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Ocular cicatricial pemphigoid: Manifestations and management
Abstract
Ocular cicatricial pemphigoid (OCP) is a chronic, progressive cicatrizing inflammatory disease of presumed autoimmune etiology affecting the mucous membranes and skin. It has sight-threatening ocular manifestations and potentially life-threatening extraocular manifestations. The ocular signs include: chronic cicatricial conjunctivitis, progressive conjunctival fibrosis, and corneal epitheliopathy. Systemic immunomodulatory therapy is the treatment of choice for controlling disease activity and limiting progression, given the systemic nature of the disease and the poor efficacy of current local or topical therapies. Systemic cyclophosphamide with short-term adjunctive high-dose prednisolone is the preferred treatment for severe and/or rapidly progressing OCP. Oral low-dose weekly methotrexate is a useful first-line treatment for mild-to-moderate OCP. The management of OCP requires a multidisciplinary approach to optimize the care of these patients.
... Patients may present with symptoms such as eye redness, excessive tearing, decreased visual acuity, burning sensation, and foreign body sensation. Extraocular manifestations can involve the skin, mouth, mucous membranes, esophagus, larynx, trachea, genitalia (vagina and urethra), and anus [52,53]. Although ocular presentations of this condition may initially be unilateral, the disease often progresses to bilateral involvement [54,55]. ...
... Various staging systems are available for categorizing OMMP, as illustrated in Fig. 5 [53,55,60]. A common early sign of OMMP is inflammation of the plica semilunaris and medial canthus (Fig. 4) [51]. ...
... Subsequently, chronic conjunctival inflammation manifests with infiltration of both the bulbar and palpebral conjunctiva. This inflammation can lead to the development of feltwork-like reticular fibrosis (Fig. 6), which may progress to symblepharon (Fig. 7), entropion, fornix foreshortening (Fig. 6A), ankyloblepharon [51,61], and ultimately, a frozen globe in the end stage [53]. Additionally, following this rapid progression, fibrosis may result in focal or diffuse conjunctival shrinkage [62]. ...
Purpose
Mucous membrane pemphigoid (MMP) is a systemic autoimmune condition characterized by blistering and cicatrization, predominantly affecting mucous membranes, including those lining the esophagus, oropharynx, nasal cavity, trachea, conjunctiva, and genitalia. Ocular mucous membrane pemphigoid (OMMP) is observed in approximately 70% of MMP cases. This study aims to review the pathophysiology, clinical manifestations, diagnosis, treatment, and complications of OMMP.
Methods
A literature search was conducted using MEDLINE and EMBASE databases.
Results
OMMP is characterized by the deposition of autoantibodies along the basement membrane zone of mucous membranes, particularly affecting the conjunctival epithelium. OMMP manifests as chronic ocular discomfort, inflammation, conjunctival scarring, eyelid abnormalities, and visual impairment. Given the extensive range of similar conditions, including drug-induced pseudo-pemphigoid and paraneoplastic conjunctival cicatrization, challenges in differential diagnosis may arise. The clinical diagnosis of OMMP is supported by confirmatory biopsy with histopathology and immunofluorescence studies. The mainstay of management includes systemic immunomodulatory medications and anti-inflammatory agents, tailored to disease severity. Surgical interventions may be necessary, although caution is warranted due to the risk of exacerbating OMMP. Prompt diagnosis and treatment are essential to halt disease progression and prevent vision loss. Complications of OMMP include corneal disorders, lid disorders, and vision disturbances. A comprehensive understanding of OMMP aids in timely intervention and improved patient outcomes.
Conclusion
OMMP is a bilateral, chronic, progressive, relapsing–remitting condition. Early diagnosis and treatment of OMMP are necessary to prevent disease progression. The management of OMMP varies according to the severity of the disease, but often involves both medical control of the underlying inflammatory process and subsequent surgical correction of residual anatomical changes.
... OCP is classified into four stages, depending on severity of the clinical signs, which may range from chronic conjunctivitis and subepithelial fibrosis to corneal scarring and ankyloblepheron. [4,5] The posterior segment is usually unaffected. Our patient suffered from both oral mucosal, as well as conjunctival inflammations for almost 30 years before she was diagnosed as a case of cicatricial pemphigoid following oral mucosal biopsy. ...
... These include azothiaprim, cyclosporine, and methotrexate. [5] Mycofenolate mofetil, immunoglobulins, and humanized monoclonal antibodies that bind to interleukin 2 on activated T cells have also been used. [6] Lubrication of the ocular surface with artificial tears may help to relieve the symptoms and allow smooth lid movements. ...
... [4] Advanced cystic degeneration and calcification in Schwannoma is an even more rarely reported. [5] We report a case of middle-aged Indian female patient with a subperiosteal located giant orbital cyst with completely luxated globe. The tumor removed surgically using combined anterior and lateral orbitotomy approach proved to be a benign Schwannoma on histopathology with areas of calcification and massive cystic degeneration. ...
We report a rare case of progressive corneal blindness in a 65-year-old female, who was diagnosed as cicatricial pemphigoid, after almost three decades of suffering recurrent oral ulcerations. The left eye was affected earlier, and to a greater extent and severity. Subsequently, the disease progressed to complete corneal keratinization in the left eye. This case highlights the natural course of the disease, wherein the patient finally sought ophthalmic consultation for the recurrent appearance of a horn like growth in the left eye along with vision impairment due to cataractous change in the less affected right eye. At this time, patient had obvious features of ocular cicatricial pemphigoid (OCP) such as formation of multiple symblephara in the right eye and a hard dry growth in an immobile, blind left eye. To the best of our knowledge, corneal keratin horn formation has not been reported as a feature of OCP so far.
... These result in ocular surface disfigurement with huge corneal compromise, resulting in corneal ulceration, infection, and ultimately blindness. 1 The challenges for clinicians are as follows: how do you make a diagnosis, especially in the early stages? What is the likely clinical course in a particular patient? ...
... 2 Some centres may use indirect immunofluorescence, which may only be positive 30-40% of the time. [1][2][3] Thus with a negative biopsy result, the clinician is then left making the diagnosis based on the early clinical course of disease, when features may be confused with other causes. 1 Because of the dilemma of starting immunosuppressive therapy, a clinician would be reluctant to make a diagnosis purely on clinical suspicions. ...
... [1][2][3] Thus with a negative biopsy result, the clinician is then left making the diagnosis based on the early clinical course of disease, when features may be confused with other causes. 1 Because of the dilemma of starting immunosuppressive therapy, a clinician would be reluctant to make a diagnosis purely on clinical suspicions. ...
Eye is the official journal of the Royal College of Ophthalmologists. It aims to provide the practising ophthalmologist with information on the latest clinical and laboratory-based research.
... quent trichiasis and corneal ulcers (1,4). Immunofluorescence has made a major contribution to the comprehension of cicatricial pemphigoid: antibodies and complement bound in a linear band at the epidermal-dermal junction were identified. ...
... Cicatricial pemphigoid usually manifests around the sixth or seventh decade of life; it is rarely observed in subjects under 20 years of age. Young patients present more severe and less easily manageable ophthalmologic symptoms than older patients (1,4). ...
... Our patient's case history shows that the advanced stage of the disease is responsible for the irreversible ophthalmologic complications that occurred despite the introduction of immunosuppressive drugs in therapy. In agreement with the relevant literature, we confirm that the ocular symptoms in childhood cicatricial pemphigoid are more severe and less manageable than in adult pemphigoid (1,4). In our patient 5 mg tacrolimus daily was more therapeutically efficient than cyclosporine therapy. ...
Purpose
Cicatricial pemphigoid is a rare chronic autoimmune disease, characterized by progressive alterations on the skin and mucous membranes. Ocular lesions consists of chronic conjunctivitis, progressive subepithelial fibrosis on the conjunctival fornix together with symblepharon formation, obstruction of the Meibomian ducts, sicca syndrome, and occasionally, entropion associated with consequent trichiasis and corneal ulcers.
Methods
A 9-year-old patient with cicatricial pemphigoid with severe eye involvement came to our observation. A complete anamnesis, ophthalmologic examination, and systemic evaluation, including serum antibody levels evaluation and biopsies of mouth, vulva, parotid, and intestine mucosa, were performed.
Results
Ocular examination showed blepharospasm, conjunctival hyperemia, symblepharon, total cicatricial corneal leucoma, severe dryness, trichiasis, and eyelid edema. The results of medical and surgical treatment are reported.
Conclusions
Given the serious clinical picture, possibly due to a late diagnosis, it was not possible to avoid relapse and appearance of new cicatricial adherences for which we considered wait and see the most appropriate approach, protecting the anterior segment of both eyes, sacrificing their function. Further follow-up was not possible as the patient died. An early diagnosis would have had a significant influence on the clinical course and on the response to therapy.
... Therefore, systemic immunosuppression is the mainstay of treatment in these individuals. This requires a multidisciplinary coordinated approach often involving ophthalmology, rheumatology, and other medical specialties [18]. Furthermore, it necessitates strict coordination with the patient since close follow-up, usually for life, is required for optimization of therapy and limiting progression or relapse [1]. ...
... Along with co-administering folic acid, weekly dosing can lead to decreased side effects [1]. This allows replicating cells to bypass the inhibition without reducing the anti-inflammatory effects of methotrexate [18]. Classic side effects include gastrointestinal discomfort, hepatotoxicity, myelosuppression, and pulmonary fibrosis. ...
Purpose of Review
This review offers an informed insight on the pathophysiology of ocular cicatricial pemphigoid in addition to up-to-date recommendations for monitoring and management.
Recent Findings
Systemic immunosuppression is required for treatment of ocular cicatricial pemphigoid when there is high suspicion, even in the absence of diagnostic findings on biopsy. New therapeutic modalities continue to emerge and provide promising results. In addition, improved options for adjunctive care are also available.
Summary
Ocular cicatricial pemphigoid is a systemic illness and a subset of mucous membrane pemphigoid that primarily affects the ocular surface. It involves a progressive and potentially blinding course of disease. Diagnosis remains challenging and mainly depends on clinical suspicion with the aid of laboratory testing. Multiple treatment modalities have emerged for management mainly consisting of systemic immunosuppression for disease control in addition to adjunctive management for alleviating symptoms and preventing complications.
... Although the exact cause of this disease is not clearly understood, due to the presence of auto-antibodies, it is presumed that this disease has an auto-immune cause. 1 OCP is a progressive disease, and it can result in blindness in the absence of proper timely treatments. Moreover, because OCP may be associated with extraocular manifestations, it is generally considered to be of medical importance. ...
... In contrast, there is no specific therapy for OCP that only targets the ocular surface. 1,11 Definition and classification of pemphigoid diseases ...
Pemphigoid disease is classified according to the phenotypical location of the disease and the presence of different types of antibodies. The ocular distribution of pemphigoid mainly occurs in patients with bullous pemphigoid and mucous membrane pemphigoid. Several immune cells, including the cells of the innate immune system (neutrophils and γδ T cells) and the adaptive immune system (T and B cells), are involved in pemphigoid disease. The treatment of pemphigoid is still wide-ranging, and the most utilized treatment is the use of immunosuppressants and corticosteroids. In this scenario, it is absolutely important to screen the immune cells that are involved in this group of diseases and to determine if a targeted treatment approach is plausible. In conclusion, this review will identify some newer treatment possibilities for the whole spectrum of pemphigoid diseases.
... As a result, systemic immunomodulatory therapy is currently the standard of care for these MMP patients. 23,89,90 Evidence for the effect of systemic immunosuppression on progression of disease The primary goals of treatment of ocular MMP are to control inflammation and arrest fibrosis, in order to prevent progression of disease to more advanced stages and blindness. Most cicatrisation is occurs during active inflammation, 85 but despite control of inflammation in 70-78% of patients with systemic immunosuppression, progressive fibrosis was still observed in 61/115 (53%) 9 and 23/54 (42%) 12 of patients. ...
... This approach has been adopted in UK specialist centres 4 and is also what has been described in the Foster publications summarized above. However, three review articles 89,90,164 have not mentioned the use of combined therapy, excepting the use of prednisolone as adjunctive therapy, and have not discussed the value of step up and step down therapy, using drug combinations, to maintain therapy during treatment changes and to minimize risk, for ocular MMP. The approach used by Thorne ocular MMP, but also for MMP affecting other sites, have been outlined above. ...
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.Eye advance online publication, 20 January 2017; doi:10.1038/eye.2016.284.
... 3,18 On the other hand, OCP is a rare autoimmune disease, characterized by a linear deposition of immunoglobulin on the conjunctival basement membrane and blistering on the mucous membrane, including the conjunctiva. 19 In this disease, sight is threatened because of conjunctival inflammation, fibrosis, and corneal and conjunctival epitheliopathy. 19 Here, we describe and discuss two cases of dry-eye disease. ...
... 19 In this disease, sight is threatened because of conjunctival inflammation, fibrosis, and corneal and conjunctival epitheliopathy. 19 Here, we describe and discuss two cases of dry-eye disease. One is associated with cGVHD, and the other, with OCP-like disease. ...
Two new drugs with mucin-inducing and secretion-promotive effects, rebamipide and diquafosol, were recently approved as topical dry-eye treatments. We report two cases in which the long-term use of mucin-inducing eye drops improved chronic ocular graft-versus-host disease (cGVHD)-related dry eye and ocular cicatricial pemphigoid (OCP)-like disease.
Case 1. A 61-year-old woman had cGVHD-related dry eye that resisted traditional medications. Next, we use topical diquafosol in addition to conventional treatments. The patient used diquafosol for 6 months without experiencing any side effects. The symptoms, including dry-eye sensation, ocular pain, foreign body sensation, and photophobia, as well as ocular surface findings including fluorescein and rose bengal scores and tear break-up time (TBUT), partly improved. To further improve the clinical signs and symptoms and decrease chronic inflammation, rebamipide was added to diquafosol. The symptoms, TBUT, and fluorescein and rose bengal scores markedly improved after long-term dual treatment without any side effects for 6 months. Case 2. A 77-year-old woman had OCP-like disease with dry eye. The patient did not improve using the currently available conventional treatments. Next, we use topical rebamipide in addition to conventional treatments. Symptoms including asthenopia, dry-eye sensation, ocular pain, and dull sensation, as well as fluorescein and rose bengal scores and TBUT, partly improved. Specifically, functional visual acuity was markedly improved after commencement of rebamipide. To further improve the clinical signs and symptoms and increase tear film stability and tear film volume, diquafosol was added to rebamipide. The combination of diquafosol and rebamipide worked for the patient. Improvements were seen in several symptoms, fluorescein and rose bengal scores, Schirmer test value, and TBUT without any side effects for 12 months.
Long-term treatment with topical rebamipide and diquafosol can improve dry eye in patients with cGVHD or OCP-like disease.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
... 7,[23][24][25][26][27][28][29][30][31][32][33][34][36][37][38]41,[43][44][45][47][48][49][50][51]53,54,56 However, the meta-analyses of OMMP frequency by race evidenced that the summarized effect was considerably higher in Caucasians [26][27][28]30,32,33,36,37,45,46,49,51,53 compared to African descents and other races, which may contradict a long-established misconception that OMMP has no racial predilection. 6,58 Nevertheless, since few studies reported on this variable, conclusions about race predilection are not reliable enough. It should also be considered that the metaanalysis of Caucasians and other races' frequencies has a high risk of publication bias, so it should be analyzed carefully. ...
Purpose:
To synthesize the evidence and generate a combined weighted measure on the frequency of ocular manifestations of mucous membrane pemphigoid (OMMP).
Methods:
Systematic literature review and meta-analysis, searching PubMed, Embase, VHL, and Google Scholar. Articles reporting patients with mucous membrane pemphigoid and ocular involvement were included. At least, two reviewers independently and in parallel participated in all the following phases; preliminary screening, full-text review, risk of bias assessment by validated tools, and data extraction. Qualitative analysis and meta-analysis were conducted. This study was previously registered in PROSPERO (CRD42023451844).
Results:
Thirty-five studies met the inclusion criteria, comprising 1,439 patients and 1,040 eyes summarized in qualitative analysis. Twenty-eight studies were included in the meta-analysis. Ages included ranged from 60.4 to 75 years. Women were reported with more frequency. The mean time for diagnosis was 55.1 months, usually with bilateral ocular disease in 90% (95% CI 78%; 96%). Trichiasis and entropion were the most frequent manifestations in up to 92%, followed by symblepharon and punctate keratitis. Ankyloblepharon, persistent epithelial defects, and visual impairment were less frequent complications. Direct immunofluorescence positivity in conjunctival biopsies was 54% (95% CI 43%; 64%). Extraocular involvement was highly frequent, being oral and skin involvement the most frequently reported.
Conclusions:
Our systematic review and meta-analysis evidenced that patients around 60 years of age are the most affected population with a female preponderance, usually with bilateral ocular involvement. Trichiasis and entropion were the most frequent findings; although visual impairment and persistent epithelial defects were less reported, they should not be overlooked in suspected OMMP.
... The morbidity of OMMP is due to the chronic discomfort and loss of vision (5) caused by both inflammation and scarring. Topical therapy is ineffective for OMMP (9)(10)(11), resulting in systemic immunosuppressive therapy being the standard of care (12). However, immunosuppression, with its accompanying side effects and failures, has a limited effect on the pro-Mucous membrane pemphigoid (MMP) is a systemic mucosal scarring disease, commonly causing blindness, for which there is no antifibrotic therapy. ...
Mucous membrane pemphigoid (MMP) is a systemic mucosal scarring disease, commonly causing blindness, for which there is no antifibrotic therapy. Aldehyde dehydrogenase (ALDH) family 1 is upregulated in both ocular MMP (OMMP) conjunctiva and cultured fibroblasts. Application of the ALDH metabolite, retinoic acid (RA), to normal human conjunctival fibroblasts in vitro induced a diseased phenotype. Conversely, application of ALDH inhibitors, including disulfiram, to OMMP fibroblasts in vitro restored their functionality to that of normal controls. ALDH1 is also upregulated in the mucosa of the mouse model of scarring allergic eye disease, used here as a surrogate for OMMP, in which topical application of disulfiram decreased fibrosis in vivo. These data suggest that progressive scarring in OMMP results from ALDH/RA fibroblast autoregulation, that the ALDH1 subfamily has a central role in immune-mediated ocular mucosal scarring, and that ALDH inhibition with disulfiram is a potential, and readily translatable, antifibrotic therapy.
... Progressive cicatrizing conjunctivitis encompasses a group of conditions that are frequently associated with significant ocular morbidity and visual loss. 1 Recurrent episodes of conjunctival inflammation lead to a compromised lacrimal functional unit characterized by progressive conjunctival subepithelial fibrosis and ocular surface failure with subsequent susceptibility to surface breakdown and blinding infections. 1,2 Objective measurement of forniceal foreshortening in conjunctival scarring disorders is necessary to confirm progression of disease and for accurate staging and monitoring of the disease process. 3e5 Such disorders include ocular mucous membrane pemphigoid, StevenseJohnson syndrome/toxic epidermal necrolysis, drug-induced cicatrizing conjunctivitis, and graft-versushost disease. ...
Purpose:
Quantifying the extent of conjunctival fibrosis for documentation of progression in conjunctival scarring disease is a clinical challenge. Measurement of forniceal foreshortening facilitates monitoring of these disorders. This study aims (1) to define the limits of the normal human conjunctival fornices and how these alter with age and (2) to provide normative data for upper and lower fornix depths (FDs) and fornix intercanthal distance (FICD) within a healthy South Asian, racially distinct population.
Design:
Epidemiologic, cross-sectional study.
Participants:
A total of 240 subjects with national origins from South Asia, with no known ocular history and normal adnexal and conjunctival examination, aged 20 to 80 years.
Methods:
An FICD modification of a custom-designed fornix depth measurer (FDM) was validated and used for measurement of both lower and upper FDs together with FICDs in 480 healthy eyes with no ocular comorbidities. Data were analyzed using repeated-measures analysis of variance and presented as means with 95% confidence intervals (CIs).
Main outcome measures:
Mean lower and upper FDs and FICD for the entire cohort, stratified according to age decade and sex.
Results:
For this South Asian population, the overall upper and lower FDs were 15.3 mm (95% CI, 14.9-15.6) and 10.9 mm (95% CI, 10.7-11.1), respectively, with FICD defined as 32.9 mm (95% CI, 32.5-33.4) (upper) and 31.7 mm (95% CI, 31.3-32.1) (lower). With increasing age, a progressive reduction of all measured parameters (P < 0.001) was noted, with female subjects having significantly shallower fornices (upper FD, P < 0.001; lower FD, P < 0.001; upper FICD, P = 0.081; and lower FICD, P = 0.015).
Conclusions:
This is the first study to define the limits of normal upper FD and FICDs in any population group. Our study demonstrates sex variations and progressive conjunctival shrinkage with age. Although it provides important, objective data for normal forniceal anatomy, further study is recommended in other populations to confirm the generalizability of these data or to enable normal comparative datasets for the assessment of conjunctival scarring disorders among all anthropological groups.
The conjunctiva is a transparent, thin mucous membrane covering the sclera. This structure extends from the limbus, or the perimeter of the cornea, and covers both the sclera, where it is termed the "bulbar conjunctiva," and the posterior eyelid surfaces, where it is called the "palpebral conjunctiva." Keratoconjunctivitis is an inflammatory condition that affects both the superficial cornea and the conjunctiva. The term is derived from the words "keratitis," which refers to superficial corneal inflammation, and "conjunctivitis," which denotes conjunctival involvement. This ocular condition can arise from an expansive list of etiologies, including viral, bacterial, autoimmune, toxic, or allergic causes.
Keratoconjunctivitis often results in significant discomfort and potential vision impairment. Viruses, particularly adenoviruses, are among the most common culprits, followed by bacterial and fungal pathogens in certain cases. Allergic keratoconjunctivitis, often associated with environmental allergens, as well as dry eye-related forms linked to tear film dysfunction, also contributes significantly to the condition. Autoimmune diseases such as Sjögren syndrome can further complicate the clinical spectrum of this disease by disrupting the ocular surface.
Epidemiologically, keratoconjunctivitis is widespread, with varying prevalence depending on the subtype and geographic location. Viral keratoconjunctivitis, for instance, tends to occur in outbreaks, especially in crowded environments like schools or workplaces. Conversely, dry eye-related keratoconjunctivitis predominantly affects older populations, particularly postmenopausal women, due to hormonal changes affecting tear production.
Patients with keratoconjunctivitis often present with a constellation of symptoms, including redness, photophobia, blurred vision, excessive tearing or dryness, and a gritty or foreign body sensation in the eye. In more severe cases, patients may report sharp pain, mucopurulent discharge, or difficulty keeping the eye open due to irritation. On examination, clinicians may note conjunctival hyperemia, corneal epithelial defects, lid swelling, or papillary reactions on the tarsal conjunctiva. These signs, combined with the patient's history, aid in differentiating the various subtypes of keratoconjunctivitis.
A thorough investigation is essential to establish a definitive diagnosis. Evaluation typically includes a detailed clinical history, slit-lamp biomicroscopy, and, where indicated, laboratory tests such as viral cultures, polymerase chain reaction (PCR) testing for adenoviruses, or conjunctival scrapings for cytology and bacterial cultures. Tear film assessments, including the Schirmer test and tear break-up time (TBUT), are valuable in diagnosing dry eye-associated keratoconjunctivitis. Advanced imaging techniques, such as anterior segment optical coherence tomography (AS-OCT) and confocal microscopy, can provide further insights into the structural integrity of the cornea and conjunctiva.
Management of keratoconjunctivitis highly depends on the underlying etiology. Viral keratoconjunctivitis typically requires supportive care, including artificial tears and cold compresses, as antiviral medications are rarely indicated. In contrast, bacterial keratoconjunctivitis demands prompt antibiotic therapy to prevent complications, such as corneal ulcers. Allergic keratoconjunctivitis often responds well to antihistamines, mast cell stabilizers, and allergen avoidance strategies. For dry eye-related cases, artificial tears, punctal plugs, and, in severe cases, immunomodulatory agents like cyclosporine can provide significant relief. Corticosteroids may be cautiously used in autoimmune-related keratoconjunctivitis, but their prolonged use must be carefully monitored due to the risk of cataracts and glaucoma.
Looking to the future, advancements in the understanding of ocular surface inflammation and tear film dynamics are paving the way for more targeted therapies. Emerging treatments, such as biologic agents targeting specific inflammatory pathways, alongside gene therapies, hold promise in addressing refractory cases. Additionally, innovations in diagnostic tools, including point-of-care tests for tear biomarkers and artificial intelligence-driven imaging technologies, are expected to enhance early detection and personalized management of keratoconjunctivitis.
Overall, keratoconjunctivitis is a complex and multifaceted condition requiring a nuanced approach to diagnosis and management. By integrating current evidence-based practices with emerging therapeutic and diagnostic advancements, healthcare providers can significantly improve outcomes for individuals affected by this debilitating condition. This activity will focus on more well-known entities causing combined keratoconjunctivitis. Specifically, this activity will discuss the entities known as epidemic keratoconjunctivitis (EKC), vernal keratoconjunctivitis (VKC), superior limbic keratoconjunctivitis (SLK), and keratoconjunctivitis sicca.
Several methods have been publicized to measure the fornix depth but the error in the measurement
makes them inconvenient for the correct diagnosis of fornix depth in the eye. In view of the
cruelty of disease the precise method is needed to correctly evaluate the fornix depth measurement.
In this report, a novel approach is being addressed, to solve the depth measuring issue with the
logical experimental design. The explanation with the proposed hypothesis is described here
with the relevant scientific approach, the emphasis of certain advantages of the present invention
over the conventional measurement approaches. In this case the diagnosis and the process of
diagnosis should be accurate, but in the field of ophthalmology an accurate measurement of
fornix depth without committing any error was a challenging task. So far in the development
of the measurement of fornix depth is concern. Currently, we discussed a novel method for the
measurements of fornix depth in ophthalmic eye, which will be beneficial to get the accurate value,
however it was not possible in the previously reported methods. It will have many advantages over
the existing methods.
Cicatricial entropion arises from contracture of the posterior lamella of the eyelid. It may occur in response to chemical insult, infection, inflammatory disease, surgery, or trauma. Inward misdirection of eyelashes towards the globe may lead to ocular surface decompensation. This chapter describes evaluation and surgical management of cicatricial entropion.
ICD-10-Code: L12 Pemphigoidkrankheit, L12.1 Vernarbendes Pemphigoid, H13.3 Okuläres Pemphigoid
Purpose:
Conjunctival cicatrizing conditions are vision threatening, with poor outcomes despite aggressive systemic therapy. This study tests the utility of serial injections of 5-fluorouracil (5-FU) into the fornices to treat conjunctival scarring in patients with ocular cicatricial pemphigoid or Stevens-Johnson syndrome/toxic epidermal necrolysis.
Methods:
Retrospective cohort study. Fisher exact test and multivariable logistic regression analyses were used to compare clinical outcomes of patients who were administered 5-FU injections versus patients who were not injected. Model fit was examined for multivariable regression.
Results:
One hundred twelve eyes (56 patients) met the inclusion criteria. Thirty-eight eyes (34%) had Stevens-Johnson syndrome/toxic epidermal necrolysis, and 74 eyes (66%) were diagnosed with ocular cicatricial pemphigoid. Twenty-five eyes received ≥1 injection of 5-FU. Sixteen eyes received 1-4 injections, while 9 received ≥5. Median follow-up until last encounter was 18 months. Analysis of each disease entity alone and in combination revealed that 5-FU injections were associated with improvement in final visual acuity, corneal scarring, trichiasis, need for/number of mucous membrane graft surgeries, and severity of symblephara.
Conclusions:
Serial injection of 5-FU in the affected fornices is a promising treatment for severe vision-threatening conjunctival scarring from ocular cicatricial pemphigoid and Stevens-Johnson syndrome/toxic epidermal necrolysis. Given the excellent safety profile of 5-FU around the eye, the solid biologic foundation for using 5-FU in this setting, and the severe risk of vision loss from these disorders, the authors suggest that serial 5-FU injections be adopted as therapy for conjunctival scarring from ocular cicatricial pemphigoid or Stevens-Johnson syndrome/toxic epidermal necrolysis despite the limitations of this retrospective study.
Several methods have been publicized to measure the fornix depth but the error in the measurement makes them inconvenient for the correct diagnosis of fornix depth in the eye. In view of the cruelty of disease the precise method is needed to correctly evaluate the fornix depth measurement. In this report, a novel approach is being addressed, to solve the depth measuring issue with the logical experimental design. The explanation with the proposed hypothesis is described here with the relevant scientific approach, the emphasis of certain advantages of the present invention over the conventional measurement approaches. In this case, the diagnosis and the process of diagnosis should be accurate, but in the field of ophthalmology, an accurate measurement of fornix depth without committing any error was a challenging task. So far in the development of the measurement of fornix depth is a concern. Currently, we discussed a novel method for the measurements of fornix depth in ophthalmic eye, which will be beneficial to get the accurate value, however it was not possible in the previously reported methods. It will have many advantages over the existing methods.
Several methods have been publicized to measure the fornix depth but the error in the measurement makes them inconvenient for the correct diagnosis of fornix depth in the eye. In view of the cruelty of disease the precise method is needed to correctly evaluate the fornix depth measurement. In this report, a novel approach is being addressed, to solve the depth measuring issue with the logical experimental design. The explanation with the proposed hypothesis is described here with the relevant scientific approach, the emphasis of certain advantages of the present invention over the conventional measurement approaches. In this case the diagnosis and the process of diagnosis should be accurate, but in the field of ophthalmology an accurate measurement of fornix depth without committing any error was a challenging task. So far in the development of the measurement of fornix depth is concern. Currently, we discussed a novel method for the measurements of fornix depth in ophthalmic eye, which will be beneficial to get the accurate value, however it was not possible in the previously reported methods. It will have many advantages over the existing methods.
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.
A middle-aged Indian female patient presented with unilateral chronic painless progressive giant orbital tumor of 15 years duration causing complete anterior globe luxation. Roentgenograms revealed enlarged orbital cavity with soft-tissue mass shadow. Computed tomography showed a giant orbital cyst filling the entire orbit displacing the orbital contents outside with intact, but thinned orbital walls. The lesion was solitary and well-encapsulated. Surgical excision using combined anterior and lateral orbitotomy approach completely removed the subperiosteal cyst and associated cosmetic blemish with recovery of extra-ocular movements. Histology confirmed the diagnosis of Schwannoma with massive cystic degeneration and areas of calcification.
Aim:
To describe the clinical features and microstructural characteristics assessed by in vivo confocal microscopy (IVCM) in patients with ocular cicatricial pemphigoid (OCP).
Methods:
A descriptive, uncontrolled case series study. Patients diagnosed with OCP were examined by clinical history, slit-lamp biomicroscopy features and IVCM images. The results of direct immunofluorescence (DIF) biopsies and indirect immunofluorescence (IIF) were also recorded. Local and systemic immunosuppressive therapy were administered and adjusted according to response.
Results:
A total of 12 consecutive OCP patients (7 male, 5 female; mean age 60.42±10.39y) were recruited. All patients exhibited bilateral progressive conjunctival scarring and recurrent chronic conjunctivitis was the most frequent clinical pattern. The mean duration of symptoms prior to diagnosis of OCP was 2.95±2.85y (range: 5mo to 10y). The Foster classification varied from stage I to IV and 20 eyes (83%) were within or greater than Foster stage III on presentation. Two of the 12 patients (17%) demonstrated positive DIF; 3 of the 12 (25%) patients reported positive IIF. The mean duration of the follow-up period was 20.17±11.88mo (range: 6 to 48mo). IVCM showed variable degrees of abnormality in the conjuctiva-cornea and conjuctival scarring was detected in all the involved eyes. Corneal stromal cell activation and dendritic cell infiltration presented as ocular surface inflammation, ocular surface keratinization along with the destroyed Vogt palisades was noted in eyes with potential limbal stem cell deficiency. After treatment, remission of ocular surface inflammation was achieved in all the patients, 18 eyes (75%) remained stable, 6 eyes (25%) had recurrent conjunctivitis and cicatrization in 2 eyes (8%) was progressing.
Conclusion:
As an autoimmune disease, OCP manifests as variable degrees of clinical and laboratory abnormalities with both local and systemic immunosuppressive treatment playing important roles in disease therapy. IVCM can be as a valuable non-invasive technique to assess ocular surface changes in a cellular level with a potential value for providing diagnostic evidence and monitoring therapeutic effects during follow-up.
ICD-10 Code M35.0 Sicca-Syndrom (Sjögren-Syndrom), H04.1 Keratoconjunctivitis sicca
Synonyme: Keratoconjunctivitis sicca, Trockenes Auge
Publisher Summary
The only known function of the eye is to facilitate the unfettered transmission of light from the external environment to the photoreceptors of the retina and from there on to the visual cortex where the signals are translated into images. Although the eye is only a few centimeters in diameter, it is an enormously complex organ that is composed of a multitude of tissues and cells, many of which are found nowhere else in the body. This remarkable organ is an extension of the brain, and, like the brain, has limited regenerative properties. Two of the crucial components of the eye that are necessary for normal vision—the corneal endothelium and the photoreceptor layer of the retina—are incapable of regeneration. Accordingly, traumatic events, such as inflammation, can inflict irreparable damage to these tissues, resulting in blindness. Yet, the consequences of ocular infection with microbial pathogens could be equally threatening to the visual apparatus and the host. The immune response to ocular antigens must be a measured one that balances protective immunity to pathogens with the potential injury to innocent bystander ocular cells that cannot regenerate. Thus, the nature of the ocular immune response is an expression of this compromise.
Ocular Cicatricial Pemphigoid: Case Report Delhi J Ophthalmol 2013; 24 (1): 37-40 Ocular Cicatricial Pemphigoid (OCP) is an autoimmune, progressive disorder that primarily affects the conjunctiva producing cicatrizing conjunctivitis and can progress to blindness. OCP can be a diagnostic and therapeutic challenge since it can present with different symptoms in different stages of the disease. We present 2 cases of OCP with such varying presentations, and highlight the need for early diagnosis and treatment with immunosuppressive agents to stabilize the ocular surface and prevent progression to blindness.
The ocular cicatricial pemphigoid (OCP) belongs to a family of chronically progressive autoimmune disorders, predominantly affecting mucous membranes (mucous membrane pemphigoids). It is an immunopathologically heterogeneous group of disorders with variable phenotypes that share the unique feature of a subepidermal blistering, through disruption of the adhesion between epidermis and dermis. A key feature is the chronically active inflammation with consecutive fibrosis, leading to a partial or complete loss of function of the affected organ. The ocular disease as a chronic cicatrising conjunctivitis is a common manifestation of the mucous membrane pemphigoid. The identification of the subtle pathology and the prompt initiation of an appropriate therapy are of pivotal importance. One purpose is to prevent further vision loss due to extensive corneal scarring and life-threatening systemic complications, such as the formation of oesophageal or tracheal strictures. So far there are no prospective, randomised studies, regarding the therapy guidelines with an evidence level more than III. The autoimmune nature of the disease implies that systemic immunosuppression is the only effective treatment option, most notably in extended stages. The aim of our study is to give a guideline for a stage adjusted therapy with conventional immunosuppressants and to give a perspective for alternative therapies, especially for recalcitrant disease.
Georg Thieme Verlag KG Stuttgart · New York.
Direct and indirect immunofluorescence (IF) plays a role in the evaluation of immunobullous diseases and their mimics, and in the investigation of vascular injury syndromes and autoimmune connective tissue disease (CTD). IF mapping may be an important adjunct in the assessment of congenital epidermolysis bullosa syndromes and in Alport disease, in which antibodies are directed at certain components of the basement membrane zone to assay for their deficiency. In many cases of immunobullous and autoimmune CTDs, correlation with direct IF results is useful and often decisive in lesional evaluation and thus in patient management.
Mucous membrane pemphigoid (MMP) is an autoimmune blistering disorder characterized by inflammation, blistering, and scarring and predominantly occurring at mucous membranes. Successful treatment can be challenging, and uncontrolled disease may result in significant morbidity with scarring of the conjunctiva and oropharynx leading to blindness and dysphagia, respectively. We report safe successful treatment of 6 patients with significant MMP-related oral inflammation with the use of a previously unreported combination of mycophenolate mofetil, dapsone, and prednisolone given at relatively low doses. We propose that this combination of treatments should be investigated further.
There is widespread misinterpretation of normal conjunctival fibrinogen. In differentiating between normal conjunctiva and cicatrizing conjunctivitis, including ocular cicatricial pemphigoid, atopic keratoconjunctivitis, and lichen planus, it is important to properly evaluate and characterize the histologic appearance of the structures seen and not base a diagnosis on just the presence or absence of certain features. One feature of conjunctival histology prone to misinterpretation and misdiagnosis is the presence of subepithelial fibrinogen, particularly when the diagnosis of lichen planus is being considered. Although the presence of subepithelial fibrinogen in oral mucous membranes and in skin can be indicative of lichen planus, such is not the case for conjunctiva. An erroneous diagnosis of lichen planus based on the presence of conjunctival subepithelial fibrinogen can initiate prolonged treatment with topical steroids leading to avoidable, blinding, complication, and further, delay therapy for the real cause of the conjunctivitis. We conducted a cross sectional, controlled, blinded and prospective Institutional Review Board-approved study on the occurrence and pattern of fibrinogen at the epithelial basement membrane zone (BMZ) of normal and inflamed conjunctiva.
Bulbar conjunctiva was obtained from 10 cases of undiagnosed chronic conjunctivitis of at least 6 months duration and 8 patients with normal conjunctiva. Immunofluorescent staining with antifibrinogen antibodies, periodic acid-schiff stain (PAS), and Giemsa staining were performed.
BMZ fibrinogen was found in all cases. This layer was linear, smooth, and continuous in normal conjunctiva and 7 cases of chronic conjunctivitis. It was fragmented and lumpy in 1 case of ocular cicatricial pemphigoid (OCP) and showed spikes and spurs in 2 cases of lichen planus.
BMZ fibrinogen is a normal component of the conjunctiva and its morphological features rather than its mere presence should be assessed as a diagnostic tool.
There has been at least 1 report¹ in the literature of MMP successfully treated with etanercept, an anti–tumor necrosis factor α (TNF-α) agent. We have also had success in treating 3 patients with MMP with etanercept at our institution. Therefore, we felt an anti–TNF-α agent would be a good therapeutic choice for our patient. Given the severity of her disease and our desire to achieve a rapid response, we elected to begin a therapeutic regimen of infliximab (Remicade; Centocor Inc, Malvern, Pa). She received a dose of 600 mg (approximately 5 mg/kg) during her hospital stay. She received additional infusions at 2 weeks and 6 weeks after her initial dose and then began a regimen of infusions every 8 weeks. Our patient experienced rapid improvement with treatment. Two weeks after her first infusion, her oral symptoms had improved significantly. Within 6 months of her first infusion, she reported no difficulty swallowing and no limitations in her selection of foods. Furthermore, no oral lesions were noted on examination (Figure 2). She sees an ophthalmologist regularly for follow-up and states that her ocular disease has stabilized. To date, she has not required additional corneal transplants of her right eye and has been able to maintain the minimal vision she has in that eye. Of note, our patient was initially referred to an otolaryngologist given her oral symptoms, and she was seen several weeks after starting the infliximab regimen. It was felt that she was effectively improving while receiving the infliximab and that no further workup or treatment was warranted.
Treatment of MMP has not been evaluated using well-controlled clinical trials; therefore, most recommendations are based on published reports and the experience of treating physicians. The consensus meeting stressed the importance of a multidisciplinary approach often requiring the involvement of ophthalmologists, dentists, dermatologists, oral surgeons, primary care physicians, gynecologists, otolaryngologists, and gastroenterologists. The consensus meeting further recommended stratifying patients into high-risk and low-risk groups when determining appropriate therapy. Patients with disease involving ocular, genital, nasopharyngeal, esophageal, and laryngeal mucosae as well as patients with rapidly progressing disease should be treated using the high-risk algorithm. This consists of initial treatment with prednisone and cyclophosphamide. Alternative therapy recommended included dapsone, azathioprine, and intravenous immunoglobulin. Low-risk patients include those with disease occurring only in the oral mucosa or oral mucosa and skin. These patients have a much lower incidence of scarring; thus, they can be treated more conservatively.²
A 57-year-old woman presented with a 1-year history of blisters and erosions on her oral mucosa with bilateral conjunctivitis and symblephara formation. A diagnosis of cicatricial pemphigoid was made based on the clinical features and immunohistological findings. A multidisciplinary team managed her with different topical and systemic immunosuppressive agents but she finally succumbed due to multi-organ failure secondary to sepsis.
Cicatricial pemphigoid is an autoimmune bullous disease characterized by mucous membrane fibrosis with resulting scarring, predominantly in the conjunctival and oral mucosa, which rarely involves skin changes. The majority of patients present with painful erosions or desquamative scarring gingivitis, resulting in eating and drinking disorders. Typical ocular lesions include chronic scarring conjunctivitis with progressive subconjunctival fibrosis, fornix foreshortening and synechia formation between the bulbar and palpebral conjunctiva, occasionally resulting in blindness. A 69-year-old woman was admitted to our Department for intense pain and severe burning sensation in the oral cavity, induced by several erosions and solitary blisters, lasting for 3 years. She was also diagnosed with the right eye symblepharon, lid entropion, trichiasis, leukoma and blindness of the right eye. The diagnosis of cicatricial pemphigoid was based on clinical picture and histopathology combined with immunofluorescence methods, with therapy initiated thereupon. Systemic corticosteroid (methylprednisolone) therapy in combination with azathioprine proved successful in the treatment of oral lesions as well as for stabilization of ocular lesions. Unfortunately, the patient was diagnosed in the advanced stage when scarring had already occurred. Prompt recognition of cicatricial pemphigoid and close patient monitoring are an imperative for the future prognosis of the disease.
Ocular cicatricial pemphigoid (OCP) can present with severe conjunctival inflammation that requires systemic immunosuppression to avoid serious ocular morbidity. This study aimed to assess the clinical response to cyclophosphamide and short term, high dose prednisolone in this group of patients.
A prospective, unmasked study assessed patients presenting with either 'severe' ocular inflammation (n = 4) or 'marked' or 'severe' ocular inflammation that had failed to respond to other systemic immunosuppression (n = 6). Nineteen inflamed eyes of 10 consecutive patients were enrolled.
The ocular inflammation resolved in 15 eyes in a mean time of 2.4 months. Two eyes perforated despite treatment and one patient was unable to tolerate the medication. Progressive cicatrisation occurred in 21%.
Cyclophosphamide and short term, high dose prednisolone are effective in severe inflammation caused by OCP but may not completely prevent cicatrisation.
Ocular cicatricial pemphigoid is an uncommon but severe and potentially blinding systemic disease. It shares many pathophysiological features with the other bullous skin diseases such as dermatitis herpetiformis, bullous pemphigoid and pemphigus vulgaris. All of these diseases have circulating antibodies that bind to the basement membrane of mucous membranes. The individual diseases differ by each having a specific component of the basement membrane complex as its antigen. In acute ocular cicatricial pemphigoid, the conjunctiva is infiltrated with neutrophils, macrophages, Langerhans cells and CD8+ and CD4+ T-cells while in the chronic disease the conjunctiva is infiltrated mainly by CD8+ T-cells. There is evidence of activation of these T-cells as CD4+ cells as shown by expression of the interleukin-2 receptor and increased expression of major histocompatibility class II antigens within the tissue. The aetiology of the fibrosis is unknown but increased amounts of several fibrogenic growth factors are demonstrable by immunohistochemistry.
Ocular cicatricial pemphigoid (OCP) is a sight threatening autoimmune disease that can lead to severe conjunctival cicatrisation and keratopathy. It has a variable course and little is known about the factors that determine disease progression. This study analysed the factors that have prognostic significance regarding disease outcome, progression, and keratopathy.
Sixty six patients with OCP were monitored prospectively at Moorfields Eye Hospital. The influence of ocular features, the systemic disease, and the management were analysed to identify factors that influence the outcomes and disease progression.
The mean age at presentation was 67 years; 56% were men. The binocular visual acuities were 6/24 or worse in 25%. Extensive cicatrisation at presentation was common but correlated only weakly with the visual prognosis. Systemic manifestations included lesions of the mouth in 44%, pharynx in 30%, oesophagus in 27%, nose/sinus in 18%, and skin in 17%. There was no association between the ocular and systemic manifestations. Persistent corneal epithelial defects and limbitis occurred in 18% and 32%, respectively, and both were associated with a worse visual prognosis. Systemic immunosuppression was ultimately prescribed in 74%, mainly in patients with advanced stages of conjunctival cicatrisation. Of patients with more than 24 months follow up, progression of cicatrisation occurred in 35% of eyes (16/46) all but one of which were associated with episodes of conjunctival inflammation.
Persistent epithelial defects, limbal inflammation, and ongoing conjunctival inflammation are important factors that lead to keratopathy and visual handicap. These require aggressive management, often with systemic immunosuppressive treatment. Close follow up is required in cases with extensive cicatrisation.
Ocular cicatricial pemphigoid (OCP) is a severe, potentially sight threatening systemic disease that sometimes requires systemic immunosuppression. This study assessed the clinical outcome of patients with OCP treated with sulphapyridine, a sulphonamide with an anti-inflammatory and immunosuppressive action but few side effects.
A prospective, single armed, unmasked clinical trial was undertaken at Moorfields Eye Hospital. Twenty consecutive patients with moderate or marked conjunctival inflammation due to OCP were treated with oral sulphapyridine 500 mg twice daily. The degree of ocular inflammation was assessed as nil, mild, moderate, marked, or severe. Success was defined as resolution to mild or less. Ocular limbitis, systemic features of the disease, and side effects of the drug were also monitored.
Follow up was a mean of 12.3 (SD 4.0) months and ranged from 7 to 17 months. A successful reduction in inflammation was recorded in 22/39 eyes (56%) and 10/20 patients (50%). This improvement occurred within 1 month in 64% and in all by 2 months. Three patients developed allergy. Other side effects included nausea (n = 3), headache (n = 1), urinary hesitancy (n = 1), and mild lymphocytopenia (n = 1). These were dose dependent. Progression of cicatrisation was observed in 1/22 eyes. Success was less likely if there were systemic features of OCP or ocular limbitis.
Sulphapyridine was clinically effective in 50% of patients with moderate marked inflammation and had few side effects. It is a good alternative to dapsone.
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.
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.
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.
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.
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.
The clinical and laboratory data on 81 patients with benign mucous membrane pemphigoid (BMMP) seen during the years 1950 through 1968 were reviewed. Mucous-membrane and cutaneous involvements were variable, but the oral mucosa and conjunctivae were eventually involved in approximately 75% of the cases. Scarring was a common complication of mucosal and cutaneous lesions. The most severe sequela was blindness. Of the 81 patients in this series 21 became blind, 17 in both eyes. Systemic administration of corticosteroids, used in 33 cases, was the single treatment of greatest benefit. Daily doses equivalent to 40 mg of prednisone were required initially to retard or arrest the disease. Of the various corticosteroid preparations employed, triamcinolone was the most effective. There were no deaths attributed to BMMP, but one patient died from the side effects of corticosteroid therapy.
Seven patients with ocular cicatricial pemphigoid displayed acute inflammatory activity that could not be attributed to secondary bacterial infections, trichiasis, or lagophthalmos secondary to symblepharon. This acute inflammatory activity was manifested either as a localized conjunctival mound that was ulcerated and intensely hyperemic or as diffuse and intense conjunctival hyperemia and chemosis. Acute disease activity developed shortly after conjunctival biopsy in three patients and appeared spontaneously in the other four patients. Conjunctival biopsy specmens disclosed a heavy infiltrate of polymorphonuclear leucocytes within and beneath the conjunctival epithelium in addition to the chronic inflammatory cells typically found in this condition. The acute manifestations of ocular cicatricial pemphigoid cause rapid shrinkage and scarring of the conjunctiva. Systemic corticosteroids suppressed the acute disease activity and prevented additional scarring in all five patients treated.
Methotrexate is a second-line anti-inflammatory agent used in the treatment of rheumatic diseases. At low doses (12.5 mg/week), it is associated with few serious side effects.
Twenty-two patients (5 men, 17 women) with chronic noninfectious ocular inflammatory disease, who had not responded to or who had become intolerant of corticosteroid or alternate cytotoxic agents, were treated weekly with oral low-dose, pulse methotrexate. Treated diseases included chronic uveitis-vitreitis (9), scleritis (4), inflammatory pseudotumor (3), orbital myositis (3), and retinal vasculitis (3).
Follow-up ranged from 2 to 39 months (mean, 11 months). Response time ranged from 3 to 9 weeks (mean, 5 weeks) after implementation of methotrexate therapy. Sixteen of 22 patients had reduction of inflammatory activity. Fourteen of these 16 patients were able to taper or discontinue corticosteroid therapy. Five patients had complete remission of their disease; six patients did not respond to methotrexate.
Treatment with low-dose methotrexate appears to be effective therapy for steroid-resistant ocular inflammatory disease.
Cicatricial pemphigoid is an autoimmune systemic disease characterized by chronic conjunctival cicatrization. The natural history is one of variable degrees of progressive scarring of the ocular surface and visual loss. Previous reports have shown systemic chemotherapy to be efficacious in halting cicatrization in progressive cases. This observation makes it of critical importance to be able to detect progression of the disease as early as possible so as to allow for earlier institution of treatment. Our experience in previous studies has led us to believe that disease staging systems currently in use are relatively insensitive in detecting disease progression. We present a revised staging system that combines the strengths of the staging systems in use today and extends their sensitivity.
Oral dapsone was used to treat five patients who presented in the acute inflammatory phase of ocular pemphigoid. The diagnosis was made clinically by identifying cicatricial changes which were in some cases difficult to find. In all cases it was the inflammatory rather than the cicatricial features which responded to treatment. An initial dose of 100 mg/day was effective without toxicity. When 150 mg/day was used patients experienced side effects. A clinical response was obtained after 1-4 weeks and could be maintained on a dose of between 50 mg on alternate days and 100 mg/day. Therapy was withdrawn during remissions which lasted up to 32 weeks but all cases required continuing therapy which has remained effective. Immunopathological examination was carried out on two occasions in all cases and although positive on at least one occasion the results did not correlate with disease activity or treatment. The inflammatory phase of ocular pemphigoid should be added to the list of diseases responsive to dapsone.
The records of 105 patients treated with three different chemotherapeutic agents for ocular cicatricial pemphigoid (OCP) were reviewed to compare long-term efficacies, side effects, and tolerance of different regimens. For the entire group, OCP progressed in 6% of eyes in 10% of patients (follow-up 35 months). More than half of the treatment failures occurred in patients intolerant of chemotherapy. Diaminodiphenylsulfone (DAP), as initial agent, failed to control disease in 2% of patients, compared with 8% after cyclophosphamide (CYC) and 9% after azathioprine (AZA) (p less than 0.05). Stratification of results revealed that DAP was the most effective initial agent for modestly active OCP, whereas CYC was the most effective initial choice for highly active cases. In patients treated with a single agent exclusively for 10 months or more, failure to control disease occurred in 4% of DAP, 4% of CYC, and 15% of AZA patients (p less than 0.01). Recommendations for a sequential approach to chemotherapy for OCP are presented.
Twenty-eight patients with refractory rheumatoid arthritis completed a randomized 24-week double-blind crossover trial comparing oral methotrexate (2.5 to 5 mg every 12 hours for three doses weekly) with placebo. The methotrexate group had significant reductions (P less than 0.01 as compared with the placebo group) in the number of tender or painful joints, the duration of morning stiffness, and disease activity according to physician and patient assessments at the 12-week crossover visit; reductions in the number of swollen joints (P less than 0.05) and 15-m walking time (P less than 0.03) also occurred. These variables, as well as the grip strength and erythrocyte sedimentation rate, showed significant (P less than 0.01) improvement at 24 weeks in the population crossed over to methotrexate. A significantly increased frequency (P less than 0.03) of the HLA-DR2 haplotype occurred in the eight patients with the most substantial response to methotrexate. Adverse reactions during methotrexate therapy included transaminase elevation (21 per cent), nausea (18 per cent), and diarrhea (12 per cent); one patient was withdrawn from the trial because of diarrhea. One patient died while receiving the placebo. Methotrexate did not affect measures of humoral or cellular immunity. We conclude that this trial provides evidence of the short-term efficacy of methotrexate in rheumatoid arthritis, but the mechanism of action is unknown. Longer trials will be required to determine the ultimate safety and effectiveness of this drug.
The clinical and laboratory data on 81 patients with benign mucous membrane pemphigoid (BMMP) seen during the years 1950 through 1968 were reviewed. Mucous-membrane and cutaneous involvements were variable, but the oral mucosa and conjunctivae were eventually involved in approximately 75% of the cases. Scarring was a common complication of mucosal and cutaneous lesions. The most severe sequela was blindness. Of the 81 patients in this series 21 became blind, 17 in both eyes. Systemic administration of corticosteroids, used in 33 cases, was the single treatment of greatest benefit. Daily doses equivalent to 40 mg of prednisone were required initially to retard or arrest the disease. Of the various corticosteroid preparations employed, triamcinolone was the most effective. There were no deaths attributed to BMMP, but one patient died from the side effects of corticosteroid therapy.
To evaluate the efficacy of systemic immunosuppressive drugs, including corticosteroids, in the long-term treatment of ocular cicatricial pemphigoid, we conducted a prospective clinical trial in 57 patients (34 women and 23 men ranging in age from 46 to 94 years). Each patient was assigned to one of five groups. Group 1 (26 patients) served as the control group (four patients in this group who showed progression were later switched to treatment groups). Group 2 (eight patients) received combination therapy with cyclophosphamide and prednisone; Group 3 (13 patients) received cyclophosphamide alone: Group 4 (nine patients) received azathioprine; and Group 5 (five patients) received prednisone alone. We found that untreated ocular cicatricial pemphigoid has a variable course and does not necessarily progress. Further, the disease may be asymmetric in severity and progression; progression is more likely in advanced stages than in the earlier stages. Although immunosuppressive therapy inhibited conjunctival shrinking in all four treatment groups, some eyes in each group progressed despite treatment. Serious complications included hemorrhagic cystitis, dermatitis, anorexia and weight loss, gastrointestinal bleeding, and leukopenia.
The characteristic feature of ocular cicatricial pemphigoid (OCP) is progressive shrinkage of the conjunctiva. In our series of 78 patients with OCP, 21% had cutaneous involvement and 50% had involvement of the oral mucosa. Immunoglobulins and the third component of complement are found bound to the conjuctival epithelium and basement membrane of patients with OCP. Circulating antibodies which bind to the conjunctival and corneal epithelium but not to the conjunctival basement membrane have also been demonstrated. OCP is associated with an increased prevalence of HLA-B12. The lids and conjunctiva of patients with OCP demonstrate an increased incidence of potential pathogens when compared with age- and sex-matched controls. When followed for a period averaging 22 months, the majority of patients not treated with systemic immunosuppressives or topical corticosteroids progress. However, OCP has a variable course because there were patients in all stages who did not progress. The acute manifestations of OCP may cause rapid shrinkage of the conjunctiva and may be suppressed systemic corticosteroids.
In a controlled, nonrandomized, longitudinal cohort study, we studied the efficacy of systemic immunosuppression in treatment of progressive cicatricial pemphigoid affecting the eyes. Twenty-six patients were studied; 18 received systemic immunosuppressive drugs, and eight received conventional therapy. Three patients who received cytotoxic agents withdrew from the study with intolerable gastrointestinal distress. Fourteen of the 15 patients who were immunosuppressed successfully for prolonged periods experienced a cessation of their episodic ocular inflammation and a halting of their progressive conjunctival cicatrization. They maintained vision at least as good as that present when disease activity was brought under control; in two patients vision improved. The one patient who was adequately immunosuppressed and successfully maintained in such a state for two years but who had progressive ocular surface pathology with eventual blindness had concomitant rheumatoid arthritis and severe sicca syndrome. The three patients who withdrew from immunosuppressive therapy and the eight concomitant controls all showed continued episodic conjunctival inflammation and conjunctival cicatrization with development of severe keratopathy and profound visual loss. Complications in this series included alopecia (100%), anemia (78%), gastrointestinal distress (22%), hemorrhagic cystitis (11.1%), and severe leukopenia (5.5%). These results support the notion that abnormal immunoregulatory mechanisms are involved in the progressive disease activity in cicatricial pemphigoid and that systemic immunosuppression may have an appropriate role in the treatment of this disease.
Ocular cicatricial pemphigoid is a chronic, progressive, autoimmune disease that scars mucous membranes and may lead to blindness. It is of critical importance to be able to make the diagnosis as early as possible to allow early treatment. Conjunctival biopsy facilitates the early diagnosis of this condition.
Conjunctival biopsy results of 166 consecutive patients seen over a 7-year period, in whom the diagnosis of ocular cicatricial pemphigoid was considered, were reviewed.
One hundred twenty-one patients ultimately received a diagnosis of ocular cicatricial pemphigoid. Immunofluorescence studies demonstrated characteristic deposition of immunoreactants at the epithelial basement membrane zone in 63 patients (sensitivity = 52%). When immunofluorescent-negative or inconclusive biopsies were processed further using an immunoperoxidase technique an additional 37 diagnoses were made. This represented an increase in sensitivity from 52% with immunofluorescence only to 83% with the addition of the immunoperoxidase technique.
The routine use of the immunoperoxidase technique in immunofluorescent-negative biopsies, allied with appropriate harvesting and handling of biopsied conjunctiva, should significantly increase the diagnostic yield in patients with clinically suspect ocular cicatricial pemphigoid.
To report on three patients with biopsy-proven ocular cicatricial pemphigoid successfully treated with sulphasalazine.
Three case reports.
A 71-year-old man, treated with dapsone for ocular cicatricial pemphigoid stopped his treatment because of an allergy to this drug. Oral sulphasalazine, 2.5 grams daily was successfully used as an alternative treatment (3 month follow-up). Two patients, aged 71 and 84 year old, were treated with dapsone for ocular cicatricial pemphigoid. Both patients stopped their treatment because of drug induced hemolytic anemia. They then received oral sulphasalazine, 4 grams daily. The disease was successfully controlled. In the first patient, sulphasalazine was discontinued after 13 months; and in the second patient no relapse was seen after a 16 month follow-up period. No adverse side effect of sulphasalazine occurred.
Sulphasalazine, that has already been proven to be effective for Crohn's disease, also can be used in ocular cicatricial pemphigoid. However, further studies including a larger series of patients along with a longer follow-up are necessary to confirm the efficacy of sulphasalazine in this disease.
To report the effects of intravenous immunoglobulin treatment of ten patients with progressive ocular cicatricial pemphigoid who did not respond to conventional immunomodulatory regimens.
Noncomparative, interventional case series.
Ten patients with biopsy-proven progressive cicatricial pemphigoid affecting the eyes who did not respond adequately to other local and systemic immunosuppressive treatment regimens.
Intravenous infusions of pooled human immunoglobulin, 2 to 3 g/kg body weight/cycle, divided over 3 days, and repeated every 2 to 6 weeks.
Reduction in conjunctival inflammation, prevention of progression of subepithelial conjunctival fibrosis, improvement in ocular symptoms (discomfort, photophobia), improved visual acuity, reduction in extraocular mucosal lesions.
Clinical deterioration was arrested and resolution of chronic conjunctivitis was documented in all ten patients. Maximum therapeutic effect was observed and maintained after a minimum of 4 cycles of therapy; three patients required 12 cycles before disease control. The duration of therapy in these ten patients has been 16 to 23 months (mean, 19.3 months) with no treatment-induced side effects. Extraocular mucosal lesion resolution has occurred in all but one patient, Visual acuity has stabilized or improved in all ten patients, and subjective complaints of discomfort and photophobia have decreased in all patients.
Intravenous immunoglobulin immunomodulatory therapy can be a safe and effective therapy for otherwise treatment-resistant ocular cicatricial pemphigoid.
To assess the outcome of patients with ocular cicatricial pemphigoid (OCP) treated with sulfasalazine as an alternative to dapsone.
Retrospective noncomparative case series.
Nine patients with biopsy-proven OCP and previous dapsone-related adverse effects (hemolysis and gastrointestinal disturbances) treated with oral sulfasalazine.
Clinical data were abstracted from patients' medical records.
Patients' symptoms, ocular inflammation, conjunctival scarring, complete blood cell count (including reticulocyte count).
At the initiation of sulfasalazine therapy, ocular inflammation was controlled in all patients but one. Mean follow-up was 12 months (range, 2-35 months). Median oral sulfasalazine dosage was 3 g (range, 1-4 g). The disease remained controlled with sulfasalazine alone in four patients (45%). Two patients (22%) required adjunctive oral cyclophosphamide. Adverse effects necessitating drug withdrawal occurred in three patients (33%): hemolysis in two and gastrointestinal disturbances in one.
Sulfasalazine may be useful in OCP patients with previous dapsone-related adverse effects.
To determine the clinical outcome of patients with ocular-cicatricial pemphigoid (OCP) and the influence of systemic treatment on clinical progression.
Noncomparative interventional case series.
Sixty-one patients with biopsy-proven OCP.
Patients with documented disease progression treated with chemotherapy and/or corticosteroids were followed between 1985 and 2000. The parameters evaluated were ocular stage at presentation, visual acuity, ocular complications, disease progression, control of ocular inflammation, and presence of extraocular involvement. Systemic treatment and related side effects were analyzed.
Visual acuity, ocular complications, extraocular involvement, disease progression, clinical outcome, systemic treatment, and related side effects.
Sixty-one patients (32 female; 29 male) with a mean age of 67 years were studied. Extraocular involvement was present in 50% of patients. Sixty percent of eyes were initially seen with stage III (advanced cicatrizing) disease at first evaluation. Seven percent of involved eyes at first visit and 21% at the end of follow-up were legally blind. The most common ocular complications encountered were dry eye, corneal abnormalities, and glaucoma. Dapsone was the most commonly used drug (51 patients), followed by methotrexate (24 patients), azathioprine (23 patients), and cyclophosphamide (15 patients); prednisone, always given as adjunctive treatment, was used in 17 patients. Control of ocular inflammation (total or partial) was achieved in 90% of patients, but 46% of them needed continuation of systemic treatment to avoid disease recurrences, and 10% progressed despite different drugs used. Two agents were required in 32% of cases to control disease activity. The most common treatment-related side effects were hematologic complications (n = 34) followed by gastrointestinal (n = 17), cardiovascular (n = 15), and urinary complications (n = 11). Dapsone was responsible for the greatest number of side effects (n = 43); methotrexate caused the least trouble (n = 6). Corticosteroid-related complications (n = 34) were mostly cardiovascular and endocrinologic.
Ocular-cicatricial pemphigoid is an autoimmune disease that, untreated, progresses to conjunctival scarring and blindness; systemic immunosuppression is required to control it. Long-term systemic treatment and more than one drug are frequently necessary to avoid recurrences, exposing elderly patients to a higher risk of drug toxicity. The most frequently encountered treatment-related side effects were anemia, leukopenia, liver toxicity, and hypertension.
To describe the clinical characteristics of patients with mucous membrane pemphigoid (MMP) and pseudopemphigoid.
Retrospective cohort study.
Two hundred eighty consecutive patients referred for the evaluation of possible ocular MMP from January 1, 1985, to December 31, 2001.
Information on patients presenting for evaluation of possible MMP was entered prospectively into a database, which was supplemented by a retrospective chart review. Mucous membrane pemphigoid was diagnosed in patients with a compatible clinical picture by the linear deposition of antibodies to the basement membrane zone (BMZ) on direct immunofluorescent analysis of a mucous membrane biopsy specimen or by the presence of circulating autoantibodies to epithelial BMZ.
Demographic and clinical characteristics of MMP and pseudopemphigoid; risk of ocular MMP among patients presenting with extraocular MMP without ocular disease.
Among patients with ocular MMP, extraocular disease was common (82.4% of patients). The risk of ocular involvement among patients with MMP seen without ocular disease was approximately 5% per year over the first 5 years of follow-up (cumulative risk at 5 years, 22%). Although immunohistologic confirmation of the diagnosis was obtained in all patients, the initial conjunctival biopsy was positive for MMP in 80% of the patients diagnosed with ocular MMP. The most frequent presumed causes of pseudopemphigoid were topical glaucoma medications (28.3%), rosacea blepharoconjunctivitis (20.0%), atopic keratoconjunctivitis (8.3%), and conjunctival lichen planus (8.3%).
Patients with ocular MMP typically have other systemic manifestations of MMP. Patients who are initially seen with extraocular MMP without ocular involvement are at risk for ocular disease developing. The clinical characteristics of ocular MMP and pseudopemphigoid are similar; therefore, immunohistologic evaluation of biopsied tissue is needed to confirm the diagnosis of MMP.
To report the use of methotrexate therapy as first-line systemic therapy in the treatment of ocular-cicatricial pemphigoid and drug-induced ocular-cicatricial pemphigoid.
Retrospective, noncomparative, interventional case series.
Twelve patients with ocular-cicatricial pemphigoid and 5 patients with drug-induced ocular-cicatricial pemphigoid treated with low-dose oral methotrexate as the sole systemic agent. In 14 of the 17 patients, methotrexate was the first systemic agent used.
Clinical data abstracted from patient medical records.
Visual acuity, conjunctival inflammation, progression of cicatrization, and treatment-related side effects.
After a mean follow-up duration of 30.2 months (range, 6-78 months), complete control or suppression, or both, of conjunctival inflammation was achieved in 89% of eyes with ocular-cicatricial pemphigoid and in 100% of eyes with drug-induced ocular-cicatricial pemphigoid using methotrexate monotherapy as the first-line systemic agent. Progression of conjunctival cicatrization was prevented in 72% of eyes with ocular-cicatricial pemphigoid and 90% of eyes with drug-induced ocular-cicatricial pemphigoid. Visual acuity was maintained or improved in 85% of total eyes treated with methotrexate monotherapy, and a final visual acuity of 6/18 or better was achieved in 74% of the eyes. Methotrexate therapy was well tolerated, with 92% of patients maintained on continued treatment experiencing no side effects. The most common side effects were gastrointestinal (50%), and most (78%) were reversible on dose reduction. In 4 of 17 cases, methotrexate was ceased as a result of possible treatment-related side effects.
Low-dose oral methotrexate monotherapy is both highly efficacious and well tolerated as the first-line systemic agent in the treatment of ocular-cicatricial pemphigoid and drug-induced ocular-cicatricial pemphigoid.
The purpose of this study was to compare the clinical outcomes of intravenous immunoglobulin (IVIg) therapy to conventional immunosuppressive therapy in patients with mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), whose disease progressed to involve the eye. Before ocular involvement, all the patients in this study were diagnosed and treated with immunosuppressive agents, for biopsy-proven MMP, affecting the skin and/or mucous membranes, other than the conjunctiva. Eight patients in group A were treated with IVIg after the diagnosis of ocular cicatricial pemphigoid (OCP) was established. The efficacy and safety of IVIg therapy were compared to a clinically similar group of eight patients treated with conventional immunosuppressive therapy (group B). The inclusion criteria for both groups were: (1). presence of MMP at extraocular sites confirmed by biopsy before entry into the study; (2). entry into the study occurred when ocular involvement was noted and confirmed by biopsy; (3). presence of conventional immunosuppressive therapy at the time of ocular involvement; (4). a minimum of 18 months of follow-up after diagnosis of ocular involvement. The mean length of the therapy, after the onset of ocular involvement, was 24 months (range 16-30) in group A and 45 months (range 21-90) in group B. The median time between initiation of therapy and clinical remission in group A and group B was 4 and 8.5 months, respectively. This difference was statistically significant (P < 0.01). No recurrence of ocular inflammation was recorded in any of the patients in group A. On the contrary, at least one recurrence (median 1) was recorded in five patients in group B (range 0-4). This difference was statistically significant (P < 0.05). All eight patients in group A and group B presented to the ophthalmologist in stage 2 of OCP at the time of the initial visit. At the last follow-up visit, no progression to advanced stages of OCP was recorded in all eight patients in group A. On the contrary, only four patients in group B remained in stage 2 of OCP at the last follow-up exam. The conjunctival scaring progressed from stage 2 to stage 3 in the remaining four patients of group B. At the last follow-up visit, both eyes of each patient in group A were free of inflammation. Some level of conjunctival inflammation at the last follow-up visit was noted in five patients in group B (range 0-1.5, P < 0.05). Both groups of patients were studied during the same time period. The results of this study suggest that ocular involvement in patients with MMP may be considered an indication for initiating IVIg therapy, since it was more effective in arresting progression of OCP, when compared to conventional immunosuppressive therapy. These data indicate that IVIg produced a faster control of the acute inflammation and that no recurrences were observed during the follow-up. This clinical difference could be because of the reduced production of pathogenic antibody, and/or restoration of the immunoregulation, which may have been disturbed.
To report the clinical outcome and long-term follow-up of 10 patients with progressive ocular-cicatricial pemphigoid (OCP), nonresponsive to conventional therapy and treated with IV immunoglobulin (IVIg) therapy, reported earlier as a preliminary study.
Noncomparative, prospective, interventional case series according to a defined protocol for IVIg therapy.
Ten patients, with a diagnosis of OCP present bilaterally confirmed by both biopsy and immunofluorescence studies and who had failed conventional therapy and had objectively demonstrated a positive response to IVIg therapy in a preliminary study, published in 1999.
Comparison of objective clinical outcome parameters before and after IVIg therapy, including visual acuity (VA) and prevention of progression of subepithelial conjunctival fibrosis and blindness.
All 10 patients initially demonstrated signs of clinical improvement with IVIg therapy. The total number of IVIg cycles ranged from 20 to 42 (mean, 32), and the total duration of IVIg therapy ranged from 25 to 43 months (mean, 35). Eight patients who completed the protocol had an improvement in their VA and did not have further progression of subepithelial conjunctival fibrosis. These 8 patients have been maintained in a sustained remission for a total follow-up period ranging from 24 to 48 months (mean, 35) after the discontinuation of IVIg therapy. Two patients did not complete the protocol. Both had initially demonstrated a positive clinical response. One patient had worsening of the OCP and, after IVIg therapy, was abruptly and involuntarily withdrawn. In the second patient, deterioration occurred after ocular surgery. Intravenous immunoglobulin therapy was not provided postoperatively. These 2 patients who did not complete the protocol lost vision.
Intravenous immunoglobulin therapy is an effective treatment in OCP in patients nonresponsive to conventional therapy. In 8 patients who completed the protocol, progression of the disease was not observed. A gradual withdrawal of IVIg therapy, as described in the protocol, may be beneficial in maintaining a sustained clinical remission. Abrupt cessation or discontinuation can result in a severe recurrence that may possibly progress to blindness.
Ocular and oral pemphigus: report of case with anatomic findings in eyeball
- R C Smith
- E A Myers
- H D Lamb
- RC Smith