Drug-Induced Bullous Disorders Workup

Updated: Apr 30, 2018
  • Author: David F Butler, MD; Chief Editor: William D James, MD  more...
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Laboratory Studies

Laboratory studies during an eczematous drug eruption may disclose eosinophilia, leukocytosis, and elevated sedimentation rate.

In AGEP, laboratory studies demonstrate neutrophilia in 90% of cases and eosinophilia in 30% of cases. Liver function is usually normal.

Laboratory studies in FDE may show leukocytosis, hypereosinophilia, and hypergammaglobulinemia. However, clinical and histologic features are the mainstay of diagnosis.

Apart from leukocytosis, laboratory studies may not be helpful in the evaluation of patients with EM. Patients with widespread lesions may develop electrolyte abnormalities and hypoalbuminemia. Immunofluorescence study results are negative.

Antinuclear antibodies may be found in patients with thiol drug-induced pemphigus.

Blood eosinophilia and increased amounts of soluble interleukin-2 receptors may be present in patients with drug-induced pemphigoid. [34] The sera and blister fluids in drug-induced pemphigoid may show increased amounts of eosinophilic cationic protein and neutrophil-derived myeloperoxidase.

Laboratory studies are not particularly helpful in diagnosing drug-induced LAD.

In pseudoporphyria, laboratory studies do not demonstrate any abnormality in heme biosynthesis or hepatic abnormalities.


Other Tests

Results of patch testing suspected drugs that cause eczematous drug reactions may be positive.

Patch testing of the offending drug in AGEP may result in a pustular patch test reaction.

Patch testing and oral provocation testing may be used to implicate a specific drug in a FDE.

Apart from skin biopsy, other tests are not helpful in evaluating EM. First-degree relatives of patients with TEN have lymphocytes that are more susceptible to the toxic effect of the culprit drug than controls.

Results of direct and indirect immunofluorescence studies in drug-induced pemphigus are identical to studies in idiopathic pemphigus. Deposition of immunoglobulin G (IgG) and C3 is observed intercellularly on direct immunofluorescence. On indirect immunofluorescence, pemphigus antibodies are found in the patient's serum.

Linear deposits of IgG and C3 may be visualized along the basement membrane zone with direct immunofluorescence in patients with drug-induced pemphigoid. Indirect immunofluorescence studies are positive for circulating antibodies against the basement membrane zone. However, circulating antibodies are less commonly found in cicatricial pemphigoid.

Direct immunofluorescence studies reveal the presence of IgA at the basement membrane zone in LAD. Results of indirect immunofluorescence studies using monkey esophagus or saline split human skin are usually negative for IgA at the basement membrane zone.

Pseudoporphyria demonstrates normal urine and serum porphyrins.


Histologic Findings

Eczematous drug eruptions

Frequently seen histologic findings include the following: hyperkeratosis, parakeratosis, exocytosis of lymphocytes, spongiosis, and a superficial perivascular lymphocytic infiltrate. Occasional histologic findings include the following: eosinophilic spongiosis, vesicle or bulla formation, papillary dermal edema, and extravasation of erythrocytes. Rarely, features suggestive of mycosis fungoides may be observed.

Acute generalized exanthematous pustulosis

Subcorneal or spongiform pustules and a mild superficial perivascular and interstitial infiltrate composed of lymphocytes, neutrophils, and eosinophils may be observed. Papillary dermal edema, extravasation of erythrocytes, and acantholytic keratinocytes may also be observed.

Fixed drug eruption

Histologic examination of FDE reveals an interface or spongiotic dermatitis pattern. In the acute phase, the epidermis is characterized by dyskeratotic cells, exocytosis, edema, nuclear pyknosis, and hydropic degeneration of basal cells. An acute infiltrate consisting of lymphocytes, histiocytes, neutrophils, and eosinophils may be found around superficial and deep blood vessels. The quiescent lesion contains macrophages replete with melanin in the upper dermis. Papillary dermal fibrosis may develop consequent to prior episodes of FDE at the same site.

Erythema multiforme

An interface dermatitis with individual cell necrosis (necrotic keratinocytes) beneath a normal basket weave stratum corneum is characteristic of EM. Other findings may include spongiosis, intrabasilar blister formation, a superficial perivascular lymphohistiocytic infiltrate with variable numbers of eosinophils and neutrophils, and papillary dermal edema. TEN shows massive and confluent necrosis of the basal cells (and possibly the entire epidermis), and the dermal infiltrate is scanty.

Drug-induced pemphigus

The hallmark of pemphigus is acantholysis, or the loss of cohesion between epidermal cells. This gives rise to an intraepidermal bulla, which may be located above the basal cell layer (low acantholysis) or subcorneally (high acantholysis). Bullae may lack inflammatory cells or may contain abundant neutrophils. A lymphocytic infiltrate may be found in the dermis in addition to numerous plasma cells and eosinophils.

Drug-induced pemphigoid

The histologic hallmark of drug-induced pemphigoid is a subepidermal blister. Neutrophils, eosinophils, and fibrin may be present in the blister cavity. The dermis is characterized by a superficial infiltrate containing neutrophils, lymphocytes, eosinophils, and occasionally plasma cells. In cicatricial pemphigoid lesions, eosinophils are sparse, whereas a dense lymphocytic inflammatory infiltrate exists in the dermis. Variable dermal fibrosis may be observed based upon chronicity of the lesions and prior involvement at the same site.

Linear IgA dermatosis

A subepidermal blister containing neutrophils and eosinophils with a dermal perivascular infiltrate may be present. IgA antibodies, sometimes accompanied by C3, localize to the dermal side of the basement membrane.


Pseudo-PCT demonstrates the same histologic features of PCT. These features include the following: subepidermal blister, cell-poor infiltrate, festooning of dermal papillae, and thickened vessel walls, which are periodic acid-Schiff positive.