The effect of treatment and its related side effects in patients with severe ocular cicatricial pemphigoid

Miserocchi, Elisabetta; Baltatzis, Stefanos; Roque, Manolette R.; Ahmed, A. Razzaque; Foster, C. Stephen

doi:10.1016/s0161-6420(01)00863-6

Cited by 89 publications

(54 citation statements)

References 34 publications

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“…92 Use of immunosuppressive therapy has been shown to slow progression of disease in one case series 92 and control of inflammation has been shown to prevent progression in one RCT. 23 With current immunosuppressive regimens, progression of cicatrisation has still been observed in 10-53% of ocular MMP patients [92][93][94] and is more rapid in patients o60 years of age. 95 A subset of MMP patients with ocular involvement have ongoing conjunctival fibrosis without overt clinical signs of inflammation.…”

Section: Use Of Systemic Immunomodulation To Control Immunemediated Imentioning

confidence: 99%

“…However, combination therapy was used in 24% of patients and a recommendation is made for this in the paper. 32 Miserocchi (2002) 94 61 patients 22% requiring monotherapy, 21% requiring combinations of 3 or more drugs, and 10% 4 drugs 33 9 Williams (2011) 12 The same approach described in a different cohort of 54 patients. long term remissions are uncommon using conventional drug therapies.…”

Section: Use Of Systemic Immunomodulation To Control Immunemediated Imentioning

confidence: 99%

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The 2016 Bowman Lecture Conjunctival curses: scarring conjunctivitis 30 years on

Dart

2017

Eye

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This review is in two sections. The first section summarises 35 conditions, both common and infrequent, causing cicatrising conjunctivitis. Guidelines for making a diagnosis are given together with the use of diagnostic tests, including direct and indirect immunofluorescence, and their interpretation. The second section evaluates our knowledge of ocular mucous membrane pemphigoid, which is the commonest cause of cicatrizing conjunctivitis in most developed countries. The clinical characteristics, demographics, and clinical signs of the disease are described. This is followed by a review and re-evaluation of the pathogenesis of conjunctival inflammation in mucous membrane pemphigoid (MMP), resulting in a revised hypothesis of the autoimmune mechanisms causing inflammation in ocular MMP. The relationship between inflammation and scarring in MMP conjunctiva is described. Recent research, describing the role of aldehyde dehydrogenase (ALDH) and retinoic acid (RA) in both the initiation and perpetuation of profibrotic activity in MMP conjunctival fibroblasts is summarised and the potential for antifibrotic therapy, using ALDH inhibition, is discussed. The importance of the management of the ocular surface in MMP is briefly summarised. This is followed with the rationale for the use of systemic immunomodulatory therapy, currently the standard of care for patients with active ocular MMP. The evidence for the use of these drugs is summarised and guidelines given for their use. Finally, the areas for research and innovation in the next decade are reviewed including the need for better diagnostics, markers of disease activity, and the potential for biological and topical therapies for both inflammation and scarring.

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Section: Use Of Systemic Immunomodulation To Control Immunemediated Imentioning

confidence: 99%

Section: Use Of Systemic Immunomodulation To Control Immunemediated Imentioning

confidence: 99%

The 2016 Bowman Lecture Conjunctival curses: scarring conjunctivitis 30 years on

Dart

2017

Eye

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“…7,8 Histological studies of chronic ocular MMP have shown that even when the conjunctiva appears clinically "white" and uninflamed, there is a significant cellular infiltrate present ("white inflammation"). 9,10 Progressive fibrosis, despite immunosuppressive treatment, may be driven by this underlying chronic inflammation and ongoing release of cytokines.…”

mentioning

confidence: 99%

Profibrotic Phenotype of Conjunctival Fibroblasts from Mucous Membrane Pemphigoid

Saw

Schmidt

Offiah

et al. 2011

The American Journal of Pathology

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Ocular mucous membrane pemphigoid is an immunobullous disease in which excessive conjunctival fibrosis causes blindness, and the pathogenesis of scarring is incompletely understood. To establish whether profibrotic fibroblasts with an altered phenotype exist in ocular mucous membrane pemphigoid, we compared the functional characteristics of pemphigoid conjunctival fibroblasts to normal conjunctival fibroblasts with respect to cell division; migration; collagen contraction; matrix metalloproteinase, secretion of collagen and chemokines; and myofibroblast differentiation. We found that pemphigoid fibroblasts showed increased cell division (P ‫؍‬ 0.01), increased migration in serum-free medium (72 ؎ 18 migrated cells versus 33 ؎ 11, P ‫؍‬ 0.04), increased collagen contraction in the presence of 10 ng/ml tumor necrosis factor-␣, increased collagen type I secretion (P ‫؍‬ 0.03), increased secretion of matrix metalloproteinase-3 (P ‫؍‬ 0.03), and increased secretion of eotaxin in response to interleukin-13 (P ‫؍‬ 0.04). Differences between pemphigoid and normal conjunctival fibroblasts with respect to collagen contraction and MMP secretion in the presence of interleukin-13 were also observed. Together, these findings indicate that pemphigoid conjunctival fibroblasts have a profibrotic phenotype that is maintained in vitro. No differences between pemphigoid fibroblasts obtained from acutely inflamed versus clinically uninflamed conjunctiva were observed. Developing effective antifibrotic therapies will require understanding of the mechanisms that both induce and maintain the profibrotic phenotype.

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“…MMP patients who do not respond to dapsone are often responsive when cyclophosphamide in the dose of 1-1.5 mg/kg/day is added [126]. Other drugs used include azathioprine, mycophenolate mofetil, sulfapyridine, tetracycline, minocycline, tetracycline with nicotinamide, and tacrolimus [90,128]. In some patients, subconjunctival injections of mitomycin-C or intravenous prednisone in combination with intravenous cyclophosphamide have been reported to be successful [10,90,128].…”

Section: Mucous Membrane Pemphigoidmentioning

confidence: 99%

Use of intravenous immunoglobulin therapy in autoimmune blistering diseases

Ahmed

2006

International Immunopharmacology

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The effect of treatment and its related side effects in patients with severe ocular cicatricial pemphigoid

Cited by 89 publications

References 34 publications

The 2016 Bowman Lecture Conjunctival curses: scarring conjunctivitis 30 years on

The 2016 Bowman Lecture Conjunctival curses: scarring conjunctivitis 30 years on

Profibrotic Phenotype of Conjunctival Fibroblasts from Mucous Membrane Pemphigoid

Use of intravenous immunoglobulin therapy in autoimmune blistering diseases

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