Resident Clinical Conference Ying Pan, MD

Case presentation cc: sore throat and eye pain HPI: 45 year old African American woman who presented with 2 days of worsening sore throat and bilateral eye pain and redness. mild eye discharge, fever 103 F, malaise PMH: Pneumonia 1990s Toothache 2 weeks ago, prescribed medication by dentist POH: none PSH: none NKDA Meds: none

cc: sore throat and eye pain

HPI: 45 year old African American woman who presented with 2 days of worsening sore throat and bilateral eye pain and redness.

mild eye discharge, fever 103 F, malaise

PMH: Pneumonia 1990s

Toothache 2 weeks ago, prescribed medication by dentist

POH: none

PSH: none

NKDA

Meds: none

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Exam Visual acuity (near card): 20/40 OU Pupils: round and reactive to light, no APD Motility: grossly intact Tp: 15 OD, 14 OS

Visual acuity (near card): 20/40 OU

Pupils: round and reactive to light, no APD

Motility: grossly intact

Tp: 15 OD, 14 OS

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Epidermal Cell Apoptosis Erythema Multiforme Minor cutaneous involvement Erythema Multiforme Major (Stevens-Johnson Syndrome) widespread skin involvement, usually < 10% of BSA at least two distinct mucosal sites (92-100% of cases) Toxic Epidermal Necrolysis (TEN) widespread skin involvement, usually > 30% of BSA at least two distinct mucosal sites (almost 100% of cases)

Erythema Multiforme Minor

cutaneous involvement

Erythema Multiforme Major (Stevens-Johnson Syndrome)

widespread skin involvement, usually < 10% of BSA

at least two distinct mucosal sites (92-100% of cases)

Toxic Epidermal Necrolysis (TEN)

widespread skin involvement, usually > 30% of BSA

at least two distinct mucosal sites (almost 100% of cases)

Etiologies Medications (30-50% of SJS, 80% of TEN) Antibiotics Anticonvulsants Cough/cold medications NSAID Anti-gout Anti-psychotics Carbonic anhydrase inhibitors Infections (15% of SJS) Herpes simplex virus Adenovirus Streptococci Mycoplasma pneumonia

Medications (30-50% of SJS, 80% of TEN)

Antibiotics

Anticonvulsants

Cough/cold medications

NSAID

Anti-gout

Anti-psychotics

Carbonic anhydrase inhibitors

Infections (15% of SJS)

Herpes simplex virus

Adenovirus

Streptococci

Mycoplasma pneumonia

Clinical Presentation Prodrome fever, flu-like symptoms, skin tenderness, photophobia Signs and symptoms Skin: ill defined, erythematous macular or palpular lesions with purpuric centers  vesicles and bullae  skin necrosis  sloughing of skin. Mucous membrane: mouth, conjunctiva, GI, respiratory tracts Facial edema Swelling of tongue Sore throat Shedding of nails

Prodrome

fever, flu-like symptoms, skin tenderness, photophobia

Signs and symptoms

Skin: ill defined, erythematous macular or palpular lesions with purpuric centers  vesicles and bullae  skin necrosis  sloughing of skin.

Mucous membrane: mouth, conjunctiva, GI, respiratory tracts

Facial edema

Swelling of tongue

Sore throat

Shedding of nails

Incidence SJS: 2-6 cases per million people per year TEN: 0.4-1.2 cases per million people per year Mean age SJS: range from 25-47 TEN: range from 46-63 Mortality SJS: 1-3 % TEN: 10-50 % Intervention Supportive care Steroids Immunoglobulin Plasmapheresis

Incidence

SJS: 2-6 cases per million people per year

TEN: 0.4-1.2 cases per million people per year

Mean age

SJS: range from 25-47

TEN: range from 46-63

Mortality

SJS: 1-3 %

TEN: 10-50 %

Intervention

Supportive care

Steroids

Immunoglobulin

Plasmapheresis

Acute Ocular Disease Lid edema, episcleritis, conjunctivitis Conjunctival bullae, ulceration M embrane or pseudomembrane, adhesion/symblepharon

Lid edema, episcleritis, conjunctivitis

Conjunctival bullae, ulceration

M embrane or pseudomembrane, adhesion/symblepharon

Acute Ocular Management Topical corticosteriods Lubricating eye drops Topical antibiotics Mechanical lysis of adhesion Scleral rings Scleral contact lens Amniotic membrane graft/patch

Topical corticosteriods

Lubricating eye drops

Topical antibiotics

Mechanical lysis of adhesion

Scleral rings

Scleral contact lens

Amniotic membrane graft/patch

Late Ocular Manifestations Lid margin scarring Entropion, Trichiasis Punctal occlusion Conjunctival scarring, keratinization, squamous metaplasia Decrease or loss of mucus-secreting goblet cells Fornix foreshortening, symblepharon, ankyloblepharon Meibomian gland orifice metaplasia Recurrent conjunctival inflammation

Lid margin scarring

Entropion, Trichiasis

Punctal occlusion

Conjunctival scarring, keratinization, squamous metaplasia

Decrease or loss of mucus-secreting goblet cells

Fornix foreshortening, symblepharon, ankyloblepharon

Meibomian gland orifice metaplasia

Recurrent conjunctival inflammation

Cicatricial lid margin, tarsal and conjunctival changes strongly correlate with corneal complications Keratopathy: recurrent or nonhealing epithelial defects, ulceration, neovascularization, limbal stem cell deficiency

Cicatricial lid margin, tarsal and conjunctival changes strongly correlate with corneal complications

Keratopathy: recurrent or nonhealing epithelial defects, ulceration, neovascularization, limbal stem cell deficiency

Chronic Ocular Complications Ocular Surface Support Perservative free artificial tears Punctal occlusion Autologous serum Ocular surface protection Gas-permeable scleral contact lenses Retinoic Acid Ointment Chronic Ocular Surface Inflammation Topical steroids Cyclosporine A Systemic immunosuppressive

Ocular Surface Support

Perservative free artificial tears

Punctal occlusion

Autologous serum

Ocular surface protection

Gas-permeable scleral contact lenses

Retinoic Acid Ointment

Chronic Ocular Surface Inflammation

Topical steroids

Cyclosporine A

Systemic immunosuppressive

Ocular surface reconstruction Trichiasis repair Entropion repair Amniotic membrane transplantation Mucous membrane graft Limbal stem cell transplantation Limbal stem grafts Keratolimbal allograft (KLAL) Penetrating keratoplasty Keratoprosthesis

Trichiasis repair

Entropion repair

Amniotic membrane transplantation

Mucous membrane graft

Limbal stem cell transplantation

Limbal stem grafts

Keratolimbal allograft (KLAL)

Penetrating keratoplasty

Keratoprosthesis

References Romero-Rangel T et al. Gas-Permeable Scleral Contact Lens Therapy in Ocular Surface Disease. Am J Ophthalmol 2000; 130:25-32 Wall V et al. Management of the Late Ocular Sequelae of Stevens-Johnson Syndrome. The Ocular Surface. 2003 (October), Vol 1, No. 4 192-200. Khalili B. and Bahna S. Pathogenesis and Recent Therapeutic Trends in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. Ann Allergy Asthma immunol. 2006; 97:272-281. Flach A, Smith RE, Fraunfelder FT. Stevens-Johnson Syndrome Associated with Methazolamide Treatment Reported in Two Japanese-American Women. Ophthalmology 1995; 102:1677-1680. Sall K, Stevenson OD, Mundorf TK et al. Two Multicenter, Randomized Studies of the Efficacy and Safety of Cyclosporine Ophthalmic Emulsion in Moderate to Severe Dry Eye Disease. Ophthalmology 2000; 107: 631-639. Tsubota K et al. Treatment of Persistent Corneal Epithelial Defect by Autologous Serum Application. Ophthalmology 1999; 106: 1984-1989. Inatomi T. et al. Ocular Surface Reconstruction with Combination of Cultivated Autologous Oral Mucosal Epithelial Transplantation and Penetrating Keratoplasty. Am J Ophthalmol 2006; 142:757-764. Power et al. Analysis of the Acute Ophthalmic Manifestation of the Erythema Multiforme/Stevens-Johnson Syndrome/Toxic EpidermalNecrolysis Disease Spectrum. Ophthalmology 1995; 102:1669-1676. Kaido M et al. Punctal Occlusion in the Management of Chronic Stevens-Johnson Syndrome. Ophthalmology 2004; 111:895-900. Singer L et al. Vitamin A in Stevens-Johnson Syndrome. Ann Ophthalmol 1989; 209-210

Romero-Rangel T et al. Gas-Permeable Scleral Contact Lens Therapy in Ocular Surface Disease. Am J Ophthalmol 2000; 130:25-32

Wall V et al. Management of the Late Ocular Sequelae of Stevens-Johnson Syndrome.

The Ocular Surface. 2003 (October), Vol 1, No. 4 192-200.

Khalili B. and Bahna S. Pathogenesis and Recent Therapeutic Trends in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. Ann Allergy Asthma immunol. 2006; 97:272-281.

Flach A, Smith RE, Fraunfelder FT. Stevens-Johnson Syndrome Associated with Methazolamide Treatment Reported in Two Japanese-American Women. Ophthalmology 1995; 102:1677-1680.

Sall K, Stevenson OD, Mundorf TK et al. Two Multicenter, Randomized Studies of the Efficacy and Safety of Cyclosporine Ophthalmic Emulsion in Moderate to Severe Dry Eye Disease. Ophthalmology 2000; 107: 631-639.

Tsubota K et al. Treatment of Persistent Corneal Epithelial Defect by Autologous Serum Application. Ophthalmology 1999; 106: 1984-1989.

Inatomi T. et al. Ocular Surface Reconstruction with Combination of Cultivated Autologous Oral Mucosal Epithelial Transplantation and Penetrating Keratoplasty. Am J Ophthalmol 2006; 142:757-764.

Power et al. Analysis of the Acute Ophthalmic Manifestation of the Erythema Multiforme/Stevens-Johnson Syndrome/Toxic EpidermalNecrolysis Disease Spectrum. Ophthalmology 1995; 102:1669-1676.

Kaido M et al. Punctal Occlusion in the Management of Chronic Stevens-Johnson Syndrome. Ophthalmology 2004; 111:895-900.

Singer L et al. Vitamin A in Stevens-Johnson Syndrome. Ann Ophthalmol 1989; 209-210