Stevens-Johnson Syndrome – Pictures, Symptoms, Causes, Diagnosis

What is Stevens-Johnson Syndrome?

Stevens-Johnson Syndrome is a life-threatening skin disorder wherein it causes separation of the epidermis to the dermis as a result of cell death. Stevens-Johnson syndrome is a result of hypersensitivity reaction in the skin and mucous membranes as a result of immune-complex mediation.

Stevens-Johnson Syndrome

Stevens–Johnson syndrome affects two to six in one million people a year. Stevens–Johnson syndrome commonly affects adults and women. It involves the mucous membranes in the eyes, nose, mouth, urethra, respiratory system and gastrointestinal system. Stevens-Johnson Syndrome eventually leads to a systemic condition that has high rates of mortality.

History of Stevens-Johnson Syndrome

Stevens-Johnson syndrome was named after two American pediatricians in 1922, Albert Stevens and Frank Johnson. They made a published description of the disorder in an American journal about two boys who had generalized skin eruptions with continuous fever, severe purulent conjunctivitis and inflamed oral mucosa.

Other physicians diagnosed the 2 children with erythema multiforme. However, the characteristic lesions of Stevens-Johnson syndrome were different so the former was ruled out. Since then, erythema multiforme was divided into two categories, which is erythema multiforme major and erythema multiforme minor. Erythema multiforme major (EMM) was synonymously considered Stevens-Johnson syndrome.

However, in the 1990s, two physicians again contradicted that EMM and Stevens-Johnson syndrome are similar. They studied that Stevens-Johnson syndrome has distinct mucous membrane erosion and small blisters on a macula different from EMM with edematous papules with or without the involvement of the mucous membranes. They hypothesized that Stevens-Johnson syndrome and EMM are two distinct skin conditions.

Classification of Stevens-Johnson Syndrome

Stevens-Johnson syndrome can be seen as a mild form of TEN or toxic epidermal necrolysis. These two conditions are different from erythema multiforme as suggested by earlier research. Stevens-Johnson syndrome and TEN is classified under exanthematic necrolysis or acute disseminated epidermal necrosis with different severity, Stevens-Johnson syndrome as the milder form.

Epidermal necrosis can be categorized into three stages:

1. Stevens-Johnson syndrome- less than 10% detachment of body surface area
2. Overlapping Stevens-Johnson syndrome- 10 to 30% body surface area detachment
3. Toxic epidermal necrolysis (TEN)- More than 30% body surface area detachment

Pathophysiology of Stevens-Johnson Syndrome

Stevens-Johnson syndrome starts from a delayed hypersensitivity reaction as a result of slow acetylators resulting from a dysfunction in the liver. Because of this, the liver cannot detoxify metabolites in the body. These metabolites may interact with the host tissues and make them as antigens. The presence of antigen presentation and the synthesis of tumor necrosis factor by the dendrocytes in the tissue cause stimulation of the T-lymphocytes. It also enhances the cytotoxic function of other immune cells. Because of this, there is an induced cellular apoptosis in the epidermis. Apoptosis of skin cells or keratinocytes leads to cell death. This causes the detachment of the epidermis from the dermis. The death of skin cells also lead to more recruitment of chemical mediators which exacerbate the inflammation which eventually lead to severe epidermal necrolysis.

Stevens-Johnson Syndrome Symptoms

Symptoms of Stevens-Johnson syndrome include some or all of the following:

• Fever
• Fatigue
• Sore throat
• Ulcerations or appearance of lesions in the mucous membranes (mouth. Lips, genital and anal areas)
• Discharges on the mucous membranes
• Extremely painful lesions
• Anorexia
• Conjunctivitis
• Rashes on the face, arms, trunk, legs and feet.
• Tachycardia
• Orthostatic hypotension
• Epistaxis
• Altered level of consciousness
• Corneal ulcerations
• Balanitis (inflammation of the glans penis)
• Vulvovaginitis
• Seizures
• Epidermal necrosis with separation of the epidermis as seen under the microscope
• Weave-like pattern in the stratum corneum

Stevens-Johnson Syndrome Causes

Stevens-Johnson syndrome is an immune-complex mediated disorder caused by several factors such as:

Infections

Infections associated with Stevens-Johnson syndrome include herpes simplex virus, cat-scratch fever, mumps, influenza, histoplasmosis, mycoplasma pneumonia, hepatitis, Coxsackie viral infections, Epstein-Barr virus, group A beta hemolytic streptococci, diphtheria, brucellosis, typhoid and mycobacterium infections. HIV infection also intensifies Stevens-Johnson syndrome caused by medications.

Medications

Hypersensitivity reactions from medications have been studied to cause Stevens-Johnson syndrome. The following drugs may result in Stevens-Johnson syndrome: Antibiotics (penicillins, sulfonamides), Allopurinol, Zyloprim, Depakote, Dilantin, Diclofenac, Levaquin, Etravirine, Isotretinoin, Valdecoxib, Fluconazole, Barbiturates, Nystatin, Sodium valproate.

Genetics

East Asian populations have an increased risk for Stevens-Johnson syndrome. They have a gene marker that increases their risk for drug-induced Stevens-Johnson syndrome.

Stevens-Johnson Syndrome Diagnosis

Diagnosis of Stevens-Johnson syndrome is initially done through a complete medical history, including medication history and a physical examination of the symptoms. The lesions are carefully examined to check the characteristic lesion of Stevens-Johnson syndrome. Confirmation of the diagnosis is done through skin biopsy and staining which reveals a weave-like pattern of the stratum corneum and a detachment of the epidermis from the dermis.

Stevens-Johnson Syndrome Treatment

The treatment of Stevens-Johnson syndrome involves emergency measures such as discontinuing of all medications taken by the patient. Patients who have ongoing bacterial infections can be treated by macrolides or doxycycline to avoid ingestion of penicillins or sulfonamides. Additional managements include:

Supportive care

Beyond supportive care, there is no specific treatment for Stevens-Johnson Syndrome because the use of other medications has been controversial.

Parenteral nutrition or Tube feedings

Feedings are given through nasogastric tube or through intravenous nutrition to support proper nutrition and to recover from protein loss and promote healing.

Intravenous Fluids

Fluids are given to prevent dehydration caused by shifting of fluid from the intracellular to the interstitial space during the first 24 hours. Oral intake of fluids is usually started after the first day of hospitalization through nasogastric tube feeding.

Oral care

Antiseptic mouth washes are used to aid in the healing of mouth ulcers and prevent further infection in the lesions.

Topical anesthetics

These are applied on painful lesions to reduce the pain sensation experienced by the patient.

Supportive bedssed if a large body surface area on the back is affected

Temperature Control

The room temperature is usually raised to 32 degrees Celsius to prevent caloric loss through the damaged skin. Heat shields are also placed to prevent heat loss.

Pulmonary support

Aerosols and chest physiotherapy is employed to prevent stasis of mucus in the lungs.

Strict asepsis and Isolation Precautions

Because of impaired primary defense as a result of broken skin, strict aseptic technique should be ensured during any patient contact. Reverse isolation is also done to prevent nosocomial infections.

Skin care

Debridement of the necrotic epidermis has been recommended, although debridement of the skin is an issue between surgeons and dermatologists. Surgeons recommend debridement to remove the non-functioning skin cells and allow new ones to grow. Biologic dressings are placed to protect the skin. Hyperbaric oxygen therapy may also be employed to improve healing of the skin.

Steroids

The use of steroids has been controversial because of an increase in complication and hospital stay. Some physicians employ corticosteroid treatment, but it should be noted that Stevens-Johnson syndrome can be treated without them.

Immunoglobulin Therapy

Intravenous immunoglobulin is also given to reduce the hypersensitivity reaction and relieve symptoms.

Immunosuppressive Therapy

The use of cyclosporins, cyclophosphamide or azathioprine is rarely used today to prevent the immune-mediated complex in Stevens-Johnson syndrome.

Anticoagulant Therapy

Heparin is recommended throughout the hospitalization to prevent blood clots as a result of injury to the skin. Antacids are given as an adjunct therapy to prevent occurrence of gastric bleeding.

Skin Transplantation

Skin allotransplantation is done to replace the damaged epidermis. This also minimizes pain, reduces heat loss, fluid loss and bacterial infections as a result of an open skin.

Ophthalmology Support

An ophthalmologist should be consulted for the management of ocular symptoms. Aggressive lubrication of the eyes is usually done to prevent further ulceration and damage of the cornea. Visual rehabilitation is done among patients who had visual impairment after hospitalization.

Stevens-Johnson Syndrome Prognosis

Lesions in Stevens-Johnson syndrome usually heal in two weeks. Most individuals with SJS recover from the disease without any complications if properly managed. Mild forms of Stevens-Johnson syndrome with 10% body surface area affectation have a low mortality rate of less than 5%. More severe forms such as skin sloughing of more than 30% have an increase in mortality rate of 25% to 35%. Mortality from Stevens-Johnson syndrome results from organ damage, extensive of affectation, sepsis and bacteremia. The SCORTEN (severity of illness score for toxic epidermal necrolysis) scale estimates the risk for death from Stevens-Johnson syndrome. The variables that indicate an increased risk for death include:

• Age 40 years old and above
• Heart rate of more than 120 beats per minute
• Presence of malignancy
• More than 10% detachment
• Glucose level of more than 14 mmol/L
• BUN of more than 10 mmol/L
• Bicarbonate level of less than 20 mmol/L
• Each of these is scored one point. Patient shaving 0-1 point have at least 3% mortality rate and patients who have a score of more than five points can have a mortality rate as high as 90.

Complications

About 40% of patient with Stevens-Johnson syndrome result in various complications, more commonly ocular diseases which include:

• Cicatrizing conjunctivitis
• Corneal Stromal Ulcers
• Corneal epithelial problems
• Perforation of the cornea

Other complications result from the affectation of other mucous membranes which include:

• Renal Failure
• Tubular necrosis
• Vaginal stenosis
• Penile scarring
• Esophageal and gastric strictures
• Respiratory failure a s a result of tracheobronchial shedding
• Cosmetic deformity

Recurrences of Stevens-Johnson syndrome may also happen in slow-healing lesions

Stevens-Johnson Syndrome Pictures

Stevens-Johnson Syndrome Symptoms

Image Source: Wikipedia

Stevens-Johnson Syndrome On the Whole Body

Stevens-Johnson Syndrome on the Tongue

Image Source: Wikipedia

Severe form of Stevens-Johnson Syndrome

Stevens-Johnson Syndrome on the Face and Lips

Stevens-Johnson Syndrome on the Eyes

Stevens-Johnson Syndrome Supportive Managements