The Experts below are selected from a list of 12804 Experts worldwide ranked by ideXlab platform

Jane Setterfield - One of the best experts on this subject based on the ideXlab platform.

  • autoantibody detection for diagnosis in direct immunofluorescence negative Mucous Membrane pemphigoid ocular and other sites compared
    Ophthalmology, 2020
    Co-Authors: Jane Setterfield, Richard Groves, Joh Mee, Gilles F H Diercks, Hendri H Pas, Darwi C Minassia
    Abstract:

    Short abstract Objective To assess whether a panel of serum pemphigoid autoantibody tests could be used to confirm an immunopathological diagnosis of Mucous Membrane pemphigoid (MMP) in direct immunofluorescent negative (DIF-) MMP patients. Design Prospective cross-sectional study. Subjects and controls 76 patients with MMP involving ocular and non-ocular sites with 45 matched controls. Tests Enzyme linked immunosorbent assays (ELISA) for BP180 and BP230 (MBL International®), IgA and IgG indirect immunofluorescence on human salt-split skin (IIF SSS) and the keratinocyte footprint assay for anti-laminin 332 antibodies. Main outcome measures Sensitivity and specificity of autoantibody detection; significant differences for individual tests and test combinations for MMP involving different sites. Results All DIF- Cases (24/76, 31.8%) had either ocular only disease or ocular involvement in multi-site disease. Serum pemphigoid autoantibodies were detected in 29/76 (38.2%) of all MMP patients compared to 3/45 (6.7%) of controls. Autoantibody reactivity detected by any one or more of the tests was present in 6/24 (25%) DIF- cases compared to 22/49 (44.9%) in DIF positive (DIF+). Compared to controls ocular only MMP serum reactivity was not significantly different for any test or test combination whereas DIF- multisite ocular MMP differed for one ELISA and 3/7 test combinations. By contrast, for DIF+ non ocular MMP all the individual tests, apart from IgA IIF, and all test combinations were significantly different compared to controls. For the whole MMP cohort the sensitivity of all tests was low having a maximum of 21.05% for BP180 reactivity, increasing to 38.16% for an optimal test combination. Disease activity was strongly associated with positive serology findings. Conclusions Pemphigoid serum autoantibody tests did not provide alternative immunopathological evidence of MMP in ocular only MMP patients but had limited value in DIF- multisite ocular MMP. The requirement for immunopathological confirmation of MMP by autoantibody detection is inappropriate for DIF- ocular only MMP resulting in missed diagnoses, delayed therapy and poor outcomes. Alternative diagnostic criteria for MMP with ocular involvement are required, to exclude the other causes of scarring conjunctivitis, until more sensitive and specific immunopathology tests become available.

  • the optimal oral biopsy site for diagnosis of Mucous Membrane pemphigoid and pemphigus vulgaris
    British Journal of Dermatology, 2020
    Co-Authors: Barbara Carey, Manoharan Andiappan, Jane Setterfield, Abedalla Abdelghani, Sandeep Joshi
    Abstract:

    BACKGROUND: Accepted 'standard practice' for the diagnosis of immunobullous disease is a perilesional sample for direct immunofluorescence (DIF). OBJECTIVES: To compare diagnostic outcomes of a normal buccal punch biopsy (NBPB) with a perilesional biopsy (PLB) for Mucous Membrane pemphigoid (MMP) and pemphigus vulgaris (PV). METHODS: A retrospective analysis of 251 DIF-positive patients with MMP and 77 DIF-positive patients with PV was undertaken. Parameters analysed included the intraoral sites of involvement and histopathological, DIF and indirect immunofluorescence (IIF) findings. RESULTS: For MMP, PLB was positive in 134 of 143 (93.7%) samples, compared with 129 of 144 (89.6%) by NBPB. The diagnostic sensitivities for PLB (81%, 39 of 48) and NBPB (77%, 37 of 48) among 48 patients who underwent both techniques were not significantly different (P = 0.62). In gingival-only MMP, PLB was positive in 63 of 69 (91%) and NBPB was positive in 63 of 75 (84%). For multisite MMP, PLB was positive in 71 of 74 (96%) and NBPB was positive in 66 of 69 (96%). In gingival-only MMP, biopsies from reflected alveolar mucosa in 17 consecutive patients were positive in 17 of 17 cases (100%). For PV, PLB was positive in 42 of 43 (98%), compared with 42 of 42 (100%) by NBPB. Histopathology was diagnostic in 93 of 134 (69.4%) cases of MMP and 38 of 41 (93%) cases of PV. IIF was positive in 126 of 197 (64.0%) MMP and 68 of 74 (92%) PV patient sera. CONCLUSIONS: In the largest series of combined oral DIF results in patients with MMP and PV, we have shown that NBPB is equivalent to PLB for the diagnosis of PV and multisite MMP, and is more sensitive than both histology and IIF. What's already known about this topic? The variation in sensitivity of oral biopsy sites for direct immunofluorescence (DIF) in the diagnosis of oral MMP and PV has not been studied in detail in large series of patients. Biopsy can be challenging due to difficult access and fragility of the oral mucosa. The diagnostic biopsy technique is therefore critical. What does this study add? We have shown that a normal buccal punch biopsy (NBPB) from uninvolved oral mucosa is as sensitive as a perilesional biopsy (PLB) for diagnosis of oral PV, and superior to serology and histology. For multisite MMP, NBPB is equivalent to PLB and is more sensitive than serology and histology. The oral punch biopsy technique on uninvolved buccal mucosa tissue is a simple and safe practical method for diagnosing oral PV and MMP.

  • the optimal oral biopsy site for diagnosis of Mucous Membrane pemphigoid and pemphigus vulgaris
    British Journal of Dermatology, 2020
    Co-Authors: Barbara Carey, Manoharan Andiappan, Jane Setterfield, Abedalla Abdelghani, Sandeep Joshi
    Abstract:

    BACKGROUND: Accepted 'standard practice' for the diagnosis of immunobullous disease is a perilesional sample for direct immunofluorescence (DIF). OBJECTIVES: To compare diagnostic outcomes of a normal buccal punch biopsy (NBPB) with a perilesional biopsy (PLB) for Mucous Membrane pemphigoid (MMP) and pemphigus vulgaris (PV). METHODS: A retrospective analysis of 251 DIF-positive patients with MMP and 77 DIF-positive patients with PV was undertaken. Parameters analysed included the intraoral sites of involvement and histopathological, DIF and indirect immunofluorescence (IIF) findings. RESULTS: For MMP, PLB was positive in 134 of 143 (93.7%) samples, compared with 129 of 144 (89.6%) by NBPB. The diagnostic sensitivities for PLB (81%, 39 of 48) and NBPB (77%, 37 of 48) among 48 patients who underwent both techniques were not significantly different (P = 0.62). In gingival-only MMP, PLB was positive in 63 of 69 (91%) and NBPB was positive in 63 of 75 (84%). For multisite MMP, PLB was positive in 71 of 74 (96%) and NBPB was positive in 66 of 69 (96%). In gingival-only MMP, biopsies from reflected alveolar mucosa in 17 consecutive patients were positive in 17 of 17 cases (100%). For PV, PLB was positive in 42 of 43 (98%), compared with 42 of 42 (100%) by NBPB. Histopathology was diagnostic in 93 of 134 (69.4%) cases of MMP and 38 of 41 (93%) cases of PV. IIF was positive in 126 of 197 (64.0%) MMP and 68 of 74 (92%) PV patient sera. CONCLUSIONS: In the largest series of combined oral DIF results in patients with MMP and PV, we have shown that NBPB is equivalent to PLB for the diagnosis of PV and multisite MMP, and is more sensitive than both histology and IIF. What's already known about this topic? The variation in sensitivity of oral biopsy sites for direct immunofluorescence (DIF) in the diagnosis of oral MMP and PV has not been studied in detail in large series of patients. Biopsy can be challenging due to difficult access and fragility of the oral mucosa. The diagnostic biopsy technique is therefore critical. What does this study add? We have shown that a normal buccal punch biopsy (NBPB) from uninvolved oral mucosa is as sensitive as a perilesional biopsy (PLB) for diagnosis of oral PV, and superior to serology and histology. For multisite MMP, NBPB is equivalent to PLB and is more sensitive than serology and histology. The oral punch biopsy technique on uninvolved buccal mucosa tissue is a simple and safe practical method for diagnosing oral PV and MMP.

  • Mucous Membrane pemphigoid and oral blistering diseases
    Clinical and Experimental Dermatology, 2019
    Co-Authors: Arbara Carey, Jane Setterfield
    Abstract:

    The autoimmune blistering disorders present with variable frequency in the oral cavity. Recognition of their key clinical features at presentation is important, as there are many causes of oral ulceration. Careful history-taking, clinical examination, an understanding of pathogenesis and appropriate investigations are essential. With the exception of the rare genodermatoses that may lead to blistering and oral ulceration, the majority of patients have an acquired disorder. These include the rare autoimmune blistering diseases Mucous Membrane pemphigoid (MMP), pemphigus vulgaris (PV), linear IgA disease, epidermolysis bullosa acquisita and paraneoplastic pemphigus. Important clinical differential diagnoses include erythema multiforme, which may be mistaken for PV in appearance, while oral lichen planus may be indistinguishable from MMP. Angina bullosa haemorrhagica may also present with tense haemorrhagic bullae, and in the absence of diagnostic tests, requires an astute clinical diagnosis based upon the history. Newer laboratory techniques have facilitated identification of target antigens and epitopes in the autoimmune blistering diseases, particularly in MMP. Current interest is in whether these relate to clinical presentation and outcomes. There have also been recent investigations into the use of saliva as an alternative medium to serum for the diagnosis of oral vesiculobullous lesions. Assessment of disease severity and measurement of quality of life at presentation and subsequent follow-up is paramount to interpreting therapeutic response. Furthermore, combining these scores with serological and/or salivary biomarkers is valuable in the assessment of clinical response. In this paper, we discuss MMP and its important differential diagnoses.

  • Mucous Membrane pemphigoid with ocular involvement the clinical phenotype and its relationship to direct immunofluorescence findings
    Ophthalmology, 2017
    Co-Authors: Jane Setterfield, Hon Shing Ong, Darwi C Minassia
    Abstract:

    Purpose This study explored the validity of the First International Consensus on Mucous Membrane Pemphigoid (MMP) guidance, which recommends that clinically indistinguishable patients, who have direct immunofluorescence (DIF)-negative biopsies, be excluded from a diagnosis of MMP. Misdiagnosis, or delayed diagnosis, of MMP with ocular involvement leads to the inappropriate use of topical therapy, the standard of care for causes of cicatrising conjunctivitis other than MMP, rather than systemic immunomodulatory therapy, resulting in irreversible clinical deterioration in patients with MMP. Design Prospective, cross-sectional study. Participants Patients meeting the clinical criteria of ocular MMP, including those with positive and negative DIF findings. Methods A case report form was used to collect the demographic details, the clinical history, and the results of a detailed clinical assessment by ophthalmologists, otolaryngologists, dermatologists, and oral medicine specialists. All anatomic sites potentially affected by MMP were examined apart from the esophagus (and larynx in a subset). The DIF results were recorded. Main Outcome Measures Differences between DIF-positive and -negative patients in demography, sites of involvement, and disease severity as determined by the degree of conjunctival scarring (using Tauber staging), central corneal disease (vascularization, scarring, ulceration, and conjunctivalization), history of conjunctival or lid surgery, and requirement for systemic immunotherapy at the time of screening. Results A total of 73 patients with ocular MMP were recruited, of whom 20 of 73 (27.4%) had ocular-only disease. There was no significant demographic or clinical difference between patients with positive and negative DIF results. This finding included differences in disease severity for which the only significant difference was that of more severe central corneal disease in DIF-negative patients. Asymptomatic disease at different sites was frequent. Conclusions These findings do not support the classification of DIF-negative patients, meeting the clinical criteria for ocular MMP, as having a different disease. This category of patients should be accepted as having DIF-negative MMP, for clinical management purposes, with patients having inflamed eyes being treated with systemic immunomodulatory therapy. The frequent finding of asymptomatic ocular, oral, and nasopharyngeal MMP is clinically significant and implies that these sites should be routinely screened in asymptomatic patients.

M Alexandre - One of the best experts on this subject based on the ideXlab platform.

  • Mucous Membrane pemphigoid bullous pemphigoid and anti programmed death 1 programmed death ligand 1 a case report of an elderly woman with Mucous Membrane pemphigoid developing after pembrolizumab therapy for metastatic melanoma and review of the lit
    Frontiers in Medicine, 2018
    Co-Authors: C Zumelzu, Frederic Cau, M Alexandre, F Aucouturie, Christelle Le Rou, Patricia Webe, Alexis Guyo, A Levy, Sabine Mignotgrootenboe, E Maubec
    Abstract:

    An 83-year-old patient developed erosions and a blister of the gingival Mucous Membrane, 6 months after discontinuation of the anti-programmed death-1 (anti PD-1) pembrolizumab therapy administered for 10 months for a metastatic melanoma. A diagnosis of mild Mucous Membrane pemphigoid (MMP) was made. Complete remission of MMP was rapidly obtained with minimal therapy (doxycycline). MMP remained in complete remission after a 3-month follow-up since discontinuation of the doxycycline therapy and no evidence of relapse of the melanoma was observed after a 14-month follow-up since discontinuation of the pembrolizumab therapy. The widespread use of anti PD-1 and anti-programmed death-ligand-1 (PD-L1) in several malignancies reveals new adverse events. MMP describes a group of chronic, inflammatory, Mucous Membrane-predominant, subepithelial auto-immune blistering diseases. It is clinically distinct from bullous pemphigoid another autoimmune blistering disease but shares some immunological similarities with it. Twenty-nine cases of bullous pemphigoid associated with anti PD-1/PD-L1 have been reported in the literature and one of MMP. Here, we described the case of a MMP developed after pembrolizumab and discussed the accountability of anti PD-1/PD-L1 in our case and the previous reported bullous pemphigoid and MMP cases using the Begaud system scoring.

  • gliptin accountability in Mucous Membrane pemphigoid induction in 24 out of 313 patients
    Frontiers in Immunology, 2018
    Co-Authors: O Gaudi, M Alexandre, F Aucouturie, Sabine Mignotgrootenboe, V Seta, Gerome Ohelay, S Ingenhouszoro, Celine Ernardeschi, Pierre Schneide, Enoi Mellottee
    Abstract:

    Mucous Membrane pemphigoids (MMPs) and bullous pemphigoid (BP) are autoimmune bullous diseases that share physiopathological features: both can result from autoantibodies directed against BP180 or BP230 antigens. An association has been reported between BP and intake of gliptins, which are dipeptidyl peptidase-IV inhibitors used to treat type 2 diabetes mellitus. Clinical and immunological differences have been reported between gliptin-induced BPs and classical BPs: mucosal involvement, non-inflammatory lesions and target BP180 epitopes other than the NC16A domain. Those findings accorded gliptins extrinsic accountability in triggering MMP onset. Therefore, we examined gliptin intrinsic accountability in a cohort of 313 MMP patients. To do so, we 1) identified MMP patients with gliptin-treated (challenge) diabetes; 2) selected those whose interval between starting gliptin and MMP onset was suggestive or compatible with gliptin-induced MMP; 3) compared the follow-ups of patients who did not stop (no dechallenge), stopped (dechallenge) or repeated gliptin intake (rechallenge); 4) compared the clinical and immunological characteristics of suggestive-or-compatible–challenge patients to 121 never-gliptin–treated MMP patients serving as controls; and 5) individually scored gliptin accountability as the trigger of each patient’s MMP using the World Health Organization–Uppsala Monitoring Center, Naranjo- and Begaud-scoring systems. Seventeen out of 24 gliptin-treated diabetic MMP patients had suggestive (≤12 weeks) or compatible challenges. Complete remission at 1 year of follow-up was more frequent in the 11 dechallenged patients. One rechallenged patient’s MMP relapsed. These 17 gliptin-treated diabetic MMP patients differed significantly from the MMP controls by more cutaneous, less buccal and less severe involvements and no direct immunofluorescence IgA labeling of the basement Membrane zone. Multiple autoantibody-target antigens/epitopes (BP180–NC16A, BP180 mid- and C-terminal parts, integrin 64) could be detected, but not laminin 332. Lastly, among the 24 gliptin-treated diabetic MMP patients, five had high (I4–I3), 12 had low (I2-I1) and 7 had I0 Begaud intrinsic accountability scores. These results strongly suggest that gliptins are probably responsible for some MMPs. Consequently, gliptins should immediately be discontinued for patients with a positive accountability score. Moreover, pharmacovigilance centers should be notified of these events.

  • oesophageal involvement in 26 consecutive patients with Mucous Membrane pemphigoid
    British Journal of Dermatology, 2017
    Co-Authors: O Zehou, M Alexandre, F Pascal, Michel Helle, Nicole Lievre, Le C Rouxville, J J Raynaud, Gheorghe Airinei, L Laroche, F Cau
    Abstract:

    SummaryBackground Oesophageal involvement of Mucous Membrane pemphigoid (MMP) has not yet been thoroughly described. Objectives To characterize systematically the endoscopic lesions of a series of patients with oesophageal symptoms seen at a referral centre for autoimmune bullous diseases. Methods Clinical, endoscopic and immunological findings of consecutively referred patients with MMP with oesophageal involvement, systemic and endoscopic treatments, and follow-up are described. Results Of 477 consecutive patients with MMP consulting between 2002 and 2012, 26 (5·4%) had symptomatic oesophageal involvement. Dysphagia, observed in 23 (88%) patients, was the most frequent symptom. Oesophageal symptoms could be the first sign of MMP. Patients with oesophageal involvement had a mean of three other involved sites. At initial oesophageal endoscopy, 17 of 26 patients had active lesions (intact bullae, erosions and/or erythema), 15 had stricture(s) and 12 had other cicatricial lesions. Systemic therapy alone achieved oesophageal symptom relief for five patients. Dilatation was combined with systemic therapy for 12 patients and was successful in nine; one perforation occurred. Conclusions Symptomatic oesophageal involvement affected 5·4% of patients with MMP. Dermatologists and gastroenterologists should be aware of these mucocutaneous diseases and their oesophageal involvement, as it could lead to earlier diagnosis and better care. Oesophageal dilatation could be a therapeutic option for symptomatic stricture not relieved by optimized systemic therapy alone.

  • oral cyclophosphamide without corticosteroids to treat Mucous Membrane pemphigoid
    British Journal of Dermatology, 2013
    Co-Authors: E M Munyangango, M Alexandre, F Pascal, S Doa, F Aucouturie, Michel Helle, Nicole Lievre, Le C Rouxville, I Soued, F Cau
    Abstract:

    Summary Background  Mucous Membrane pemphigoid (MMP) still represents a potentially life- and sight-threatening disease. Immunosuppressants, such as cyclophosphamide (CYC), are indicated for patients with severe and/or refractory MMP. Objectives  To evaluate the efficacy and safety of daily oral CYC without corticosteroids as therapy for severe MMP. Methods  Thirteen patients with severe refractory MMP, who received oral CYC at an initial dose of 2 mg kg−1 without corticosteroids, were retained. Previous treatments, for example dapsone, sulfasalazine or topical agents, were maintained during CYC treatment. Initial clinical severity and response to treatment were assessed by scoring. CYC was stopped after complete remission (CR), or when MMP progressed or lymphopenia (< 0·7 × 109 cells L−1) occurred. Results  After 52 weeks of CYC treatment, the overall response rate was 69% (9/13 patients) with a median time to disease control of 8 weeks (range 4–52 weeks). Seven patients (54%) entered CR with a median time to CR of 24 weeks (range 16–52 weeks), all remaining in CR at week 52. The mean duration of CYC administration was 12 weeks (range 2–52 weeks). The most common side effect was lymphopenia (10/13 patients), which led to CYC withdrawal for six patients. No sepsis was observed. Conclusions  CYC without corticosteroids had rapid efficacy in patients with severe refractory MMP and was safe.

  • rituximab for patients with refractory Mucous Membrane pemphigoid
    Archives of Dermatology, 2011
    Co-Authors: Christelle Le Rouxville, Frederic Cau, C Prostsquarcioni, M Alexandre, F Pascal, S Doa, Mariedominique Ette, Isaac Soued, E Gabiso, F Aucouturie
    Abstract:

    Background Mucous Membrane pemphigoid (MMP) still represents a potentially life- and sight-threatening disease. In a subset of patients with severe MMP, conventional immunosuppressants are ineffective or contraindicated. Observations Twenty-five patients with severe refractory MMP, including 5 with Mucous Membrane –dominant epidermolysis bullosa acquisita, received 1 or 2 cycles of rituximab (375 mg/m 2 weekly for 4 weeks). Twenty-one of the patients were receiving concomitant therapy with dapsone and/or sulfasalazine therapy, which was maintained during rituximab cycles. Complete responses in all affected sites (ocular and/or extraocular) were obtained in 17 patients (68%) by a median time of 12 weeks after the first cycle, and 5 additional patients responded completely after a second cycle, yielding an 88% complete response rate. In all but 1 of the 10 patients with ocular lesions, their eyes became noninflammatory within a mean of 10 weeks. Among the 3 patients (12%) who developed severe infectious complications, 2 (8%) died; they had been receiving concomitant conventional immunosuppressants and high-dose corticosteroids and were hypogammaglobulinemic. Treatment with immunosuppressants was discontinued for all other patients, and no other infection was observed. Ten patients experienced relapse after a mean of 4 (range, 1-16) months after achieving complete responses. Conclusions Rituximab appears to have rapid and dramatic efficacy in patients with severe, refractory MMP. The occurrence of severe infections in patients receiving concomitant conventional immunosuppressants supports using rituximab without other immunosuppressants. Controlled prospective studies are warranted to define an optimal treatment protocol.

F Aucouturie - One of the best experts on this subject based on the ideXlab platform.

  • Mucous Membrane pemphigoid bullous pemphigoid and anti programmed death 1 programmed death ligand 1 a case report of an elderly woman with Mucous Membrane pemphigoid developing after pembrolizumab therapy for metastatic melanoma and review of the lit
    Frontiers in Medicine, 2018
    Co-Authors: C Zumelzu, Frederic Cau, M Alexandre, F Aucouturie, Christelle Le Rou, Patricia Webe, Alexis Guyo, A Levy, Sabine Mignotgrootenboe, E Maubec
    Abstract:

    An 83-year-old patient developed erosions and a blister of the gingival Mucous Membrane, 6 months after discontinuation of the anti-programmed death-1 (anti PD-1) pembrolizumab therapy administered for 10 months for a metastatic melanoma. A diagnosis of mild Mucous Membrane pemphigoid (MMP) was made. Complete remission of MMP was rapidly obtained with minimal therapy (doxycycline). MMP remained in complete remission after a 3-month follow-up since discontinuation of the doxycycline therapy and no evidence of relapse of the melanoma was observed after a 14-month follow-up since discontinuation of the pembrolizumab therapy. The widespread use of anti PD-1 and anti-programmed death-ligand-1 (PD-L1) in several malignancies reveals new adverse events. MMP describes a group of chronic, inflammatory, Mucous Membrane-predominant, subepithelial auto-immune blistering diseases. It is clinically distinct from bullous pemphigoid another autoimmune blistering disease but shares some immunological similarities with it. Twenty-nine cases of bullous pemphigoid associated with anti PD-1/PD-L1 have been reported in the literature and one of MMP. Here, we described the case of a MMP developed after pembrolizumab and discussed the accountability of anti PD-1/PD-L1 in our case and the previous reported bullous pemphigoid and MMP cases using the Begaud system scoring.

  • gliptin accountability in Mucous Membrane pemphigoid induction in 24 out of 313 patients
    Frontiers in Immunology, 2018
    Co-Authors: O Gaudi, M Alexandre, F Aucouturie, Sabine Mignotgrootenboe, V Seta, Gerome Ohelay, S Ingenhouszoro, Celine Ernardeschi, Pierre Schneide, Enoi Mellottee
    Abstract:

    Mucous Membrane pemphigoids (MMPs) and bullous pemphigoid (BP) are autoimmune bullous diseases that share physiopathological features: both can result from autoantibodies directed against BP180 or BP230 antigens. An association has been reported between BP and intake of gliptins, which are dipeptidyl peptidase-IV inhibitors used to treat type 2 diabetes mellitus. Clinical and immunological differences have been reported between gliptin-induced BPs and classical BPs: mucosal involvement, non-inflammatory lesions and target BP180 epitopes other than the NC16A domain. Those findings accorded gliptins extrinsic accountability in triggering MMP onset. Therefore, we examined gliptin intrinsic accountability in a cohort of 313 MMP patients. To do so, we 1) identified MMP patients with gliptin-treated (challenge) diabetes; 2) selected those whose interval between starting gliptin and MMP onset was suggestive or compatible with gliptin-induced MMP; 3) compared the follow-ups of patients who did not stop (no dechallenge), stopped (dechallenge) or repeated gliptin intake (rechallenge); 4) compared the clinical and immunological characteristics of suggestive-or-compatible–challenge patients to 121 never-gliptin–treated MMP patients serving as controls; and 5) individually scored gliptin accountability as the trigger of each patient’s MMP using the World Health Organization–Uppsala Monitoring Center, Naranjo- and Begaud-scoring systems. Seventeen out of 24 gliptin-treated diabetic MMP patients had suggestive (≤12 weeks) or compatible challenges. Complete remission at 1 year of follow-up was more frequent in the 11 dechallenged patients. One rechallenged patient’s MMP relapsed. These 17 gliptin-treated diabetic MMP patients differed significantly from the MMP controls by more cutaneous, less buccal and less severe involvements and no direct immunofluorescence IgA labeling of the basement Membrane zone. Multiple autoantibody-target antigens/epitopes (BP180–NC16A, BP180 mid- and C-terminal parts, integrin 64) could be detected, but not laminin 332. Lastly, among the 24 gliptin-treated diabetic MMP patients, five had high (I4–I3), 12 had low (I2-I1) and 7 had I0 Begaud intrinsic accountability scores. These results strongly suggest that gliptins are probably responsible for some MMPs. Consequently, gliptins should immediately be discontinued for patients with a positive accountability score. Moreover, pharmacovigilance centers should be notified of these events.

  • oral cyclophosphamide without corticosteroids to treat Mucous Membrane pemphigoid
    British Journal of Dermatology, 2013
    Co-Authors: E M Munyangango, M Alexandre, F Pascal, S Doa, F Aucouturie, Michel Helle, Nicole Lievre, Le C Rouxville, I Soued, F Cau
    Abstract:

    Summary Background  Mucous Membrane pemphigoid (MMP) still represents a potentially life- and sight-threatening disease. Immunosuppressants, such as cyclophosphamide (CYC), are indicated for patients with severe and/or refractory MMP. Objectives  To evaluate the efficacy and safety of daily oral CYC without corticosteroids as therapy for severe MMP. Methods  Thirteen patients with severe refractory MMP, who received oral CYC at an initial dose of 2 mg kg−1 without corticosteroids, were retained. Previous treatments, for example dapsone, sulfasalazine or topical agents, were maintained during CYC treatment. Initial clinical severity and response to treatment were assessed by scoring. CYC was stopped after complete remission (CR), or when MMP progressed or lymphopenia (< 0·7 × 109 cells L−1) occurred. Results  After 52 weeks of CYC treatment, the overall response rate was 69% (9/13 patients) with a median time to disease control of 8 weeks (range 4–52 weeks). Seven patients (54%) entered CR with a median time to CR of 24 weeks (range 16–52 weeks), all remaining in CR at week 52. The mean duration of CYC administration was 12 weeks (range 2–52 weeks). The most common side effect was lymphopenia (10/13 patients), which led to CYC withdrawal for six patients. No sepsis was observed. Conclusions  CYC without corticosteroids had rapid efficacy in patients with severe refractory MMP and was safe.

  • rituximab for patients with refractory Mucous Membrane pemphigoid
    Archives of Dermatology, 2011
    Co-Authors: Christelle Le Rouxville, Frederic Cau, C Prostsquarcioni, M Alexandre, F Pascal, S Doa, Mariedominique Ette, Isaac Soued, E Gabiso, F Aucouturie
    Abstract:

    Background Mucous Membrane pemphigoid (MMP) still represents a potentially life- and sight-threatening disease. In a subset of patients with severe MMP, conventional immunosuppressants are ineffective or contraindicated. Observations Twenty-five patients with severe refractory MMP, including 5 with Mucous Membrane –dominant epidermolysis bullosa acquisita, received 1 or 2 cycles of rituximab (375 mg/m 2 weekly for 4 weeks). Twenty-one of the patients were receiving concomitant therapy with dapsone and/or sulfasalazine therapy, which was maintained during rituximab cycles. Complete responses in all affected sites (ocular and/or extraocular) were obtained in 17 patients (68%) by a median time of 12 weeks after the first cycle, and 5 additional patients responded completely after a second cycle, yielding an 88% complete response rate. In all but 1 of the 10 patients with ocular lesions, their eyes became noninflammatory within a mean of 10 weeks. Among the 3 patients (12%) who developed severe infectious complications, 2 (8%) died; they had been receiving concomitant conventional immunosuppressants and high-dose corticosteroids and were hypogammaglobulinemic. Treatment with immunosuppressants was discontinued for all other patients, and no other infection was observed. Ten patients experienced relapse after a mean of 4 (range, 1-16) months after achieving complete responses. Conclusions Rituximab appears to have rapid and dramatic efficacy in patients with severe, refractory MMP. The occurrence of severe infections in patients receiving concomitant conventional immunosuppressants supports using rituximab without other immunosuppressants. Controlled prospective studies are warranted to define an optimal treatment protocol.

L H Weiland - One of the best experts on this subject based on the ideXlab platform.

  • Mucous Membrane plasmacytosis of the upper aerodigestive tract a clinicopathologic study
    The American Journal of Surgical Pathology, 1994
    Co-Authors: Jorge A Ferreiro, E V Egorshi, K D Olse, Pete M Anks, L H Weiland
    Abstract:

    We report 9 patients with an unusual plasma cell proliferative disorder of the upper aerodigestive tract. Six patients were men and three, women. The age at presentation ranged from 40 to 67 years with a mean of 54 years. Symptoms at presentation included dysphonia, dysphagia, difficulty breathing, and oral pain. These plasma cell lesions typically produced a cobblestone or warty appearance of the upper aerodigestive tract mucosa including the larynx, pharynx, palate, lips, mouth, tongue, and trachea in varying combination of multiple sites in each patient. Histologically, all lesions were characterized by psoriasiform epithelial hyperplasia with dyskeratosis and dense subepithelial plasmacytosis. Plasma cells were mature but so expansive and diffuse in infiltration as to suggest extramedullary plasmacytoma. Immunohistochemistry for kappa and lambda light chain showed polyclonal immunoglobulin content in all cases examined. Microbial cultures and Warthin-Starry stains were negative for organisms. A variety of treatments including antibiotic therapy, corticosteroid administration, and surgical resection were unsuccessful. In two patients, the process required tracheostomy. This disorder has not been previously described with the exception of a single reported case, which is included in this series. The etiology, pathogenesis, and successful management of Mucous Membrane plasmacytosis remain unknown.

Razzaque A Ahmed - One of the best experts on this subject based on the ideXlab platform.

  • identification of epitopes within integrin β4 for binding of auto antibodies in ocular cicatricial and Mucous Membrane pemphigoid preliminary report
    Investigative Ophthalmology & Visual Science, 2013
    Co-Authors: Khwaja Aftab Rashid, Stephe C Foste, Razzaque A Ahmed
    Abstract:

    PURPOSE To identify the epitopes on human β4 integrin to which the sera of patients with ocular cicatricial pemphigoid (OCP) and Mucous Membrane pemphigoid (MMP) without ocular involvement bind. METHODS Fragments of the intracellular domain of the β4 molecule were cloned, expressed, purified and peptides were synthesized. Antibodies to various fragments and peptides were produced in rabbits. Binding specificity was determined via Western blot and blocking experiments. Test sera and controls were injected into neonatal BALB/c mice for in vivo passive transfer. RESULTS Sera from patients with OCP, MMP, and both OCP and MMP were bound to cloned fragments of IC3.0. Its subcloned fragments IC3.4 (1489 aa-1572 aa) and IC3.4.1 (1489 aa-1510 aa) were bound with the sera from patients with OCP only. Subcloned fragments IC3.6 (1573 aa-1822 aa) and IC3.6.1 (1689 aa-1702 aa) were bound with MMP sera only. No cross-reactivity in binding was observed. Immuno-affinity-purified sera from patients with OCP, MMP, and rabbit antibodies to IC3.0, IC3.4, IC3.4.1, IC3.6, and IC3.6.1, when injected in neonatal BALB/c mice, produced subepidermal blisters in their skin. CONCLUSIONS These preliminary observations identified IC3.4.1 as the possible epitope for the binding of OCP auto-antibody and IC3.6.1 as the possible epitope for the binding of MMP auto-antibody without ocular disease. Antibodies specific to these peptides produced blisters when injected in mice. Still-unidentified epitopes may exist. These observations may enhance our understanding of the role of β4 integrin in the pathobiology of OCP and MMP. Early diagnosis may be possible if serologic tests with specificity and sensitivity can be developed.

  • critical analysis of the use of rituximab in Mucous Membrane pemphigoid a review of the literature
    Journal of The American Academy of Dermatology, 2013
    Co-Authors: Shaw Shetty, Razzaque A Ahmed
    Abstract:

    Background Mucous Membrane pemphigoid (MMP) is an autoimmune blistering disease. In patients who do not respond to conventional therapy, rituximab (RTX) may be an option. The current literature on the treatment of MMP with RTX is limited. Objective In this review, the data on 28 patients with MMP treated with RTX are critically analyzed. The goal is to provide objective information useful in decision making and treatment. Methods A PubMed search using the key words "rituximab" and "Mucous Membrane pemphigoid" was made in the English language only. The studies were divided into case reports and case series. Results In the final analysis, 20 of 28 patients had a complete response, 3 had a partial response, 2 were nonresponders, and 1 had stabilization of disease. In 1 patient, stabilization of upper airway disease was observed but the patient developed bilateral blindness as a result of progression of disease. Hence, the patient was considered a treatment failure. One died from infection. At least half of the patients were treated with a second cycle because of relapse or lack of response. Limitations Long-term follow-up after RTX therapy is lacking. Hence, the clinical benefit of inducing long-term remissions cannot be assessed. Responses of individual mucosal sites cannot be differentiated. Studies on B-cell levels and antibody responses are lacking. Conclusion Using the protocol described, RTX benefits patients with recalcitrant MMP. Some patients fail treatment or experience a relapse. The ability of RTX to influence the clinical course of MMP remains to be determined.

  • antigen specificity in subsets of Mucous Membrane pemphigoid
    Journal of Investigative Dermatology, 2006
    Co-Authors: Razzaque A Ahmed, Khwaja Aftab Rashid, Haka M Gurca
    Abstract:

    Mucous Membrane pemphigoid (MMP) has several subsets based on target antigens recognized by their sera. MMP and ocular cicatricial pemphigoid (OCP) sera recognize β4 integrin subunit, oral pemphigoid sera recognize α6 integrin subunit, and anti-epiligrin cicatricial pemphigoid sera recognize laminin 5. Our aim is to determine if autoantibodies in the sera of patients with MMP, OCP, and oral pemphigoid (OP) recognize only their target antigens, and to see if this specificity is maintained throughout the clinical course. An immunoblot assay using bovine gingival lysate was used as substrate. Fifteen MMP patients, eight with OCP, and 15 OP patients were studied before therapy and at multiple intervals during the clinical course. Absorption and blocking studies were performed to determine binding specificity. Sera of patients with MMP and OCP recognize only β4 integrin subunit, and sera of OP patients recognize α6 integrin throughout the clinical course. The sera of patients in the subsets of MMP described in this report show adherence and selectivity to target antigen during the entire clinical course, without crossover, interaction, or change. Hence, these subsets of MMP provide an excellent model to study clinical correlation with antigen and antibody specificity, in autoimmunity.

  • the first international consensus on Mucous Membrane pemphigoid definition diagnostic criteria pathogenic factors medical treatment and prognostic indicators
    Archives of Dermatology, 2002
    Co-Authors: L S Cha, Stephe C Foste, Grant James Anhal, Razzaque A Ahmed, W Ernaue, Kevi D Coope, Mark J Elde, Jodavid Fine, Reza F Ghohestani, Takashi Hashimoto
    Abstract:

    Objective We aimed to develop consensus-based recommendations for streamlining medical communication among various health care professionals, to improve accuracy of diagnosis and treatment, and to facilitate future investigations for Mucous Membrane pemphigoid. Participants Because of the highly specific nature of this group of diseases, the 26 invited participants included either international scholars in the field of Mucous Membrane pemphigoid or experts in cutaneous pharmacology representing the 3 medical disciplines ophthalmology, oral medicine, and dermatology. Evidence The first author (L.S.C.) conducted a literature search. Based on the information obtained, international experts who had contributed to the literature in the clinical care, diagnosis, and laboratory investigation for Mucous Membrane pemphigoid were invited to participate in a consensus meeting aimed at developing a consensus statement. Consensus Process A consensus meeting was convened and conducted on May 10, 1999, in Chicago, Ill, to discuss the relevant issues. The first author drafted the statement based on the consensus developed at the meeting and the participants' written comments. The draft was submitted to all participants for 3 separate rounds of review, and disagreements were reconciled based on literature evidence. The third and final statement incorporated all relevant evidence obtained in the literature search and the consensus developed by the participants. The final statement was approved and endorsed by all 26 participants. Conclusions Specific consensus-based recommendations were made regarding the definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators for Mucous Membrane pemphigoid. A system of standard reporting for these patients was proposed to facilitate a uniform data collection.

  • intravenous immunoglobulin therapy in patients with multiple mucosal involvement in Mucous Membrane pemphigoid
    Clinical Immunology, 2002
    Co-Authors: Naveed Sami, Kailash Hol, Razzaque A Ahmed
    Abstract:

    Mucous Membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), is an autoimmune mucocutaneous, blistering disease which can lead to blindness and/or death from sudden asphyxiation, secondary to a scarring process. Conventional therapy for the treatment of MMP consists of high-dose systemic corticosteroids and/or immunosuppressive agents. Some patients do not respond to these treatments and develop multiple serious side effects, which can be potentially fatal. In such patients, alternative treatment modalities are needed. This study presents the use of intravenous immunoglobulin (IVIg) therapy in 15 patients with severe MMP whose disease was nonresponsive to the prolonged use of high-dose systemic corticosteroids and immunosuppressive agents and who developed multiple side effects to them. All 15 patients received an IVIg dose of 1-2 g/kg/cycle. The following objective parameters were used to assess the clinical outcome pre- and post-IVIg therapy: number of side effects, frequencies of recurrences and relapses, duration and total dosage of prednisone therapy, and the quality of life. The differences in these variables between the pre- and post-IVIg data were statistically analyzed using the SAS UNIVARIATE software running the two-sided Wilcoxon signed-rank and sign tests. A statistically significant difference was observed between pre- and post-IVIg therapy data when comparing the aforementioned variables. All 15 patients had an effective clinical response, were able to discontinue previous systemic therapies, and eventually achieved a prolonged clinical remission. IVIg improved the quality of life in all 15 patients and demonstrated a steroid-sparing effect. No serious side effects were observed. IVIg therapy is a safe and effective alternative modality in the treatment of patients with nonresponsive and progressive MMP and can induce a sustained clinical remission.