44: Epidermal Necrolysis Flashcards
What are the components of the SCORTEN?
The components of SCORTEN are:
1. Cancer/Hematologic Malignancy
2. Heart Rate > 120 bpm
3. Age > 40 years old
4. BSA > 10%
5. Bicarbonate < 20 mM
6. Urea > 10 mM
7. Glucose > 14 mM
What is the mortality rate for a SCORTEN score of 4?
The mortality rate for a SCORTEN score of 4 is 58.3%.
What is the primary lesion of SJS-TEN?
The primary lesion of SJS-TEN is purpuric/erythematous macules that progress to flaccid blisters and epidermal detachment.
What is the significance of early identification and withdrawal of the drug in SJS-TEN treatment?
Early identification and withdrawal of the offending drug are essential for good patient outcomes in SJS-TEN, as they can significantly reduce the severity of the reaction and improve prognosis.
What is the mortality rate associated with SJS and TEN?
The mortality rates are as follows:
- SJS: 10%
- TEN: 50%
- Combined EN (SJS and TEN): 22-27%
What are the high-risk drugs associated with SJS/TEN?
High-risk drugs include:
- Allopurinol
- Sulfonamides
- Aromatic anti-epileptic drugs
- Phenylbutazone
- Oxicam NSAIDs
- Lamotrigine
- Nevirapine
What is the risk level of valproic acid for causing SJS-TEN?
Valproic acid is classified as a moderate-risk drug for causing SJS-TEN.
What is the risk level of nevirapine for causing SJS-TEN?
Nevirapine is classified as a high-risk drug for causing SJS-TEN.
What is the risk level of diclofenac for causing SJS-TEN?
Diclofenac is classified as a moderate-risk drug for causing SJS-TEN.
What is the risk level of metformin for causing SJS-TEN?
Metformin is classified as a drug with no increased risk for causing SJS-TEN.
What is the risk level of macrolides for causing SJS-TEN?
Macrolides are classified as drugs with no increased risk for causing SJS-TEN.
What is the risk level of meloxicam for causing SJS-TEN?
Meloxicam is classified as a high-risk drug for causing SJS-TEN.
What is the predicted mortality rate for a SCORTEN score of 4?
The predicted mortality rate is 58.3%.
What is the risk level of lamotrigine for causing SJS-TEN?
Lamotrigine is a high-risk drug for causing SJS-TEN. Slow dose escalation can decrease the rate of mild rashes but does not reduce the risk of SJS-TEN.
What is the predicted mortality rate for a SCORTEN score of 2?
The predicted mortality rate for a SCORTEN score of 2 is 12.1%.
What is the risk level of oxicam NSAIDs for causing SJS-TEN?
Oxicam NSAIDs are classified as high-risk drugs for causing SJS-TEN.
What is the risk level of sulfonamides for causing SJS-TEN?
Sulfonamides are classified as high-risk drugs for causing SJS-TEN.
What is the relationship between corticosteroids and the risk of developing EN?
Corticosteroids are associated with an increased relative risk of developing EN, but confounding factors cannot be excluded.
What infectious causes have been reported in relation to EN?
Infectious causes reported include M. pneumoniae, viral infections, and immunization, especially in children.
What role does granulysin play in the pathogenesis of EN?
Granulysin is present in the blister fluid of patients with EN at concentrations much higher than those of perforin, granzyme B, or Fas-L, and is the only substance shown to kill human keratinocytes in vitro.
How do cytotoxic T cells contribute to the damage seen in EN?
Cytotoxic T cells target the native form of the drug rather than its metabolite, killing keratinocytes directly and indirectly through the recruitment of other cells that release soluble death mediators, primarily granulysin and IL-15.
What genetic susceptibility is associated with carbamazepine and allopurinol in relation to EN?
The genetic susceptibility associated with carbamazepine is HLA-B1502, which is not present in European patients without Asian ancestry. For allopurinol, the associated genetic marker is HLA-B5801, confirmed in Japan and Europe.
What infectious agents have been reported in cases of EN, particularly in children?
Infectious agents reported in cases of EN include M. pneumoniae, various viral infections, and immunization factors, especially in children.
How does granulysin contribute to the pathogenesis of EN?
Granulysin plays a critical role in the pathogenesis of EN by being present in blister fluid at much higher concentrations than other mediators like perforin and granzyme B.
What genetic susceptibility factors are associated with drug-induced EN?
In the Han-Chinese population, specific genetic susceptibility factors associated with drug-induced EN include HLA-B1502 and HLA-B5801.
What is the risk level of ibuprofen for causing SJS-TEN?
Ibuprofen is classified as a drug with no increased risk for causing SJS-TEN.
What genetic marker should have been tested prior to prescribing allopurinol?
The patient should have been tested for HLA-B*5801, which is associated with allopurinol-induced SJS-TEN.
What genetic marker is associated with an increased risk of SJS-TEN in the context of carbamazepine?
The genetic marker HLA-B*1502 is associated with an increased risk of carbamazepine-induced SJS-TEN.
What are the initial symptoms that precede mucocutaneous lesions in patients with EN?
Nonspecific prodromal symptoms such as pain on swallowing and burning or stinging of the eyes typically precede mucocutaneous lesions by 1-3 days.
What are the characteristics of cutaneous lesions associated with EN?
Cutaneous lesions in EN are characterized by:
1. Eruption: Initially symmetrically distributed on the face, upper trunk, and proximal limbs.
2. Initial skin lesions: Erythematous, dusky red, irregularly shaped purpuric macules that progressively coalesce.
3. Atypical target lesions: Often with dark centers.
4. Nikolsky sign: Positive on erythematous zones.
5. Lesion evolution: Lesions evolve to flaccid blisters that spread with pressure.
6. Extent of involvement: SJS (less than 10% BSA), SJS-TEN overlap (10-30% BSA), TEN (more than 30% BSA).
What is the significance of mucous membrane involvement in EN?
Mucous membrane involvement is nearly always present in at least 90% of cases and can precede or follow skin eruption.
What systemic complications can arise from EN?
Systemic complications of EN may include high fever, pain, weakness, pulmonary complications, gastrointestinal involvement, and renal involvement.
What is the role of laboratory values in diagnosing EN?
There are no specific laboratory tests to support the diagnosis of EN. However, laboratory values are essential for assessing the severity and prognosis of the condition.
What are the key prodromal symptoms that precede mucocutaneous lesions in patients with EN?
Key prodromal symptoms include nonspecific symptoms that appear 1-3 days before mucocutaneous lesions, such as pain on swallowing and burning or stinging of the eyes.
How does the presence of Nikolsky sign relate to the diagnosis of SJS/TEN?
The presence of Nikolsky sign indicates that the epidermis is fragile and can be dislodged by lateral pressure on erythematous zones.
What is the clinical significance of mucous membrane involvement in SJS/TEN?
Mucous membrane involvement is clinically significant because it occurs in nearly 90% of cases, often affecting at least two sites.
What systemic complications can arise in patients with SJS/TEN?
Systemic complications in SJS/TEN can include high fever, pain, weakness, and pulmonary complications.
What is the likely cause of malabsorption and diarrhea in a patient with SJS-TEN?
These symptoms are likely caused by epithelial necrosis of the gastrointestinal tract.
What is the most common renal finding in patients with SJS-TEN?
The most common renal findings are proteinuria, microalbuminuria, hematuria, and azotemia.
What is the most common renal finding in SJS-TEN?
The most common renal findings are proteinuria, microalbuminuria, hematuria, and azotemia.
What does tracheal involvement in SJS-TEN indicate?
Tracheal involvement indicates mucous membrane necrosis and is associated with respiratory complications.
What is the classification of a patient with 15% BSA affected by SJS-TEN, and what is the next step in management?
The condition is classified as SJS-TEN overlap (10-30% BSA). The patient should be transferred to a specialized center for further management.
What does a positive Nikolsky sign indicate in a patient with suspected SJS-TEN?
A positive Nikolsky sign indicates that the epidermis can be dislodged by lateral pressure, which is characteristic of SJS-TEN.
What percentage of SJS-TEN cases involve mucous membrane involvement in at least two sites?
Mucous membrane involvement in at least two sites is seen in 90% of SJS-TEN cases.
What is the prognosis if acute respiratory failure develops rapidly after skin involvement in SJS-TEN?
Acute respiratory failure developing rapidly after skin involvement is associated with a poor prognosis.
What are the first steps in assessing a patient with suspected SJS/TEN?
- Check respiratory rate (RR) and blood oxygenation.
- Check arterial blood gas (ABG).
- Assess bicarbonate levels; a level < 20 mM indicates poor prognosis due to respiratory alkalosis or metabolic acidosis.
- Monitor for massive transdermal fluid loss, which can lead to electrolyte imbalances, hypoalbuminemia, and hypoproteinemia.
- Evaluate for renal insufficiency and prerenal azotemia.
- Check BUN as a marker of severity.
- Look for anemia, mild leukocytosis, and thrombocytopenia.
- Note that neutropenia is an unfavorable prognostic factor but is rare.
- Assess for transient peripheral CD4+ lymphopenia and decreased T-cell function.
What histopathological features are observed in early and fully developed stages of SJS/TEN?
Early Stages:
- Epidermal involvement characterized by sparse apoptotic keratinocytes in the suprabasal layers.
Fully Developed Stages:
- Epidermal detachment and epidermolysis occur.
- Subepidermal vesiculation due to extensive vacuolar alteration and confluent necrosis of keratinocytes.
- Apoptosis may involve sweat glands and hair follicles.
- A moderately dense mononuclear cell infiltrate in the papillary dermis, mainly lymphocytes (often CD8+) and macrophages.
- The cornified layer remains unchanged.
- Direct immunofluorescence (DIF) is negative.
What are the complications associated with SJS/TEN in the acute phase?
- The most common complication in the acute phase is sepsis.
- It is recommended to avoid central venous lines (source of infection) and use peripheral lines if possible.
- Common pathogens include S. aureus and Pseudomonas.
- Approximately 1/3 of blood cultures may contain Enterobacteriaceae, indicating bacterial translocation from the gut.
- Other complications include multisystem organ failure (30%) and pulmonary complications (15%).
What are the common laboratory findings in patients with SJS/TEN?
- Mild and transient renal insufficiency and prerenal azotemia are common.
- Raised BUN serves as a marker of severity.
- Anemia and mild leukocytosis may occur.
- Thrombocytopenia is noted, and neutropenia is considered an unfavorable prognostic factor, though rare.
- Transient peripheral CD4+ lymphopenia is often seen, indicating decreased T-cell function.
What distinguishes generalized bullous fixed drug eruption (GBFDE) from erythema multiforme (EN) in terms of prognosis and complications?
- GBFDE has a better prognosis compared to EN.
- GBFDE typically involves mild mucous membrane involvement and no visceral complications.
- Hallmarks of GBFDE include rapid onset after drug intake, prior attacks, and very large well-demarcated blisters.
What is the frequency of systemic organ failure in SJS-TEN cases?
Systemic organ failure occurs in approximately 30% of SJS-TEN cases.
What does a blood glucose level above 14 mM indicate in SJS-TEN?
A blood glucose level above 14 mM is a marker of severity and poor prognosis in SJS-TEN.
What are the most common pathogens responsible for sepsis in SJS-TEN?
The most common pathogens responsible for sepsis in SJS-TEN are Staphylococcus aureus and Pseudomonas species.
What causes hypoalbuminemia and electrolyte imbalances in SJS-TEN?
These findings are caused by massive transdermal fluid loss due to extensive skin detachment.
What is the significance of anemia and mild leukocytosis in SJS-TEN?
Anemia and mild leukocytosis are common in SJS-TEN but do not significantly impact the SCORTEN score.
What are the common long-term sequelae experienced by patients who survived epidermal necrolysis (EN)?
Common long-term sequelae include:
- Psychological impact: PTSD symptoms are not rare.
- Ophthalmic complications: 20% to 75% experience dryness and abnormal lacrimal film, leading to chronic inflammation and vision issues.
- Skin changes: Hypo/hyperpigmentation, nail changes (30% of cases), and permanent anonychia.
- Oral complications: 1/3 of patients report dryness and altered taste.
- Vulvar and vaginal issues: 25% of patients experience dyspareunia and related complications.
- Gastrointestinal issues: Rare esophageal, intestinal, and urethral strictures may develop.
- Chronic lung disease: Often attributed to bronchiolitis obliterans, occasionally requiring lung transplantation.
What is the typical progression of epidermal necrolysis (EN) after admission?
The typical progression of EN after admission includes:
1. Initial phase: Maximum skin detachment occurs for up to 5 days.
2. Epidermal detachment: Progresses for 5 to 7 days.
3. Plateau phase: Corresponds to progressive re-epithelialization, during which life-threatening complications such as sepsis or systemic organ failure may occur.
What factors do not affect the prognosis of epidermal necrolysis (EN)?
The prognosis of EN is NOT affected by:
- The cause of the reaction.
- Whether it was due to drug, infection, or unknown causality.
- The type or dose of the responsible drug.
- The presence of HIV infection.
What is the overall mortality rate associated with epidermal necrolysis (EN)?
The overall mortality rates are as follows:
| Condition | Mortality Rate |
|———–|—————-|
| EN | 22% to 27% |
| SJS | 10% |
| TEN | >50% |
| Children with severe EN | Very low compared to older adults |
What are the long-term sequelae experienced by patients who survive epidermal necrolysis (EN) one year after the acute stage?
Patients who survive EN experience a range of long-term sequelae, including:
1. Negative impact on quality of life for about half of the patients.
2. Psychiatric symptoms suggesting PTSD are not rare.
3. Ophthalmic complications: 20% to 75% may experience dryness and abnormal lacrimal film, leading to chronic inflammation and other issues.
4. Nail changes: 30% may have pigmentation, ridging, dystrophic nails, or permanent anonychia.
5. Mouth sequelae: 1/3 report dryness, altered taste, and dental issues.
6. Vulvar and vaginal complications: 25% may experience dyspareunia related to vaginal dryness and other symptoms.
7. Gastrointestinal complications: Rare esophageal, intestinal, urethral, and anal strictures may develop.
8. Chronic lung disease: Often attributed to bronchiolitis obliterans, occasionally requiring lung transplantation.
What is the significance of the plateau phase in the progression of epidermal necrolysis (EN)?
The plateau phase in the progression of EN is significant because:
1. It corresponds to progressive re-epithelialization, which is crucial for recovery.
2. During this phase, patients are at risk for life-threatening complications such as sepsis or systemic organ failure.
3. The overall mortality rate during this phase is concerning, with rates of 22% to 27% for EN, 10% for SJS, and 50% for TEN.
4. Understanding this phase helps in monitoring and managing patients effectively to mitigate risks during recovery.
What factors do NOT affect the prognosis of patients with severe epidermal necrolysis (EN)?
The prognosis of patients with severe EN is NOT affected by the following factors:
1. The cause of the reaction (whether drug, infection, or unknown causality).
2. Type or dose of the responsible drug.
3. Presence of HIV infection.
4. Age: Mortality rates in children with severe EN are low compared to older adults.
What are the common nail changes seen in SJS-TEN?
Common nail changes include pigmentation of the nail bed, ridging, dystrophic nails, and permanent anonychia, occurring in 30% of cases.
How common are esophageal strictures as a complication of SJS-TEN?
Esophageal strictures are a rare complication of SJS-TEN.
What is the recommended management for PTSD symptoms in SJS-TEN survivors?
Psychiatric consultation and psychological support are recommended for managing PTSD symptoms in SJS-TEN survivors.
What is the likely cause of dyspareunia in SJS-TEN?
Dyspareunia is likely caused by vaginal dryness, itching, pain, and bleeding, which are complications of SJS-TEN.
What are the potential long-term ocular complications in SJS-TEN?
Long-term ocular complications include chronic inflammation, fibrosis, entropion, trichiasis, symblepharon, and metaplasia of the corneal epithelium, leading to painful ulcerations, scarring, and altered vision.
What is the recommended management for genital adhesions in SJS-TEN?
Genital adhesions may require surgical treatment to restore function and alleviate symptoms.
What is the likely underlying condition for chronic lung disease in SJS-TEN?
Chronic lung disease in SJS-TEN is often attributed to bronchiolitis obliterans.
What is the frequency of hypo- and hyperpigmentation as a complication of SJS-TEN?
Hypo- and hyperpigmentation are the most frequent complications of SJS-TEN.
What is the significance of prompt withdrawal of offending drugs in drug-induced EN cases?
Prompt withdrawal is associated with an increased rate of survival in patients with EN induced by drugs with short half-lives. It is preferable to continue every important and nonsuspected medication, and all not life-sustaining drugs should be stopped if initiated and administered within the previous 8 weeks.
What are the key components of symptomatic treatment for EN?
The key components of symptomatic treatment for EN include:
1. SCOTEN score: 0 or 1 indicates nonspecialized wards; otherwise, ICU/burn unit.
2. Supportive treatment: Most important to manage fluid loss and electrolyte imbalance.
3. Temperature management: Should be raised to 28-30°C.
4. Nutritional support: Preferably provided by nasogastric tube.
5. Skin care: Skin, blood, and urine specimens should be cultured; prophylactic antibiotics are not indicated.
What are the controversies surrounding the use of corticosteroids in the treatment of EN?
Corticosteroids are controversial in the treatment of EN due to:
- Some studies suggest they could prevent disease extension when administered early, especially as intravenous pulses.
- Other studies indicate that corticosteroids did not stop disease progression and were associated with increased mortality and sepsis when administered for 2 to 3 weeks.
- A large cohort study suggested a benefit when steroids were given in a medium dose for a few days.
- A recent systematic review revealed a beneficial effect on corticosteroids in the treatment of SJS and TEN.
What is the conclusion regarding the use of IVIG in treating EN?
IVIG should not be considered the standard of care in treating EN. Although it was based on the hypothesis that Fas-mediated cell death could be abrogated by anti-Fas activity, large cohort studies could not demonstrate a beneficial effect. The conclusion is that IVIG should not be used to treat patients with EN.
What is the conclusion regarding the use of IVIG in treating EN?
IVIG should not be considered the standard of care in treating EN. Large cohort studies could not demonstrate a beneficial effect.
What are the benefits of using Cyclosporine A in the treatment of EN?
Cyclosporine A activates T helper cells and cytokines, inhibits CD8+ cytotoxic mechanisms, and has an antiapoptotic effect. It halts skin detachment progression without significant side effects when administered early.
What are the dosing considerations for Cyclosporine A in the treatment of EN?
The initial dosing protocol is 3 mg/kg body weight for 10 days, followed by 2 mg/kg for 10 days, then 1 mg/kg for 10 days. Adjustments are made for renal failure.
What are the findings regarding the use of anti-TNF agents in treating EN?
Anti-TNF agents have been successfully used to treat a few patients with EN. A study showed improved outcomes with etanercept compared to corticosteroids.
What is the significance of prompt withdrawal of offending drugs in drug-induced EN cases?
Prompt withdrawal is associated with an increased rate of survival in patients with drug-induced EN. Non-life-sustaining drugs should be stopped if administered within the previous 8 weeks.
What are the key components of symptomatic treatment for patients with EN?
Key components include SCOTEN score assessment, supportive treatment for fluid loss, temperature management, nutritional support, and careful skin care.
What are the controversies surrounding the use of corticosteroids in the treatment of EN?
Corticosteroids may prevent disease extension if administered early, but prolonged use is linked to increased mortality and sepsis.
What is the conclusion regarding the use of IVIG in treating patients with EN?
IVIG should not be used for treating EN as recent studies indicate it does not demonstrate a beneficial effect.
What is the recommended acute management for ocular involvement in SJS-TEN?
Acute management includes preservative-free emollients, antibiotic or antiseptic eye drops, and Vitamin A every 2 hours.
What is the current recommendation regarding IVIG treatment for SJS-TEN?
IVIG is not recommended for treating SJS-TEN, as findings suggest the Fas-L–Fas pathway is not significantly involved in the disease mechanism.
What is the evidence regarding corticosteroids in SJS-TEN?
Corticosteroids may prevent disease extension if administered early, but prolonged use is associated with increased mortality and sepsis.
What are the recommended treatments for ocular sequelae in patients with EN?
Recommended treatments include gas-permeable scleral lenses, grafting of autologous stem cells, and photoprotection.
What is the FDA recommendation regarding HLA-B*1502 testing for patients of Han Chinese and Thai origin?
Patients of Han Chinese and Thai origin should be tested for HLA-B*1502 before prescribing carbamazepine due to potential associations with EN.
What criteria are most useful for evaluating drug causality in patients with a history of EN?
Useful criteria include duration of treatment before onset, absence of prior intake, and use of a drug known for a high risk of EN.
What should be done for patients with recurrent SJS or TEN that are actually cases of EMM?
Recurrent cases of SJS or TEN that are actually cases of Erythema Multiforme Major are caused by inadvertent readministration of the same or closely related medication.
What types of medications should be contraindicated in patients with a history of adverse reactions to sulfonamides?
Only antinfectious sulfonamides and sulfasalazine should be contraindicated in patients with a history of adverse reactions to sulfonamides.
What precautions should be taken when prescribing carbamazepine to patients of Han Chinese and Thai origin?
Test for HLA-B*1502 before prescribing carbamazepine and consider alternative antiepileptic drugs if necessary.
What is the significance of narrow cross-reactivity between drugs in the context of SJS/TEN?
Narrow cross-reactivity indicates that antimicrobial sulfonamides do not cross-react with S-diuretics or S-antidiabetics.
What should be provided to patients regarding suspected medications that may cause SJS/TEN?
Patients should receive a personal ‘allergy card’ that includes a list of suspected medications and related molecules to avoid future exposure.
What genetic marker is associated with an increased risk of SJS-TEN in patients taking phenytoin?
The genetic marker HLA-B*1502 is associated with an increased risk of phenytoin-induced SJS-TEN, particularly in Han Chinese and Southeast Asian populations.
