眼瘢痕性类天疱疮

瘢痕性类天疱疮是一种少见的慢性、进行性自身免疫性大疱性疾病,主要累及黏膜,以瘢痕化为特征。眼部受累时结膜炎症、溃疡、瘢痕形成,继发角膜受损、混浊而视力下降。仅有眼部受累时诊断较为困难,如治疗不及时,有25％的患者视力丧失。本文就眼瘢痕性类天疱疮的定义、病因及发病机制、眼部表现、分期、诊断、鉴别诊断、治疗等进行综述。     

Management and outcome of cataract surgery in ocular cicatricial pemphigoid

· Background: Patients with ocular cicatricial pemphigoid (OCP) lose vision due to corneal disease or cataract, which may be senile, drug induced or complex. The success of cataract surgery in these patients may be limited by an increased risk of surgical complications due to difficult access and visualisation, exacerbation of the cicatrising disease following surgery or later progression of the corneal disease. We report our experience on cataract surgery in OCP. · Methods: Cataract surgery was performed on 15 eyes of 13 patients. In the pre- and postoperative examinations the stage of the condition (according Foster’s classification), the degree of conjunctival hyperaemia and the visual acuity (VA) were evaluated and topical and systemic medication recorded. All procedures used a corneal incision. The technique was intracapsular (ICCE) in 1, extracapsular (ECCE) in 4 and phacoemulsification in 10 eyes. In 13 of 15 cases an intraocular lens was implanted. The unoperated fellow eyes constituted a control group. Duration of postoperative follow-up was 35.8±39.1 months. · Results: 10 of 15 eyes had stage III disease or worse before surgery. Two eyes following ECCE showed early postoperative progression of the disease. Postoperative visual acuity improved in 14 eyes by 2 or more lines. Preoperatively 5 eyes met the criteria for blind registration, whereas postoperatively all eyes achieved a VA of at least 0.1. In 6 eyes the VA was sufficient to allow driving. However, by the 22nd postoperative month progressive cicatricial and ocular surface disease resulted in a regression of the achieved visual rehabilitation in 8 eyes. · Conclusion: OCP does not prevent successful cataract surgery if appropriate techniques are used and precautions taken. Systemic perioperative immunosuppression is necessary in patients with active conjunctival inflammation. The use of small clear corneal incision surgery is recommended to reduce the risk of an acute exacerbation of conjunctival inflammation. Although visual rehabilitation may be only temporary due to progression of the conjunctival or corneal disease in OCP, cataract surgery can provide some benefit, in severely disabled patients, without precipitating an acute exacerbation of OCP. Received: 25 February 1999 Revised: 23 August 1999 Accepted: 24 August 1999     

Immunosuppressive therapy in ocular cicatricial pemphigoid

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.     

Penetrating keratoplasty in ocular cicatricial pemphigoid

PURPOSE: Ocular cicatricial pemphigoid (OCP) is a chronic progressive disease characterised by exacerbations of immunologically driven conjunctival inflammation. In the advanced stages of the disease, severe xerosis with mechanical factors may contribute to the development of blinding keratopathy. The authors report two cases of penetrating keratoplasty (PK) in patients with OCP and discuss the modalities of the surgical procedure for this particular disease. METHODS: Two patients with stage III OCP according to Foster's classification, underwent PK. Initial and final visual acuity, indications of PK, surgical procedure, postoperative therapy, and complications were recorded. RESULTS: For the first patient, after 3 months of follow-up, the graft is still clear, with a remarkable improvement in vision (3/10). For the second patient, however, graft rejection developed 15 days after the operation, complicated later by endophthalmitis, which was controlled with an antibiotic. DISCUSSION: The progression of ocular pemphigoid involves the filling of the conjunctival fornices, formation of symblepharon with lagophthalmos, and dry eye, from which blinding keratopathy can originate. A corticosteroid-based or immunosuppressant treatment blocks the progression of the fibrosis but does not get rid of palpebrale or corneal anomalies, making surgery necessary. This surgery generally gives disappointing results and should be planned when the disease is perfectly under control, during a lull in the disease so as to avoid reactivation of the fibrosis process. Reconstruction of the conjunctival fornices should also precede any corneal transplantation. CONCLUSION: These results indicate that PK may be performed to restore of sight in patients with advanced OCP after controlling the primary immunological process and aggressive treatment of the mechanical factors damaging the ocular surface.     

Pure ocular cicatricial pemphigoid: A distinct immunopathologic subset of cicatricial pemphigoid

ObjectiveTo determine whether ocular cicatricial pemphigoid (OCP) may represent a distinct immunopathologic disease when it is pure ocular cicatricial pemphigoid (POCP) (e.g., only confined to the conjunctiva) or when it is associated with skin or extraocular mucous membrane lesions or both (OCP⁺).DesignProspective, immunologic, and immunopathologic study with special emphasis on direct immunoelectron microscopy.ParticipantsSix patients with POCP and seven patients with OCP⁺.InterventionAfter informed consent was obtained, a conjunctival biopsy was performed in all patients. Skin and extraocular mucosa biopsy specimens were harvested in selected cases only.Main outcome measuresResults of direct immunofluorescence and direct immunoelectron microscopy without freezing on conjunctival and skin biopsy specimens, indirect immunofluorescence, and Western immunoblotting analysis were analyzed.ResultsResults of direct immunoelectron microscopic examination of the conjunctiva showed the presence of immune deposits in the upper lamina lucida of the basement membrane zone in the six patients with POCP, whereas the immune reactants were located in the lower part of the lamina lucida and in the lamina densa of the basement membrane zone (conjunctiva, buccal mucosa, and skin) in the seven patients with OCP⁺. Direct immunofluorescence was positive in the biopsy specimens of three patients with POCP (50%) and the seven patients with OCP⁺ (100%). Results of indirect immunofluorescence study showed circulating autoantibody levels only in two patients with OCP⁺, and results of Western immunoblot analysis were negative.ConclusionsResults of direct immunoelectron microscopic examination of the conjunctiva support the hypothesis that POCP may be a disease entity distinct from mucocutaneous cicatricial pemphigoid.     

Methotrexate therapy for ocular cicatricial pemphigoid

PURPOSE: 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. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: 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. METHODS: Clinical data abstracted from patient medical records. MAIN OUTCOME MEASURES: Visual acuity, conjunctival inflammation, progression of cicatrization, and treatment-related side effects. RESULTS: 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. CONCLUSIONS: 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.     

眼瘢痕性类天疱疮病例的回顾性分析

目的 探讨眼瘢痕性类天疱疮(OCP)的临床特点.方法 回顾性系列病例研究.回顾2005年1月至2008年10月于北京大学第一医院眼科和皮肤科联合确诊为OCP的系列病例5例(10只眼)患者的病史、眼科常规检查、结膜囊细菌培养及全身免疫学常规检查的结果,分析其误诊原因.结果 确诊前,5例患者在早期均误诊为慢性结膜炎,在这些病例瘢痕较明显时,1例曾被误诊为Stevens-Johnson综合征,1例误诊为干燥综合征,患者从首次就诊至确诊的时间长达2～5年.在确诊前均经过长期抗菌滴眼液的局部治疗,1例经3次内翻倒睫矫正术,术后病情加重.5例患者中诊断为OCPⅡ期3只眼、Ⅲ期5只眼、Ⅳ期2只眼,3例患者结膜囊细菌培养阳性,仅1例患者肿瘤标记物铁蛋白轻度升高,其余患者常规免疫学检查均正常.确诊后经合理治疗病情控制,但2例患者结膜瘢痕继续进展.结论 OCP早期表现类似慢性结膜炎,提高对OCP的警惕和认识是避免误诊的重要手段.     

应用免疫荧光技术对眼瘢痕性类天疱疮的研究

目的 探讨免疫荧光技术对眼瘢痕性类天孢疮（ＯＣＰ）的实验诊断意义。方法 应用直接免疫荧光（ＤＩＦ）检测１６例ＯＣＰ患者的结膜和应用间接免疫荧光（ＨＦ）以鼠食道和正常人结膜为基质检测３４例ＯＣＰ患者的血清。结果 ＤＩＦ证实６例结膜上皮细胞基底膜上有免疫复合物（ＩｇＧ和／或ＩｇＡ）和／或Ｃ３呈线状沉积。以结膜为基质的ＨＦ证实血清中抗基底膜（ＢＭＺ）抗体４例,抗细胞间物质（ＨＳ）抗体１４例,总阳性率为５     

Glaucoma in patients with ocular cicatricial pemphigoid

This retrospective review of 111 patients with ocular cicatricial pemphigoid (CP) identifies 29 patients (26%) with glaucoma. Twenty-seven of these patients had a history of glaucoma for a mean of 11.3 years before the diagnosis of CP was made. Most had advanced glaucoma, with a long history of medication use, optic nerve damage, and visual field loss. Patients with CP and glaucoma were more likely to manifest continued high-grade conjunctival inflammation than those with CP alone despite treatment for CP (P less than 0.05). Possible mechanisms including genetic susceptibility to both diseases, drug-induced conjunctival cicatrization, and CP-induced alterations in aqueous outflow are discussed. Physicians who care for patients with CP should remain mindful of the possible coexistence or development of glaucoma in this group of patients. Patients with glaucoma and chronic conjunctivitis of uncertain etiology should be referred for evaluation by physicians experienced in the detection and management of CP.     

Systemic chemotherapy for ocular cicatricial pemphigoid

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.     

HLA antigens in ocular cicatricial pemphigoid.

HLA antigen frequencies were studied in 20 patients with ocular cicatricial pemphigoid and 245 normal persons. HLA-B12 demonstrated an increased frequency of 45% in patients with ocular cicatricial pemphigoid which was statistically significant when compared to a frequency of 19.6% in the general population (P less than 0.02). In patients with ocular cicatricial pemphigoid the prevalance of HLA-A3 was increased to 35% when compared to 22.9% in the general population, but this was not statistically significant. The frequency of finding either HLA-A3 or B12 in patients with ocular cicatricial pemphigoid was increased to 75% in comparison with 38.8% in the general population (P less than 0.005). The present study suggests that HLA-B12 and possibly HLA-A3 are genetic markers for ocular cicatricial pemphigoid.     

Treatment of ocular cicatricial pemphigoid with sulfasalazine

PURPOSE: To assess the outcome of patients with ocular cicatricial pemphigoid (OCP) treated with sulfasalazine as an alternative to dapsone. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Nine patients with biopsy-proven OCP and previous dapsone-related adverse effects (hemolysis and gastrointestinal disturbances) treated with oral sulfasalazine. METHODS: Clinical data were abstracted from patients' medical records. MAIN OUTCOME MEASURES: Patients' symptoms, ocular inflammation, conjunctival scarring, complete blood cell count (including reticulocyte count). RESULTS: 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. CONCLUSIONS: Sulfasalazine may be useful in OCP patients with previous dapsone-related adverse effects.     

Biology of interleukin-5 in ocular cicatricial pemphigoid

BACKGROUND: Ocular cicatricial pemphigoid (OCP) is an autoimmune disease characterized by the presence of autoantibodies, T-cell dysregulation, and abnormal serum levels of cytokines such as interleukin-6, interleukin-1, and tumor necrosis factor-alpha. The purpose of the present study was to investigate levels of interleukin-5 (IL-5) in the sera, eosinophil counts in the peripheral blood, and eosinophil and mast cell counts in the inflamed conjunctivae of patients with active OCP. METHODS: Seven patients diagnosed in the active phase of OCP presenting with chronic cicatrizing conjunctivitis were studied. The serum levels of IL-5 were compared to a group of seven age-, race-, and sex-matched normal human subjects. Eosinophil and mast cell counts in the patients' conjunctivae were compared to those in normal conjunctivae harvested during cataract surgery from seven normal individuals. In addition, eosinophil counts in peripheral blood of patients with active OCP were compared to those in normal individuals. RESULTS: The mean serum level of IL-5 in patients with active OCP was higher (67.23 pg/ml, range 46.33-98.26 pg/ml) than that in normal individuals (12.18 pg/ml, range 7.66-18.86). The difference was statistically significant ( P<0.001). On light microscopy the biopsied conjunctivae stained with hematoxylin and eosin revealed statistically significant differences ( P<0.001) in the mean numbers of eosinophils in the substantia propria between the patients with active OCP (6.8 cells/cm(2), range 4.8-8.2 cells/cm(2)) and normal controls (0.91 cells/cm(2), range 0.4-1.8 cells/cm(2)). The average number of mast cells found in the substantia propria of the biopsied conjunctivae was statistically significantly higher in patients with OCP (13.79 cells/cm(2), range 6.6-19.4) than in normal individuals (4.34 cells/cm(2), range 3.2-7.8; P<0.01). The average number of eosinophils in the peripheral blood of patients with active OCP (6.6x10(7)/l, range 2.9 - 9.3x10(7)/l) was statistically significantly higher ( P<0.01) than in normal controls (2.09x10(7)/l, range 0 - 4.5x10(7)/l). CONCLUSIONS: The results suggest that IL-5 may play an important role in the pathogenesis of OCP.     

Progression of disease in ocular cicatricial pemphigoid.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Cryotherapy for trichiasis in ocular cicatricial pemphigoid.

Trichiasis is a common and potentially sight threatening complication of ocular cicatricial pemphigoid and is usually secondary to cicatricial entropion. This study aimed to assess the success and complications of eyelid cryotherapy for trichiasis in a group of patients with long term follow up. The case records of all patients with ocular cicatricial pemphigoid that attended the external disease clinic at Moorfields Eye Hospital from 1980 to 1992 were reviewed. Each eyelid was divided into three horizontal zones. Cryotherapy was delivered with an Amoilette cryoprobe for approximately 30 seconds. Failure of the cryotherapy was defined as a regrowth of the eyelashes within the treated zone that either required epilation for symptom control or caused keratopathy. Ninety two lid zones were treated, involving 25 lids of 12 patients. The cumulative chance of success decreased rapidly to 40% over the first year. Thereafter, the chance of success declined slowly to 34% at 4 years. Complications included lid notching (n = 2), tarsal atrophy (n = 1), altered lid contour (n = 1), and temporarily raised intraocular pressure (n = 1). All patients had quiescent disease at the time of the cryotherapy and no patients showed increased conjunctival disease activity after treatment. Six patients were taking systemic immunosuppression medication. When ocular cicatricial pemphigoid is quiescent, lid cryotherapy has an acceptable complication rate. The major reason for recurrence of the trichiasis was attributed to inadequate follicle freezing.     

Eosinophil granule proteins expressed in ocular cicatricial pemphigoid

BACKGROUND—Blister formation and tissue damage in bullous pemphigoid have been attributed to the release of eosinophil granule proteins—namely, to eosinophil derived cationic protein (ECP) and major basic protein (MBP). In the present investigation these eosinophil granule proteins were studied in the conjunctiva of patients with ocular cicatricial pemphigoid (OCP).
METHODS—Conjunctival biopsy specimens obtained from patients with subacute (n=8) or chronic conjunctival disease (n=13) were analysed histologically and immunohistochemically using antibodies directed against EG1 (stored and secreted ECP), EG2 (secreted ECP), MBP, CD45 (common leucocyte antigen), CD3 (pan T cell marker), and HLA-DR (class II antigen).
RESULTS—Subepithelial mononuclear cells, mast cells, and neutrophils were detected in all specimens. The number of mononuclear cells, neutrophils, CD45+ cells, CD3+ cells, and the HLA-DR expression were significantly higher in the subacute than in the chronic disease group. Some eosinophils were found in specimens from five of eight patients with subacute OCP, but in none of the patients with chronic disease. The eosinophil granule proteins (ECP and MBP) were found in the epithelium and substantia propria in patients with subacute conjunctivitis.
CONCLUSIONS—Subepithelial cell infiltration in the conjunctiva greatly differs between subacute and chronic ocular cicatricial pemphigoid specimens. The findings suggest that eosinophil granule proteins may participate in tissue damage in acute phase of inflammation in OCP.

     

Blood group related antigens in ocular cicatricial pemphigoid

AIM: To study the MUC5AC and the blood group related antigen expression in ocular cicatricial pemphigoid (OCP) according to the distribution of Lewis and secretor phenotypes in OCP patients compared to normal subjects. METHODS: Immunostaining was performed on conjunctival biopsy specimens from 22 consecutive patients suffering from OCP, using monoclonal antibodies (Mabs) directed against the peptidic core MUC5AC mucin (anti-M1/MUC5AC Mabs) and against the saccharide moieties (anti-blood group related antigens). These latter included anti-Le(a), anti-Le(b), anti-sialyl Le(a), and H type 2 Mabs, which immunoreact with Lewis positive and non-secretor (Le(a)), Lewis positive and secretor (Le(b)), Lewis positive (sialyl Le(a)), and secretor (H type 2) phenotypes respectively. Serological tests were also performed to confirm the phenotype of each patient. The immunohistopathological patterns and the distribution of Lewis and secretor phenotypes were compared with the results of a previous study in normal individuals. RESULTS: (1) In OCP patients compared to the normal population, anti-M1 immunoreactivity of goblet cells was unchanged, whereas anti-Le(a), anti-Le(b), and anti-sialyl Le(a) immunoreactivities of epithelial and/or goblet cells were markedly decreased. (2) 41% of OCP patients had a non-secretor phenotype, which is statistically significantly more than the estimated incidence of the same phenotype in the French population (20%) (p approximately 0.04). CONCLUSIONS: Mucins in OCP patients showed a decreased expression of blood group related antigens whereas the MUC5AC peptidic core detected by anti-M1 Mab remained unchanged. These results also seem to indicate that OCP may be associated with a non-secretor phenotype.     

Cataract surgery combined with ocular surface reconstruction in patients with severe cicatricial keratoconjunctivitis

PURPOSE: To present the technique and outcome of cataract surgery combined with ocular surface reconstruction in patients with severe cicatricial keratoconjunctivitis. SETTING: Department of Ophthalmology, Tokyo Dental College, Chiba, Japan. METHODS: Phacoemulsification with transplantation of a limbal allograft and an amniotic membrane was performed in 4 eyes of 3 patients with cataract and end-stage cicatricial keratoconjunctivitis. The surgical technique and the improvements in visual acuity were reviewed. The follow-up ranged from 13 to 27 months. RESULTS: Phacoemulsification and intraocular lens implantation were performed in all cases without intraoperative complications. In 3 of the 4 eyes, the best corrected visual acuity improved from hand motions to 20/100, hand motions to 20/30, and counting fingers to 20/50. The visual acuity recovered to 20/60 postoperatively in 1 eye in which the preoperative visual acuity was light perception; at 1 year, the visual acuity decreased to hand motions because of recurrent fibrous tissue over the cornea. CONCLUSION: Small-incision phacoemulsification was performed safely in combination with ocular surface reconstruction in patients with cataract and end-stage cicatricial keratoconjunctivitis.