Urban legend series: mucous membrane pemphigoid. Oral Diseases 2014;20:35-54

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原文題目(出處): Urban legend series: mucous membrane pemphigoid. Oral Diseases 2014;20:35-54

原文作者姓名: Zenzo GDi, Carrozzo M, Chan LS

通訊作者學校: Department of Oral Medicine, Centre for Oral Health Research, Newcastle University, Newcastle upon Tyne, UK 報告者姓名(組別) 陳孟泉 Intern J 組

報告日期: 103/05/12



1. Mucous membrane pemphigoid (MMP) is a heterogeneous group of putative autoimmune subepithelial blistering diseases affecting primarily mucous membranes

2. MMP can develop autoantibodies that target epithelial basement membrane structure

3. Scarring is the clinical hallmark; however, this is not always obvious, particularly in the oral mucosa

4. The relative frequency of mucous membrane location affected is estimated to be oral > ocular > nasal > nasopharyngeal > anogenital > laryngeal > esophageal 5. It is recommended that the diagnosis of MMP should be established by both

clinical morphology and a direct immunofluorescence (DIF) finding of linear deposition of IgG, IgA, or C3 at the epithelial basement membrane zone

6. In this chapter we focused on four questions about MMP:

 Does oral pemphigoid really exist as a separate entity?

 Is mucous membrane pemphigoid curable?

 What is the best therapeutic option?

 Does exclusive oral IgA dermatitis exist as a distinct entity from MMP?

Does oral pemphigoid really exist as a separate entity?

1. From a therapeutic point of view

 OP was reported to be better prognosis compared to other MMP variants

 In patients with MMP, scarring and the associated loss of function are the major complications, except patients disease restricted to the oral mucosa

 Both IL-4 and IL-13 are thought to be involved in cicatricial scarring process in MMP. Very recently, has been found a genotype that has been found in 90% of patients with OP, is associated with a reduced response to IL-4 and thus may explain a better clinical outcome for OP patients

 More amenable to medical treatments

 However, there is a paucity of long-term follow-up studies on MMP, and several case reports the difficult treatment for OP

 Because the limited number of reports , it is not possible to determine whether the exclusive oral involvement may account for a difference in the response to therapy and more research is needed

2. From a clinical presentation point of view

 Because MMP is not a single entity, it does not have a unified and predictable natural history

 MMP with exclusive oral involvement does not develop lesions in other sites

 A long-term follow-up (mean length of follow-up was 9.1 years) study of a large cohort of 70 patients with OP showed that no other mucosae or the skin was involved during the course of the disease

 Notably, a recent research suggests that patients with OP, with antibodies to


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integrin alpha6 , may have a possible reduced relative risk for developing cancer compared to anti-laminin 332-positive patients

 In several long-term follow-up studies, MMP with exclusive oral involvement does not develop lesions in other sites during the course of the disease and also seems to be often associated with a good prognosis

3. From an immunological point of view

 Circulating autoantibodies (IgG and rarely IgA) can be detected in MMP

 Patients with OP often do not have circulating IgG antibodies

 OP has autoantibodies target the a 6 integrin subunit but MMP doesn’t

 These data show that the IgG reactivity against a6 integrin 4. Conclusion

 It is still unclear whether patients with OP could be considered as a distinct subset of MMP

 (i) exclusive involvement of oral mucosa, rarely scarring and typically associated with a good prognosis

 (ii) specific recognition of a6 integrin subunit Is mucous membrane pemphigoid curable?

 Theoretically, MMP, as an autoimmune disease, cannot be cured

 However, it has been shown that complete and longlasting remission without treatment can be induced

What is the best therapeutic option for MMP?

1. Introduction

 Because of the rarity of the disease clinical treatments for MMP are scarce

 MMP is highly variable and does not have a predictable natural history

 If the mucosal lesions are localized to oral cavity, topical corticosteroid and dapsone (DDS) should be the first line of medications

2. Results

 Three RCTs, all of uncertain quality, and 42 non-randomized trials on the treatment for MMP

 Some studies commented on sulfa drugs , but complete and permanent remissions were rare

 Prednisolone is also used, and generally, systemic corticosteroids were successful

 Some used cyclophosphamide(CYC), it seems particularly effective for aggressive OCP or recalcitrant MMP

 Some commented on azathioprine (AZA), was used as steroid-sparring agent and the results were usually positive

 Some trials assessed intravenous immunoglobulins (IVIg) also as a monotherapy, and the overall response rate was 100%

 Topical corticosteroids have been used in some studies, mostly are patients with OP and with apparently very positive results

 Some commented on cycline family of drugs (mainly minocycline), change drug rate is 67%

 Some use mycophenolate mofetil (MMF) efficacy with general positive results

 Two trials used rituximab (RTX) in particular recalcitrant MMP cases, and this drug showed encouraging results, but two patient die as a result of RTX treatment

3. Discussion

 The amount of evidence to determine the best treatment for this disease remains


 Adverse effects (AE) are supposed to be dose related and mostly not serious at daily dose below 100 mg, but the evidences are controversial

4. Anti-inflammatories

 Cycline group of medications can rarely cause clinical remission, have little effect on ocular disease, and can cause serious and frequent adverse effects, particularly minocycline

 Sulfa drugs, particularly dapsone (DDS), have been widely employed in MMP, but still their efficacy is unclear because of the lack of good-quality RCTs

5. Corticosteroids

 Topical corticosteroids have an excellent compliance and seem effective, particularly clobetasol propionate used for OP

 The main longterm complication of systemic corticosteroids, which is osteoporosis, can be now efficiently prevented

 The overall safety and optimal dosage regimen are still an issue Immunosuppressives

 Diverse drugs such as CYC, AZA, and MMF have been proposed as systemic immunomodulatory agents for MMP

 CYC and prednisolone are more effective than the latter alone

 CYC use without corticosteroids has a rapid efficacy in refractory MMP.

However, half of the patients discontinued CYC due to the AE 6. Intravenous Immunoglobulin (IVIg)

 IVIg is a blood product prepared by cold ethanol fractionation from the pooled plasma of 10 000 -20 000 donors per batch

 The use of IVIg improve clinical status and reduce systemic corticosteroids and also prevent disease progression and relapse

 IVIg is a relatively safe and well-tolerated therapy, but serious adverse effects requiring discontinuation have been reported in MMP

7. Rituximab (RTX)

 RTX is a anti-CD20 antibody that targets pre-B cells and mature B cells and has been increasingly used in blistering diseases

 It almost always in association with immunosuppressive and anti-inflammatory drugs

 Although 96% of the patients went in complete remission, major attention should focus also on the adverse effects of RTX treatment, as two patients died as a result of severe bacterial infections

8. Conclusion

 There is a lack of good-quality trials on MMP, and available recommendations are solely based on generally small patients’ case series.

 Some of the 2002 consensus experts’ opinions should be possibly updated

 Medicine with high-potency: topical corticosteroids, MMF, and IVIg, should be urgently examined in RCTs given the promising preliminary results

Does exclusive oral IgA dermatitis exist as a distinct entity from MMP?

1. Introduction

 Linear immunoglobulin A (IgA) bullous dermatitis(LABD) or linear IgA disease (LAD) is a unique immunobullous disease that was first recognized as an entity distinct from dermatitis herpetiformis (DH) or bullous pemphigoid (BP)

 There is also a childhood variant of LAD termed chronic bullous dermatosis of childhood (CBDC)

 Two variants: adult-onset LAD vs childhood-onset LAD


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 CBDC occurs in children with a peak incidence of about 4.5 years, the lesions can appear as ‘cluster of jewels’

 LABD is a disease of adults mainly aged 60–65 years, are generally like linear or

‘sausage’ like in shape and frequently tend to form annular or polycyclic

 LAD may be diagnosed based on the following three criteria:

(i) The presence of a vesicular or bullous eruption,usually confined to the skin, but which may involve the mucous membranes;

(ii) The presence of a subepidermal vesicle with a predominantly neutrophilic infiltrate on histology of lesional skin; and

(iii) The presence of BMZ specific IgA antibody deposited in a linear pattern in the absence of other immunoglobulins on DIF of perilesional skin

2. Results

 The literature search retrieved 29 cases of suspicious predominantly mucosal LAD

 Four of the cases were diagnosed as cases of MMP

 25 had oral lesions and 18 had exclusive oral, in most of the cases, gingival lesions

 clinical pictures provided, almost all the oral lesions had the appearances suggestive of MMP

 Main histologic features were subepithelial split and a dermal inflammatory infiltrate, but only one patient with predominance of neutrophils

 All but three cases had exclusive linear IgA staining at BMZ

 The course of the cases was mixed and not always reported but mostly with partial remission of the lesions

3. Discussion

 In 2002, an international consensus proposed that subepithelial blistering disorders with predominant mucosal involvement previously classified as LAD should be comprised under the same term of MMP

 So, perilesional mucosa and/or skin showing continuous deposits at the BMZ of IgG, IgA, or C3 or combination are diagnostic of MMP

 More importantly, almost all the published cases of oral LAD did not show any common features clinically, histologically, and/or immunologically to justify a diagnosis different from MMP

 Two of the reported patients with predominantly oral LAD had IgA or IgG against BPAg 1 and 2 and were both associated with the typical MMP HLA-DQB* 03:01 allele, supporting MMP as the final diagnosis

4. Conclusion

 We did not find any strong evidence to support an exclusive oral form of LAD as a separate entity

 We urge to investigate target antigens and typical HLA allele’s link in every case suggestive of MMP

 we would suggest that future reports follow the 2002 consensus proposal as a standard reporting method

題號 題目

1 78 歲男性,最近三個星期於軀幹及上下肢發生數個大水皰。皮膚病

理檢查顯現表皮下裂解,且有嗜伊紅性細胞浸潤於真皮上層。最可 能的診斷為:

帶狀皰疹(herpes zoster)


(B) 膿痂疹(impetigo)

(C) 類天皰瘡(pemphigoid)

(D) 天皰瘡(pemphigus)

答案(C) 出處:

題號 題目

2 Which one is wrong about benign mucous membrance ? (A) The cause of benign mucous membrance was unknown (B) It’s frequency :women twice higher than man

(C) The disease affects younger individuals (D) It is usually reported in the white population 答案(C) 出處:DD of oral and maxillofacial lesions




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