Page 1819 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1288 PART 11: Special Problems in Critical Care

TABLE 129-7 Classification of Severe Cutaneous Adverse Drug Reactions TABLE 129-9 SCORTEN: A Prognostic Scoring System for Patients With TEN
Hypersensitivity/ Prognostic Factors Points
SJS TEN DRESS
Age >40 years 1
Mucous membrane >90% >90% <30% Heart rate >120 bpm 1
BSA involvement a <10% >30% <10% Cancer or hematologic malignancy 1
Erosions Several sites Several sites Mouth and lips BSA involved on day 1 above 10% 1
Detachment of Yes Yes No Serum urea level (>10 mmol/L) 1
epidermis
Serum bicarbonate level (<20 mmol/L) 1
Hyperkeratosis/ No No Usual
desquamation Serum glucose level (>14 mmol/L) 1
Neutropenia No 30% No SCORTEN Mortality rate (%)
Eosinophilia No No 90% 0-1 3.2
Atypical lymphocytes No No 30%-40% 2 12.1
Respiratory tract Bronchial erosions/ Bronchial erosions/ Interstitial 3 35.8
ARDS ARDS pneumonitis 4 58.3
Liver Hepatitis 10% Hepatitis 10% Hepatitis 60% > or = 5 90
Heart No No Myocarditis BSA, body surface area.
Lymph node enlarged No No Usual Reproduced with permission from Bastuji-Garin S, Fouchard N, Bertocchi M, et al. SCORTEN: a severity-
of-illness score for toxic epidermal necrolysis. J Invest. August 2000;115(2):149-153.
a When detachment involves 10%-29% of BSA, we classify the case as SJS-TEN overlap. ARDS, adult respi-
ratory distress syndrome; BSA, Body surface area; dress, drug reaction with eosinophilia and systemic
symptoms; SJS, Stevens-Johnson syndrome; ten, toxic epidermal necrolysis. HIV-infected individuals, especially those receiving sulfonamides
or nevirapine. Precipitation of SJS and TEN by infectious agents is
following drugs: anticonvulsants (phenytoin, valproic acid, phenobarbital, much less common. Infection with Mycoplasma pneumoniae is the best
and carbamazepine), antibiotics (sulfonamides and aminopenicillins), documented. 47
NSAIDs (oxicam derivatives), chlormezanone, allopurinol, and, interest- The pathogenesis of SJS and TEN remains unclear. Humoral and cell-
39
ingly, corticosteroids (Table 129-8). Drugs with long half-lives, known mediated cytotoxicities, drug metabolites, and apoptotic mechanisms
to be frequent culprits, have been associated with higher fatality have been implicated, with inconsistent data. Experimental data suggest
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rates. SJS is associated with a 5% mortality rate, whereas TEN, which that activation of Fas (CD95) through its ligand, FasL (CD95L), results
is the most severe form of drug eruption known, has a mortality rate in caspase-mediated keratinocyte apoptosis, possibly an important
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of approximately 30%. Mortality is mainly a result of respiratory pathophysiologic mechanism in TEN. Fas (CD95) is a cell surface
complications and sepsis. Prognosis is influenced by age (>60 years), receptor expressed on most cells, including keratinocytes, and can be
the presence of comorbidities, sepsis, and extent of body surface area activated by FasL, which is expressed by natural killer cells and activated
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involved. 43-45 A prognostic scoring system, also known as SCORTEN, T lymphocytes. FasL can also exist in a soluble form (sFasL), capable
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has been proposed (Table 129-9). TEN occurs more frequently in of inducing apoptosis. Soluble FasL results from metalloproteinase-
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mediated cleavage of cell surface FasL, and stimulation of peripheral
blood mononuclear cells by an offending drug results in upregulated
TABLE 129-8 Factors Associated With SJS and TEN sFasL expression. Sera from SJS and TEN patients can induce Fas- FasL–
Drugs Infections (Isolated Cases) mediated keratinocyte apoptosis in vitro, and contain elevated concen-
trations of sFasL when compared with control patients. 51
Antibiotics Mycoplasma Pneumoniae Initial symptoms of both SJS and TEN include pain, tenderness, or
• Sulfonamides Histoplasmosis a burning sensation in the skin. These symptoms often begin abruptly
• Aminopenicillins Hepatitis A and are associated with fever and general malaise. Over the next 1 to
3 days, ill-defined erythematous macules or diffuse erythema develop
• Cephalosporins Epstein-Barr virus over the trunk and extremities. The palms and soles can be an early site
• Quinolones Coxsackievirus B5 of involvement. As the red areas enlarge, central dusky necrotic sites
Anticonvulsants Milkers’ nodules develop with subsequent bullae formation. Bullae result from edema
occurring beneath the necrotic epidermis. As the disease progresses,
• Phenobarbital Yersiniosis
sheets of full-thickness epidermis slough off, revealing dark red, moist
• Phenytoin Adenovirus dermis (resembling severe second-degree burns). The Nikolsky sign
• Valproic acid Gram-negative septicemia (separation of the skin with lateral traction) is positive and an important
clinical diagnostic clue. Criteria to predict which patients with SJS are
• Carbamazepine
likely to progress to full-blown TEN are currently unavailable.
NSAIDs Mucous membrane involvement occurs in 85% to 95% of patients and
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• Piroxicam may be the presenting sign. The oropharynx and conjunctivae are most
affected, resulting in severe erosions and pain. Keratitis, ocular erosions,
• Tenoxicam
and symblepharon may result in blindness. Dysuria is a sign of urethral
Allopurinol involvement. Erosions in the lower respiratory tract and the intestine have
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Chlormezanone also been described. Involvement of the epithelium of the trachea, bronchi,
Graft-versus-host disease or gastrointestinal tract increases morbidity. Laboratory, histopathology,
and immunofluorescence findings are outlined in Table 129-10.
SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis.
The clinical differential diagnosis includes staphylococcal scalded
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SOURCES: Roujeau and Stern, and Ducic et al. 45 skin syndrome, acute GVHD, scarlet fever, erythema multiforme, and

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