Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Clinical Characteristics

Initial Presentation and Distribution

• The rash typically begins on the upper torso, proximal limbs, and face, then spreads to involve the rest of the trunk and distal limbs, with prominent involvement of the palms and soles, according to the British Journal of Dermatology 1, 2
• Initial sites of involvement are commonly the upper torso, proximal limbs, and face, as reported by the British Journal of Dermatology 1, 2
• The rash then spreads to involve the rest of the trunk and distal limbs, as described in the British Journal of Dermatology 1
• Involvement of the palms and soles is often prominent, as noted in the British Journal of Dermatology 1, 2
• Mucosal involvement of the eyes, mouth, nose, and genitalia is usually an early feature, according to the British Journal of Dermatology 2, 3

Rash Characteristics and Progression

• Lesions typically appear as numerous circular, dark red macules characterized by a dark red center surrounded by a pink ring, as described in the British Journal of Dermatology 1, 4
• Lesions expand and coalesce, reaching maximum extent 5-7 days after disease onset, as reported by the British Journal of Dermatology 2
• Large areas of confluent erythema develop in severe cases, according to the British Journal of Dermatology 1
• Lesional skin is tender to touch; minimal shearing forces cause the epidermis to peel back (positive Nikolsky sign), as noted in the British Journal of Dermatology 2, 4
• Blistering ensues with necrotic epidermis separating from underlying dermis, producing flaccid bullae, as described in the British Journal of Dermatology 2
• Extensive necrolysis results in detachment of sheets of epidermis, leaving areas of exposed dermis, according to the British Journal of Dermatology 3

Classification Based on Extent of Involvement

• SJS: Epidermal detachment <10% body surface area (BSA) plus widespread purpuric macules or flat atypical targets, as defined by the British Journal of Dermatology 4
• Overlap SJS-TEN: Detachment of 10-30% BSA plus widespread purpuric macules or flat atypical targets, as reported by the British Journal of Dermatology 4
• TEN with spots: Detachment >30% BSA plus widespread purpuric macules or flat atypical targets, according to the British Journal of Dermatology 4
• TEN without spots: Detachment >30% BSA with loss of large epidermal sheets without purpuric macules or target lesions, as described in the British Journal of Dermatology 4

Mucosal Involvement

• Involvement of the mucous membranes of the eyes, mouth, nose, and genitalia is usually an early feature, as noted in the British Journal of Dermatology 2
• Mucosal involvement leads to an erosive and hemorrhagic mucositis, according to the British Journal of Dermatology 2
• In some cases, particularly those associated with Mycoplasma pneumoniae, there may be predominantly mucous membrane involvement with little or no cutaneous lesions, as reported by the British Journal of Dermatology 5

Clinical Pitfalls and Important Considerations

• Cutaneous pain is a prominent early feature in SJS/TEN and should alert physicians to incipient epidermal necrolysis, as described in the British Journal of Dermatology 2, 3
• The Nikolsky sign (epidermal detachment with gentle lateral pressure) is helpful but not specific for SJS/TEN, according to the British Journal of Dermatology 2, 6
• Differentiation from erythema multiforme major (EMM) is important: EMM has typical targets or raised atypical targets predominantly on limbs and extremities, while SJS has atypical targets more widely distributed, as noted in the British Journal of Dermatology 5
• Documentation of both the extent of erythema AND epidermal detachment is crucial for prognosis assessment, as reported by the British Journal of Dermatology 7
• Denuded dermis exudes serum, becomes secondarily infected, and readily bleeds, according to the British Journal of Dermatology 2

Clinical Presentation, Classification, and Key Diagnostic Pitfalls of Stevens‑Johnson Syndrome and Toxic Epidermal Necrolysis

Prodromal Phase

• Fever and malaise are prominent early systemic features that typically appear 4–28 days after initiation of a culprit drug. 8
• Flu‑like upper‑respiratory symptoms often accompany the prodrome. 8
• Severe cutaneous pain that precedes any visible skin changes is a critical early warning sign and should prompt immediate evaluation for incipient epidermal necrolysis. 8
• Ocular inflammation may develop before cutaneous lesions become apparent. 8

Cutaneous Manifestations

Initial Lesion Characteristics

• The earliest skin lesions are atypical flat targets or purpuric macules with a dark‑red centre surrounded by a pink ring. 9
• Lesions first appear on the upper torso, proximal limbs, and face before spreading to the trunk and distal extremities. 8
• Palmar and plantar surfaces are frequently involved early in the disease course. [8][9]

Progression Pattern

• Lesions expand and coalesce, reaching maximal extent 5–7 days after disease onset. 8
• In severe cases, large confluent areas of erythema develop. [8][9]
• Affected skin is exquisitely tender to touch. 8
• A positive Nikolsky sign (gentle lateral pressure causes epidermal peeling) is commonly observed. 8

Advanced Skin Findings

• Flaccid blisters form as necrotic epidermis separates from the underlying dermis. 8
• Extensive necrolysis leads to sheet‑like epidermal detachment, exposing a denuded dermis that exudes serum, bleeds, and is prone to secondary infection. [8][9]

Mucous Membrane Involvement (Early Feature)

• Erosive and hemorrhagic mucositis affects multiple sites (ocular, oral, genital, nasal). 8
• Oral mucositis presents with erythema, blistering, and painful erosions that may require enteral feeding support. 9
• In some Mycoplasma‑associated presentations, mucosal involvement predominates while cutaneous lesions are minimal. 9

Classification by Extent of Epidermal Detachment

• Stevens‑Johnson syndrome (SJS): <10 % body‑surface‑area (BSA) detachment plus widespread purpuric macules or flat atypical targets. [9][10]
• SJS‑TEN overlap: 10–30 % BSA detachment with the same lesion morphology. [9][10]
• Toxic epidermal necrolysis (TEN): >30 % BSA detachment. [9][10]

Critical Clinical Pitfalls

• Cutaneous pain that precedes visible skin changes is a red‑flag symptom demanding urgent assessment. 8
• Although the Nikolsky sign is helpful, it is not specific for SJS/TEN and can also be positive in pemphigus. 8
• Differentiation from erythema multiforme major is essential: erythema multiforme shows raised target lesions mainly on the limbs, whereas SJS exhibits flat atypical targets distributed more widely. [8][9]
• Accurate documentation should include both the extent of erythema and the percentage of epidermal detachment, noting that detachable epidermis may appear as dusky erythema before frank blistering. 10

Stevens‑Johnson Syndrome and Toxic Epidermal Necrolysis: Definitions, Mortality, Diagnosis, Management, and Histopathology

Definition and Classification

Mortality

Clinical Features

Positive Nikolsky Sign

Early Mucosal Involvement

Mycoplasma‑Associated Presentations

Diagnostic Procedures

Transfer and Level of Care

SJS (< 10 % BSA)

Overlap SJS‑TEN (10–30 % BSA) or TEN (> 30 % BSA)

Multidisciplinary Consultation

Differential Diagnosis

Causative Agents with Unclear Attribution

Histopathology

All histopathologic observations are supported by the cited literature. 11, 12

Clinical Presentation and Diagnostic Features of Stevens‑Johnson Syndrome

Prodromal Phase

• Fever, malaise and upper‑respiratory‑tract symptoms typically appear several days before the skin eruption. 13
• Severe cutaneous pain may precede any visible skin change and should be regarded as an early red‑flag for incipient epidermal necrolysis. 14
• Ocular inflammation (e.g., conjunctivitis) can develop before any cutaneous signs become apparent. 15

Early Cutaneous Manifestations

• The first lesions are atypical flat targets or purpuric macules with a dark‑red centre surrounded by a pink ring. 14
• Initial distribution commonly involves the upper torso, proximal limbs and face, with early involvement of palms and soles. 14
• Lesions expand and coalesce, reaching maximal extent within 5–7 days after disease onset. 14
• A positive Nikolsky sign (gentle lateral pressure causes the epidermis to peel) is frequently observed, although it is not specific to SJS/TEN. 14

Advanced Skin Findings

• Flaccid blisters form as necrotic epidermis separates from the dermis. 14
• Sheet‑like epidermal detachment exposes a denuded dermis that exudes serum, bleeds readily, and is prone to secondary infection. 14

Mucosal Involvement (Early Feature)

• Erosive and hemorrhagic mucositis affecting the eyes, oral cavity, nasal passages and genitalia is typically present early in the disease course. 15
• Ocular signs include purulent keratoconjunctivitis, eyelid edema and persistent inflammation. 16
• Genital involvement may manifest as pain and urinary retention. 13
• In Mycoplasma‑associated cases, mucosal involvement can predominate while cutaneous lesions remain minimal. 17

Respiratory and Gastrointestinal Manifestations

• Cough, dyspnea, bronchial hypersecretion and hemoptysis indicate respiratory tract involvement. 13
• Diarrhea and abdominal distension suggest gastrointestinal (bowel) involvement. 13

Diagnostic Pitfalls and Differentiation

• Early cutaneous pain should never be dismissed; it is a critical warning sign of impending necrolysis. 14
• Differentiate SJS from erythema multiforme major: EMM shows raised target lesions mainly on limbs, whereas SJS presents with flat atypical targets that are more widely distributed. 16
• Differentiate SJS/TEN from staphylococcal scalded skin syndrome (SSSS): SSSS lacks mucosal involvement and demonstrates intra‑epidermal cleavage on histology, unlike the sub‑epidermal cleavage of SJS/TEN. 13

Infectious Triggers to Consider

• In addition to drugs, infectious agents such as herpes simplex virus, Mycoplasma pneumoniae and Chlamydia should be evaluated, especially in children presenting with predominant mucositis and limited skin lesions. 13