Fig. 91.1
(a, b) Large loose flaccid bullae which quickly desquamate leaving behind moist erosions. Nikolsky sign was positive with gentle pressure on non-bullous skin causing sloughing. Asboe-Hansen sign was positive with gentle pressure on bullae causing advancement of bullae. Both indicate epidermal necrosis and are sensitive signs for SJS/TEN
Question
What is the most likely diagnosis for this patient’s skin eruption?
Answer
Stevens-Johnson syndrome
Stevens-Johnson syndrome and the more severe toxic epidermal necrolysis (TEN) encompass a spectrum of potentially life threatening cutaneous diseases with systemic manifestations [1]. It presents typically with a prodrome of fever, anorexia, pharyngitis and headaches, followed by extensive detachment of the epidermis, in a widespread erythematous or confluent purpuric macules or atypical flat targetoid lesions, which evolve into vesicles or bullae. Skin sloughing follows, and can occur in sheets during the acute phase. Lateral pressure on the skin can produce sloughing of the epidermis and exposure of the dermis, known as Nikolsky sign, characteristic of the syndrome but seen in other severe skin eruptions.
Mucosal involvement is almost universal, occurring in more than 95 % of cases of SJS/TEN, and usually precedes the skin manifestations by a few days. It is characterized by painful, hemorrhagic erosions that can be widespread and commonly involve the eyes, oropharyngeal, anal and genital mucosae. Ulcers and crusts form on the affected mucosal sites and can result in bleeding or infection.
Ocular involvement occurs in more than 60 % of SJS/TEN cases, and can range from mild conjunctivitis, to the more severe membranous or pseudomembranous conjunctivitis, with goblet cell and lachrymal gland loss leading to alterations in the amount and consistency of the tear film, with resultant photophobia, eye dryness and severe pain, prompting an ophthalmologic evaluation early in the course of the disease [2].
The severity of the SJS/TEN syndrome is based on the percentage of epidermal detachment of the body surface area (BSA). It ranges from a BSA of less than 10 % in SJS, to 10–30 % of BSA involvement in the SJS/TEN overlap, to more than 30 % of BSA involved in TEN. The mortality can range from 9 % for SJS to 48 % for TEN [3].
It remains a rare disease, with an incidence of 2–7 cases per million per year, and SJS incidence is almost 3 times that of TEN [4]. It can affect virtually any age group, even occurring in newborns, with an average age of presentation in the sixth decade. It is more prevalent in women and the elderly.
The SCORTEN score was developed to predict the risk of death early in the course of the disease (Table 91.1). It contains seven clinical criteria and laboratory values, with one point given for the worse of each criterion, and a maximal score of seven predicting the expected highest mortality [5].
Table 91.1
Scorten Score
Clinical | Score | |
|---|---|---|
Age | ≥40 years | 1 |
BSA involveda | ≥10 % | 1 |
Malignancy | yes | 1 |
Tachycardia | ≥120 BPM | 1 |
BUN | ≥27 mg/dLb | 1 |
Serum glucose | ≥250 mg/dLc | 1 |
Serum bicarbonate | ≤20 mEq/L | 1 |
Total | 0–7 |
In most instances, SJS/TEN is caused by drugs, emphasizing the need for obtaining a detailed history focusing on patterns of drug intake, and on any new added drugs and their association with the onset of the disease [6]. Drugs most associated with SJS include anti-infective agents such as nevirapine, sulfonamide antibiotics, allopurinol, anti-epileptics such as carbamazepine, lamotrigine, phenytoin, phenobarbital, cyclooxygenase inhibitors including NSAIDs.
Fewer cases of SJS/TEN are due to infections, especially Mycoplasma pneumonia [7] or viruses, such as coxsakie, Epstein–Barr, human herpes virus 6 and 7, cytomegalovirus, especially in children [8].
SJS, and more commonly TEN, can have systemic manifestations by involving the epithelial linings of internal organs, which include acute renal failure with micro albuminuria, as a result of glomerular and tubular epithelial involvement. Pulmonary manifestations such as adult respiratory distress syndrome, bronchiolitis obliterans and infectious pneumonitis, can lead to respiratory failure and death [9]. Gastrointestinal manifestations present with oral and pharyngeal mucosal lesions that can evolve into painful crusts from ruptured vesicles, leading to dysphagia. In the severe cases, it can result in inadequate nutritional and fluid intake. Extension to the entire gastrointestinal tract has been reported [10] leading to diarrhea, gastrointestinal bleeding, cholestatic hepatitis [11] and intestinal necrosis [12].
Pathogenesis
SJS/TEN syndrome is considered a delayed, type IV hypersensitivity reaction to an offending agent, usually a drug. It has been recently established that certain drugs can bind non-covalently to peptide grooves on human leukocyte antigen (HLA) proteins in susceptible individuals. The drug-HLA complex is then presented on keratinocyte cell surface and recognized by the TCR of CD8+ cells, leading to activation of these cells into cytotoxic T lymphocytes, (CTLs) and NK cells, which triggers the secretion of effector chemokines such as granulysin, a cationic cytolytic protein with direct cytotoxic effects leading to extensive keratinocyte apoptosis [13].
SJS/TEN has been linked to certain HLA alleles, such as the association of Carbamazepine-induced SJS to the HLA-B 15:02 allele, found in Han ethnic Chinese with the US Food and Drug Administration to recommending screening for HLA-B 15:02 prior to starting carbamazepine therapy for patients of Southeast Asian ancestry [14]. Other associations include Abacavir, linked to the HLA-B 57:01 allele, or Allopurinol, linked to HLA-b 58:01 [15].
Principles of Management
Supportive Care
The key aspects of treatment for SJS/TEN consists of removal of any suspected offending drug agent with supportive care, and prompt transfer to preferentially a burn unit or a skilled intensive care unit with experience in treating these patients. Adjuvant systemic therapies have shown equivocal outcomes across the literature [16–19].
Supportive therapy is aimed at limiting associated complications. Burn units have experience in handling patients with extensive epidermal damage and sloughing as seen in SJS/TEN. Prompt identification of SJS/TEN via skin biopsy is critical, since minimizing the time between the onset of skin symptoms and transfer to a burn unit has been shown to directly influence survival [16]. Supportive care is focused on fluid and electrolyte replacement, preserving the barrier function of the skin, promoting re-epithelialization of denuded areas, prevention and treatment of infection, and prevention of ocular damage. Volume status, protein and electrolyte replacement is crucial due to significant losses of fluid and protein. This contributes to an overall catabolic state which can lead to mortality. Administration of large volumes of fluids, electrolytes, crystalloids, and TPN are often needed. Venous access sites should be obtained away from involved areas [17]. Gentle and meticulous daily wound care is essential and dermatology consult is necessary when available.
Intact areas of skin should be left dry. Blistered and detached skin surfaces should have vaseline gauze applied until re-epithelialization, as it provides a low friction coverage to these areas [17]. Silicone dressings can also be applied to more eroded areas and left in place until re-epithelialization has occurred. Topical antibiotics such as mupirocin should be applied to the most affected areas, especially to facial mucosal areas such as the nares, mouth and ears [19], but silver sulfadiazine should be avoided if sulfa was suspected offending agent [18]. Systemic antibiotic prophylactic therapy, which used to be the standard of care, is no longer practiced routinely because of risk of cross reactivity with prescribed antibiotics [18]. Damage to the eye and ocular structures is a significant risk and an ophthalmology consult is essential, for frequent evaluation during the disease course but also for follow up and to treat any sequelae that may have occurred. Damage can be minimized by topical antibiotic use, frequent lubrication, and lysis of adhesions by an ophthalmologist [20]. Oral cleaning should be done frequently with antiseptic spray and removal of any oral crusting should be done as needed [20].
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