STEVENS JOHNSON STEVENS JOHNSON SYNDROMESYNDROME

Ward Case PresentationWard Case PresentationBy:By:

Airamsherlyn P. Natinga, M.D.Airamsherlyn P. Natinga, M.D.Pediatric ResidentPediatric Resident

General data:General data:- 15 year old, female15 year old, female- born on April 4.1995born on April 4.1995- Filipino, Roman Catholic- Filipino, Roman Catholic- Capul, Northern Samar- Capul, Northern Samar- Admitted July 4, 2010 - Admitted July 4, 2010 - @ 2:44 pm- @ 2:44 pm

•Chief Complaint:Chief Complaint: Multiple SkinMultiple Skin

LesionsLesions

HISTORY OF PRESENT HISTORY OF PRESENT ILLNESSILLNESS• 2 weeks PTA2 weeks PTA - loss of consciousness for 5 min- loss of consciousness for 5 min

- brought to Allen District - brought to Allen District Hospital, admitted and Hospital, admitted and

managed managed as Epilepsy, UTI as Epilepsy, UTI - Medications:- Medications: 1. Phenytoin Capsule1. Phenytoin Capsule 2. Unrecalled antibiotics2. Unrecalled antibiotics

- 2 days after discharged:- 2 days after discharged:

* noted with fever, low grade, * noted with fever, low grade, fatigue, associated with fatigue, associated with maculopapular rashes on the face maculopapular rashes on the face

- consulted to a private MD and given - consulted to a private MD and given Cetirizine tabletCetirizine tablet

- rashes progressed all over the body- rashes progressed all over the body

• 2 days PTA2 days PTA- readmitted at Allen District - readmitted at Allen District Hospital for progression of Hospital for progression of rashes/lesionsrashes/lesions- medications:- medications: * Cetirizine tablet* Cetirizine tablet

* Acyclovir* Acyclovir * Vit. B Complex* Vit. B Complex

* Sulbactam/Ampicillin tablet * Sulbactam/Ampicillin tablet * Phenytoin capsule* Phenytoin capsule

• Morning PTAMorning PTA- referred to this center for - referred to this center for

further further evaluation and managementevaluation and management

• AdmissionAdmission

• Personal History:Personal History:

– Born NSVD at home, assisted by a trained birth Born NSVD at home, assisted by a trained birth attendant, with good cry and activityattendant, with good cry and activity

- Negated any complications during the course of Negated any complications during the course of pregnancy and deliverypregnancy and delivery

- Breastfeed for 2 years, then to milk formulaBreastfeed for 2 years, then to milk formula

- Growth and development: at par at age Growth and development: at par at age

• ‘‘

•Past Medical HistoryPast Medical History- No previous Hospitalizations- No previous Hospitalizations- With hx of fainting: Dec. 2009 - With hx of fainting: Dec. 2009 - Non – asthmatic- Non – asthmatic- No known allergies to food or - No known allergies to food or

drugs drugs•ImmunizationImmunization

- - primary immunizations complete primary immunizations complete c/o Barangay Health Center c/o Barangay Health Center

•Family History:Family History:- UnremarkableUnremarkable

•Psychosocial History:Psychosocial History:- father: 54 year old, farmer- father: 54 year old, farmer

Barangay TanodBarangay Tanod- mother: 51 year old,- mother: 51 year old,

housewifehousewife

•‘‘

- 7- 7thth child of 9 children child of 9 children- 4- 4thth year High School year High School- Average schooler- Average schooler- menarche : 14 yr old- menarche : 14 yr old- other siblings: apparently well - other siblings: apparently well

Review of Systems:Review of Systems:General: decrease appetiteGeneral: decrease appetiteIntegument: with tender lesionsIntegument: with tender lesionsHEENT: with conjunctivitis, andHEENT: with conjunctivitis, and

eye discharges, with soreeye discharges, with sore throatthroat

Respiratory: with occasional coughRespiratory: with occasional coughCardiovascular: no chest painCardiovascular: no chest pain

GIT: no abdominal painGIT: no abdominal pain

GUT: with adequate outputGUT: with adequate output

Musculoskeletal: with body malaise Musculoskeletal: with body malaise and or fatigueand or fatigue

Hematologic: no bleeds Hematologic: no bleeds

•Physical Examination:Physical Examination:General: General: - awake, conscious, coherent, on - awake, conscious, coherent, on

wheel chair, febrile, not in distresswheel chair, febrile, not in distressVital SignsVital Signs

- RR: 24 cpm - RR: 24 cpm - HR: 100 bpm- HR: 100 bpm - Temp: 38- Temp: 38OOCC

- BP: 100/60 mmHg- BP: 100/60 mmHg - Weight: 42 kg- Weight: 42 kg

• Skin: * with dry patchy pigmented Skin: * with dry patchy pigmented lesions on the face, lesions on the face, * * with bullae lesions diffusely with bullae lesions diffusely

distributed to the distributed to the different different areas of the areas of the bodybody

• HEENT: * with conjunctival HEENT: * with conjunctival suffusion and discharges suffusion and discharges * hyperemic tonsils* hyperemic tonsils

* oral lesions* oral lesions

• Neck: * no cervical lymph adeno-Neck: * no cervical lymph adeno- pathiespathies• C/L: * symmetrical chest C/L: * symmetrical chest

expansion, with noexpansion, with no retractions, harsh breath retractions, harsh breath sounds, with no crackles, with sounds, with no crackles, with occasional wheezeoccasional wheeze

• Heart: * adynamic precordium, no Heart: * adynamic precordium, no thrills, no heaves, normal thrills, no heaves, normal rate and regular rhythm, rate and regular rhythm, no murmurno murmur

• Abdomen: * globular, normoactive Abdomen: * globular, normoactive bowel sounds, bowel sounds,

soft, no soft, no tenderness, tenderness, liver not liver not palpable, palpable,

no organomegalyno organomegaly• Genitals: * with tender lesions Genitals: * with tender lesions • Anus: patent, and with lesionsAnus: patent, and with lesions• Extremities: with multiple lesions, Extremities: with multiple lesions, equal, full pulsesequal, full pulses

•SALIENT FEATURES:SALIENT FEATURES:* 15 yr old female, on Phenytoin* 15 yr old female, on Phenytoin

(Dilantin) medication(Dilantin) medication* low grade fever* low grade fever* sore throat, occasional cough* sore throat, occasional cough* body malaise / fatigue* body malaise / fatigue* tender, dry patchy lesions on* tender, dry patchy lesions on the facethe face

* with conjunctivitis / * with conjunctivitis / conjunctival suffusion, conjunctival suffusion, eye dischargeseye discharges

* oral lesions, tender* oral lesions, tender* bullae lesions diffusely * bullae lesions diffusely

distributed to different distributed to different areas of the body includingareas of the body including

buccal mucosa and the buccal mucosa and the anogenital areasanogenital areas

ADMITTING IMPRESSION:ADMITTING IMPRESSION:

STEVENS JOHNSON STEVENS JOHNSON SYNDROMESYNDROME

•On admission:On admission:

- placed on hypoallergenic diet- placed on hypoallergenic diet - venoclysis continued with PLR- venoclysis continued with PLR regulated at mild x 8Hregulated at mild x 8H - Diagnostics requested- Diagnostics requested

CBC & platelet count CBC & platelet count Na, K, SGPT, BUN, CreatininNa, K, SGPT, BUN, Creatinin ee Urinalysis Urinalysis

•Medications:Medications:

• - Paracetamol P.O.,15mg/kg/dose, - Paracetamol P.O.,15mg/kg/dose, PRN for feverPRN for fever

- Hydrocortisone Hydrocortisone 4mg/kg/dose q 6H4mg/kg/dose q 6H- Ranitidine I mg/kg/dose q 8HRanitidine I mg/kg/dose q 8H- Loratadine 10mg/tab ODLoratadine 10mg/tab OD

- Diphenhydramine 1mkd Diphenhydramine 1mkd q 8Hq 8H

- Oxacillin 100mkd q 6HOxacillin 100mkd q 6H- Amikacin 5mkd, ODAmikacin 5mkd, OD- I and O monitoringI and O monitoring- Vital signs monitoring q 6HVital signs monitoring q 6H

•Laboratory Exam. Results:Laboratory Exam. Results:•CBCCBC: : Hemoglobin 126 Neutrophils 0.82Hemoglobin 126 Neutrophils 0.82 Hematocrit 0.39 Lymphocytes 0.14Hematocrit 0.39 Lymphocytes 0.14 RBC Count 4.11 Monocytes 0.04RBC Count 4.11 Monocytes 0.04 WBC Count 15.2 WBC Count 15.2 •Platelet count: Platelet count: 217217• Urinalysis: Urinalysis: Lt.yellow color , sl. TurbidLt.yellow color , sl. Turbid pH 6.0, Sp. Gr. 1.015pH 6.0, Sp. Gr. 1.015 proteins (+), Sugar (-)proteins (+), Sugar (-) pus cells (22=30), red cells nonepus cells (22=30), red cells none

• Serum determination:Serum determination:

• Sodium = 135.4 mmol/L (N)Sodium = 135.4 mmol/L (N)• Potasium = 4.04 mmol/L (N)Potasium = 4.04 mmol/L (N)• BUN = 2.90 mmol/L (N)BUN = 2.90 mmol/L (N)• Creatinine = 51 umol/L (N)Creatinine = 51 umol/L (N)• SGPT = 32.63 U/L (N)SGPT = 32.63 U/L (N)

•COURSE IN THE WARDCOURSE IN THE WARD::

•11stst Hospital Day Hospital Day– Noted with fair appetiteNoted with fair appetite– complains pain upon eatingcomplains pain upon eating– (+) tender bullae lesions(+) tender bullae lesions– (+) dry pigmented lesions on all (+) dry pigmented lesions on all

areas of the bodyareas of the body– adequate outputadequate output

– referred and seen by an referred and seen by an Ophthalmologist, started with Ophthalmologist, started with

Tobr amycin Tobr amycin +Dexamethasone+DexamethasoneOintment (Tobradex) to both Ointment (Tobradex) to both Eyes BIDEyes BID - advised to apply Cetaphil - advised to apply Cetaphil liquid to desquamated areas liquid to desquamated areas of the skinof the skin

•22ndnd Hospital Day Hospital Day

* afebrile, still with multiple * afebrile, still with multiple bullaesbullaes * started with Betadine gargle * started with Betadine gargle TIDTID

* medications continued* medications continued * IVF rate decreased to 2cc/k* IVF rate decreased to 2cc/k

•33rdrd , 4 , 4thth and 5 and 5thth Hospital days: Hospital days:* afebrile, good appetite* afebrile, good appetite* noted with areas of * noted with areas of desquamated skindesquamated skin* stable vital signs* stable vital signs* adequate output* adequate output* medications continued* medications continued* repeat urinalysis requested * repeat urinalysis requested and revealed a normal result and revealed a normal result

•66thth Hospital day: Hospital day:* * afebrile, BP 100/60 mmHgafebrile, BP 100/60 mmHg* adequate urine output* adequate urine output* Hydrocortisone decreased to* Hydrocortisone decreased to

every 8 Hoursevery 8 Hours* started oral Prednisone * started oral Prednisone

20mg/tab after 20mg/tab after breakfastbreakfast

•77thth – 8 – 8thth Hospital Day Hospital Day- With areas of desquamation- With areas of desquamation- with good appetite- with good appetite- afebrile- afebrile- with stable v/s, with adequate - with stable v/s, with adequate output, full pulses output, full pulses

• 99thth Hospital Day Hospital Day- patient improved, discharged with - patient improved, discharged with

stable vital signs with the ff. stable vital signs with the ff. home home medications:medications:1. Prednisone tablet1. Prednisone tablet

20mg, 1 tab after breakfast20mg, 1 tab after breakfast10 mg, 1 tab after lunch10 mg, 1 tab after lunch

2. Ranitidine 20 mg tablet, 1 tab OD2. Ranitidine 20 mg tablet, 1 tab OD3. Oxacillin 500 mg capsule, 1 cap3. Oxacillin 500 mg capsule, 1 cap

every 6 hours x 2 days every 6 hours x 2 days

Differential DiagnosisDifferential DiagnosisToxic Epidermal NecrolysisToxic Epidermal Necrolysis R/I : Hx of fever , malaiseR/I : Hx of fever , malaise

and blistersand blisters R/O : R/O :

scalp is not spared from scalp is not spared from blisters blisters

mucuos membranes are mucuos membranes are spared spared

SSSSSSR/I : Hx of skin lesionsR/I : Hx of skin lesions

malaise /fatigue, fevermalaise /fatigue, fever skin tenderness upon skin tenderness upon

palpation palpation R/O : (+) Nikolsky signR/O : (+) Nikolsky sign not a reaction to a not a reaction to a

drug drug

STEVENS STEVENS JOHNSON JOHNSON SYNDROMESYNDROME

HistoryHistory•Stevens-Johnson Syndrome is Stevens-Johnson Syndrome is

named for Albert Mason Stevens named for Albert Mason Stevens and Fran Chamblis Johnson, and Fran Chamblis Johnson, American pediatricians who in American pediatricians who in 1922 jointly published a 1922 jointly published a description of the disorder in the description of the disorder in the American Journal of Diseases of American Journal of Diseases of ChildrenChildren..

Stevens–Johnson syndromeStevens–Johnson syndrome (SJS) (SJS)

= is a life-threatening condition = is a life-threatening condition affecting the skin in which cell affecting the skin in which cell death causes the epidermis to death causes the epidermis to separate from the dermis.separate from the dermis.

• The syndrome is thought to be a The syndrome is thought to be a hypersensitivity complex hypersensitivity complex affecting the skin and the mucous affecting the skin and the mucous membranes. membranes.

•majority of cases are majority of cases are idiopathic idiopathic

• the main class of known the main class of known causes is medications, causes is medications, followed by infections and followed by infections and (rarely) cancers.(rarely) cancers.

EpidemiologyEpidemiology• Stevens-Johnson syndrome Stevens-Johnson syndrome = a rare condition,= a rare condition, = reported incidence of around 2.6 to = reported incidence of around 2.6 to

6.1 cases per million people per year. 6.1 cases per million people per year. In the United States, there are about In the United States, there are about 300 new diagnosis per year.300 new diagnosis per year.

= more common in adults than in = more common in adults than in children. Women are affected more children. Women are affected more often than men, with cases occurring often than men, with cases occurring at a 3:6 ratio.at a 3:6 ratio.

ClassificationClassification• Stevens–Johnson syndrome (SJS) Stevens–Johnson syndrome (SJS) = considered a milder form of Toxic = considered a milder form of Toxic

Epidermal Necrolysis (TEN). First Epidermal Necrolysis (TEN). First recognized in 1922.recognized in 1922.

= Both diseases can be mistaken for = Both diseases can be mistaken for Erythema Multiforme. Erythema Erythema Multiforme. Erythema multiforme is sometimes caused by a multiforme is sometimes caused by a reaction to a medication but is more reaction to a medication but is more often a type IV hypersensitivity often a type IV hypersensitivity reaction to an infection (caused most reaction to an infection (caused most often by Herpes simplex) and is often by Herpes simplex) and is relatively benign. relatively benign.

•Although both SJS and TEN Although both SJS and TEN can also be caused by can also be caused by infections, they are most infections, they are most often adverse effects of often adverse effects of medications. Their medications. Their consequences are potentially consequences are potentially more dangerous than those more dangerous than those of erythema multiforme.of erythema multiforme.

PathogenesisPathogenesis• Carbamazepine- and Phenytoin-Carbamazepine- and Phenytoin-

induced SJS is strongly associated induced SJS is strongly associated with HLA-B*1502 (HLA-B75), an HLA-with HLA-B*1502 (HLA-B75), an HLA-B serotype of the broader serotype B serotype of the broader serotype HLA-B15.HLA-B15.

• A study in Europe suggested that A study in Europe suggested that the gene marker is only relevant for the gene marker is only relevant for East Asians.East Asians.

•Cutaneous lesions in Cutaneous lesions in Stevens-Johnson syndromeStevens-Johnson syndrome

• initially of erythematous initially of erythematous macules macules

•that rapidly and variably that rapidly and variably develop central necrosis to develop central necrosis to form vesicles, bullae, and form vesicles, bullae, and areas of denudation on the areas of denudation on the face, trunk, and extremities.face, trunk, and extremities.

Signs and Symptoms:Signs and Symptoms:• SJS usually begins with fever, sore throat, SJS usually begins with fever, sore throat,

and fatigue, which is misdiagnosed and and fatigue, which is misdiagnosed and usually treated with antibiotics. usually treated with antibiotics.

• Ulcers and other lesions begin to appear Ulcers and other lesions begin to appear in the mucous membranes, almost in the mucous membranes, almost always in the mouth and lips but also in always in the mouth and lips but also in the genital and anal regions. Those in the the genital and anal regions. Those in the mouth are usually extremely painful and mouth are usually extremely painful and reduce the patient's ability to eat or reduce the patient's ability to eat or drink.drink.

• Conjunctivitis of the eyes Conjunctivitis of the eyes occurs in about 30% of occurs in about 30% of children who develop SJS. children who develop SJS.

•A rash of round lesions about A rash of round lesions about an inch across which arises an inch across which arises on the face, trunk, arms and on the face, trunk, arms and legs, and soles of the feet, legs, and soles of the feet, but usually not the scalp.but usually not the scalp.

•Lesions may be preceded Lesions may be preceded by a flu-like upper by a flu-like upper respiratory illness.respiratory illness.

• Pain from mucosal Pain from mucosal ulceration is often severe, ulceration is often severe, but skin tenderness is but skin tenderness is minimal to absent, in minimal to absent, in contrast to Toxic contrast to Toxic Epidermal Necrolysis.Epidermal Necrolysis.

•Disseminated cutaneous bullae Disseminated cutaneous bullae and erosions may result in and erosions may result in increased insensible fluid loss increased insensible fluid loss and a high risk of bacterial and a high risk of bacterial superinfection and sepsis. superinfection and sepsis.

•New lesions occur in crops, and New lesions occur in crops, and complete healing may take 4–6 complete healing may take 4–6 wk; ocular scarring, visual wk; ocular scarring, visual impairment, and strictures of impairment, and strictures of the esophagus, bronchi, vagina, the esophagus, bronchi, vagina, urethra, or anus may remain.urethra, or anus may remain.

CausesCauses• SJS is thought to arise from a disorder of SJS is thought to arise from a disorder of

the immune system. the immune system. • InfectionsInfections• It can be caused by infections (usually It can be caused by infections (usually

following infections such as herpes simplex following infections such as herpes simplex virus, influenza, mumps, cat-scratch fever, virus, influenza, mumps, cat-scratch fever, histoplasmosis, Epstein-Barr virus, histoplasmosis, Epstein-Barr virus, mycoplasma pneumoniae or similar).mycoplasma pneumoniae or similar).

•Medication/drugsMedication/drugs• It can be caused by adverse effects It can be caused by adverse effects

of drugs (allopurinol, diclofenac, of drugs (allopurinol, diclofenac, etravirine, Isotretinoin aka Accutane, etravirine, Isotretinoin aka Accutane, fluconazole, valdecoxib, sitagliptin fluconazole, valdecoxib, sitagliptin oseltamivir, penicillins, barbiturates, oseltamivir, penicillins, barbiturates, sulfonamides, sulfonamides, phenytoin, phenytoin, azithromycin, oxcarbazepine, azithromycin, oxcarbazepine, zonisamide, modafinil, lamotrigine, zonisamide, modafinil, lamotrigine, nevirapine, pyrimethamine, nevirapine, pyrimethamine, ibuprofen, ethosuximide, ibuprofen, ethosuximide, carbamazepine, nystatin, and gout carbamazepine, nystatin, and gout medications).medications).

• Although Stevens–Johnson Syndrome Although Stevens–Johnson Syndrome can be caused by viral infections, can be caused by viral infections, malignancies or severe allergic malignancies or severe allergic reactions to medication, the leading reactions to medication, the leading cause appears to be the use of cause appears to be the use of antibiotics and sulfa drugs.antibiotics and sulfa drugs.

• Has also been consistently reported Has also been consistently reported as an uncommon side effect of as an uncommon side effect of herbal supplements containing herbal supplements containing ginseng may also caused SJS and ginseng may also caused SJS and also cocaine usage.also cocaine usage.

DiagnosticsDiagnostics•Nonspecific laboratory Nonspecific laboratory

abnormalities in Stevens-abnormalities in Stevens-Johnson syndrome include Johnson syndrome include Leukocytosis, elevated Leukocytosis, elevated Erythrocyte Sedimentation Erythrocyte Sedimentation Rate, and, occasionally, Rate, and, occasionally, increased liver transaminase increased liver transaminase levels and decreased serum levels and decreased serum albumin valuesalbumin values. .

Treatment Treatment • Management of Stevens-Johnson Management of Stevens-Johnson

syndrome is supportive and syndrome is supportive and symptomatic. symptomatic.

• Potentially offending drugs must Potentially offending drugs must be discontinued as soon as be discontinued as soon as possible. possible.

• Ophthalmologic consultation is Ophthalmologic consultation is mandatory because ocular mandatory because ocular sequelae such as corneal sequelae such as corneal scarring can lead to vision loss. scarring can lead to vision loss.

• Topical steroids may reduce Topical steroids may reduce ocular morbidity. Oral lesions ocular morbidity. Oral lesions should be managed with should be managed with mouthwashes and glycerin swabs.mouthwashes and glycerin swabs.

• Antibiotic therapy is appropriate Antibiotic therapy is appropriate for documented secondary for documented secondary bacterial infection. bacterial infection.

• Vaginal lesions should be Vaginal lesions should be observed closely and treated to observed closely and treated to prevent vaginal stricture or prevent vaginal stricture or fusion. fusion.

• Topical anesthetics Topical anesthetics (diphenhydramine, dyclonine, and (diphenhydramine, dyclonine, and viscous lidocaine) may provide viscous lidocaine) may provide relief from pain, particularly relief from pain, particularly when applied before eating.when applied before eating.

• Denuded skin lesions can be Denuded skin lesions can be cleansed with saline or Burow cleansed with saline or Burow solution compresses solution compresses

• Intravenous immunoglobulin (1.5–Intravenous immunoglobulin (1.5–2.0 g/kg/day × 3 days) has also 2.0 g/kg/day × 3 days) has also been used and believed by many been used and believed by many to be effective.to be effective.

•An ophthalmologist should be An ophthalmologist should be consulted immediately, as SJS consulted immediately, as SJS frequently causes the formation frequently causes the formation of scar tissue inside the eyelids, of scar tissue inside the eyelids, leading to corneal leading to corneal vascularization, impaired vision vascularization, impaired vision and a host of other ocular and a host of other ocular problems. Also, an extensive problems. Also, an extensive physical therapy program ensues physical therapy program ensues after the patient is discharged after the patient is discharged from the hospital.from the hospital.

PrognosisPrognosis•SJS proper (with less than 10% of SJS proper (with less than 10% of

body surface area involved) has a body surface area involved) has a mortality rate of around 5%. The risk mortality rate of around 5%. The risk for death can be estimated using the for death can be estimated using the SCORTEN scale, which takes a SCORTEN scale, which takes a number of prognostic indicators into number of prognostic indicators into account. Other outcomes include account. Other outcomes include organ damage/failure, cornea organ damage/failure, cornea scratching and blindness.scratching and blindness.

• Phenytoin sodiumPhenytoin sodium is a commonly is a commonly used used antiepileptic. Phenytoin (fen-i-. Phenytoin (fen-i-TOE-in) acts to suppress the TOE-in) acts to suppress the abnormal brain activity seen in abnormal brain activity seen in seizure by reducing electrical seizure by reducing electrical conductance among brain cells by conductance among brain cells by stabilizing the inactive state of stabilizing the inactive state of voltage-gated sodium channels. voltage-gated sodium channels. Aside from seizures, it is an option in Aside from seizures, it is an option in the treatment of the treatment of trigeminal neuralgia in the event that carbamazepine is in the event that carbamazepine is deemed inappropiatedeemed inappropiate..

• HistoryHistory• Phenytoin (diphenylhydantoin) Phenytoin (diphenylhydantoin) was first was first

synthesized by German chemist synthesized by German chemist Heinrich Biltz in 1908. Biltz sold his in 1908. Biltz sold his discovery to Parke-Davis, which did not discovery to Parke-Davis, which did not find an immediate use for it. In 1938, find an immediate use for it. In 1938, outside scientists including outside scientists including H.

• DilantinDilantin made an appearance in the made an appearance in the 1962 novel 1962 novel One Flew Over the Cuckoo's Nest by by Ken Kesey, both as an , both as an anticonvulsant and as a mechanism to control inmate and as a mechanism to control inmate behavior.behavior.

• In autoimmune diseaseIn autoimmune disease• PhenytoinPhenytoin has been known to cause has been known to cause

drug-induced drug-induced lupus..[11]

• Phenytoin therapy Phenytoin therapy has been linked to has been linked to the life-threatening skin reactions the life-threatening skin reactions Stevens-Johnson syndrome (SJS) and (SJS) and toxic epidermal necrolysis (TEN). (TEN). These conditions are significantly more These conditions are significantly more common in patients with a particular common in patients with a particular HLA-B allele, , HLA-B*1502..[12] This allele This allele occurs almost exclusively in patients occurs almost exclusively in patients with ancestry across broad areas of with ancestry across broad areas of Asia, including South Asian Indians.Asia, including South Asian Indians.

Good Good afternoon…afternoon…

•Side-effectsSide-effects•NeurologicNeurologic• At therapeutic doses, phenytoin produces At therapeutic doses, phenytoin produces

horizontal gaze horizontal gaze nystagmus, which is , which is harmless but occasionally tested for by harmless but occasionally tested for by police as a marker for as a marker for alcohol intoxication

• At toxic doses, patients experience At toxic doses, patients experience sedation, cerebellar , cerebellar ataxia, and , and ophthalmoparesis, as well as paradoxical, as well as paradoxical[[clarification needed]] seizures. Idiosyncratic side-. Idiosyncratic side-effects of phenytoin, as with other effects of phenytoin, as with other anticonvulsants, include rash and severe , include rash and severe allergic reactions. reactions.

• Phenytoin may accumulate in the Phenytoin may accumulate in the cerebral cortex over long periods of over long periods of time, as well as causing atrophy of time, as well as causing atrophy of the the cerebellum when administered at when administered at chronically high levels. Despite this, chronically high levels. Despite this, the drug has a long history of safe the drug has a long history of safe use, making it one of the more use, making it one of the more popular anti-convulsants prescribed popular anti-convulsants prescribed by doctors, and a common "first line by doctors, and a common "first line of defense" in seizure cases.of defense" in seizure cases.

• HematologicHematologic• It has been suggested that phenytoin It has been suggested that phenytoin

causes a reduction in causes a reduction in folic acid levels, levels, predisposing patients to predisposing patients to megaloblastic anemia. Folic acid is . Folic acid is presented in foods as polyglutamate, presented in foods as polyglutamate, which is then converted into which is then converted into monoglutamates by intestinal monoglutamates by intestinal conjugase. Phenytoin acts by inhibiting conjugase. Phenytoin acts by inhibiting this enzyme, thereby causing folate this enzyme, thereby causing folate deficiency.deficiency.[4][4] Other side effects may Other side effects may include: agranulocytosis, aplastic include: agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia.anemia, leukopenia, thrombocytopenia.

• TeratogenicityTeratogenicity• Phenytoin is a known teratogen. The Phenytoin is a known teratogen. The

syndrome consists of craniofacial syndrome consists of craniofacial anomalies (broad nasal bridge, cleft anomalies (broad nasal bridge, cleft lip and palate, microcephaly) and a lip and palate, microcephaly) and a mild form of mental retardation mild form of mental retardation (average IQ=71).(average IQ=71).[5][5] This syndrome This syndrome resembles the well-described Fetal resembles the well-described Fetal Alcohol SyndromeAlcohol Syndrome[6][6] and has also and has also been called the "fetal hydantoin been called the "fetal hydantoin syndrome".syndrome".

• GingivalGingival• Phenytoin has been associated with Phenytoin has been associated with

drug induced gingival enlargement drug induced gingival enlargement (hyperplasia) in the oral cavity (hyperplasia) in the oral cavity probably due to above mentioned probably due to above mentioned folate defiency. folate defiency.

• DermatologicDermatologic• Hypertrichosis, rash, exfoliative Hypertrichosis, rash, exfoliative

dermatitis, pruritis.dermatitis, pruritis.