Prospective Study of Ocular Manifestations of Pemphigus and Bullous Pemphigoid Identifies a High Prevalence of Dry Eye Syndrome

Tan, Jeremy; Tat, Lien; Francis, Kristy B.; Mendoza, Clarisse Garcia; Murrell, Dédée F.; Coroneo, Minas T.

doi:10.1097/ico.0000000000000335

Cited by 22 publications

(22 citation statements)

References 28 publications

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“…A deepened understanding of the impact of intercellular cohesion among meibocytes during differentiation and the associated processes is of relevance because an increasing number of case reports also described eye involvement in patients with PV. 39e41 In a broad case study from 2015, Tan et al 7 further identified a high prevalence of DED in patients with PV. Here as well as in the recent in situ study, 5 we demonstrated that meibocytes display a composition of adhesion molecules similar to the epidermis, including Dsg1 and Dsg3 as the primary targets of PV autoantibodies.…”

Section: The Role Of Mgd For Ocular Involvement In Pemphigusmentioning

confidence: 99%

“…42,43 Therefore, it cannot currently be ruled out that autoantibodies in pemphigus interfere with signaling pathways required for physiologic processes of meibocytes besides cell adhesion and lipid production. Because ocular pemphigus still remains underdiagnosed 7,39 and no eye biopsy specimens of patients with PV are available, the novel ex vivo slice culture model of human eyelids may be a promising model for further studies on the signaling pathways involved in PV pathogenesis. Moreover, the model may provide new insights into the role of intercellular cohesion and its regulation, which ultimately may also allow the establishment and testing of new therapeutic approaches for treatment of MGD-associated diseases.…”

Section: The Role Of Mgd For Ocular Involvement In Pemphigusmentioning

confidence: 99%

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E-Cadherin Is Important for Meibomian Gland Function as Revealed by a New Human ex Vivo Slice Culture Model

Rötzer

Melega

Garreis

et al. 2019

The American Journal of Pathology

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Meibomian glands within the eyelid are important for the maintenance of the integrity and health of the ocular surface. Patients with the blistering skin disease pemphigus vulgaris (PV), which is caused by autoantibodies against desmosomal cadherins, often have dry eye disease. Therefore, we studied the regulation of cell cohesion in human meibomian gland epithelial cells (HMGECs). During serum-induced differentiation for 1 to 6 days, HMGECs drastically enhanced intercellular cohesion, whereas lipid production did not change. The expression profiles of the desmosomal PV antigens desmoglein (Dsg) 3 and 1 but not of the adherens junction component E-cadherin (Ecad) was dependent on the presence of serum. Surprisingly, after 1 day but not after 6 days of serum-induced differentiation, an inhibitory antibody against Ecad drastically reduced intercellular cohesion and blocked lipid production of HMGECs. In contrast, antibodies against desmosomal cadherins, including human and mouse pemphigus autoantibodies, had no effect on monolayer integrity and lipid production. Because lipid production was unaltered in meibomian glands from Dsg3-deficient mice, we established an ex vivo slice culture model of human eyelids to allow studies in a more physiologic environment. Here, the inhibitory antibody against Ecad but not a Dsg3-specific PV antibody interfered with stimulated lipid production. Together, these data demonstrate that cell cohesion is maintained differently in meibomian gland cells and indicate that Ecad is important for meibomian gland function.

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Section: The Role Of Mgd For Ocular Involvement In Pemphigusmentioning

confidence: 99%

Section: The Role Of Mgd For Ocular Involvement In Pemphigusmentioning

confidence: 99%

E-Cadherin Is Important for Meibomian Gland Function as Revealed by a New Human ex Vivo Slice Culture Model

Rötzer

Melega

Garreis

et al. 2019

The American Journal of Pathology

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“…Most reports of ocular involvement include single cases or case series, and underreporting has been suggested (Palleschi et al , ). Blepharitis and mild conjunctivitis are the most common presentations with signs of dry eye disease in almost all patients (Tan et al , ). Eyelid and conjunctival erosions as well as conjunctival masses have also been reported (Broussard et al , ).…”

Section: Ocular Involvement In Vesiculobullous Disordersmentioning

confidence: 99%

Management of patients with ocular manifestations in vesiculobullous disorders affecting the mouth

et al. 2016

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Pemphigoid and pemphigus diseases as well as Stevens-Johnson syndrome present as vesiculobullous disorders of the skin and may additionally involve both the oral cavity and the ocular surface. Ocular involvement ranges from mild irritation and dry eye disease to chronic conjunctivitis, symblepharon, eyelid malposition, ocular surface scarring and severe visual loss. In addition to diagnostic assessments, ophthalmologists must treat the dry eye and meibomian gland dysfunction components of these diseases using a stepladder approach, including eyelid hygiene and lubricants. Topical anti-inflammatory therapy is used to treat acute inflammatory exacerbations of the ocular surface, but it cannot prevent scarring alone. Intralesional antimetabolite therapy can cause regression of conjunctival pathology in selected cases. Hence, patients with vesiculobullous disorders should be managed by a multidisciplinary team representing ophthalmology, dermatology, otolaryngology, oral medicine and pathology, internal medicine and intensive care. Systemic treatments including corticosteroids, azathioprine, cyclophosphamide, cyclosporine and mycophenolate mofetil help control inflammation. Intravenous immunoglobulins, plasmapheresis and targeted antibody therapy can be used in selected, severe and treatment-resistant cases. Local surgical management may include debridement of pseudomembranes, lysis of symblepharon, amniotic and mucous membrane grafting as well as reconstructive procedures. Prospective, multicentre, international studies are recommended to further support evidence-based practice.

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“…Further, severity scores from such tools can be utilised to guide treatment decisions and evaluate outcomes. Both EB/AIBD have been documented to cause severe ocular complications [ 3 , 5 – 8 ]. Thus, careful ophthalmological assessment, ideally with the aid of a validated scoring system, should be an essential part of the multidisciplinary management of these patients.…”

Section: Introductionmentioning

confidence: 99%

A review of scoring systems for ocular involvement in chronic cutaneous bullous diseases

Lee

Tan

Radjenovic

et al. 2018

Orphanet J Rare Dis

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BackgroundEpidermolysis bullosa (EB) and autoimmune blistering diseases (AIBD) describe a group of rare chronic dermatoses characterized by cutaneous fragility and blistering. Although uncommon, significant ocular surface disease (OSD) may occur in both and require ophthalmological assessment. Disease scoring systems have a critical role in providing objective and accurate assessment of disease severity. The objectives of this report were, firstly, to document the prevalence and severity of ocular involvement in EB/AIBD. Secondly, to review and evaluate existing ocular and systemic scoring systems for EB/AIBD. Finally, to identify areas where further development of ocular specific tools in EB/AIBD could be pursued.MethodsA literature search was performed in October 2017 utilising Medline, Embase, and Scopus databases. The results were restricted by date of publication, between 01.01.1950 and 31.10.2017. The reference lists of these articles were then reviewed for additional relevant publications. Articles of all languages were included if an English translation was available. Articles were excluded if they were duplicates, had no reference to ocular involvement in EB/AIBD or described ocular involvement in other diseases.ResultsDescriptions of ocular involvement in EB/AIBD were identified in 88 peer-reviewed journal articles. Findings reported include but are not limited to: cicatrising conjunctivitis, meibomian gland dysfunction, dry eye disease, trichiasis, symblepharon, fornix fibrosis, keratopathy, ectropion/entropion, ankyloblepharon, corneal ulceration, visual impairment and blindness. Although scoring systems exist for assessment of OSD in mucous membrane pemphigoid, no such tools exist for the other AIBD subtypes or for EB. Several systemic scoring systems exist in the dermatological literature that are efficacious in grading overall EB/AIBD severity, but have limited inclusion of ocular features. To the best of our knowledge, there is no recognised or validated scoring systems which comprehensively stages or grades the spectrum of ocular manifestations in EB/AIBD.ConclusionsThere are a range of ocular complications documented in EB and AIBD. Development of a comprehensive ocular scoring system for EB/AIBD which incorporates the delineation between ‘activity’ and ‘damage’ would facilitate more objective patient assessment, improved longitudinal monitoring, comparison of intervention outcomes, and provide commonality for discussion of these patients due to the multidisciplinary nature of their care.

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Prospective Study of Ocular Manifestations of Pemphigus and Bullous Pemphigoid Identifies a High Prevalence of Dry Eye Syndrome

Cited by 22 publications

References 28 publications

E-Cadherin Is Important for Meibomian Gland Function as Revealed by a New Human ex Vivo Slice Culture Model

E-Cadherin Is Important for Meibomian Gland Function as Revealed by a New Human ex Vivo Slice Culture Model

Management of patients with ocular manifestations in vesiculobullous disorders affecting the mouth

A review of scoring systems for ocular involvement in chronic cutaneous bullous diseases

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