case 77
ª 2009 The Authors
Journal compilationª 2009 BSPD, IAPD and Blackwell Publishing Ltd
symptoms recurred after 6 months. Again they responded to 2 weeks topical treatment with fluocinonide. During the 4 years of follo- w-up (Fig. 2c,d), signs and symptoms recurred at approximately six monthly intervals, although there was a remission for 1 year gap before the last recurrence. Patient was also reviewed every 6 months for extra-oral examination particularly ophthalmological.
Comment
Mucous membrane pemphigoid rarely affects children. Only seven previous cases of child- hood OP (oral lesions only) have been reported in the international English literature2,3,6–10. This case is thought to be the eighth.
Desquamative gingivitis is a non-specific clinical manifestation of several diseases, the most common being MMP, lichen planus, and pemphigus vulgaris successively. DIF shows intercellular epithelial antibodies in pemphigus vulgaris whereas lichen planus shows fibrin staining of the basement mem- brane11.
Several studies indicated that HLA- DQB1*0301 alleles confer a predisposition to all subgroups of MMP in Caucasian patients.
It may have a role in T cell recognition of basement membrane antigens and the subse- quent B cell production of anti-basement membrane zone autoantibodies. It has been suggested that OP and ocular pemphigoid are part of a spectrum of a single disorder and that they have the same genetic predisposi- tion4,5, thus it is interesting to note that the patient we describe has this allele.
Use of vacuum-formed trays in children has not previously been reported. We designed an artificial space in the tray to allow eruption of the permanent incisors. We found that open- ing windows around the erupting teeth ren- dered the tray non-retentive.
There is no absolute effective agent for the treatment of OP but corticosteroids are the drugs of choice. Topical corticosteroids are the treatment of choice for MMP, espe- cially for localized oral lesions, although immunosuppressants and dapsone have also been used. In this case, we found fluocino- nide to be more effective than betametha-
sone. Yet, similar reported cases are very few and the true benefits of such drugs are there- fore not yet clear3,12,13.
Intervals between relapses may lengthen as the child becomes older and more attentive to oral hygiene and aware of the stimulating factors. At the same time, shedding and erup- tion mechanisms could be among the predis- posing factors.
In conclusion, MMP should be considered in the differential diagnosis of chronic desquamative gingivitis in childhood. Occlu- sive therapy with topical fluocinonide until symptoms resolve is recommended, with repeated courses if symptoms recur. This approach has fewer side effects than systemic corticosteroids or dapsone, particularly in childhood. We also recommend periodic oph- thalmologic examination in affected patients.
What this paper adds
d Recording a very rare case of childhood OP.
d Using occlusive topical steroid therapy in the treat- ment of childhood OP.
Why this paper is important to paediatric dentists
d Oral pemphigoid that is common in old age can also affect children and must be considered in the differen- tial diagnosis of chronic desquamative gingivitis in childhood.
d Adding a new clinical experience for OP cases, as these cases are extremely rare.
Acknowledgements and conflict of interest This work was carried out under the annual research fund for the National Research Cen- ter. The authors thank Dr Maha R. Abou-zeid and Dr Mennat I. Mehrez, the National Research Center, Cairo, Egypt, for their help in manuscript preparation and Professor Dr Judith Goodship, Professor of Medical Genet- ics, Newcastle University, England, for scien- tific editing of the manuscript. All authors have declared no conflict of interest.
References
1 Scully C, Carrazzo M, Gandolfo S, Puiatti P, Monteil R. Update on mucous membrane pemphigoid. A heterogeneous immune-mediated subepithelial 78 M. I. Mostafa et al.
ª 2009 The Authors Journal compilationª 2009 BSPD, IAPD and Blackwell Publishing Ltd
blistering entity. Oral Surg Oral Pathol Oral Med Oral Radiol Endod 1999; 88: 56–68.
2 Musa NJ, Kumar V, Humphreys L, Aguirre A, Neiders ME. Oral pemphigoid masquerading as necrotizing ulcerative gingivitis in a child.
J Periodontol 2002; 73: 657–663.
3 Laskaris G, Triantafyllou A, Economopoulou P.
Gingival manifestations of childhood cicatricial pemphigoid. Oral Surg 1988; 66: 349–352.
4 Yunis JJ, Mobini N, Yunis EJ et al. Common major histocompatibility complex class II markers in clinical variants of cicatricial pemphigoid. Proc Natl Acad Sci U S A 1994; 91: 7747–7751.
5 Carrozzo M, Fasano ME, Broccoletti R et al. HLA- DQB1 alleles in Italian patients with mucous membrane pemphigoid predominantly affecting the oral cavity. Br J Dermatol 2001; 145: 805–808.
6 Worsaae N, Dabelsteen E. Benign mucous membrane pemphigoid in an 18-year-old woman.
Arch Dermatol 1978; 114: 1093–1094.
7 Sklavounou A, Laskaris G. Childhood cicatricial pemphigoid with exclusive gingival involvement.
J Oral Maxillofac Surg 1990; 19: 179–199.
8 Roche C, Field EA. Benign mucous membrane pemphigoid presenting as desquamative gingivitis in a 18-year-old child. Int J Paediatr Dent 1997; 7: 31–34.
9 Cheng YS, Rees TD, Wright JM, Plemons JM.
Childhood oral pemphigoid: a case report and review of the literature. J Oral Pathol Med 2001; 30:
372–377.
10 Lourenco SV, Boggio P, Agner Machado Martins LE, Santi CG, Aoki V, Menta Simonsen Nico M.
Childhood oral mucous membrane pemphigoid presenting as desquamative gingivitis in a 4-year-old girl. Acta Derm Venereol 2006; 86: 351–354.
11 Sklavounou A, Laskaris G. Frequency of desquamative gingivitis in skin diseases. Oral Surg 1983; 56: 141–144.
12 Lozada F, Silverman S. Topically applied fluocinonide in an adhesive base in the treatment of oral vesiculoerosive diseases. Arch Dermatol 1980;
116: 898–901.
13 Sacher C, Hunzelmann N. Cicatricial pemphigoid (mucous membrane pemphigoid): current and emerging therapeutic approaches. Am J Clin Dermatol 2005; 6: 93–103.
Childhood oral pemphigoid: management of a case 79
ª 2009 The Authors
Journal compilationª 2009 BSPD, IAPD and Blackwell Publishing Ltd
