Oral Manifestations of Autoimmune Blistering Diseases

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two forms of a life-threatening skin condition, in which cell death causes the epidermis to separate from the dermis. The syndrome is thought to be[by whom?] a hypersensitivity complex that affects the skin and the mucous membranes. The majority of cases are idiopathic (without a known cause). The main known cause is certain medications, followed by infections and, rarely, cancers.
The medical literature agrees that Stevens–Johnson syndrome (SJS) can be considered a milder form of toxic epidermal necrolysis (TEN).[1] These conditions were first recognised in 1922.[2]
Both diseases can be mistaken for erythema multiforme.[citation needed] Erythema multiforme is sometimes caused by a reaction to a medication, but is more often a type III hypersensitivity reaction to an infection (caused most often by Herpes simplex) and is relatively benign. Although both SJS and TEN can also be caused by infections, they are most often adverse effects of medications.[citation needed] Their consequences are potentially more dangerous than those of erythema multiforme.[citation needed]
]Signs and symptoms

Mucosal desquamation in a person with Stevens–Johnson syndrome

Conjunctivitis (inflammation of eye and eyelid) in SJS
Stevens–Johnson syndrome (SJS) usually begins with fever, sore throat, and fatigue, which is misdiagnosed and usually treated with antibiotics. Ulcers and other lesions begin to appear in the mucous membranes, almost always in the mouth and lips but also in the genital and anal regions. Those in the mouth are usually extremely painful and reduce the patient’s ability to eat or drink. Conjunctivitis of the eyes occurs in about 30% of children who develop SJS. A rash of round lesions about an inch across arises on the face, trunk, arms and legs, and soles of the feet, but usually not the scalp.

Micrograph showing full thickness epidermal necrosis with a basket weave-like stratum corneum and separation of the dermis and epidermis. Skin biopsy. H&E stain.
SJS, like toxic epidermal necrolysis and erythema multiforme, are characterized by confluent epidermal necrosis with minimal associated inflammation. The acuity is apparent from the (normal) basket weave-like pattern of the stratum corneum.
Causes

Stevens–Johnson syndrome (SJS) is thought to arise from a disorder of the immune system.[3] The immune reaction can be triggered by infections, drugs, or medications.[citation needed] In some groups, drug reaction may be aggravated by genetic factors.
SJS can be caused by infections. It usually follows common infections such as herpes simplex virus, influenza, mumps, cat-scratch fever, histoplasmosis, Epstein-Barr virus, mycoplasma pneumoniae, or similar.
Medication/drugs
See also: List of SJS inducing substances
Although Stevens–Johnson Syndrome can be caused by viral infections, malignancies, or severe allergic reactions to medication, the leading cause appears to be the use of antibiotics and sulfa drugs.
SJS can be caused by adverse effects of drugs allopurinol, valproate, levofloxacin, diclofenac, etravirine, isotretinoin, fluconazole,[4] valdecoxib, sitagliptin, oseltamivir, penicillins, barbiturates, sulfonamides, phenytoin, azithromycin, oxcarbazepine, zonisamide, modafinil,[5] lamotrigine, nevirapine, pyrimethamine, ibuprofen, ethosuximide, carbamazepine, bupropion [1], and nystatin.
Medications that have traditionally been known to lead to SJS, erythema multiforme and toxic epidermal necrolysis include sulfonamides (antibiotics), penicillins (antibiotics), cefixime (antibiotic), barbituates (sedatives), lamotrigine, and phenytoin (e.g., Dilantin) (anticonvulsants). Combining lamotrigine with sodium valproate increases the risk of SJS.
Non-steroidal anti-inflammatory drugs are a rare cause of SJS in adults; the risk is higher for older patients, women and those initiating treatment.[2] Typically, the symptoms of drug-induced SJS arise within a week of starting the medication. People with systemic lupus erythematosus or HIV infections are more susceptible to drug-induced SJS.[3]
Genetics
In some East Asian populations studied (Han Chinese and Thai), carbamazepine- and phenytoin-induced SJS is strongly associated with HLA-B*1502 (HLA-B75), an HLA-B serotype of the broader serotype HLA-B15.[9][10][11] A study in Europe suggested that the gene marker is only relevant for East Asians.[12][13]
Based on the Asian findings, similar studies in Europe showed 61% of allopurinol-induced SJS/TEN patients carried the HLA-B58 (phenotype frequency of the B*5801 allele in Europeans is typically 3%). One study concluded: "Even when HLA-B alleles behave as strong risk factors, as for allopurinol, they are neither sufficient nor necessary to explain the disease."[14]
Treatment

SJS constitutes a dermatological emergency. All medications should be discontinued, particularly those known to cause SJS reactions. Patients with documented mycoplasma infections can be treated with oral macrolide or oral doxycycline.[3]
Initially, treatment is similar to that for patients with thermal burns, and continued care can only be supportive (e.g. intravenous fluids and nasogastric or parenteral feeding) and symptomatic (e.g., analgesic mouth rinse for mouth ulcer). Dermatologists and surgeons tend to disagree about whether the skin should be debrided.[3]
Beyond this kind of supportive care, there is no accepted treatment for SJS. Treatment with corticosteroids is controversial. Early retrospective studies suggested that corticosteroids increased hospital stays and complication rates. There are no randomized trials of corticosteroids for SJS, and it can be managed successfully without them.
Other agents have been used, including cyclophosphamide and cyclosporine, but none has exhibited much therapeutic success. Intravenous immunoglobulin (IVIG) treatment has shown some promise in reducing the length of the reaction and improving symptoms. Other common supportive measures include the use of topical pain anesthetics and antiseptics, maintaining a warm environment, and intravenous analgesics. An ophthalmologist should be consulted immediately, as SJS frequently causes the formation of scar tissue inside the eyelids, leading to corneal vascularization, impaired vision and a host of other ocular problems.
SJS proper (with less than 10% of body surface area involved) has a mortality rate of around 5%. The risk for death can be estimated using the SCORTEN scale, which takes a number of prognostic indicators into account.[15] Other outcomes include organ damage/failure, cornea scratching, and blindness