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What is Stevens-Johnson Syndrome?

Stevens-Johnson syndrome is a rare disease of the skin and mucous membranes that occurs with very painful sores and blisters. Its severity reaches a point that it prevents adequate swallowing and breathing. Although its presence is more noticeable when this type of injury appears in the mouth and eyes, it is extremely annoying when it appears in the mucous membranes, this is when natural and daily actions can become real torture. This condition affects the general well-being of the person who suffers from it.

“Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life-threatening conditions almost exclusively attributed to drugs. The incidence in children is lower than in adults and has a better outcome. Mycosplama pneumoniae infection may be involved in some cases of paediatric SJS. The main etiologic factors for both SSJ and TEN are sulphonamides and anticonvulsants, followed by penicillins and non-steroidal anti-inflammatory drugs. In rare instances, paracetamol is the only suspected drug. By contrast with adults, allopurinol, oxicams and nevirapine are not identified as causative agents in children, probably due to differences in drug prescriptions. The only aspects of treatment that have been proved to improve survival are the rapid withdrawal of the suspected offending drugs and an optimal supportive therapy with emphasis in nutritional support, accompanied by management of denuded skin areas. The use of specific therapies remains controversial.”1

“Epidermal necrolysis is an acute life-threatening mucocutaneous reaction characterized by extensive necrosis and detachment of the epithelium of the skin (epidermis) and many mucous membranes. Most often resulting from hypersensitivity to drugs, it includes Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and overlap SJS/TEN, based on the extent of skin area involved. Necrosis of the epithelium is likely initiated by drug-specific cytotoxic T cells and nonspecific cytotoxic cells that kill epithelial cells directly, and also indirectly through the release of soluble death mediators, the principal being granulysin. To some extent the process is close to what happens during the acute rejection of a skin graft. Epidermal necrolysis is occasionally observed in a context of acute graft-versus-host disease after bone marrow transplantation. As an immunological mechanism had been suspected long before recent evidence, ‘specific’ therapeutic interventions proposed over years included corticosteroids, immunosuppressive drugs, and agents expected to block soluble death mediators or their receptors. Among the latter, thalidomide was used because of its antitumor necrosis factor alpha activity, and high-dose intravenous human immunoglobulins (IVIG) because of their Fas-ligand blocking activity.

With the exception of thalidomide that proved detrimental, none of the proposed treatments was evaluated in a randomized controlled trial (RCT). The main reasons are the extreme rarity of the disease, with an incidence estimated to be around two cases per million inhabitants per year.”2

“Fever is often the first symptom. A sore throat, cough, red eyes, and tender, pink skin are early symptoms. A red rash appears, and some areas blister. Blisters on the lips and in the mouth break, leaving sores that make it painful to eat, drink, and swallow. The eyes often feel scratchy, gritty, and dry. The vagina and penis can blister, and damaged skin in these sites may be overlooked if not pointed out to doctors.

As the skin heals, it may look darker or lighter than before. Hair and nails may fall out and regrow differently. The vagina and penis can be permanently scarred. The eyes may remain dry, and some vision may be lost. The mouth may be scarred and dry, leading to tooth decay.”3

A person with Stevens-Johnson syndrome may start to have small sores that instead of healing, become worse over time. In addition to this, it presents some of the following symptoms: fever with chills, sore throat, headache, sensation of fatigue and coughs. As we can see, it could be easy to confuse these symptoms with the flu. However, it is necessary to pay attention to the look of our skin, if it begins to fall and becomes very sensitive with the appearance of burns, it is very likely this is a case of Stevens-Johnson syndrome.

Clinical Course

“Initial manifestations are commonly fever and flu-like symptoms (malaise, myalgias, arthralgias, dysphagia, photophobia, conjunctival itching/burning). Involvement of skin and mucosa arises 1 to 3 days later. Macules with purpuric centers give way to large blisters, vesicles, and bullae. Epidermal detachment with Nikolsky’s sign of the bullae (sloughing of the superficial skin layer with slight rubbing pressure) then presents 3 to 5 days later and leaves behind large denuded areas of skin. These signs manifest first on the face and thorax, and then spread outward symmetrically. Distal portions of the arms and legs are relatively spared but palms and soles can be an early site for lesions. Affected areas are tender to touch. Re-epithelization begins 1 week after onset and may take up to 3 weeks, though faster in children.

The large wound areas may cause severe pain, massive fluid and protein loss, electrolyte imbalances, bleeding, evaporative heat loss with subsequent hypothermia, insulin resistance, hypercatabolic state, infection and bacteremia, hypovolemic shock with renal failure, and multiple organ dysfunction.

Of note, the denuded skin predisposes the patient to bacterial superinfection, most commonly by Staphylococcus aureus and Pseudomonas aeruginosa. Sepsis thereby serves as the main cause of death in SJS/TEN cases.

Ophthalmic complications also present in up to 30% of surviving children and adults, occurring within 2 to 6 weeks of drug initiation. These include severe conjunctivitis with purulent discharge, swollen and erythematous eyelids, suppurative keratitis, endophthalmitis, pain, and photophobia. Most concerning is the longterm vision loss that may occur from chronic corneal inflammation. Other physiologic systems potentially affected include pulmonary (pneumonia, interstitial pneumonitis, acute respiratory distress syndrome, mechanical ventilation in 25% with its associated higher mortality), gastrointestinal (diarrhea, melena, small bowel ulcerations, colonic perforation, small bowel intussusception, stenosis, strictures, stomatitis), vulvovaginitis, and urologic (urethritis).”4

This illness has multiple causes, some of them are:

  • Viruses such as HIV, herpes, poliomyelitis, echovirus and hepatitis A.
  • Bacterial infections such as diphtheria, tuberculosis and tularemia.
  • Sarcoidosis
  • Drug use, especially cocaine.
  • Medications, mainly antibiotics.

Stevens-Johnson syndrome can occur due to multiple factors. Despite of having suspicions or presenting all the symptoms already exposed, the doctor will do some tests to verify that a true Stevens-Johnson syndrome is the culprit. Once we have confirmed Stevens-Johnson syndrome, it is time to work on the treatment of wounds with the necessary care. To do this, you must protect wounds with dressings and always keep them clean. This process can be very painful, however, making an effort will be worth it.

If you have sores in your mouth, you should pay attention and be careful with the toothbrush. Brushing must be very soft and without brusqueness. It is also recommended to use special toothpaste to help heal those wounds.

The positive thing about Stevens-Johnson syndrome is that it has a cure. However, we should go to the doctor at the very first sign of symptoms. As much as we believe that sores in the mouth will disappear on its own, or that the falling skin is the result of an allergy, going to the doctor will free us from any doubt.

“SJS and TEN are severe and life-threatening. The average reported mortality rate of SJS is 1-5%, and of TEN is 25-35%; it can be even higher in elderly patients and those with a large surface area of epidermal detachment. In order to standardize the evaluation of risk and prognosis in patients with SJS/TEN, different scoring systems have been proposed. The SCORTEN is now the most widely used scoring system and evaluates the following parameters: age, malignancy, tachycardia, initial body surface area of epidermal detachment, serum urea, serum glucose, and bicarbonate. […]

More than 50% of patients surviving TEN suffer from long-term sequelae of the disease. These include symblepharon, conjunctival synechiae, entropion, ingrowth of eyelashes, cutaneous scarring, irregular pigmentation, eruptive nevi, and persistent erosions of the mucous membranes, phimosis, vaginal synechiae, nail dystrophy, and diffuse hair loss.”5

“The definitive management of SJS/TEN remains to be established. The importance of supportive care and identification and withdrawal of potential offending drugs is underscored; these are the measures that provide the most proven benefit to SJS/TEN patients. It is incumbent on the consulting subspecialists to make these supportive care recommendations clear as they differ from the protocol employed for burn patients with the same body surface involvement. Unfortunately, the data regarding adjunctive systemic therapy are, thus far, underwhelming. TNF inhibitors (such as etanercept and infliximab) and cyclosporine A are promising potential therapies. It is worth noting that the treatment outcomes for cyclosporine, etanercept, and infliximab have been unidirectional (have only shown benefit) compared with conflicting outcomes described with many of the other adjunctive therapies. From a pathophysiologic standpoint, their use should be efficacious. However, randomized controlled trials have yet to provide definitive evidence of improved outcomes with these agents.”6

If you don’t see a specialist when the symptoms have worsened, the results can be fatal. Not breathing well, pain and difficulty swallowing can seriously endanger the life of anyone with this syndrome. If it affects the eyes and is not resolved on time, it can cause blindness. Stevens-Johnson syndrome can also affect internal organs, leading to massive complications.

References:

(1) Ferrandiz-Pulido, C., & Garcia-Patos, V. (2013). A review of causes of Stevens–Johnson syndrome and toxic epidermal necrolysis in children. Archives of disease in childhood, 98(12), 998-1003. Available online at https://adc.bmj.com/content/98/12/998

(2) Roujeau, J. C., & Bastuji-Garin, S. (2011). Systematic review of treatments for Stevens–Johnson syndrome and toxic epidermal necrolysis using the SCORTEN score as a tool for evaluating mortality. Therapeutic advances in drug safety, 2(3), 87-94. Available online at https://journals.sagepub.com/doi/full/10.1177/2042098611404094

(3) Ergen, E. N., & Hughey, L. C. (2017). Stevens-Johnson syndrome and toxic epidermal necrolysis. JAMA dermatology, 153(12), 1344-1344. Available online at https://jamanetwork.com/journals/jamadermatology/fullarticle/2664616

(4) Alerhand, S., Cassella, C., & Koyfman, A. (2016). Stevens-Johnson syndrome and toxic epidermal necrolysis in the pediatric population: a review. Pediatric emergency care, 32(7), 472-476. Available online at https://cme.lww.com/files/StevensJohnsonSyndromeandToxicEpidermalNecrolysisinthePediatricPopulation-1474572375090.pdf

(5) Harr, T., & French, L. E. (2010). Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet journal of rare diseases, 5(1), 39. Available online at https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-39

(6) Schneider, J. A., & Cohen, P. R. (2017). Stevens-Johnson syndrome and toxic epidermal necrolysis: a concise review with a comprehensive summary of therapeutic interventions emphasizing supportive measures. Advances in Therapy, 34(6), 1235-1244. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487863/

Robert Velasquez
14 December, 2018

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Hello everyone, my name is Robert Velazquez. I am a content marketer currently focused on the medical supply industry. I studied Medicine for 5 years. I have interacted with many patients and learned a lot...read more:

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