Ocular Cicatricial Pemphigoid (OCP)
No Results
No Results
processing….
Ocular cicatricial pemphigoid (OCP) is one of the subsets of mucous membrane pemphigoid (MMP), a group of systemic autoimmune diseases characterized by T-lymphocyte dysregulation, the production of circulating autoantibodies directed against a variety of adhesion molecules in the hemidesmosome-epithelial membrane complex, and the production of proinflammatory cytokines and immune system activation markers. OCP can affect the skin and other mucous membranes (eg, oral mucosa, pharynx, larynx, trachea, esophagus, vagina, urethra, anus), in addition to its hallmark feature, chronic cicatrizing conjunctivitis. [1]
See image below depicting stage II ocular cicatricial pemphigold.
The pathophysiologic mechanisms of ocular cicatricial pemphigoid (OCP), as well as conjunctival fibrosis, are not completely understood. Clearly, a defect exists in immunoregulation, with production of autoantibodies directed against the beta 4 subunit of alpha 6 beta 4 integrin, and, reportedly, in some instances, against alpha 3, beta 3, or gamma 2 subunits of laminin 5. [2]
A triggering agent in the genetically susceptible individual, leading to clinical manifestations of the disease, may occur in a “2-hit” mechanism. It is probably operative in some patients. Human leukocyte antigen DR2 (HLA-DR2), human leukocyte antigen DR4 (HLA-DR4 [HLA-DR*0401]), and human leukocyte antigen DQw7 (HLA-DQw7 [DQB1*0301]) genotypes have been identified as conferring increased susceptibility to the development of OCP.
In some patients, systemic practolol therapy and topical antiglaucoma drugs, such as pilocarpine, timolol, epinephrine, Humorsol, idoxuridine, and phospholine iodide, have triggered the onset of OCP. The term pseudopemphigoid or drug-induced pemphigoid may be used to describe these cases. Whether or not these cases associated with medication use are identical to OCP is not completely clear.
On the molecular level, the initial trigger may be a process by which the OCP antigen undergoes a conformational change that provides antigenic stimulation. This signal results in the generation of B-cell clones that produce antibodies against antigens located at the basement membrane zone (BMZ), initiating a type II Gell and Coombs hypersensitivity reaction. The antibodies of immunoglobulin G (IgG), immunoglobulin A (IgA), and/or immunoglobulin M (IgM) bind to the antigen and initiate complement activation.
Circulating autoantibodies are difficult to demonstrate by classic indirect immunofluorescence technique in patients with OCP. Specialized radioimmunoassay and immunoblot techniques allow the circulating autoantibodies to be seen in all patients with OCP who have active conjunctivitis. The resultant inflammatory mediators that are produced induce migration of lymphocytes, eosinophils, neutrophils, and mast cells to the BMZ. The separation of the epithelium from the underlying tissues within the BMZ may be the result of direct cytotoxic action or the effect of lysosomal proteolytic enzymes.
Fibroblast activation secondary to inflammatory cytokine influences, with collagen production and subsequent cicatrization, is the end result in the conjunctiva. Progressive fibrosis causes profound tear insufficiency, meibomian gland dysfunction, and mucin deficiency. Symblepharon formation, trichiasis, distichiasis, and keratinization cause corneal epitheliopathy, persistent corneal epithelial defects, stromal ulcers, corneal scarring, neovascularization, and even perforation.
OCP is a chronic, slowly progressive, bilateral blinding, systemic autoimmune disease. Multiple antigens in the BMZ of squamous epithelia may serve as targets for a spectrum of autoantibodies observed in OCP. Molecular definition of these autoantigens facilitates the classification and characterization of subsets of OCP. Sera from patients with OCP have been shown to recognize beta 4 integrin, which is a 205-kDa protein, also known as CD104. A subset of patients with clinical features similar to OCP also has been shown to have autoantibodies against epiligrin, which is identified as laminin 5, a ligand for alpha 6 beta 4 integrin, and autoantibodies to the alpha 6 integrin subunit. OCP probably is a spectrum of several different diseases associated with different target antigens, different triggers, and different therapeutic responses.
United States
The incidence of ocular cicatricial pemphigoid (OCP) is estimated at between 1 in 8,000 and 1 in 46,000 ophthalmic patients. It is likely that early stages of OCP are not reflected in these estimates because of difficulties in making the correct diagnosis. The real frequency of the disease is probably higher.
International
Distribution appears to be worldwide. No geographical predilection is reported.
Oral lesions occur in 75-100% of patients with OCP. Skin involvement (eg, face, neck, scalp) occurs in approximately 25% of patients with OCP.
OCP can occur in all races.
Females predominate patients diagnosed with OCP. The female-to-male ratio is estimated to be 1.5:1 to 3:1.
Average age of onset is 50-60 years; however, the exact age of onset may be younger, since most patients with early stages of OCP remain undiagnosed. Some cases have been diagnosed as early as 12 and 19 years.
Foster CS. Cicatricial pemphigoid. Trans Am Ophthalmol Soc. 1986. 84:527-663. [Medline].
Chan RY, Bhol K, Tesavibul N, et al. The role of antibody to human beta4 integrin in conjunctival basement membrane separation: possible in vitro model for ocular cicatricial pemphigoid. Invest Ophthalmol Vis Sci. 1999 Sep. 40(10):2283-90. [Medline].
Nguyen QD, Foster CS. Cicatricial pemphigoid: diagnosis and treatment. Int Ophthalmol Clin. 1996 Winter. 36(1):41-60. [Medline].
Cordero Coma M, Yilmaz T, Foster CS. Tumour necrosis factor-alpha in conjunctivae affected by ocular cicatricial pemphigoid. Acta Ophthalmol Scand. 2007 Nov. 85(7):753-5. [Medline].
Power WJ, Neves RA, Rodriguez A, et al. Increasing the diagnostic yield of conjunctival biopsy in patients with suspected ocular cicatricial pemphigoid. Ophthalmology. 1995 Aug. 102(8):1158-63. [Medline].
Hall VC, Liesegang TJ, Kostick DA, et al. Ocular mucous membrane pemphigoid and ocular pemphigus vulgaris treated topically with tacrolimus ointment. Arch Dermatol. 2003 Aug. 139(8):1083-4. [Medline].
Foster CS, Wilson LA, Ekins MB. Immunosuppressive therapy for progressive ocular cicatricial pemphigoid. Ophthalmology. 1982 Apr. 89(4):340-53. [Medline].
Foster CS, Ahmed AR. Intravenous immunoglobulin therapy for ocular cicatricial pemphigoid: a preliminary study. Ophthalmology. 1999 Nov. 106(11):2136-43. [Medline].
Sami N, Letko E, Androudi S, et al. Intravenous immunoglobulin therapy in patients with ocular-cicatricial pemphigoid: a long-term follow-up. Ophthalmology. 2004 Jul. 111(7):1380-2. [Medline].
Foster CS, Chang PY, Ahmed AR. Combination of rituximab and intravenous immunoglobulin for recalcitrant ocular cicatricial pemphigoid: a preliminary report. Ophthalmology. 2010 May. 117(5):861-9. [Medline].
Daoud Y, Amin KG, Mohan K, Ahmed AR. Cost of intravenous immunoglobulin therapy versus conventional immunosuppressive therapy in patients with mucous membrane pemphigoid: a preliminary study. Ann Pharmacother. 2005 Dec. 39(12):2003-8. [Medline].
Heiligenhaus A, Shore JW, Rubin PA, et al. Long-term results of mucous membrane grafting in ocular cicatricial pemphigoid. Implications for patient selection and surgical considerations. Ophthalmology. 1993 Sep. 100(9):1283-8. [Medline].
Sainz de la Maza M, Tauber J, Foster CS. Cataract surgery in ocular cicatricial pemphigoid. Ophthalmology. 1988 Apr. 95(4):481-6. [Medline].
Neumann R, Tauber J, Foster CS. Remission and recurrence after withdrawal of therapy for ocular cicatricial pemphigoid. Ophthalmology. 1991 Jun. 98(6):858-62. [Medline].
Foster CS, Neumann R, Tauber J. Long-term results of systemic chemotherapy for ocular cicatricial pemphigoid. Doc Ophthalmol. 1992. 82(3):223-9. [Medline].
Saw VP, Dart JK, Rauz S, et al. Immunosuppressive therapy for ocular mucous membrane pemphigoid strategies and outcomes. Ophthalmology. 2008 Feb. 115(2):253-261.e1. [Medline].
Goldich Y, Ziai S, Artornsombudh P, Avni-Zauberman N, Elbaz U, Rootman DS, et al. Characteristics of patients with ocular cicatricial pemphigoid referred to major tertiary hospital. Can J Ophthalmol. 2015 Apr. 50 (2):137-42. [Medline].
Friedman J, Marcovich AL, Kleinmann G, Schattner A. Low-dose pulsed intravenous cyclophosphamide for severe ocular cicatricial pemphigoid in elderly patients. Cornea. 2014 Oct. 33 (10):1066-70. [Medline].
C Stephen Foster, MD, FACS, FACR, FAAO, FARVO Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary; Founder and President, Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution
C Stephen Foster, MD, FACS, FACR, FAAO, FARVO is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Association of Immunologists, American College of Rheumatology, American College of Surgeons, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, American Uveitis Society, Association for Research in Vision and Ophthalmology, Massachusetts Medical Society, Royal Society of Medicine, Sigma Xi
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Aldeyra Therapeutics (Lexington, MA); Bausch & Lomb Surgical, Inc (Rancho Cucamonga, CA); Eyegate Pharma (Waltham, MA); Novartis (Cambridge, MA); pSivida (Watertown, MA); Xoma (Berkeley, CA)<br/>Received research grant from: Alcon; Aldeyra Therapeutics; Allakos Pharmaceuticals; Allergan; Bausch & Lomb; Clearside Biomedical; Dompé pharmaceutical; Eyegate Pharma; Mallinckrodt pharmaceuticals; Novartis; pSivida; Santen.
Erik Letko, MD Corneal Consultants of Colorado
Disclosure: Nothing to disclose.
Rola Hamam, MD Assistant Professor, Department of Ophthalmology, American University of Beirut
Rola Hamam, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.
Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Glaucoma Society
Disclosure: Nothing to disclose.
Christopher J Rapuano, MD Professor, Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital
Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Ophthalmological Society, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, International Society of Refractive Surgery
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, AAO, OMIC, Allergan; Avedro; Bio-Tissue; GSK, Novartis; Shire; Sun Ophthalmics; TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Avedro; Bio-Tissue; Shire.
Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.
Jerre Freeman, MD Founder and Chairman, Memphis Eye and Cataract Associates; Clinical Professor, Department of Ophthalmology, University of Tennessee Health Science Center College of Medicine
Jerre Freeman, MD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, American Society of Cataract and Refractive Surgery, Tennessee Medical Association
Disclosure: Nothing to disclose.
Ocular Cicatricial Pemphigoid (OCP)
Research & References of Ocular Cicatricial Pemphigoid (OCP)|A&C Accounting And Tax Services
Source
0 Comments