Stevens-Johnson Syndrome: Lecture 18

• Stevens-Johnson Syndrome is the topic of Lecture 16.
• Objectives include describing the difference between Stevens-Johnson Syndrome and toxic epidermal necrolysis, identifying SJS-TEN pathogenesis and risk factors, and understanding the clinical presentation, diagnosis, and complications. Also covered are the therapeutic options and the multidisciplinary treatment role.

Differential Diagnosis: Signs/Phenomenon

• Nikolsky sign: the top layers of the skin slip away from the lower layers when rubbed.
• Braverman's sign: fine telangiectasias around the nail, associated with connective tissue disease.
• Darier's sign: skin becomes swollen, itchy, and red after stroking lesions, often seen in systemic mastocytosis or urticaria pigmentosa; skin biopsy will show increased dermal mast cells.
• Koebner phenomenon: the appearance of new skin lesions on previously unaffected skin secondary to trauma.

Toxic Epidermal Necrolysis (TEN)

• TEN is a delayed-type hypersensitivity reaction to drugs
• Symptoms include:
  • More than 30% of the body surface area is affected, similar to an extensive burn
  • A painful, red to purple area that spreads quickly
  • The skin may peel without blistering, resulting in raw areas
  • Discomfort and fever
  • Condition spreads to eyes, mouth/throat, and genitals/urethra/anus
• Later stages can lead to toxic shock syndrome

Steven Johnson Syndrome (SJS)

• SJS is a delayed-type hypersensitivity reaction to drugs.
• Symptoms include:
  • Less than 10% of the body surface area is affected
  • Presents with nonspecific upper respiratory tract infection in a 1- to 14-day prodrome.
  • Sore throat, chills, headache, fever, body aches (malaise), red rash, and cough
  • Blisters and sores on the skin and mucous membranes of the mouth, throat, eyes, genitals, and anus
  • Peeling skin; Drooling because closing the mouth is painful
  • Eyes sealed shut due to blisters and swelling.
  • Painful urination due to blistered mucous membranes
• SJS Prognosis: Factors associated with a poor prognosis
  • old age (> 70 years)
  • intestinal involvement
  • pulmonary involvement

SJS/TEN Overlap

• SJS/TEN Overlap is a delayed-type hypersensitivity reaction to drugs
• Used to describe cases in which 10%-30% of the body surface area is detached.
• Long-term complications include ocular issues (including blindness), cutaneous changes (pigmentary changes and scarring), and renal involvement.
• Mucosal involvement with blisters and erosions can lead to strictures and scarring.

Overview of SJS

• SJS involves cell-mediated hypersensitivity and clinical presentation.
• Precipitating factors include drugs (antibiotics, anticonvulsants) and infective agents (Mycoplasma).
• Multiorgan/system involvement: eye, kidney, liver

Etiology

• Drugs precipitate over 50% of SJS cases and up to 95% of TEN cases.
• Common drug causes include:
  • Sulfa drugs (e.g., cotrimoxazole, sulfasalazine)
  • Other antibiotics (e.g., aminopenicillins [ampicillin, amoxicillin], fluoroquinolones, cephalosporins)
  • Antiepileptics (e.g., phenytoin, carbamazepine, phenobarbital, valproate, lamotrigine)
• Miscellaneous individual drugs (less common causes)
  • Analgesics (pain killers)
  • Cough and cold medication
  • NSAIDs
  • Psycho-epileptics
  • Antigout drugs
• Cases not caused by drugs can be attributed to:
  • Infection (mostly with Mycoplasma pneumoniae, Cytomegalovirus)
  • HIV/ Systemic Lupus Erythematosus
  • Vaccination
  • Graft-vs-host disease
• Rarely, a cause cannot be identified.

Symptoms

• SJS typically begins with a nonspecific upper respiratory tract infection.
• This is usually part of a 1- to 14-day prodrome, with fever, sore throat, chills, headache, and malaise.
• Vomiting and diarrhea may occur.
• The typical lesion has the appearance of a target and is considered pathognomonic.
• Typical prodromal symptoms include:
  • Cough productive of a thick purulent sputum
  • Headache; Malaise
  • Arthralgia

Pathophysiology of SJS

• The exact mechanism is unknown
• Altered drug metabolism triggers a T-cell-mediated cytotoxic reaction to drug antigens in keratinocytes.
• CD8+ T cells are important mediators of blister formation.
• Recent findings suggest that granulysin released from cytotoxic T cells and natural killer cells may play a role in keratinocyte death.
• Granulysin concentration in blister fluid correlates with disease severity.
• Interactions between Fas and its ligand lead to cell death and blister formation; a genetic predisposition has been suggested.

Diagnosis

• Physical exam (clinical evaluation), doctors can often identify Stevens-Johnson syndrome, toxic epidermal necrolysis, and SJS/TEN overlap based on medical history and physical exam.
• Steps to conform the diagnosis include:
  • Skin biopsy with showing necrotic epithelium
  • Skin or oral culture may be taken to confirm/rule out infection; Imaging depending on symptoms to check for pneumonia
  • Blood tests confirm other possible causes

Treatments

• Early recognition: treated in an inpatient dermatologic or ICU setting; treatment in a burn unit may be needed for severe disease.
• Ophthalmology consultation and specialized eye care are mandatory for patients with ocular involvement.
• Potentially causative drugs should be stopped immediately.
• Supportive care:
  • Patients are isolated to minimize exposure to infection and are given fluids, electrolytes, blood products, and nutritional supplements as needed.
  • Skin care includes prompt treatment of secondary bacterial infections and daily wound care as for severe burns.
  • Prophylactic systemic antibiotics are controversial and often avoided.
• Controversial treatments:
  • Cyclosporine inhibits CD8 cells and slows progression, possibly decreasing mortality.
  • Plasma exchange or intravenous immunoglobulin treatment. -High-dose corticosteroid therapy may induce SJS/TEN in certain patients.