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
內文：
Introduction
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
