Stevens-Johnson Syndrome

Definition and classification

Stevens-Johnson syndrome is considered a severe form of erythema multiforme exsudativum. The disease presents with pronounced systemic intoxication and belongs to the group of life-threatening adverse drug reactions (toxicoderma).

In dermatological practice, this condition is frequently associated with toxic epidermal necrolysis (Lyell's syndrome), which represents the extreme degree of involvement with massive epidermal detachment, total mucosal involvement, and extremely high mortality (up to 50%).

Etiological factors (triggers)

The primary causative factor is the administration of pharmacological agents. In risk groups, including HIV-infected patients, the reaction is most commonly triggered by the following classes of medications:

• Antimicrobial agents (especially sulfonamides, in particular co-trimoxazole).
• Beta-lactam antibiotics and penicillins (including the combination of amoxicillin with clavulanic acid).
• Anticonvulsants.
• Antiretroviral therapy drugs (NNRTI class — non-nucleoside reverse transcriptase inhibitors).

The main rule in the development of a severe cutaneous reaction with pronounced symptoms is the immediate discontinuation of the offending drug.

Clinical presentation

The disease manifests acutely. The patient rapidly develops symptoms of severe intoxication:

1. Fever (body temperature rises up to 40 °C).
2. Intense headaches, myalgia, and arthralgia.
3. Onset of seizures.
4. Secondary complications, such as bronchopneumonia, frequently develop.

Skin manifestations present as a generalized dark red macular rash. Multiple erosions and blisters form on the surface of the skin and mucous membranes. One of the most severe manifestations is erosive stomatitis, which severely impairs the patient's ability to eat and speak.

Ocular complications

Eye involvement is a specific and disabling outcome of Stevens-Johnson syndrome. The disease leads to cicatricial shortening of the conjunctiva and deformation of the eyelid cartilage, resulting in cicatricial entropion.

The process is frequently combined with trichiasis — misdirected eyelash growth due to scarring at their roots. A pathogenetic vicious circle is established: constant friction of the eyelashes and eyelid margin against the cornea causes spasmodic contraction of the pretarsal part of the orbicularis oculi muscle, further exacerbating the entropion.

Continuous trauma to the ocular tissues leads to a cascade of complications:

• Chronic conjunctivitis and mucosal edema.
• Keratopathy, erosions, and corneal dystrophy.
• Ulcerative keratitis.

The end stage of the process results in a permanent corneal opacity — a leukoma.

Association with severe liver injury

In some cases, severe forms of drug-induced liver injury (DILI) with immunoallergic manifestations, which may include Stevens-Johnson-like rashes, lead to the development of vanishing bile duct syndrome (VBDS).

• Pathogenesis: immune-mediated or direct damage to cholangiocytes occurs due to drugs and their metabolites. The protective function of the epithelium is disrupted, leading to prolonged toxic effects of bile acid salts.
• Timeline: develops 1–6 months after an episode of severe unresolved cholestatic hepatitis.
• Histology: $\ge$ 50% of interlobular ducts are lost (or the ratio of duct count to portal tracts falls below 0.5).
• Clinical and laboratory findings: fatigue, jaundice, persistent pruritus, xanthomas. Laboratory tests show a persistent elevation of bilirubin, alkaline phosphatase (ALP), cholesterol, and bile acids.

Even with clinical improvement, ductopenia and fibrosis persist histologically. In severe cases, the condition leads to liver failure requiring liver transplantation.

Differential diagnosis of toxicoderma

In the diagnosis of severe forms of drug eruptions, Stevens-Johnson syndrome should be differentiated from other conditions:

• Anaphylactic reaction: characterized by life-threatening shock, laryngeal edema, and dyspepsia.
• Hypersensitivity syndrome (DRESS syndrome): differs by delayed onset (2–6 weeks from the start of therapy). It manifests as a skin rash combined with systemic involvement (hepatitis, arthralgia, lymphadenopathy) and laboratory abnormalities (eosinophilia, atypical lymphocytes).
• Ordinary urticaria: maculopapular erythematous elements with clear borders and pruritus, but without severe mucosal involvement.

Class and exam questions

What else to study on this topic

• Toxic epidermal necrolysis (Lyell's syndrome)
• Drug eruption: anaphylaxis and DRESS syndrome
• Vanishing bile duct syndrome (VBDS)
• Pathogenesis of cicatricial entropion and trichiasis
• Histological criteria for liver injury in DILI

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.