SECTION
5
Vesiculobullous Diseases
A B
A B
that are speculated to interact with the sulfhydryl groups in Dsg1 and
Dsg3. This interaction may modify the antigenicity of the desmogleins,
which may lead to autoantibody production, or their interaction may
directly interfere with the adhesive function of the desmogleins. Most,
but not all, patients with drug-induced pemphigus go into remission
after the offending drug is discontinued.
Paraneoplastic Pemphigus
Paraneoplastic pemphigus is associated with underlying neoplasms,
both malignant and benign. The most commonly associated neoplasms
are non-Hodgkin lymphoma and chronic lymphocytic leukemia, fol-
lowed by Castleman disease, malignant and benign thymomas, sarco-
mas, and Waldenström macroglobulinemia2. Non-Hodgkin lymphoma
and chronic lymphocytic leukemia together account for two-thirds of
patients. Castleman disease, a very rare lymphoproliferative disorder, is
the third most commonly associated neoplasm in adults and the most
commonly associated tumor in children and adolescents; its association
with paraneoplastic pemphigus is strikingly disproportionate to its
general occurrence. The absence of common tumors, such as adenocar-
cinomas of the breast or colon and squamous cell carcinomas, is notable.
The most constant clinical feature of paraneoplastic pemphigus is
the presence of intractable stomatitis. Severe stomatitis is usually the
earliest presenting sign and, after treatment, it is the one that persists
and is extremely resistant to therapy. This stomatitis consists of ero-
sions and ulcerations that affect all surfaces of the oropharynx and
characteristically extend onto the vermilion lip (Fig. 29.10). Most
patients also have a severe pseudomembranous conjunctivitis, which
may progress to scarring and obliteration of the conjunctival fornices.
502 Nasopharyngeal, esophageal, vaginal, labial, penile and perianal lesions
may also be seen.
Fig. 29.10 Paraneoplastic
pemphigus. A The characteristic
clinical feature is severe intractable
stomatitis with multiple erosions;
there may be a resemblance to
erosive oral lichen planus. B The
erosions, along with hemorrhagic
crusts, can extend onto the
vermilion lip and involve the nasal
mucosa. A, Courtesy, Luis Requena, MD.
Fig. 29.11 IgA pemphigus
– subcorneal pustular dermatosis
(SPD) type. A Numerous superficial
pustules arising within areas of
erythema; these pustules rupture
easily. The desquamation has a
figurate configuration and overall
there is a resemblance to pustular
psoriasis. B Pustules tend to
coalesce to form an annular or
figurate pattern with crusts present
centrally. Note the accumulation of
the pustular component in the
dependent portion of the
vesiculopustule. A, Courtesy, Luis
Requena, MD.
Cutaneous findings are quite polymorphic and may present as erythe-
matous macules, flaccid blisters and erosions resembling pemphigus
vulgaris, tense blisters resembling bullous pemphigoid, erythema
multiforme-like lesions, and lichenoid eruptions. The occurrence of
blisters and erythema multiforme-like lesions on the palms and soles
is often used to differentiate paraneoplastic pemphigus from pemphigus
vulgaris, in which lesions on the palms and soles are unusual. In the
chronic form of the disease, a lichenoid eruption may predominate over
blistering lesions. Some patients with paraneoplastic pemphigus
develop bronchiolitis obliterans, which can be fatal as a result of respi-
ratory failure50. Although its pathophysiologic mechanism is still
unclear, ectopic expression of epidermal antigens in the setting of squa-
mous metaplasia is thought to render the lung a target organ51. Of note,
a chest X-ray or CT scan obtained at the onset of bronchiolitis obliter-
ans may be normal but pulmonary function tests will show small
airway obstruction that does not reverse with bronchodilators.
IgA Pemphigus
IgA pemphigus represents a more recently characterized group of auto-
immune intraepidermal blistering diseases presenting with a vesicu-
lopustular eruption, neutrophilic infiltration of the skin, and in vivo
bound and circulating IgA autoantibodies against the cell surface of
keratinocytes; no IgG autoantibodies are present. IgA pemphigus
usually occurs in middle-aged or elderly persons. Two distinct types of
IgA pemphigus have been described: the subcorneal pustular dermato-
sis type and the intraepidermal neutrophilic type. Patients with both
types of IgA pemphigus present with flaccid vesicles or pustules on
either erythematous or normal skin (Fig. 29.11A). In both types, the
pustules tend to coalesce to form an annular or circinate pattern with
crusts in the center of the lesion (Fig. 29.11B), although a sunflower-like