Oral Mucous Membrane Pemphigoid Without Skin Involvement Treated

Central Journal of Dermatology and Clinical Research

Case Report *Corresponding author Manas Bajpai, Associate Professor, Departmentt of Oral and Maxillofacial Pathology, NIMS Dental Oral Mucous Membrane College, Jaipur, India, Email: Pemphigoid without Skin Submitted: 08 June 2017 Accepted: 22 June 2017 Published: 23 June 2017 Involvement Treated by Intra- Copyright © 2017 Bajpai et al. Venous Immunoglobulins: A Case OPEN ACCESS

Keywords Report with the Correlation of • Mucous membrane pemphigoid • Oral mucosa • Immunoflurescence Clinical, Histopathological and • Intra – venous immunoglobulins Direct Immunoflurescence Findings and a Literature Review of the Treatment Modalities Manas Bajpai*and Nilesh Pardhe Department of Oral and Maxillofacial Pathology, NIMS Dental College, India

Abstract Mucous membrane pemphigoid (MMP) is an autoimmune blistering disorder of mucosa, characterized by subepithellial bullae. The involvement of skin is only seen in one quarter of the patients with MMP. We report a case of 37 years old male presented with painful erosions involving gingiva, tongue and palatal mucosa without any skin involvement. Hisopathological features and direct immunofluroscene l to the final diagnosis of MMP.

INTRODUCTION since 6 months for which no response was found. The lesions of palate, tongue and lip were extremely painful due to which he group of autoimmune heterogeneous disorder characterized Mucous membrane pemphigoid (MMP) can be defined as a contributory to the presenting symptom. Intra oral examination by subepithelial blistering disease primarily affecting mucous revealedexperienced erosions difficulty of labial in eating. mucosa His (Figure family 1) historyand palate was (Figure non – membrane with or without involvement of skin [1,2]. Various 2). Localized desquamative marginal gingivitis was noted with relation to teeth #12, #21, #22 and #33 (Figure 3). Marginal targets of autoantibodies in MMP [3]. Intra–orally MMP shows gingiva showed a tendency to bleed and peel off on pressure. variedcomponents manifestation of basement i.e. painful membrane erosion, have desqumative been identified gingivitis, as erythematous patches etc [2,4]. We present a case of oral MMP Dorsal surface of the tongue showed bullae covered by a without skin and other mucous membrane involvement; we also pseudomembrane with reddish and yellowish in color (Figure 4). No ocular and genital lesions were found. Tzank test was the case. performed which was found to be negative. On clinical grounds a describe the histopathological and immunoflurosence findings of provisional diagnosis of mucous membrane pemphigoid with the CASE PRESENTATION differential diagnosis of pemphigus vulgaris was made. An otherwise healthy 37 year old Indian male presented to a An incisional biopsy was taken from the surrounding mucos private dental clinic with the chief complaint of painful erosions of the bulla of the dorsum of the tongue under local anesthesia of lip, gingiva and palate from 8 months. He had been treated and the tissue was submitted to the Department of Oral and by oral prednisolone (0.5mg/kg/day) from a general physician Maxillofacial Pathology NIMS Dental College Jaipur (India). The

Cite this article: Bajpai M, Pardhe N (2017) Oral Mucous Membrane Pemphigoid without Skin Involvement Treated by Intra-Venous Immunoglobulins: A Case Report with the Correlation of Clinical, Histopathological and Direct Immunoflurescence Findings and a Literature Review of the Treatment Modalities. J Dermatolog Clin Res 5(4): 1106. Bajpai et al. (2017) Email: Central

was found after the completion of third cycle. The therapy was further continued till six months. The follow up period of 1 year was found to be uneventful. DISCUSSION MMPs are autoimmunaneoe, vesicobullous disease that affects mucosa or mucosa and skin both [1]. There are several variants of MMP, each with distinctive clinical features, pattern of immunopathology and They are oral pemphigoid, anti epiligrin pemphigoid, anti antigenic specificity of autoantibodies.

Figure 1 Erosive lesion of labial mucosa.

Figure 4 Bullae present on the dorsum of the tongue.

Figure 2 Erythematous patch on palate.

Figure 5 Histopathological examination shows sub basilar split between epithelium and connective tissue stroma (Hematoxylin and Eosin stain X20).

Figure 3 Localized desquamative marginal gingivitis. histopathological examination of hematoxylin and eosin stained subepithelial separation with the underlying connective tissue stromasoft tissue (Figure section 5). revealed The connective a stratified tissue squamous stroma epithelium was densely with infiltrated with chronic inflammatory cells chiefly lymphocytes ofand epithelium plasma cells and basement (Figure 6). membrane Direct immunuflurosence (Figure 7). Based on (DIF) these of peribullous mucosa revealed a linear band of IgA, IgG at the zone Figure 6 features a final diagnosis of MMP was rendered. Intravenous repeated every three months. Complete remission of the lesions Connective tissue stroma shows dense infiltration of chronic immunoglobulin (IVIG) (2gm/Kg/cycle) started which was inflammatory cells (Hematoxylin and Eosin stain X40). J Dermatolog Clin Res 5(4): 1106 (2017) 2/5 Bajpai et al. (2017) Email: Central

as a clinical differential diagnosis of blistering diseases (Table 1). Histopathologically it shows subepithelial blisters without

acantholysis and connective tissues shows a dense infiltration of junctioninflammatory between cells the [3-5]. connective Direct immunofluorescenttissue and epithelium techniques [1]. The show homogeneous IgG and C3 complement deposits along the

bypresent subepithelial case revealed blisters a withlinear the band production of IgG and of autoantibodies IgG on DIF at targetedepithelium to – certain basement components membrane of zone. the MMP basal is lamina characterized of the

[11].epithelium The diagnosis immunoglobulin of MMP Gis based(IgG) (97%), upon the C3 correlation complement of factor (78%) and, to a lesser degree, IgA (27%) and IgM (12%) Figure 7 clinical, histopathological and DIF findings. DIF is a useful adjunct Direct immunoflurescence shows a linear band of IgG, IgA and C3 at the zone of epithelium and basement membrane. (Original helpsfor the to definitive rule out thediagnosis differential of bullous diagnoses diseases, which especially differ in when their magnification X40). the clinical and histopathological findings are not conclusive.DIF BP antigen mucosal pemphigoid, ocular pemphigoid & multiple the response of the treatment [3]. treatment protocol. DIF may also be used in order to determine case reports of MMP in English language revealed that MMP is The treatment of MMP depends upon the severity of antigens. An exhaustive literature review of the published disease ranging from topical steroids to systemic steroids hand, it is up to 3 times more common than pemphigus, which itselfapproximately has an annual 7 times incidence less common of 0.5 tothan 3.2 BP per [4]. 100000 On the people other modulators comprised of polyclonal antibodies derived and ant metabolites [12]. (Table 2) IVIgs are biologic immune [1,2]. There are no known racial or geographic predilections. from a large pool of healthy plasma donors [20]. They are Most patients ranged from 23 to 75 years age; maximum being 50 approved treatment modality for several diseases including immune thrombocytopenic purpura, primary and secondary to 60 years old. The female/male ratio was found to be 1.8:1[3]. by soft and hard palate, presenting as thick walled bullae immunodeficiency, pediatric HIV, Systemic lupus eryhematosus Intra – orally, it most commonly involves gingiva followed persisting for 1 to 2 days before rupturing, leaving raw, eroded clearly(SLE), understood, Kawasaki although disease, several multiple theories sclerosis, have been pemphigus, proposed erythematous or bleeding surface [2,3,5]. The present case pemphigoid etc [20-23]. The mechanism of action of IVIg is not showed the involvement of gingiva, labial mucosa and hard palate. Skin lesions are seen in only 25% of the patients. unresponsive(Figure 8). For toautoimmune the conventional diseases therapy IVIg is not and considered patients withas a Erythema multiforme, pemphigus vulgaris, bullous pemphigoid. first line treatment and it is reserved for the patients who are bullous lichen planus and lichenoid reaction can be considered are the well accepted mode of treatment for the patients with rapidly progressive disease [22]. Immuno suppressive drugs

Figure 8

Mode of action of IVIg. J Dermatolog Clin Res 5(4): 1106 (2017) 3/5 Bajpai et al. (2017) Email: Central

Table 1:

S. No Differential diagnosesDifferential of MMP diagnosis with differentiating features [6-10]. Differentiating features EM is generally associated with reaction infections of herpes simplex and mycoplasma 1 Erythema multiforme (EM) easily differentiated from EM. and/or drug reactions while MMP is autoimmune disease. Histopathologically MMP can be

2 Histopathologically PV shows suprabasilar splitting and MMP shows sub basilar splitting between basement membrane zone and underlying connective tissue stroma. In Pemphigus vulgaris (PV) epitheliumpemphigus, and direct basement immunofluorescence membrane zone. shows deposition of IgG and C3 in lower layer of BPepithelium, seldom affects in MMP mucosa direct unlikeimmunofluorescence MMP. Histopathologically exhibits a linear BP exhibits band of relatively IgG, IgA andnormal C3 at 3 Bullous pemphigoid (BP) epithelium without acantholysis and the basement membrane remains attached to the underlying connective tissue.

Bullous lichen planus (BLP) shows classical features of lichen planus including degeneration of basal cell layer, saw toothedClinically rete BLP ridges is usually and subbilaterally epithelial symmetrical band of lymphocytes. unlike MMP. Histopathologically OBLP 4 LR is a drug reaction so the cause effect relationship can be made. Histopathological 5 Lichenoid reaction (LR) features of LR resemble LP.

Table 2:

SeverityTreatment of modalities the disease for mild and severe forms of MMP [14-19] Treatment modalities For mild disease without rapid progression, dapsone can be given at 25 to 50 mg per day, increasing Mild disease monthly by 25 to 50 mg until clinical remission is achieved. Systemic therapy Corticosteroids day. are the choice of initial medication. Prednisone is usually prescribed with 1 -1.25 mg/kg/ Cyclophosphamides are traditional steroid sparing agents can be prescribed in severe disease with 2 when given monthly intravenous. conjunction of systemic steroids. Dosage ranges between 50 – 200 mg/day orally and 0.5 – 1g/m Methotrexate

Severe disease Intravenous immunoglobulinsare antimetabolites can be given in severe MMP with the dosage range of 5 -25 mg/week. despite treatment. For patients that fail therapy with systemic steroids and cyclophosphamide, or Indicated for patients present with progressive, recalcitrant disease therapeutic alternative. for those with rapidly progressive disease, high-dose intravenous immunoglobulin (IVIG) provides a Mycophenolate mofetil blocks de novo purine synthesis resulting in inhibition of the response of T cell

andTopical B cell. therapy Dosage ranges between 1000 – 2000 mg/day. Topical steroid (Tacrolimus and cyclosporines) can be given with the conjunction of systemic therapy and to patients with relatively milder disease. autoimmune diseases, but this type of therapy is associated with a an ideal mode of treatment for the patients who are unresponsive tocommonly the conventional used in limitedtherapy diseases. and at a riskIVIgs of are infections. although new but ansignificant ideal means risk of of developing treatment infections for the patients owing to who the aresuppression at a risk of immune system. IVIGs are immune modulators and could be REFERENCES successfully, considering the fact that patient had been treated 1. withof viral predniselone infections [24]. from The last present six months case was without treated any with positive IVIgs DA Culton, LA Diaz. “Treatment of subepidermal immunobullous results. 2. diseases”. Clinics in Dermatology. 2012; 30: 95-102. Neville WB, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial and histopathological grounds with other diseases makes its 3. Pathology. 3rd ed. Elsevier; 2009. 771-774. diagnosisIt can be challenging concluded moreoverthat the resemblance the means of of MMP investigations on clinical Rajendran R, Sivapathasundharam B. Shafer’s Textbook of Oral in order to differentiate MMP with other lesions are costly, Pathology; Elsevier: 6th ed; 2009. 822. technique sensitive and not routinely performed. The diagnosis intravenous therapy to conventional immunosuppressive therapy of MMP needs a thorough evaluation clinical, histopathological 4. inDaoud treating YJ, Amin patients KG. with Comparison autoimmune of cost mucocutaneous of immune blistering globulin

5. diseases. Int Immunopharmacol. 2006; 6: 600-606. steroids;and immunofluroscence hence the mode findings. of treatment The treatment we adopted of MMP is not is often very difficult. In present case also patient did not respond to systemic Eisen D, Ellis CN, Voorhees JJ. Topical cyclosporine for oral bullous disorders. J Am Acad Dermatol. 1990; 23: 936-937. J Dermatolog Clin Res 5(4): 1106 (2017) 4/5 Bajpai et al. (2017) Email: Central

6. 16. Successful treatment of mucous membrane pemphigoid with Scully C, Lo Muzio L. Oral mucosal diseases: mucous membrane Canizares MJ, Smith DI, Conners MS, Maverick KJ, Heffernan MP. 7. pemphigoid. Br J Oral Maxillofac Surg. 2008; 46: 358-366. 17. etanercept in 3 patients. Arch Dermatol. 2006; 142: 1457-1461. Bajpai M, Agarwal D, Bhalla A, Vatchala Rani RM, Kumar M. Unilateral lichen planus: a rare case report. J Nat Sci Biol Med. 2014; 5: 453-455. Elder MJ, Lightman S, Dart JK. Role of cyclophosphamide and high dose steroid in ocular cicatricial pemphigoid. Br J Ophthalmol. 1995; 8. Regezi JA, Sciubba JJ, Jordan RCK, Kazmierowski JA, Krik D, Sapp JP, Maxillofacial Pathology. 79: 264-266. et al. 2nd ed. St. Louis (MI): Mosby; 2004. Contemporary Oral and 18. Kirtschig G, Murrell D, Wojnarowska F, Khumalo N. Interventions for mucous membrane pemphigoid/cicatricial pemphigoid and 9. Kazmierowski JA, Wuepper KD. Erythema Multiforme: epidermolysis bullosa acquisita: a systematic literature review. Arch Clinical Spectrum and Immunopathogenesis. Springer Semin: 10. Dermatol. 2002; 138: 380-384. Immunopathology. 1981; 4: 45-53. clobetasol propionate ointment in adhesive paste for treatment of 19. Lozada-Nur F, Huang MZ, Zhou GA. Open preliminary clinical trial of Bajpai M. Lichenoid reaction - A diagnostic dilemma. Int J Clin Prev 11. Dent 2013; 9: 15-17. chronic oral vesiculoerosive diseases. Oral Surg Oral Med Oral Pathol. Ata-Ali F, Ata-Ali J. Pemphigus vulgaris and mucous membrane 20. 1991; 71: 283-287. pemphigoid: update on etiopathogenesis, oral manifestations and Lourenço SV, Boggio P, Agner Machado Martins LE, Santi CG, Aoki 12. management. J Clin Exp Dent. 2011; 3: e246-250. V, Menta Simonsen Nico M. Childhood oral mucous membrane Bajpai M, Pardhe N, chandolia B. Oral pemphigus vulgaris in a pediatric pemphigoid presenting as desquamative gingivitis in a 4-year-old 13. patient. J Ayub Med Coll Abbottabad. 2016; 28: 636. 21. girl. Acta Derm Venereol. 2006; 86: 351-354.

involvementLetko E, Miserocchi in patients E, Daoud with YJ, Christen mucous W, membrane Foster CS, (cicatricial)Ahmed AR. Foster CS, Ahmed AR. Intravenous immunoglobulin therapy for ocular pemphigoidA nonrandomized between comparison conventional of the clinical immunosuppressive outcome of ocular and cicatricial pemphigoid: A preliminary study. Ophthalmology. 1999; 22. 106: 2136-2143. Urcelay ML, McQueen A, Douglas WS. Cicatricial pemphigoid treated intravenous immunoglobulin therapies. Clin Immunol. 2004; 111: 23. with intravenous immunoglobulin.í Br J Dermatol. 1997; 137: 477-478. 303-311. R, et al. Role of amniotic membrane transplantation for conjunctival Galdos M, Etxebarr a J. Intravenous immunoglobulin therapy for 14. Barabino S, Rolando M, Bentivoglio G, Mingari C, Zanardi S, Bellomo refractory ocular cicatricial pemphigoid: Case report. Cornea. 2008; 27: 967-969. ø reconstruction in ocular-cicatricial pemphigoid. Ophthalmology. 2003; 15. 110: 474-480. 24. Hommes OR, S rensen PS, Fazekas F, Enriquez MM, Koelmel HW, Fernandez O, et al. Intravenous immunoglobulin in secondary Brody HJ, Pirozzi DJ. Benign mucous membrane pemphigoid. Response progressive multiple sclerosis: Randomised placebo-controlled to therapy with cyclophosphamide. Arch Dermatol. 1977; 113: 1598- trial. Lancet. 2004; 364: 1149-1156. 1599.

Cite this article Bajpai M, Pardhe N (2017) Oral Mucous Membrane Pemphigoid without Skin Involvement Treated by Intra-Venous Immunoglobulins: A Case Report with the Cor- relation of Clinical, Histopathological and Direct Immunoflurescence Findings and a Literature Review of the Treatment Modalities. J Dermatolog Clin Res 5(4): 1106.

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