Like idiopathic bullous pemphigoid, the clinical picture of DIBP is heterogeneous. The varying presentations can make diagnosis difficult. Morphology ranges from classic tense bullae arising from erythematous urticarial basis that inconsistently involves the oral mucosa, to few bullous lesions with no erythematous bases, to target lesions, to scarring plaques and nodules with bullae or excoriations (papular or nodular pemphigoid). It can even mimic other diseases such as bullous erythema multiforme and pemphigus. DIBP is typically present in a younger population than idiopathic bullous pemphigoid. Other common clinical features of DIBP include positive Nikolsky sign, appearance of lesions on normal-appearing skin, target lesions on the palms and soles, involvement of the lower legs, and mucosal involvement. Nikolsky’s sign involves the application of pressure to a blister, resulting in exfoliation of the superficial layers of the skin. Table 18.2 presents a summary of suggested differences between DIBP and classic bullous pemphigoid.

Because many associated drugs are commonly prescribed yet only a few patients develop DIBP, drugs likely act as triggers in patients with underlying genetic susceptibility. A number of mechanisms have been proposed regarding the pathogenesis of DIBP. These include:

Vaccinations have rarely been reported to trigger bullous pemphigoid. In less than 20 cases in recent years, anti-influenza vaccine, tetanus toxoid booster, and tetracoq vaccine have been associated with the onset of bullous pemphigoid. It has been postulated that the underlying mechanism is due to inflammation in the skin at the vaccination site with disruption of the basement membrane architecture and subsequent generation of anti-basement membrane-specific antibodies. Alternatively, vaccinations may trigger an enhanced autoimmune response in patients with a predisposition to or subclinical bullous pemphigoid. In addition, cases of DIBP have also been linked to topical treatments, radiation therapy, and UV therapy.

Diagnosis is confirmed by histopathological staining and immunofluorescence studies. Typical histopathological findings in DIBP include perivascular infiltrate of lymphocytes with eosinophils and neutrophils, subepidermal blisters, intraepidermal vesicles, foci of necrotic keratinocytes, and thrombi in dermal vessels. Blister cavities may contain numerous eosinophils, neutrophils, and fibrin. Of these histologic features, necrotic keratinocytes, intraepidermal vesicles, and thrombi are commonly seen in DIBP but are not associated with classic bullous pemphigoid. Notably, samples taken from normal skin do not show diagnostic findings.

Direct immunofluorescence and indirect immunofluorescence are consistent with idiopathic bullous pemphigoid. Direct immunofluorescence in bullous pemphigoid demonstrates IgG antibodies and C3 linear along the basement membrane zone in 90 % of cases. Circulating IgG antibodies are detected in 75 % of cases with indirect immunofluorescence.

Labs may show marked eosinophilia in serum and increased soluble IL-2 receptor. Other immunological markers such as macrophage migration inhibitory factor may be present. Mast cell degranulation toward the offending drug may also be present.

The course of the disease varies based on the type of DIBP. Two main types have been defined, with the most common being the pure drug eruption form of bullous pemphigoid. In this case, the disease is acute and self-limited; relapses are uncommon. It resolves with cessation of the culprit drug with or without steroid therapy (Figs. 18.1 and 18.2).

The second type is better described as drug-triggered bullous pemphigoid. Drug administration seems to precipitate the onset of a chronic form of bullous pemphigoid that evolves to have all features of the classic form of the disease. Additional therapy aside from drug withdrawal is often necessary in these cases, which can be managed similarly to idiopathic bullous pemphigoid.

Pemphigus is a group of intraepidermal blistering disorders caused by a disruption of desmosomes leading to acantholysis, or a loss of keratinocyte adhesion. There are five main variants of pemphigus classified by the level of intraepidermal acantholysis: pemphigus vulgaris (PV), pemphigus foliaceus (PF), pemphigus erythematosus, drug-induced pemphigus, and paraneoplastic pemphigus. Drug-induced pemphigus is an increasingly common variant of pemphigus, accounting for approximately 10 % of all reported cases. In drug-induced pemphigus, PF is most often reported; however, PV can be seen as well. Most cases have been described in patients ranging from 30 to 90 years of age.