What is Stevens-Johnson Syndrome?

Stevens-Johnson syndrome (SJS) is a rare and severe kind of erythema multiforme (EM). It is a severe skin reaction that is frequently caused by drugs. SJS frequently starts with a fever and flu-like symptoms.

SJS was first identified in 1922 by two American doctors named Stevens and Johnson. In two young boys, they described an acute mucocutaneous condition marked by severe purulent conjunctivitis, severe stomatitis, and widespread mucosal necrosis.

Toxic epidermal necrolysis and Stevens-Johnson syndrome

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are acute mucocutaneous vesiculobullous illnesses that can be deadly.

TEN and SJS are regarded as a disease continuum, with severity assessed mostly by the percentage of body surface area (BSA) damaged by erosive blistering.

Stevens-Johnson syndrome is at the milder end of the disease range, whereas toxic epidermal necrolysis is at the more severe end.

Causes of Stevens-Johnson syndrome

Stevens-Johnson syndrome is frequently triggered by your body's reaction to certain medications, including epilepsy medications, antibiotics, and anti-inflammatory pain relievers.

The syndrome has an unpredictable reaction on medications, which involves drug-specific CD8+ cytotoxic lymphocytes, the Fas-Fas ligand (FasL) apoptotic pathway, granule-mediated exocytosis, and the tumor necrosis factor TNF-alpha receptor pathway.

It can affect anybody with a genetic predisposition, regardless of age, gender, or ethnicity. Human leukocyte antigen (HLA) allotypes are genetic variables that raise the incidence of SJS.

The HLA-B gene has the highest genetic variants related to SJS. This gene belongs to a group of genes known as the human leukocyte antigen (HLA) complex.

According to research, HLA-B gene variants linked to SJS/TEN cause the immune system to react improperly to specific drugs. Variations in several other HLA and non-HLA genes have also been investigated as possible risk factors for SJS.

However, even if they are exposed to medicines that can trigger SJS, most people with genetic variants that enhance their risk never get the condition. Additional genetic and nongenetic factors, many of which are unknown, are thought to have a role in whether a person gets SJS.

Symptoms of Stevens-Johnson syndrome

SJS is a potentially fatal skin reaction characterized by sheet-like skin and mucosal loss, as well as systemic symptoms. SJS frequently starts with a fever and flu-like symptoms.

Within a few days, the skin begins to blister and peel, resulting in extremely painful raw regions known as erosions that mimic a severe hot water burn. Skin erosions typically begin on the face and chest before spreading to the rest of the body.

The condition also destroys the mucous membranes, particularly the lining of the mouth and the airways, in most affected persons.

Pneumonia, overwhelming bacterial infections (sepsis), shock, multiple organ failure, and death are serious complications. SJS can cause pigmentation, xerosis, hyperhidrosis, alopecia, and abnormal development or loss of fingernails and toenails in the long run.

Impaired taste, difficulties urinating, and genital abnormalities can all be long-term issues. A small proportion of those affected experiences chronic dryness or inflammation of the eyes, which can result in photophobia and vision impairment.

Epidemiology

Each year, SJS is predicted to impact two to seven million people. Stevens-Johnson syndrome occurs three times as frequently as toxic epidermal necrolysis.

SJS is more common in elderly persons and women. It has an estimated prevalence of 1/1000 and is significantly more likely to occur among people infected with the human immunodeficiency virus (HIV).

SJS mortality rates have been reported to vary from 25% to 70%, with significant morbidity.

Case report

In a case study, doctors reported a 14-year-old girl with SJS associated with Enterovirus infection. She went to A&E because she had rhinoconjunctivitis, lip edema, and a sore throat that had developed after a day spent at a stable.

Due to a grass allergy, she had a history of rhinoconjunctivitis and asthma. She did not use any medicines for 8 weeks before the commencement of symptoms. A potential allergic reaction was treated with methyl prednisone 40 mg I.M. and chlorphenamine maleate 10 mg I.M.

Her symptoms persisted, so she went to the local hospital's A&E the next day. She was given cetirizine, prednisone, and salbutamol by mouth.

The patient experienced fever, seropurulent ocular discharge, crusty lips lesions, and de-epithelialization of the oral mucosa the next day. The patient was seen by a doctor after two days, who diagnosed bronchitis and prescribed second-generation cephalosporin.

The girl was admitted to the hospital with SJS. Azithromycin was also given since a mycoplasma pneumonia infection was suspected. Antibodies against Mycoplasma pneumoniae, EBV, HSV 1-2, Coxsackievirus, and Adenovirus were found to be negative in serological tests.

The pharyngeal swab nucleic acid amplification assay indicated the presence of Enterovirus RNA.

Renal and liver functions were both normal. She had a SCORTEN score of about 0. During her hospitalization, the girl's ocular problems worsened, with the advent of pain and vision loss.

Lubricant eye drops, corticosteroid eye ointment, and chloramphenicol eye ointment were used to treat the condition. Simultaneously, she had skin erosions on both ankles, as well as hyperemia, edema, and painful ulcerous lesions on the genitals, palate, and tongue.

The girl was given daily chlorhexidine oral rinses, viscous lidocaine at the oral cavity, and daily cleaning with neutral detergents at the external genitals. Because of severe mouth pain, difficulty feeding, and vaginal discomfort, morphine hydrochloride was administered for 5 days as a pain reliever.

The patient began eating again on the sixth day of her stay, and her genital, cutaneous, and oral lesions gradually improved. On the eleventh day of hospitalization, the patient was discharged with slight de-epithelialization on the dorsal surface of the tongue.

An ophthalmological check-up was done one month after discharge, and the eye was reported to be recovering.

Diagnosis and treatment

Diagnostic investigations include skin biopsy, complete blood count, liver function, and renal function tests among others. SCORTEN is used to determine the severity of Stevens-Johnson syndrome.

At admission, each of the seven criteria is considered one point. The severity of SJS is determined by this score.

Treatment varies greatly from center to center, but most experts agree that early transfer to a burn center, adequate wound care, and robust nutritional support result in the best outcomes. Systemic corticosteroids, ciclosporin, and TNF-alpha inhibitors have all been shown to be effective.

References

• Oakley AM, Krishnamurthy K. Stevens Johnson Syndrome. [Updated 2022 Aug 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459323/
• De Guido C, Calderaro A, Ruozi MB, et al. (2020). An unusual cause of Steven-Johnson Syndrome. Acta Bio-Medica: Atenei Parmensis, 91(1), 128–131. doi:10.23750/abm.v91i1.7692
• Rocha AL, Souza AF, Nunes L, et al. (2019). Treatment of oral manifestations of toxic epidermal necrolysis with low-level laser therapy in a pediatric patient. Pediatric Dermatology, 36(1), e27–e30. doi:10.1111/pde.13719
• Miya R, Malpani AK, Keri S, et al. (2019). Drug Induced Steven-Johnson Syndrome (SJS). Indian Journal of Pharmacy Practice, 12(2).
• McCullough M, Burg M, Lin E, et al. (2017). Steven Johnson Syndrome and Toxic Epidermal Necrolysis in a burn unit: A 15-year experience. Burns: Journal of the International Society for Burn Injuries, 43(1), 200–205. doi:10.1016/j.burns.2016.07.026
• Rajput R, Sagari S, Durgavanshi A, et al. (2015). Paracetamol induced Steven-Johnson syndrome: A rare case report. Contemporary clinical dentistry, 6(Suppl 1), S278–S281.  doi:10.4103/0976-237X.166838
• Naveen KN, Pai VV, Rai V, et al. (2013). Retrospective analysis of Steven Johnson syndrome and toxic epidermal necrolysis over a period of 5 years from northern Karnataka, India. Indian Journal of Pharmacology, 45(1), 80–82. doi:10.4103/0253-7613.106441
• Stevens-Johnson syndrome/toxic epidermal necrolysis. [Online] Medline Plus. Available at: https://medlineplus.gov/genetics/condition/stevens-johnson-syndrome-toxic-epidermal-necrolysis/

Further Reading

• All Skin Content
• Cutaneous Manifestations of Internal Malignancy
• What is Subcutaneous Tissue?
• Milia in Babies
• Why Does Skin Go Wrinkly in Water?