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Sections Peripheral Ulcerative Keratitis
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Medication
Follow-up
Questions & Answers
Media Gallery
References

Presentation

History

Peripheral ulcerative keratitis (PUK) is frequently a manifestation of an occult systemic disease. Thus, a thorough systemic history is very important and should include chief complaint, characteristics of present illness, past medical history, family history, and a meticulous review of systems.^[4]

Ocular symptoms vary, but nonspecific foreign body sensation with or without eye pain, tearing, photophobia, and reduced visual acuity are the most common symptoms for patients with PUK.

Loss of vision can occur quickly when PUK progresses.

PUK associated with RA, GPA, PAN, and RP is often linked with scleritis, and eye pain may be pronounced in these individuals.^[4]PUK in patients with Mooren ulcer may also produce pain, although there is no scleral involvement.

Past medical history and review of systems helps to determine the possible underlying systemic diseases. RA, SLE, PAN, GPA, or RP may present with the following symptoms, which should be emphasized in the review of systems^[12]:

General - Constitutional symptoms, such as chills, fever, poor appetite, recent weight loss, and fatigue
Skin - Rashes, nodules, vesicles, ulcer, nail changes, and periungual infarcts
Respiratory - Coughing, wheezing, pneumonia, and shortness of breath
Cardiac - Chest pain or discomfort and dyspnea
Gastrointestinal - Abdominal pain, nausea, vomiting, difficulty swallowing, and diarrhea
Musculoskeletal - Muscle or joint pain, arthritis, back pain, and limitation of motion
Neurologic - Headaches, seizures, psychiatric, paralysis, and numbness/tingling
Other systemic symptoms - Deafness, swollen ear lobes, ear infections, vertigo, and noises in ears (suggestive of RP)

Physical

Examination should be complete and include an overview of the head (including the nose, mouth, and external ear), trunk, joints, and extremities.^[4]Skin lesions should also be noted.

A complete ophthalmic examination should be performed with special emphasis on the conjunctiva, sclera, and cornea. Anterior chamber, vitreous, and fundus examinations are also important.

Patients with PUK typically present with decreased visual acuity (secondary to induced irregular astigmatism), tearing, and eye irritation with or without pain of variable duration.^[5]

Bilateral disease may be present in 21% of patients.^[13]

Slit lamp examination reveals a crescent-shaped destructive lesion of the juxtalimbal corneal stroma associated with an epithelial defect, stromal yellow-white infiltrates composed of inflammatory cells, and varying degrees of corneal stromal thinning (minimal to full thickness) adjacent to the limbus.^[6]

In severe cases, the peripheral cornea is progressively destroyed circumferentially, and the central corneal is also damaged.

PUK accompanied by necrotizing scleritis almost always indicates the presence of a potentially lethal systemic disease.^[4]

The anterior chamber should be evaluated for depth and inflammation.

A posterior segment examination is typically indicated to help determine the underlying etiology.

Causes

The etiologies for developing peripheral ulcerative keratitis (PUK) are multiple and extensive. Connective tissue and vasculitic diseases are the major risk factors. Other disorders that can cause PUK include systemic and local infectious conditions, as well as local degenerative disorders. Although vitamin A deficiency is commonly associated with central corneal ulceration, it has also been reported to cause peripheral ulceration with or without bacterial infection of the ulcer.^{[14, 15]}

The differential diagnosis of PUK is outlined below.^[4]

Noninfectious conditions
- Systemic - RA, SLE, RP, sarcoidosis, progressive systemic sclerosis, rosacea, GPA, PAN, juvenile idiopathic arthritis,^[16]giant cell arteritis, Behçet disease,^[17]inflammatory bowel disease, pyoderma gangrenosum,^[18]metabolic conditions, nutritional deficiencies, and drug-induced side effect (checkpoint inhibitor ipilimumab)^[19]
- Local - Mooren ulcer, marginal keratitis, blepharitis (eg, staphylococcal infection, rosacea), contact lens use, chemical injury to the eyes,^[20]trauma, neurotrophic and neuroparalytic causes, keratoconjunctivitis sicca, Terrien marginal degeneration, pellucid marginal degeneration, and furrow degeneration^[5]
- Surgery - Trabeculectomy,^[21]cataract surgery^[22]
Infectious conditions
- Systemic -Shigella species, tuberculosis, syphilis, hepatitis, HIV, gonococcus, Salmonella species, and bacillary dysentery
- Local - Herpes simplex keratitis, varicella-zoster keratitis, bacterial keratitis, fungal keratitis, and Acanthamoeba species
Masquerade - Malignancy - Leukemia^{[23, 24]}

Differential Diagnoses

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Shiuey Y, Foster CS. Peripheral ulcerative keratitis and collagen vascular disease. Int Ophthalmol Clin. 1998 Winter. 38(1):21-32. [QxMD MEDLINE Link].
Messmer EM, Foster CS. Vasculitic peripheral ulcerative keratitis. Surv Ophthalmol. 1999 Mar-Apr. 43(5):379-96. [QxMD MEDLINE Link].
Foster CS, Sainz de la Maza M. Immunological considerations of the sclera. Foster CS, ed. The Sclera. 1st ed. New York: Springer-Verlag; 1993:33-58.
Gregory JK, Foster CS. Peripheral ulcerative keratitis in the collagen vascular diseases. Int Ophthalmol Clin. 1996 Winter. 36(1):21-30. [QxMD MEDLINE Link].
Eiferman RA, Carothers DJ, Yankeelov JA Jr. Peripheral rheumatoid ulceration and evidence for conjunctival collagenase production. Am J Ophthalmol. 1979 May. 87(5):703-9. [QxMD MEDLINE Link].
Brown SI, Grayson M. Marginal furrows. A characteristic corneal lesion of rheumatoid arthritis. Arch Ophthalmol. 1968 May. 79(5):563-7. [QxMD MEDLINE Link].
Tauber J, Sainz de la Maza M, Hoang-Xuan T, et al. An analysis of therapeutic decision making regarding immunosuppressive chemotherapy for peripheral ulcerative keratitis. Cornea. 1990 Jan. 9(1):66-73. [QxMD MEDLINE Link].
Hoang-Xaun T, Foster CS, Rice BA. Scleritis in relapsing polychondritis. Response to therapy. Ophthalmology. 1990 Jul. 97(7):892-8. [QxMD MEDLINE Link].
Watson PG, Hazelman BC. The Sclera and Systemic Disorders. Philadelphia: WB Saunders Co; 1976. 241.
Sangwan VS, Zafirakis P, Foster CS. Mooren's ulcer: current concepts in management. Indian J Ophthalmol. 1997 Mar. 45(1):7-17. [QxMD MEDLINE Link].
Tabbara KF. Mooren's ulcer. Int Ophthalmol Clin. 1986 Winter. 26(4):91-8. [QxMD MEDLINE Link].
Knox Cartwright NE, Tole DM, Georgoudis P, Cook SD. Peripheral ulcerative keratitis and corneal melt: a 10-year single center review with historical comparison. Cornea. 2014 Jan. 33(1):27-31. [QxMD MEDLINE Link].
Mattern RM, Ding J. Keratitis with Kocuria palustris and Rothia mucilaginosa in Vitamin A Deficiency. Case Rep Ophthalmol. 2014 Jan. 5(1):72-7. [QxMD MEDLINE Link].
Lange AP, Moloney G, Sheldon CA, Sasaki S, Holland SP. Bilateral Corneal Ulceration Caused by Vitamin A Deficiency in Eosinophilic Gastroenteropathy. Case Report Ophthalmol. 2011 Sep. 2(3):302-306. [QxMD MEDLINE Link]. [Full Text].
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Papavasileiou E, Prasad S, Freitag SK, Sobrin L, Lobo AM. Ipilimumab-induced Ocular and Orbital Inflammation-A Case Series and Review of the Literature. Ocul Immunol Inflamm. 2016 Apr. 24 (2):140-6. [QxMD MEDLINE Link].
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Papaconstantinou D, Georgopoulos G, Kalantzis G, Krassas A, Georgalas I. Peripheral ulcerative keratitis after trabeculectomy in a patient with rheumatoid arthritis. Cornea. 2009 Jan. 28(1):111-3. [QxMD MEDLINE Link].
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Chawla B, Agarwal P, Tandon R, et al. Peripheral ulcerative keratitis with bilateral optic nerve involvement as an initial presentation of acute lymphocytic leukemia in an adult. Int Ophthalmol. 2007 Nov 16. [QxMD MEDLINE Link].
Morjaria R, Barge T, Mordant D, Elston J. Peripheral ulcerative keratitis as a complication of acute myeloid leukaemia. BMJ Case Rep. 2014 Oct 31. 2014:[QxMD MEDLINE Link].
Carson DA. Rheumatoid factor. Kelley WN, Harris ED Jr, Ruddy S, Sledge CB, eds. Textbook of Rheumatology. 3rd ed. Philadelphia: WB Saunders Co; 1989. 664-679.
Lüdemann G, Gross WL. Autoantibodies against cytoplasmic structures of neutrophil granulocytes in Wegener's granulomatosis. Clin Exp Immunol. 1987 Aug. 69(2):350-7. [QxMD MEDLINE Link].
Savage CO, Winearls CG, Jones S, et al. Prospective study of radioimmunoassay for antibodies against neutrophil cytoplasm in diagnosis of systemic vasculitis. Lancet. 1987 Jun 20. 1(8547):1389-93. [QxMD MEDLINE Link].
Nolle B, Specks U, Ludemann J, et al. Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener granulomatosis. Ann Intern Med. 1989 Jul 1. 111(1):28-40. [QxMD MEDLINE Link].
Garg A, De Rojas J, Mathews P, Hazan A, Lin J, Trief D, et al. Using Anterior Segment Optical Coherence Tomography to Monitor Disease Progression in Peripheral Ulcerative Keratitis. Case Rep Ophthalmol Med. 2018. 2018:3705753. [QxMD MEDLINE Link].
Squirrell DM, Winfield J, Amos RS. Peripheral ulcerative keratitis 'corneal melt' and rheumatoid arthritis: a case series. Rheumatology (Oxford). 1999 Dec. 38(12):1245-8. [QxMD MEDLINE Link].
Sharma N, Sinha G, Shekhar H, Titiyal JS, Agarwal T, Chawla B, et al. Demographic profile, clinical features and outcome of peripheral ulcerative keratitis: a prospective study. Br J Ophthalmol. 2015 Nov. 99 (11):1503-8. [QxMD MEDLINE Link].
Liegner JT, Yee RW, Wild JH. Topical cyclosporine therapy for ulcerative keratitis associated with rheumatoid arthritis. Am J Ophthalmol. 1990 May 15. 109(5):610-2. [QxMD MEDLINE Link].
Miyazaki D, Tominaga T, Kakimaru-Hasegawa A, et al. Therapeutic effects of tacrolimus ointment for refractory ocular surface inflammatory diseases. Ophthalmology. 2008 Jun. 115(6):988-992.e5. [QxMD MEDLINE Link].
Chen J, Xie H, Wang Z, et al. Mooren's ulcer in China: a study of clinical characteristics and treatment. Br J Ophthalmol. 2000 Nov. 84(11):1244-9. [QxMD MEDLINE Link].
Clewes AR, Dawson JK, Kaye S, et al. Peripheral ulcerative keratitis in rheumatoid arthritis: successful use of intravenous cyclophosphamide and comparison of clinical and serological characteristics. Ann Rheum Dis. 2005 Jun. 64(6):961-2. [QxMD MEDLINE Link].
Thomas JW, Pflugfelder SC. Therapy of progressive rheumatoid arthritis-associated corneal ulceration with infliximab. Cornea. 2005 Aug. 24(6):742-4. [QxMD MEDLINE Link].
Atchia II, Kidd CE, Bell RW. Rheumatoid arthritis-associated necrotizing scleritis and peripheral ulcerative keratitis treated successfully with infliximab. J Clin Rheumatol. 2006 Dec. 12(6):291-3. [QxMD MEDLINE Link].
Pham M, Chow CC, Badawi D, Tu EY. Use of infliximab in the treatment of peripheral ulcerative keratitis in Crohn disease. Am J Ophthalmol. 2011 Aug. 152(2):183-188.e2. [QxMD MEDLINE Link].
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Albert M, Beltrán E, Martínez-Costa L. [Rituximab in rheumatoid arthritis-associated peripheral ulcerative keratitis]. Arch Soc Esp Oftalmol. 2011 Apr. 86(4):118-20. [QxMD MEDLINE Link].
Ebrahimiadib N, Modjtahedi BS, Roohipoor R, Anesi SD, Foster CS. Successful Treatment Strategies in Granulomatosis With Polyangiitis-Associated Peripheral Ulcerative Keratitis. Cornea. 2016 Nov. 35 (11):1459-1465. [QxMD MEDLINE Link].
Lambiase A, Sacchetti M, Sgrulletta R, et al. Amniotic membrane transplantation associated with conjunctival peritomy in the management of Mooren's ulcer: a case report. Eur J Ophthalmol. 2005 Mar-Apr. 15(2):274-6. [QxMD MEDLINE Link].
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Foster CS, Forstot SL, Wilson LA. Mortality rate in rheumatoid arthritis patients developing necrotizing scleritis or peripheral ulcerative keratitis. Effects of systemic immunosuppression. Ophthalmology. 1984 Oct. 91(10):1253-63. [QxMD MEDLINE Link].
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Media Gallery

Peripheral ulcerative keratitis in the right eye of a patient with rheumatoid arthritis. Cyanoacrylate glue has been placed.
Same patient as in previous image, 1 year posttreatment.
Left eye of same patient as in previous images. Note the corneal thinning and scarring.

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Author

Ellen N Yu-Keh, MD Consulting Staff, Department of Ophthalmology, St Luke's Medical Center, Quezon City, Philippines

Ellen N Yu-Keh, MD is a member of the following medical societies: Philippine Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

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, The Scientific Research Honor Society

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); Allakos (Redwood City, CA) Serve(d) as a speaker or a member of a speakers bureau for: Alcon (Geneva, Switzerland); Allergan (Dublin, Ireland); Mallinckrodt (Staines-upon-Thames, United Kingdom) Received research grant from: Alcon; Aldeyra Therapeutics; Allakos Pharmaceuticals; Allergan; Bausch & Lomb; Clearside Biomedical; Dompé pharmaceutical; Eyegate Pharma; Mallinckrodt pharmaceuticals; Novartis; pSivida; Santen; Aciont Stock for: Eyegate Pharma.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Christopher J Rapuano, MD Professor, Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University; Director of the Cornea Service, 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: AAO; OMIC; American Society of Ophthalmic Trauma (ASOT); Avellino, Baxis; Bio-Tissue; Celularity; Dompe; Emmecell; Glaukos; Kala; Oyster Point; Sun Ophthalmics; Tarsus; TearLab Serve(d) as a speaker or a member of a speakers bureau for: Glaukos; Dompe; Bio-Tissue Received research grant from: Glaukos Received income in an amount equal to or greater than $250 from: AAO; OMIC; Baxis; Bio-Tissue; Cellularity; Dompe; Glaukos; Kala; Sun Ophthalmics; TearLab stock options for: RPS, Fount Bio.

Chief Editor

Andrew A Dahl, MD, FACS Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center

Andrew A Dahl, MD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Intraocular Lens Society, American Medical Association, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Medical Society of the State of New York, New York State Ophthalmological Society, Outpatient Ophthalmic Surgery Society

Disclosure: Nothing to disclose.

Additional Contributors

Fernando H Murillo-Lopez, MD Senior Surgeon, Unidad Privada de Oftalmologia CEMES

Fernando H Murillo-Lopez, MD is a member of the following medical societies: American Academy of Ophthalmology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Lijing Yao, MD, to the development and writing of this article.

Sections Peripheral Ulcerative Keratitis
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Medication
Follow-up
Questions & Answers
Media Gallery
References

Peripheral Ulcerative Keratitis Clinical Presentation

History

Physical

Causes

References

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