Download Emmett, Sarah - American Academy of Optometry

American Academy of Optometry
Residents Day Application
Stevens-Johnson Syndrome: A Case Report
Sarah A. Emmett, O.D.
3900 Crosby Dr. #813
Lexington, KY 40515
[email protected]
Abstract
A 33-year-old Indian male presents to the Urgent Care Clinic complaining of red, swollen
eyes with photophobia and mucous discharge. After examination, treatment and multiple
follow up visits the diagnosis of Stevens-Johnson Syndrome is made.
Case Report
On August 4, 2009, a 33-year-old Indian male presented to the Urgent Care Clinic with
complaints of red, swollen eyes. The patient also reported photophobia and mucous
discharge. The symptoms began four days prior, at which time Polytrim Solution was
used that had been prescribed in the past for another family member. The patient started
taking Azithromycin (Z-Pak) two days earlier for an upper respiratory infection. He was
not taking any other medications and does not have any medical diagnoses.
Upon further questioning, he reported oral ulcers, fatigue and fever. Due to the many
disconcerting symptoms, he referred himself to the Infectious Disease Clinic the day
before. At that visit he received reassurance to continue the Z-pak and if symptoms
persisted or increased, to report back to the clinic. The patient had been recently
traveling within the United States. He also mentioned that he was undergoing a lot of
stress at work.
Pertinent Findings
His corrected visual acuity at distance was 20/50 OD and 20/60 OS. Pinhole acuity was
20/40 OD and 20/50 OS. Pupils were round and equal with adequate reactivity and no
APD. Intraocular pressure was taken using the Tonopen and was 15mmHg OU. The
periorbital area was mildly edematous OU. Slit-lamp exam revealed a mucous, white
discharge lining the eyelid margins. There was moderate conjunctival injection of both
eyes. Corneal edema was present OU, although no epithelial defects were present. The
anterior chamber was deep and quiet. No lymphadenopathy was present. A Rapid
Pathogen Screener study was preformed on initial visit with a negative result for all
Adenoviral subtypes. The clinical performance of the Rapid Pathogen Screener is
detailed below as detailed on the website.12
Clinical performance*:
Sensitivity:
Specificity:
Overall agreement:
Positive predictive value:
Negative predictive value:
Adeno
Detector
89%
93%
93%
82%
96%
Cell
Culture
92%
100%
98%
100%
98%
* measured in a blinded, multi center study in 4 hospitals, "gold standard" was cell culture, cell culture
showed a sensitivity of 92, a specificity of 100 and a total agreement 98 %, discrepant results were tested
with PCR as a referee, out of the 12 culture negative and RPS positive samples 3 were found to be PCR
positive.
The initial impression was non-specific acute conjunctivitis. Gatifloxacin was prescribed
to use four times a day OU and samples of non-preserved artificial tears were dispensed
to use between antibiotic dosing. Follow-up was scheduled for forty-eight hours.
The patient returned in two days for follow-up #1. Vision had improved to 20/20- OU.
Anterior exam revealed pseudomembranes inferiorly and superiorly OU with continued
discharge. Patient was suffering from severe lethargy and confusion. He also reported an
increase in ulcers in his mouth and throat and said that ulcers were now on his genitalia
as well. The patient was sent back to the Infectious Disease Clinic immediately and was
admitted to the hospital for concern of Behcet Disease.
While spending seven days as an inpatient, multiple studies were preformed. The patient
underwent numerous hematology, chemistry, microbiology and radiology studies.
During the course of his stay in the hospital he was tested numerous infectious agents
including Epstein Barr Virus, Hepatitis B and C, HIV, Syphilis, Neisseria, Chlamydia,
Mycoplasma and Herpes Virus. Results of all tests were negative. The only remarkable
lab finding was an elevated C-reactive protein of 5.1 mg/dL, approximately five times the
normal level. The elevated C-reactive protein provides evidence of systemic
inflammation, although the origin was never determined. The patient was treated with
Clindamycin and Diflucan and was discharged one week after admission with
improvement in his symptoms.
On follow-up visit #2, the ophthalmic exam revealed a decrease in vision to 20/40 OD
and 20/30 OS. Pseudomembrances were evident superiorly and inferiorly in both eyes.
The pseudomembranes were removed using a moistened cotton-tipped applicator. A
viral culture was preformed with a negative result. Gatifloxicin was discontinued and
Tobradex Ointment TID and Xylet TID were instituted. The disgnosis of StevensJohnson syndrome was suspected. Below are pictures demonstrating the appearance of
the pseudomembranes on this patient on this date.
Over the next ten days the patient was seen on three more occasions. The
pseudomembranes continued to be removed at each visit. The treatment regimen was
altered to Pred Forte 1% Q2H and Tobradex Ointment QHS. On the last visit there were
not any pseudomembranes apparent. Mild sub-epithelial fibrosis was evident. The Pred
Forte 1% was tapered to QID and the patient was instructed to return in one week.
Differential Diagnosis
The primary differential diagnosis for this patient was Behcet Disease. Behcet Disease is
a vasculitis with signs and symptoms including oral and genital ulcers, intraocular
inflammation, fever and disorientation. The neurological symptoms the patient exhibited
on the first follow up visit were especially alarming and warranted further investigation.
This potential diagnosis was eliminated following dilated fundus exam and MRI results.
The interpretation of the MRI included, “no evidence of neuro-Behcet’s desease.”
Some other differential diagnoses include ocular cicatricial pemphigoid, squamous cell
carcinoma, scleroderma, viral, bacterial or allergic conjunctivitis, trachoma, sarcoidosis,
ocular rosacea, radiation or chemical burn.
-Ocular cicatricial pemphigoid is an autoimmune disease, typically in patients
over 55 years characterized by anterior segment inflammation. Ocular Cicatricial
Pemphigoid has an insidious onset versus the acute onset of Stevens-Johnson syndrome.
-Squamous cell carcinoma is a malignant epithelial neoplasm that is almost
always unilateral, unlike the symmetric, bilateral sings and symptoms in this case.
-Scleroderma is a connective tissue disease that has ocular manifestations
including burning, itching and discharge in the eye. Scleroderma was ruled out based on
the negative result for anti-nuclear antibodies.
-Conjunctivitis is a swelling of the eye with multiple potential causes. The patient
in this case did not have any signs of allergic conjunctivitis, whereas signs for bacterial
and viral conjunctivitis were both present. Consistent with common viral
conjunctivitides, the patient’s symptoms were bilateral and followed the onset of another
systemic infection, although viral culture and Rapid Pathogen Screening were both
negative. Similar to many bacterial conjunctivitides, the patient was experiencing a
mucous discharge, but uncommon to most bacterial infections, this patient had bilateral
signs and symptoms.
-Trachoma is a bacterial infection of the eye that leads to conjunctivitis. In this
patient the labs yielded a negative culture result for Chlamydia trachomatis.
-Sarcoidosis is a disease that causes inflammation in multiple organs, the lungs in
particular. In this patient the chest x-rays were reported as, “clear without opacity.”
-Ocular Rosacea is an inflammatory condition of the eye that is associated with
the chronic skin condition, Acne Rosacea. The patient in this case did not have any signs
of Acne Rosacea including telaniectasias or papules.
-Radiation and chemical burn were ruled out per patient history.
Diagnosis and Discussion
Stevens-Johnson Syndrome (SJS) is thought to be an immunologic hypersensitivity
reaction secondary to either drugs or microorganisms. Acute blistering of the skin and at
least two mucous membranes is characteristic of SJS.3 SJS can be a life-threatening
condition that is often associated with severe ocular complications. The most common
drugs inducing SJS are antibiotics, anti-epileptic medications or non-steroidal antiinflammatory drugs. A few examples of medications that have been known to cause SJS
include Sulfonamides, Carbamazipine and Aspirin. Some microorganisms that have been
known to induce SJS are Mycoplasma, Herpes Virus and Adenovirus.
SJS is a self-limited disease with an acute phase that typically lasts approximately six
weeks. It can develop into Toxic Epidermal Necrolysis that is thought to be a continuum
of SJS. Mortality rates for SJS have been reported as high as 30%.6 Death is usually the
result of infection secondary to compromise of the skin.
Diagnosis of SJS is based on a history of fever and acute inflammation of mucosal
membranes.5 Some of the common presenting signs of acute SJS include target skin
lesions and mucous membrane ulceration. It is reported that two-thirds of patients have
conjunctivitis as part of the syndrome.9 In addition to conjunctivitis, other ocular signs
and symptoms that may manifest during acute SJS include eyelid edema, conjunctival
injection, decrease in visual acuity, pseudomembranes, anterior uveitis and scleritis. One
study reported ocular involvement with SJS as 81.3%.2 It is important to note that
mucosal inflammation involving the mouth and eyes frequently persists longer than skin
lesions.14
After the initial attack of SJS has taken place, 50% of patients continue to have ocular
surface complications.8 Chronic ocular problems include symblepharon, entropion,
ectropion, trichiasis, dry eye, persistent conjunctival inflammation, conjunctival injection
and corneal opacities. Management of ocular sequelae secondary to SJS involves ocular
surface reconstruction, support and protection.14
In addition to the potential of having the responsibility of reporting an acute SJS episode
and treating a chronic ocular complication, progressive changes in the cornea altering
refraction also can occur. A gradual increase in astigmatism from subepithelial scarring
and keratitis has also been documented. These patients may require multiple prescription
changes in a relatively short amount of time. It is important to be aware of the initial
inciting agent, give good patient education and recognize the pathological process
causing the change in corneal astigmatism. Below are pictures of a patient two months
post acute SJS demonstrating symblephara and irregular astigmatism.9
Ultimately, the diagnosis of Stevens-Johnson syndrome of unknown etiology was made
for this particular case. Although the patient did not have the textbook target skin lesions,
he did have fever, conjunctivitis and ulcers on his mucosal surfaces. This case
was particularly unique because the patient had already been to infectious disease and
they approached the case with conservative patient management involving only the use of
oral systemic antibiotics. It was not until the patient reported to the optometrist with
pseudomembranes and confusion that a more serious underlying problem was
acknowledged.
Treatment and Management
Stevens-Johnson syndrome needs to be managed on both an acute and chronic basis.
Acute management involves systemic and neuro-ophthalmic care. Systemically, any
potential known cause for the reaction needs to be removed immediately. Supportive
care is currently the only systemic intervention, although intravenous immunoglobulin
(IVIG) and systemic corticosteroids remain contrroversial.4 Ophthalmologic
management includes surgical intervention such as amniotic membrane grafts and nonsurgical management using topical therapies. Some of the topical treatments used are
antibiotics to decrease the chance of secondary infection, cycloplegics to decrease the
chance of secondary uveitis and corticosteroids that may control vasculitis and prevent
necrosis.9 It has also been documented that mechanical lysis of pseudomembranes that
occur in one-third of these cases may decrease the chance of future symblepharon
formation.9
Chronic management of Stevens Johnson Syndrome also involves surgical and nonsurgical management depending on the particular ocular sequelae. Ocular surface
protection can be achieved with the use of scleral contact lenses or silicone rubber contact
lenses. Both of which are reported to heal corneal defects and improve the patients’
ocular comfort14. Ocular surface support may be addressed through the use of one or
more of the following. Autologous serum contains factors that protect and support the
ocular surface, therefore helping maintain the health of the eye.14 All-trans retinoic acid
treatment is reported to decrease keratinization of the lid margin and conjuntiva leading
to experienced decrease in dry eye symptoms and increase in visual acuity in patients
with Stevens Johnson Syndrome.14 Cyclosporin A is another topical that may improve
both signs and symptoms of ocular manifestations from SJS and it does so by increasing
aqueous tear production.14
Patients who have suffered acute Stevens-Johnson syndrome often have serious ocular
complications that require aggressive treatment. Patients with secondary
keratoconjunctivitis sicca have reported improvement in ocular irritation from punctual
occlusion.14 Some patients may require trichiasis repair, correction of eyelid
malpositions, (particularly entropion), amniotic and mucous membrane transplantation,
limbal stem cell transplantation, penetrating keratoplasty, keratoprosthesis, salivary gland
autotransplantation and/or subcutaneous abdominal artificial tear reservoir.
Bibliography
1. Araki, Yayoi, et al. “Successful Treatment of Stevens-Johnson Syndrome with
Steroid Pulse Thereapy at Disease Onset.” American Journal of Ophthalmology Vol.
147, No. 6 (June 2009).
2. Chang, Yi-Sheng, et al. “Erythema Multiforme, Stevens-Johnson Syndrome and
Toxic Epidermal Necrolysis.” Cornea Vol. 26, No. 2 (2007): 123-129.
3. De Rojas, Victoria M., et al. “The natural history of Stevens-Johnson syndrome:
patterns of chronic ocular disease and the role of systemic immunosuppressive therapy.”
Br J Ophtalmol (2007); 91: 1048-1053.
4. Gregory, Darren G. “The Ophthalmologic Management of Acute Stevens-Johnson
Syndrome.” The Ocular Surface Vol. 6, No. 2 (2008): 87-95.
5. Kaido, Minako, et al. “Functional Visual Acuity in Stevens-Johnson Syndrome.”
American Journal of Ophthalmology Vol. 142, No. 6 (2006): 917-922.
6. Kaiser, Peter, K., Neil J. Friedman, Roberto Pineda II. The Massachusetts Eye and
Ear Infirmary Illustrated Manual of Ophthalmology. 2nd ed. China: Elsevier, Inc., 2004.
Print.
7. Kanski, Jack J. Kanski: Clinical Ophthalmology. 6th ed. China: Elservier Inc.,
2007. Print.
8. Kawasaki, Satoshi, et al. “Conjunctival inflammation in the chronic phase of StevensJohnson syndrome.” Br J Ophthalmol (2000); 84: 1191-1193.
9. Kivela, Tero, et al. “Pseudomembranous and Membranous Conjunctivitis.” Acta
Ophthalmologica 70 (1992): 543-542.
10. Kumar, Vinay, Ramzi S. Cotran, Stanley L. Robbins. Robbins Basic Pathology. 7th
ed. China: Saunders, 2003. Print.
11. Kunimoto, Derek, Y., et al. The Wills Eye Manual. 4th ed. USA: Lippincott
Williams and Wilkins, 2004. Print.
12. Rapid Pathogen Screening. Web. 27 August 2009.
<http://www.rps-tests.com/products_ad.html>.
13. Tseng, Scheffer C.G. “Acute Management of Stevens-Johnson Syndrome and Toxic
Epidermal Necrolysis to Minimize Ocular Sequelae.” American Journal of
Ophthalmology Vol. 147, No. 6 (June 2009).
14. Wall, Vicki, et al. “Management of the Late Ocular Sequelae of Stevens-Johnson
Syndrome.” The Ocular Surface Vol. 1, No. 4 (2003): 192-201.
Conclusion
This case is of particular pertinence to optometrists because it is an example of a systemic
condition with ocular manifestations that required close attention and proactive decisionmaking by the optometrist to ensure that the patient got appropriate care. Long-term
sequelae of chronic or recurrent Stevens-Johnson syndrome is important for the
optometrist to be able to identify and treat accordingly. Many of the severe cases of
Stevens Johnson Syndrome require surgical intervention, but the majority of these chronic
cases have mild to moderate ocular symptoms that can be effectively treated by
the primary eye care provider.