SJS is an uncommon, severe, mucocutaneous blistering disorder with an acute and unpredictable

onset causing considerable morbidity. Its more severe form is called TEN. Previously, SJS was
considered as EM major, but now is considered distinct from EM on the basis of severity, presence of
constitutional signs, atypical target lesions with tendency to confluence, positive Nikolsky's sign,
more than one mucosal site involvement, and residual sequelae.

In the oral cavity, SJS causes widespread ulcerative lesions. Prodromal symptoms seen in about 30%
of cases and may possibly initiate within 1–3 weeks of starting a new drug, and lasts for 1–2 weeks,
presenting with flu-like symptoms, sore throat, headache, arthralgias, myalgias, fever, and other
rashes.

Ocular changes such as dry eyes that resemble those of mucous membrane pemphigoid may be
noted in few cases. Urethritis and vulval ulcers may occur.[7] Our patient did not report any
prodrome, but the eye and genital ulcerations were present, along with skin and mouth ulcers.

Although many factors have been proposed as risk factors of SJS, including drug-induced, infections,
malignant disorders, and graft rejection, most of them were due to the adverse effect of drugs. The
most common drugs are a nonsteroidal anti-inflammatory drug (NSAIDs), antipsychotics, antibiotics,
allopurinol, and anticonvulsants.[4]

SJS can be differentiated from other skin conditions on three clinical criteria, (i) the pattern of
individual skin lesions, (ii) distribution of lesions, and (iii) extent of epidermal detachment.

The characteristic findings in SJS are widespread erythematous or purpuric macules which form flat
atypical target lesions as the disease progresses to cause full thickness epithelial necrosis.[3]

Our case showed ulceration of oral cavity, crusting of lips and profuse bleeding, involvement of eye
with redness and watery discharge, ulceration of genital region along with numerous healed lesions
on chest, axilla which showed typical appearance of “target lesions” or “bull's eye “appearance. The
lesions were widespread as compared to EM, which is localized.

In a study done among children in the hospital, it was found that anticonvulsant drugs were
reported the highest risk for SJS and paracetamol lest and vaccines presented no risk at all. Among
the NSAIDs, paracetamol and nimesulide are most common reported. The Severe cutaneous adverse
reactions (SCARs) study has found an overall risk of SJS with oxicam derivatives. It reports the
increased risk with paracetamol from Germany, Italy, and Portugal except France but very few cases
from India.[6,8]
However, paracetamol is found to be a potential risk factor in children according to survey data from
pediatric patients from the SCAR.[6] The present case was diagnosed as paracetamol induced SJS
based upon the fact that a sequential relationship with the drug was established, and correlation
with exposure with signs and symptoms was made.

Khawaja et al.[1] reported a case of Acetaminophen induced SJS and TEN with widespread macula-
papular rash, stinging in the eyes, oral mucosal ulcerations, and high-grade fever. Similar features
were seen in our case, but there was the absence of high-grade fever and epithelial detachment.

The first step in the management was an immediate withdrawal of the offending agent followed by
supportive care. Garcia-Doval et al., report that earlier the drug is withdrawn, better the prognosis
while exposure to drugs with longer half-lives increases the risk of death. Supportive care must
include the management of fluid and electrolyte requirements.[9]

Routine antibiotics are not indicated unless there is the evidence of infection as fever may be part of
the disease process. Debridement of necrotic skin should not be performed before disease activity
ceases. However, in our case, there were lesions on axilla, abdomen, thighs and trunk region in the
healing phase, so debridement was not a necessary step.

Topical antiseptics (0.5% silver nitrate or 0.05% chlorhexidine) are used to paint, bathe, or dress the
patients. Dressings may be gauzes with petrolatum, silver nitrate, povidone-iodine, and hydrogels.
Some authors use biologic skin covers after epidermal stripping cadaveric allografts, cultured human
allogeneic or autologous epidermal sheets. In our case, gentian violet application for lips and skin
lesions were advocated.

Dramatic improvement in both SJS-TEN has been reported with the use of intravenous
immunoglobulin, 0.2–0.75 g/kg body weight. Alternative systemic treatment methods for the acute
phase of SJS-TEN include hemodialysis, plasmapheresis, cyclophosphamide, and cyclosporine.[10]

Use of corticosteroid in the management of SJS is controversial. According to some, their use can
lead to delayed wound healing, increased chances of infection, masking of early signs of sepsis,
gastrointestinal bleeding, and increased mortality. If steroids are to be used, it should be initiated
during initial stage and rapidly tapered off.[11,12] Antibiotics with intravenous corticosteroid shown
a remarkable improvement in a similar case.[13] Hence, we prescribed tablet predinsolone 30 mg
three times daily daily for 7 days. Further tapered to 20 mg twice daily for next 7 days. Gradually, 10
mg and 5 mg for consecutive 7 days. His condition improved no sequelae were found during 35–40
days of follow-up.

Toxic epidermal necrolysis (TEN) is a severe cutaneous reaction, often to a medication,

with significant potential for morbidity and mortality. Key clinical features of TEN include
fever, mucosal involvement, malaise, and dusky patches representing full-thickness skin
necrosis, associated with blistering or imminent blistering involving >30% of the body-
surface area. Stevens–Johnson syndrome has similar clinical features but involves
<10% of body-surface area; SJS–TEN involves 10% to 30% of body-surface area.
Potentially implicated medications in all three diagnoses include antibiotics, aromatic
anticonvulsants (carbamazepine, phenytoin, phenobarbital), lamotrigine, allopurinol,
nonsteroidal antiinflammatory drugs, and antiretrovirals.

Fixed drug eruption is most commonly characterized by a solitary, oval violaceous patch
on the skin or mucosa that often recurs in the same anatomic location after each
exposure to culprit medications. Multiple patches may occur, but this is rare.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous
reaction characterized by fevers, facial swelling, and variable erythematous dermatitis.
Patients often exhibit lymphadenopathy. Laboratory abnormalities include peripheral
eosinophilia or atypical lymphocytosis and elevations in liver function test results.
Notably, these laboratory findings are not always present in cases of DRESS and can
also be seen in SJS–TEN, so the diagnosis is primarily clinical. The clinical finding of
“dusky centers” indicates incipient skin necrosis and detachment, a finding more
commonly seen in SJS–TEN. Mucosal involvement can occur in DRESS but is less
severe than in SJS–TEN. When in doubt, skin biopsy can assist the clinician in arriving
at the correct diagnosis. Full-thickness epidermal necrosis would be seen in SJS–TEN.

Acute generalized exanthematous pustulosis, a severe cutaneous reaction that occurs

quickly after drug exposure (24 to 72 hours), is characterized by erythema with minute
pustules but not full-thickness skin necrosis in widespread areas. Mucosal involvement
is less common.

From the description (which was lousy) it’s impossible to differentiate between EM Major, SJS/TEN
overlap, or a severe DRESS. I write as a dermatologist.

Really makes no difference, since therapy is effective IF begun early in the course. IVIG or
cyclosporine would be the treatment of choice. Some might add high dose steroids for a short time.

In any case, it’s always touch and go with type of patient.

too much overlap with SJS, anyway I think whatever the final diagnosis was, the most important is
that both of TEN and SJS has similar treatments, and physicians will cease the last medications
before the symptoms appear. so differences may be just theoretical

Ok.But I had idea that once a drug gets exposed to body and gives a milder allergic reaction the
second dose,e exposure eg of sulfa or drugs you mentioned causes this type of More generalised
severe linear artio spasm with immune clits blocking vertical vessels of mucosa skin causing TEN.
WHICH is treated as burns and one if my old man with 90 %disease suvived as I protected him from
secondary infection and supportive fluid therapy.

TEN definitely as more than 30% skin necrosis . Should respond well with IVIG/cyclosporine IV
hydration surveillance cultures & trying to avoid unnecessary antibiotics, the offender needs to be
omitted immediately.
bullae is not a clasical feature of ten overlap is likly diagnosis
clinically the bullae are more prevallent in SJS, pure TEN if confirmmed by a jelly-roll biopsy show the
sfacellation of the skin through a direct appoptotic proccess and large tense bullae are not the
clinical hallmark. So even if it is 40% of BSA I would still consider it an overlap presentation.

SJS involve more body surface that TEN and more frecuent reaction after exposure drug as
anticonvulsants

The most likely diagnosis in a patient who recently started a new medication and presents with
fever, eye changes, mucosal changes, and dusky patches on >30% of body-surface area is toxic
epidermal necrolysis.

Dress

https://www.jaad.org/article/S0190-9622(14)01331-0/fulltext

The presence of iris shaped/ targetoid lesions is very suggestive of Erythema Multiforme. The term
"multiforme" describes the myriad clinical manifestations that may be observed. Though most
lesions appear similar in a particular patient at a given time, the morphology of erythema
multiforme (EM) lesions may vary between patients and also may evolve over the course of the
disease in a single patient.

Images attached show a mixture of both typical and atypical target lesions. Target lesions are the
hallmark of the disorder, although they may not always be present. Initial lesions may begin as
round erythematous papules that evolve into classic target lesions. Typical target lesions consist of
three components: a dusky central area or blister, a dark red inflammatory zone surrounded by a
pale ring of edema, and an erythematous halo on the extreme periphery of the lesion.Atypical target
lesions may also occur in patients with EM. These manifest as raised, edematous, palpable lesions
with only two zones of color change and/or a poorly defined border.Cutaneous lesions most
commonly appear in a symmetrical distribution on the extensor surfaces of the acral extremities,
and subsequently spread in a centripetal manner. The face, neck, palms, soles, flexural surfaces of
the extremities, and/or trunk may also be involved. Although cutaneous lesions are usually
asymptomatic, some patients may experience itching and burning. EM can also be accompanied by
mucosal lesions and often prodromal symptoms in cases with extensive mucosal involvement

Many factors, including infections, medications, malignancy, autoimmune disease, immunizations,

radiation, sarcoidosis, and menstruation have been linked to the development of erythema
multiforme (EM). Infections (viral, bacterial, or fungal) account for approximately 90 percent of
cases, with HSV as the most commonly identified precipitant. Mycoplasma pneumoniae infection is
another important cause of EM, particularly in children
In less than 10 percent of cases, drugs induce EM. A wide variety of medications have been
associated with the eruption. The most common precipitators include NSAIDs, sulfonamides,
antiepileptics, and antibiotics.

Description of lesions in above case:

1. Extensive confluent macules forming erythematous patches mainly on trunk (both anterior
and posterior aspects), upper and lower limbs, with exfoliation covering more than 30% of the body
surface area, revealing underlying erythematous dermis (diffuse erythroderma, ‘scalded
appearance’).

2. Margins of patches and macules appears flat, irregular and well defined.

3. Margins of erythematous macules and patches on forearm appear to be grayish at the

margins (possible ongoing necrosis).

4. No ulceration or bloody /purulent discharge seen.

5. Hair follicles appear intact despite extensive erythroderma, suggesting only involvement of
epidermis.

6. Bullae (some ruptured) seen on palmar aspect of fingers and palmar aspect of hands, with
serous discharge, and the detached skin appears like ‘crumpled wet cigarette paper’. Nikolsky sign
presumed positive.

7. Unable to comment on oral, conjunctival, urethral and perineal mucosal surfaces as not
shown.

8. Unable to comment on involvement of lymph nodes.

9. The lesions are probably non-indurated, non-fixed, and tender on palpation

There were scaly, erythematous plaques with small, round, “punched out,” and crusted erosions
(approximately 1 mm in diameter) and scattered larger erosions with scalloped borders, with
larger confluent areas on the chest, arms, and legs

Chief Diagnosis: Toxic epidermal necrolysis (TEN); (Id: Sindrom Lyell)

Given the dermatological examination findings, and in view of the history whereby certain
antiepileptic agents were used the chief diagnoses to emergently manage is ‘toxic epidermal
necrolysis’ Note that although TEN is more common with aromatic compound-based AED such as
phenytoin and carbamazepine, cutaneous drug reactions (DRESS - Drug rash with eosinophilia and
systemic symptoms, Antiepileptic Hypersensitivity Syndrome - AHS, and even TEN) have been
reported with non-aromatic AEDs.

Drugs commonly associated with SJS/TEN:

1. Allopurinol

2. Aminopenicillins ,cephalosporins, quinolones

3. Anti-TB medications
4. Antiretroviral drugs, especially NNRTIs (eg. nevirapine, efavirenz)

5. Barbiturates

6. AED esp aromatic AED like phenytoin, lamotrigine esp if combined with valproate,
carbamazepine, diphenylhydantoin, phenobarbital

7. Checkpoint inhibitors (eg. ipilimumab, nivolumub)

8. NSAIDS of the ‘-oxicam’ class (meloxicam, piroxicam, tenoxicam)

9. Sulfa-compound drugs including these: Sulfonamide antibiotics, especially sulfamethoxazole,

sulfadiazine and sulfasalazine

Nkolsky's sign is the easy exfoliation of the top layer of the skin from the lower layers when slightly
rubbed. SJS usually does not demonstrate Nikolsky's sign, but the more severe spectrum TENS does
demonstrate Nikolsky's.

If inquired further:

1. This patient will probably recall experiencing about a week ago certain prodromal
symptoms, like fever, malaise, rhinitis, laryngitis and myalgia, followed suit by development of a
macular rash that mimics erythema multiforme’s target lesions (except that there are no concentric
rings).

2. This exanthematous macules become confluent, and dermal-epidermal disjunction occurs

giving you positive Nikolsky's sign.

3. Mucous membrane involvement including involvement of conjunctivae, urethra and cornea

may lead to permanent scarring and blindness.

4. Systemic eruptions in TEN may occur, with renal, gastrointestinal, or respiratory lining
lesions, resulting in hematuria, diarrhea, bronchitis and cholestasis (‘disappearing bile duct’).

To confirm diagnosis,

Two full-thickness punch biopsy specimens for frozen section and formalin-fixed examination,
accompanied by skin specimens are taken from the border of intact epidermis surrounding bullous
lesions.

This finding will nail your diagnosis of TEN/SJS: Necrosis is seen, characterized by keratinocyte
destruction and detachment of epidermis from dermis

Differentials for a diffuse rash with erythema and exfoliation (any epidermolytic dermatoses):

1. SJS, similar presentation and etiology as TEN but involving <10% BSA (body surface area)

2. SJS-TEN overlap, ditto with involvement 10-30% BSA

3. Erythema multiforme major. Previously, this was equated with Stevens-Johnson syndrome,
but now distinguished from it because now we understand that EM tends to manifest as target
lesions having 3 or more concentric rings in a symmetrical distribution with or without blisters,
without Nikolsky sign
Differentiated histologically by mononuclear cell infiltration and less necrosis than in SJS/ TEN

4. Staphylococcal scalded skin syndrome, SSSS (Id: penyakit Ritter). This one tends to present
like TEN but mainly in infants/young children. Like TEN/SJS, SSSS also has positive Nikolsky sign.
However, on histopathology there is subcorneal split with or without mild acantholysis (loss of cell-
to-cell adhesion). The ‘higher-in-the-epidermis’ cleavage seen in SSSS also means SSSS bullae are
thinner walled and more fragile. In addition, Gram stain and culture of exudates from the nose and
conjunctivae may be positive for S. aureus

5. AGEP (acute generalized exanthematous pustulosis). Presents as widespread erythematous

and edematous rash with fever and abrupt onset, and distinguished from the SJS/TEN spectrum by
small nonfollicular whitish pustules that self-resolve in <1 week. The histolopath hallmark of AGEP is
spongiform, subcorneal, and intraepidermal pustules containing plenty of PMN, and lack of necrotic
keratinocytes (non-necrotic cleavage)

6. DRESS (drug reactions with eosinophilia with systemic symptoms). The hypersensitivity drug
reaction par excellence, starting about 2–6 weeks after drug exposure. Like TEN/SJS you also have a
prodromal stage, with fever, lymphadenopathy, influenza-like symptoms, burning pain, or pruritus.
Clinical findings are facial oedema, erythroderma, purpura, pustules, and only focal mucosal
involvement

7. 2nd degree burns (common sense)

Skin biopsy demonstrated prominent epidermal necrosis, suggestive of toxic epidermal necrolysis
(skin sloughing > 30% of the body surface area). Given the widespread skin detachment, the
patient’s clinical picture was most consistent with toxic epidermal necrolysis, a rare life-threatening
mucocutaneous eruption, with up to 95% of cases attributed to a drug-induced hypersensitivity
reaction. Vandetanib, temozolomide, omeprazole, and levetir- acetam were potential initiating
agents in our patient’s case, and all had been stopped.

Therefore, rapid and definitive biopsy diagnosis is essential in the differentiate diagnosis

Conditions to consider in the differen- tial diagnosis are other drug reactions, including the so- called
DRESS syndrome—drug reaction with eosinophilia and systemic symptoms—and erythema
multiforme/ Stevens-Johnson syndrome, cutaneous T-cell lymphoma, toxic shock syndrome,
staphylococcal scalded skin syn- drome, and Kawasaki disease in children.

Patient was started on intravenous gamma globulin and pulse-dose methylprednisolone therapy. In
addition, he received extensive topical wound care in the medical step-down unit (MDSU). His
symptoms ultimately remitted over the course of a month-long hospitalization, after which he was
discharged to an inpatient short-term physical rehabilitation facility. When he succumbed to his
cancer approximately 12 months later, he had no evidence of any ongoing dermatologic sequelae.

The Stevens-Johnson syndrome is a skin disease that includes oral and eye manifestations. The oral
aspect of the disease may predominate which makes the diagnosis difficult. The oral lesions do not
occur simultaneously and each lesion's life cycle can be classified into five stages. The eye
involvement is usually limited to the conjunctiva, although much more severe ocular forms can
occur. When this disease is limited to the oral cavity it is usually confused with herpes simplex.
Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are closely related severe, acute
mucocutaneous reactions usually caused by drugs. They are acute life-threatening conditions and cause
widespread necrosis of the epithelium. There is persistence of a high risk of SJS or TEN in relation to human
immunodeficiency virus (HIV) infection associated with exposure to nevirapine (NVP). In this article, we present
nine cases of SJS and one case of TEN in HIV-seropositive individuals who developed cutaneous, oral, ocular
and genital lesions while being treated with NVP.

In 1922, Stevens and Johnson first described Stevens-Johnson syndrome More Details (SJS) as an
immune complex hypersensitivity reaction that can be caused by many factors such as infections,
drugs and malignancies. [1] It is a progressive, fulminating, severe variant of erythema multiforme
with other variant being toxic epidermal necrolysis (TEN). TEN is a rare and potentially fatal
dermatological condition. Reported incidence rates of SJS are 1-6 cases/106 person-years, and for
TEN 0.4-1.2 cases/106 person-years. [2] SJS refers to cases with less than 10% of body surface
involvement and TEN to those with more than 30% involvement. [3] Burning sensation, edema,
erythema of the lips and buccal mucosa are some of the first signs. Skin lesions are initially
erythematous macules that rapidly develop central necrosis with vesicles, bullae and denudation on
the face, trunk and extremities. Diffuse oral and genital ulcerations may be present. The most
common sites include labial mucosa, buccal mucosa, tongue, floor of the mouth and the soft palate.
Hemorrhagic crusting of the vermillion zone of the lips is common. There is severe involvement of
the conjunctiva, nasopharynx and larynx. [4] TEN and SJS are acute life-threatening conditions with a
significant impact on high mortality rate (5-35%). [5],[6]

Human immunodeficiency virus (HIV) infected patients on exposure to nevirapine (NVP) have
significantly increased risk of SJS or TEN. The underlying mechanism for cutaneous reactions is not
clear, but the probable hypothesis could be drug-specific cytotoxic lymphocytes

SJS and TEN are cytotoxic hypersensitivity reactions resulting in systemic disease, characterized by
sloughing of the skin and mucous membranes at the dermal-epidermal junction. [8] There is a
growing evidence that SJS and TEN belong to a single group of diseases with common causes and
mechanisms. [9] Both are acute life-threatening conditions. [8]

Recent reports have linked SJS to the use of drugs rather than other etiologic factors. Antibiotics
(sulphonamides) are the most common cause of SJS, followed by analgesics, cough and cold
medication, nonsteroidal antiinflammatory drug (NSAID), and psycho-epileptics. NVP has also been
implicated in the pathogenesis of SJS. There may be a genetic predisposition in developing SJS.
Individuals with antigens like human leukocyte antigen Bw44, HLA-B12, and HLADQB1 * 0601 appear
to be more susceptible to developing SJS. [1] SJS in children is frequently attributed to infectious
agents but may also be related to drug intake. [10] Granulysin is a cationic cytolytic protein released
primarily by cytotoxic T cells (CTLs) and NK cells. It is the key molecule responsible for the
disseminated keratinocyte death and tissue damage and results in the unique clinical presentation of
SJS/TEN. [11]

NVP is a nonnucleoside reverse transcriptase inhibitor approved by the US Food and Drug
Administration (FDA) used in HAART, combination regimens for the treatment of HIV infection.
Major adverse reactions, including skin rashes and hepatotoxicity occur in approximately 3% of HIV-
infected individuals who receive long-term course of NVP. The greatest risk occurred during the first
few weeks of NVP treatment. [12] There is persistence of a high risk of SJS or TEN in relation to HIV
infection associated with exposure to NVP. The mechanisms probably involve drug specific cytotoxic
lymphocytes. [7] Upregulation of keratinocyte Fas L expression is the critical trigger for keratinocyte
destruction during TEN. [13] According to the EuroSCAR, study was designed as an international
multicenter study aiming at an ongoing surveillance of medication risks for SJS and TEN based on a
case-control methodology. A few medications are associated with high risk of SJS or TEN. Prescribing
any one of the following drugs requires thorough evaluation of expected benefits:

Nevirapine

Lamotrigine

Carbamazepine

Phenytoin

Phenobarbital

Cotrimoxazole and other antiinfective sulfonamides

Sulfasalazine

Allopurinol

Oxicam-NSAIDs

A delay of 4-28 days between beginning of drug use and onset of the adverse reaction is the most
suggestive timing supporting drug causality in SJS or TEN. [9] In our 10 cases, the lesions developed
between 1 and 2 weeks after the initiation of HAART, which consisted of NVP.

Burning sensation, edema and erythema of the lips and buccal mucosa are some of the initial signs.
Diffuse oral ulcerations of the labial mucosa, buccal mucosa, tongue, floor of the mouth and the soft
palate are present. Skin lesions are initially erythematous macules that rapidly develop central
necrosis with vesicles, bullae and denudation on the face, trunk and extremities. Mucosal erosions
can occur in at least two sites, including conjunctivae, mucous membranes of the nares, mouth,
anorectal juctions, vulvovaginal and urethral meatus. Other clinical features include pneumonitis,
productive cough, fever, headache and malaise. [14]

In all 10 cases, the mucocutaneous manifestations were similar and associated prodromal symptoms
were fever, headache and malaise.

The clinical differential diagnosis of SJS includes Staphylococcal Scalded Skin Syndrome, Kawasaki
disease, acute Graft-Versus-Host disease and bullous Systemic Lupus Eythematosus. [14]
Investigations include a complete blood count (CBC), which may be normal. Markedly raised values
may indicate a superimposed infection. Liver function tests, electrolytes and other chemistries may
be needed. Cultures of blood, urine and wounds are indicated when an infection is coexistent. [1]
There are no specific diagnostic tests and the diagnosis is mainly clinically supported. Biopsy of peri-
lesional tissue, with histological and immunofluorescence examination are essential if a specific
diagnosis is required. [15]

All the 10 cases revealed classic clinical presentation of SJS/TEN. As the patients were in a severe
debilitating condition we could not subject to histopathology and immunofluorescence. Blood
picture showed normal values except for altered ESR, indicating superimposed infection.

Treatment of these two life-threatening conditions includes prompt recognition and withdrawal of
suspected drugs and hospitalization. Infection control, isolation measures and management of
cutaneous coverage improve the symptoms and facilitate injuries toward epithelization. Mucosal
hygienic measures are of prime importance to increase the patient's comfort and to prevent
complications.[16] Oral lesions were treated with topical lignocaine gel. In some patients, oral
hygiene was maintained by the use of chlorhexidine mouth wash. Application of paraffin externally
was recommended for crusting skin lesions. [1]

After recovery, patients should be advised to avoid not only the suspected drug(s), but also
chemically related compounds. [17]

NVP was stopped in all the 10 cases and patients were treated symptomatically by administering
intravenous 5% dextrose, dexamethasone 2 ml and high protein supplements were included in the
diet. HAART (lamivudine, efavirenz, zidovudine/staruvudine) was initiated again and continued
without rechallenge of NVP. All the patients were followed up regularly for 6 months and the
response to the treatment was satisfactory.

Conclusion Top

SJS and TEN are two rare but severe blistering mucocutaneous diseases that share common clinical
and histopathological features but vary in the extent of epidermal detachment. Both are frequently
associated with drug use.
Antiretroviral therapy is not only becoming increasingly effective, but also increasingly complex.
Close monitoring and follow-up for patients placed on NVP for HIV are paramount not only for
therapeutic response but also for the development of severe complications such as SJS/TEN. As
documented in our cases, prompt recognition and institution of appropriate therapies, including
transfer to a burn centre, can positively impact survival of patients affected by SJS/TEN. As efforts
continue in the development of medications with more favorable adverse effect profiles, treating
physicians must remain aware of new and developing syndromes associated with antiretroviral use.

One must be careful and suspect SJS, if a patient is on HAART regimen containing NVP and presents
with symptoms arising from irritation of the skin and mucous membranes.

Erythema Multiforme (EM) is a rare mucocutaneous disease with a variety of clinical manifestations.
EM it was recognized in the early 1800's, and still the etiology is unknown. It has been recently
suggested erythema multiforme (EM) major and Stevens-Johnson Syndrome (SJS) could be
separated as two distinct clinical disorders with similar mucosal erosions, but different patterns of
cutaneous lesions. In particular SJS should be used for a syndrome characterized by mucous
membrane erosions and widespread small blisters that appear on erythematous or purpuric
maculae, which are different from classic targets. In SJS mouth, eyes, skin, genitalia and occasionally
the esophagus and respiratory track may be affected. Oral lesions may cause severe pain and usually
lips may become encrusted. Concerning ocular involvement, if there is conjunctivitis or uveitis this
may lead to scarring and blindness. Also, the course of disease and the prognosis are in most cases
severe.

Sweet syndrome

Sweet syndrome or febrile neutrophilic dermatosis..commonly presented as plague,sometimes even

nodules or vesicles on hand/feet,head or neck (trunk will usually be spared i think?)

it is usually associated with inflammatory disorders like in this case RA,things that comes along
include an elevated white count,fever,arthralgia,conjunctivitis..

other than RA, sweet syndrome is also linked to leukaemia & inflammatory bowel condition..skin
biopsy should be the gold standard

The correct answer is Sweet’s syndrome. Sweet’s syndrome (also called acute febrile neutrophilic
dermatosis) is a rare disease associated with inflammatory disorders including rheumatoid arthritis.
A skin biopsy can confirm the diagnosis and demonstrate papillary dermal edema and perivascular
and interstitial lymphohistiocytic and neutrophilic infiltration. Therapeutic interventions for Sweet’s
syndrome include topical and systemic corticosteroids.

On examination, there are multiple nonblanchable red macules and papules coalescing
into patches and plaques with dusky centers (figure)
 extensive confluent erythematous maculopapular rash with a morbilliform appearance
(Figure 1) on his entire trunk,

buttocks, extremities and face; her palms and soles were spared.

On the face, neck, trunk, and extremities, there are large areas of erythema underlying intact
bullae admixed with. The rash involves approximately 40% of her body-surface area. No
lymphadenopathy is noted on examination.

A diffuse rash involved nearly all areas of her body, including the
There were scaly, erythematous plaques with small, round, “punched out,” and crusted erosions
(approximately 1 mm in diameter) and scattered larger erosions with scalloped borders, with
larger confluent areas on the chest, arms, and legs; lesions were less prominent on the posterior
trunk, buttocks, and posterior knees.
. There was a fine, almost confluent, erythematous, maculopapular rash on the forearms that
was nonpruritic, with petechiae on the lower shins and ankles.
Blanching, blistering, nonpruritic
blisters rise nearer the skin's surface
Non tender
Morbiliform rash
erythematous, vesicular-appearing rash,
widespread 'target lesions' over her arms, legs and trunk, highly characteristic of erythema
multiforme
Skin lesion was sparing of the palms, soles. The greatest concentration of lesions was on the
extensor surfaces of the knees.
The skin examination revealed edematous plaques and papules, with pseudovesicular lesions
that were most notable on the back
the rashes were typically
erythematous and vesicular in nature with blisters
spreading all over the body.
Induration?
With no epidermal detachment
 Multiple erythematous papules, plaques were present all over the body
diffuse erythema of the skin with a questionable superimposed diffuse, macular,
blanching erythroderma that involved the palms and the soles;

Numerous healed lesions were also seen on the chest, axilla which gave the typical
appearance of “target lesions” or “bull's eye “appearance”
The rashes appears to be erythematous maculo-papular rash distributed
evenly(widespread) over the back of the patient with no skin lesion elsewhere. There is no
bullous/exfoliative/blistering changes seen. It does not follow a dermatomal distribution/has a
distinct pattern of distribution.
The entire skin covering the body surface was denuded and peeled off with minor
manipulation and appeared blackish in color in one patient
On physical examination, erythematous macules were confluent on >80% of the total body
surface with numerous and widespread sheets of flaccid blistering (Fig. 1). Nikolsky's sign was
positive
She evolved rapidly with increased epidermal detachment in the face, neck, thorax,
dorsum, and limbs, affecting more than 30% of her body.
intense erythema, progressing rapidly to epidermolysis
Rash sparing palms and soles
Morbiliform rash, generalised maculopapular rash, not tender, not scaly

a— Maculopapular eruptions on his back; b— oval erythema on his abdomen; c— oval

erythema and blisters; d— ruptured blister with desquamation.
Up to mid thigh, no pustule or vesicles
Generalised Confluent erythema with morbilliform rash with occasional blistering
lesion
Crops of elevated lesion with some ruptured blisters over his whole body.
Erythema with central necrotic patches on body
Some erosion and blister on lateral trunk and back
Noted on facem truncal, front and back, bilateral upper limbs and
1 mucosa involved
40% involved based on burn chart
 round-shaped targetoid lesion with dusky center where the three concentric colour
zones can be appreciated in above picture. This lesion is pathognomonic for erythema
multiforme

Typical target lesions consist of three components: a dusky central area or blister, a
dark red inflammatory zone surrounded by a pale ring of edema, and an erythematous halo on
the extreme periphery of the lesion.Atypical target lesions may also occur in patients with EM.
These manifest as raised, edematous, palpable lesions with only two zones of color change
and/or a poorly defined border.Cutaneous lesions most commonly appear in a symmetrical
distribution on the extensor surfaces of the acral extremities, and subsequently spread in a
centripetal manner. The face, neck, palms, soles, flexural surfaces of the extremities, and/or
trunk may also be involved.

The first of these is an absolute

lymphopenia ie; an isolated low lymphocyte count in the absence of any
other abnormalities in the blood count. Earlier reports suggested a
prevalence of lymphopenia of 80% in adults and 50% in children with HIV
infection [1]. This parameter on the blood count is often overlooked and
many physicians are often only concerned about low total white cell count
or neutropenia. It is also useful to note that lymphoenia has been linked
to autoimmune disorders, which are more prevalent with HIV [2].
Thrombocytopenia has been associated with acquired immunodeficiency
syndrome even before the discovery of HIV with an incidence of about 30%
in individuals infected with HIV [3]. A low platelet count is often
overlooked in these cases, since HIV-associated thrombocytopenia is often
mild and does not cause excess bleeding. But it is important to remember
that HIV seropositive patients can develop thrombocytopenia much before
more commonly recognised complications of HIV develop. A recent
international consensus guideline recommended "routine serologic
evaluation for HIV infection in adult patients with suspected immune
thrombocytopenia (ITP), regardless of local background prevalence and
personal risk factors documented in the patient history"
https://www.medicinenet.com/drug_induced_liver_disease/article.htm

https://gut.bmj.com/content/66/6/1154

https://www.msdmanuals.com/professional/hepatic-and-biliary-disorders/drugs-and-the-liver/liver-
injury-caused-by-drugs

https://emedicine.medscape.com/article/169814-overview

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160634/

https://www.uptodate.com/contents/drug-induced-liver-injury#H18157466

Toxic epidermal necrolysis (TEN) is a severe cutaneous reaction with significant potential for
morbidity and mortality.
Potentially implicated medications in all three diagnoses include antibiotics, aromatic
anticonvulsants (carbamazepine, phenytoin, phenobarbital), lamotrigine, allopurinol, nonsteroidal
antiinflammatory drugs, and antiretrovirals. Common drugs that cause this are anticonvulsants
(most of the time), antibiotics (sulphonamides), antifungals, NSAIDS, allopurinol, analgesics,
antimalarials, corticosteroids, anti-HIV and antihellmintics.

SJS can be associated with infections such as herpes, EBV, mycoplasma pneumoniae,
cytomegaloviruses, URTI, pharyngitis and otitis media. It's also associated with smallpox vaccination.

The dermatologic manifestations of either toxic epidermal necrolysis or Stevens-Johnson syndrome

may constitute a true emergency. Toxic epidermal necrolysis, an acute disorder, is characterized by
widespread erythematous macules and targetoid lesions; full-thickness epidermal necrosis, at least
focally; and involvement of more than 30% of the cutaneous surface. Commonly, the mucous
membranes are also involved. Nearly all cases of toxic epidermal necrolysis are induced by
medications, and the mortality rate can approach 40%.

Manifestations of Stevens-Johnson syndrome include purpuric macules and targetoid lesions; full-
thickness epidermal necrosis, although with lesser detachment of the cutaneous surface; and
mucous membrane involvement. As with toxic epidermal necrolysis, medications are important
inciting agents, although Mycoplasma infections may induce some cases. The mortality rate is much
lower than in toxic epidermal necrolysis, approaching 5% of cases.

80 year old with a background history of hematological malignancy and hypertension presented with
(as shown in the image above) painful hemorrhagic erosion confined to the oral mucosa associated
with crusting. The first thing that crossed my mind was

We all know that SJS/TEN are adverse cutaneous reaction and the causes are plenty. But one should
ideally think about ADVERSE DRUG REACTION. Anti-epileptics (phenytoin,
carbamazepine,lamotrigene)are notoriously known to cause SJS but however, there is no history of
epilepsy of history of such drug being taken.

How about antibiotics? Sulphonamides, penicillin, bactrim are the important ones. Drug history
focusing on drugs that are used to treat pneumonia (penicillin group/cephalosporin) should be paid
extra attention. Generally, SJS/TEN tends to occur 1-2 weeks after initiation of a particular drug

Stevens-Johnson syndrome is a severe idiosyncratic reaction, most commonly triggered by

medications, and is characterized by fever and mucocutaneous lesions leading to necrosis and
sloughing of the epidermis. Oral lesions such as mucosal blistering may precede skin lesions. The skin
lesions are flat, atypical target lesions characterized by blisters or purpuric macules

Hypersensitivity syndromes are most strongly associated with anticonvulsant agents — specifically,
phenytoin and carbamazepine (which the patient received) — occurring in 1 of 5000 patients
receiving these drugs. The syndromes occur approximately two to six weeks after the initiation of
therapy and usually present with fever, a rash, and lymphadenopathy. Hepatitis and hematologic
abnormalities, especially eosinophilia and atypical lymphocytosis resembling that of infectious
mononucleosis, are common. The symptoms often resolve after the drug has been discontinued,
although the reaction may progress to lymphoma. Recovery is usually complete, and corticosteroid
therapy has been reported to speed improvement in the rash and hepatic-enzyme abnormalities.
Although many of these signs and symptoms are consistent with the features of this case (including
the six-week delay in the onset of symptoms), the progression of symptoms for several weeks after
both anticonvulsant drugs had been discontinued and the minor degree of hepatitis, as reflected by
elevated enzyme levels, in contrast to the presence of clinically significant hepatomegaly, call this
diagnosis of exclusion into question.The most likely diagnosis in a fever, eye changes, mucosal
changes, and dusky patches on >30% of body-surface area is toxic epidermal necrolysis.

2) Presence of systemic symptoms like fever? joint pain? palpable lymph nodes? I am thinking along
the line of DRESS syndrome. Take temperature, blood work to look for hepatic and renal
involvement.

3) SJS/TEN. Although there are no similar rashes elsewhere and blistering/target like skin lesions are
not typically seen. Any skin lesion that occur following medication which is red, painful, abrupt and
rapidly progressing would prompt me to think about SJS/TEN.

Our patient exhibited classical findings of DRESS with mild hepatitis. Toxic shock syndrome shares
similar features with DRESS (fever, diffuse rash and hepatitis); however, the patient did not meet the
diagnostic criteria (no associated shock, and only two organ systems were involved: hepatic and
gastrointestinal). Serum sickness-like reaction (hypersensitivity vasculitis) from cephalosporin use is
a consideration, but our patient did not exhibit palpable purpura, symptom onset is usually more
rapid (seven to 10 days after antigen exposure) and patients are usually older (older than 16 years).

The classic triad seen in DRESS consists of rash, fever

. Eosinophilia is common, but may be absent.

DRESS is commonly caused by the aromatic anticonvulsants (phenytoin, carbamazepine and

phenobarbital), sulpha drugs and allopurinol. It occurs two to eight weeks following initiation of
therapy.

DRESS is potentially fatal, and diagnosis may be delayed due to its similar presentation to various
viral or bacterial infections.

A: DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome, also known as
anticonvulsant hypersensitivity syndrome. This syndrome is a medication-induced complex of
symptoms consisting of fever, pruritic rash, lymphadenopathy, and internal organ involvement. It is
associated with several anticonvulsant medications, as well as allopurinol, sulfonamides, and other
medications.1 Laboratory abnormalities include hepatitis with leukocytosis and eosinophilia.2
Patients usually have a macular or papular rash or erythroderma; pustules are rare.2 Management
includes discontinuing the offending agent and initiating supportive systemic steroids. Medication-
induced complex of symptoms consisting of fever, pruritic rash, lymphadenopathy, and internal
organ involvement; rash appears as papules or erythroderma

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous reaction
characterized by fevers, facial swelling, and variable erythematous dermatitis. Patients often exhibit
lymphadenopathy. The clinical finding of “dusky centers” indicates incipient skin necrosis and
detachment, a finding more commonly seen in SJS–TEN.

Atopic dermatitis is a chronic inflammation of the skin that is common in children. It is characterized
by pruritus, and exacerbations and remissions. Patients develop thickened skin, increased skin
markings (lichenification), and excoriated papules. Diagnosis relies on a history of exposure to
certain irritants or allergens.3

Now question, what about other possible drug eruptions?

With above lesion morphology and history of self-limiting,

hypersensitivity syndromes, small-vessel vasculitis, serum sickness, and angioedema

Fixed drug eruption
Erythema nodosum
Atopic dermatitis

Erythema nodosum is a nodular erythematous eruption usually limited to the extensor aspects
of the extremities. The characteristic lesions begin as red, node-like swellings over the shins,
and commonly affect both legs.2 Sulfonamides, bromides, and oral contraceptives have been
reported to cause erythema nodusum.2 It is also associated with streptococcal infections and
some cancers, such as lymphoma.

Fixed drug eruption is most commonly characterized by a solitary, oval violaceous patch on
the skin or mucosa that often recurs in the same anatomic location after each exposure to culprit
medications. Multiple patches may occur, but this is rare. Due to the appearance of the skin
lesion and recurrence in the same location, parents were questioned about any medications
previously used and disclosed that it had started 48 h after the ingestion of a non-steroidal anti-
inflammatory (NSAID), in both episodes, confirming therefore the diagnosis of fixed drug
eruption (FDE). FDE is a benign reaction triggered by exposure to drugs,most commonly
NSAIDs and antibiotics, characterised by a sudden onset of violaceous oval plaques or patches,
which heal usually with residual hyper-pigmentation. Recurrences in the same areas are typical.
The main involved areas are the trunk, limbs and genitals. Most cases are asymptomatic or
develop slight pain or local itch. Diagnosis is made upon clinical characteristics, and
differential diagnoses include insect bites, urticaria, erythema multiforme, Stevens–Johnson
syndrome and toxic epidermal necrolysis. If the clinical appearance of the lesion and its history
are not typical for the diagnosis, skin biopsy can be helpful. Drug reactions are very frequent,
especially because many over-the-counter products are available (particularly NSAIDs in
Brazil, as in our case), and their use is sometimes omitted by the parents. Withdrawal of the
drug is usually enough to rapidly improve the lesion and prevent recurrences. Has had no
previous dermatological manisfestation, particularly n the same area. at exactly the same
locations, a year before, after taking the same drug. On examination he presented well-
demarcated erythematous patches The Fixed drug eruption (FDE) is defined as recurrent
lesions that, upon repeated uptake of the causative drug, always appear at the same skin or
mucosal sites.

He had no erythema on his soles, and no facial rash or periungual erythema. He also had no
muscle pain, arthralgia, Gottron papules, heliotrope rash, or shawl sign. Therefore, derma-
tomyositis, which could manifest as a paraneoplastic syndrome, seemed unlikely