Approach Considerations
There are no specific laboratory studies (other than biopsy) that can definitively establish the diagnosis of Stevens-Johnson syndrome.
Serum levels of the following typically are elevated in patients with Stevens-Johnson syndrome:
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Tumor necrosis factor (TNF)-alpha
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Soluble interleukin 2-receptor
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Interleukin 6
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C-reactive protein
However, none of these serologic tests is used routinely in diagnosing and managing Stevens-Johnson syndrome.
A complete blood count (CBC) may reveal a normal white blood cell (WBC) count or a nonspecific leukocytosis. A severely elevated WBC count indicates the possibility of a superimposed bacterial infection. Electrolytes and other chemistries may be needed to help manage related problems.
Skin and blood cultures have been advocated because the incidence of serious bacterial bloodstream infections and sepsis contribute to morbidity and mortality. [32] In addition, cultures of urine and wounds are indicated when an infection is clinically suspected. Determine renal function and evaluate urine for blood.
Skin biopsy specimens demonstrate that the bullae are subepidermal. However, skin biopsy is not an emergency department (ED) procedure. Epidermal cell necrosis may be noted. Perivascular areas are infiltrated with lymphocytes.
Bronchoscopy, esophagogastroduodenoscopy (EGD), and colonoscopy may be indicated. Chest radiography may indicate the existence of a pneumonitis when clinically suspected. Otherwise, routine plain films are not indicated.
Histologic Findings
Minimal dermal inflammatory cell infiltrate and full-thickness necrosis of epidermis are typical histopathologic findings in patients with Stevens-Johnson syndrome. The epidermal-dermal junction shows changes, ranging from vacuolar alteration to subepidermal blisters. The dermal infiltrate is superficial and mostly perivascular. Keratinocytes undergo apoptosis.
In the dermis, CD4+ T lymphocytes predominate, whereas in the epidermis, the T cells are predominantly CD8+. The dermoepidermal junction and epidermis is infiltrated mostly by CD8+ T lymphocytes. Complement 3 component and immunoglobulin G (IgG) deposits at the dermoepidermal junction and around small dermal vessels were interpreted as the result of a nonspecific exudative phenomenon. The activated state is underlined by human leukocyte antigen (HLA)-DR expression on keratinocytes, similar to other skin inflammatory disorders.
CD8+ T cells that recognize major histocompatibility complex I (MHC-I) modified by an antigen may produce skin lesions of Stevens-Johnson syndrome, or they may be produced by T cells that recognize an antigen that is restricted by MHC-I.
Conjunctival biopsies from patients with active ocular disease show subepithelial plasma cells and lymphocyte infiltration. Lymphocytes also are present around vessel walls. The predominant infiltrating lymphocyte is the helper T cell.
Immunohistology of the conjunctiva reveals numerous HLA-DR–positive cells in the substantia propria, vessel walls, and epithelium. In the epithelium, HLA-DR is presented by Langerhans cells, macrophages, and activated T cells.
Immunoreactant deposition in vessel walls, comprised of immunoglobulin and complement components, is another prominent feature.
On transmission electron microscopy, the conjunctivae of patients with episodic conjunctival inflammation revealed squamous epithelial metaplasia, vascular basement membrane zone disruption, reduplication, and thickening.
In vivo confocal microscopy may be a useful tool for therapeutic indications and follow-up of ocular problems associated with Stevens-Johnson syndrome. [34]
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A patient with severe eye involvement associated with Stevens-Johnson syndrome. Note corneal neovascularization and conjunctivalization of the ocular surface.
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Epithelial defect of the cornea with neovascularization and surface conjunctivalization.
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Note extensive sloughing of epidermis from Stevens-Johnson syndrome. Courtesy of David F. Butler, MD.
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Sheetlike desquamation on the foot in a patient with toxic epidermal necrolysis. Courtesy of Robert Schwartz, MD.
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Hemorrhagic crusting of the mucous membranes in toxic epidermal necrolysis. Similar lesions are seen in Stevens-Johnson syndrome. Courtesy of Robert Schwartz, MD.
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Note early cutaneous slough with areas of violaceous erythema.
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Extensive sloughing on the face.
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Note the presence of both 2-zoned atypical targetoid lesions and bullae.
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Extensive blistering and sloughing on the back.
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Extensive sloughing on the back.
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Note extensive sloughing.
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Low-power view showing full-thickness epidermal necrosis.
