PEMPHIGUS FOLIACEUS
Pemphigus foliaceus is a chronic autoimmune blistering disease. Pemphigus foliaceus can be seen in an isolated form or as an endemic form called fogo selvagem. These diseases are caused by autoantibody production against desmosomal proteins. The endemic form of the disease is seen in small regions in the jungles of South America, predominantly in Brazil. Pemphigus foliaceus is closely related to pemphigus vulgaris, and in some cases the clinical picture and antibody profile can shift from one disease to the other, leading to difficulty in classification.
Clinical Findings: Pemphigus
foliaceus is a rare disease that most frequently affects patients who are about
50 years of age. There is no sex or race predilection. Blistering of the skin
is prominent and can affect large body surface areas. The blisters tend to be
more superficial than those of pemphigus vulgaris. The blisters are rarely
found intact because of their superficial and fragile nature. Mucous membranes
are rarely affected, because the mucocutaneous surfaces do not contain high
concentrations of the desmoglein 1 protein. Patients exhibit a positive
Nikolsky’s sign. This sign is positive when exertion of pressure (rubbing) induces a blister or
erosion on nonaffected skin.
Fogo
selvagem (Portuguese for “wild fire”) affects a younger population, occurring
in patients approximately 25 years of age. It is believed to be transmitted by
the bite of the black fly or the mosquito in patients who are susceptible to
the disease. It has been postulated that the bite begins a cascade of immune
system antibody production, resulting in formation of the pathogenic
antibodies against desmoglein 1. The infectious agent transmitted by the flies
has not been discovered. A fair percentage of patients have a family member who
is also affected, and this provides some clinical evidence for a genetic
predisposition to the disease. The disease exhibits photosensitivity in the
ultraviolet B range. Indirect
immunofluorescence testing of the patient’s serum shows autoantibodies against
desmoglein 1.
Histology:
The
histological findings of pemphigus foliaceus and its endemic form, fogo selvagem, are
identical. Intraepidermal blistering is caused by acantholysis. The
acantholysis is most prominent in the upper epidermis, usually starting in the
granular cell layer and above. Typically, a mixed inflammatory infiltrate is
seen within the dermis. Varying amounts of crust and superficial bacteria are
seen in areas of chronic erosion. Immunofluorescence staining shows a fishnet
pattern of intercellular staining with immunoglobulin G and complement.
Pathogenesis:
Abnormal
antibody production is directed against the desmoglein 1 protein, which is a
critical component of the desmosomal attachment between adjacent keratinocytes.
Desmogleins are calcium-dependent adhesion proteins known as cadherins. As the
autoantibodies attach to the desmoglein protein and are deposited within the epidermis,
they activate complement. Complement activation, along with the cytotoxic
effects of lymphocytes, leads to acantholysis of keratinocytes and the eventual
blistering of the epidermis. The hemidesmosome is unaffected, and the basilar
layer of keratinocytes stays attached to the basement membrane zone.
Treatment:
Because
mucous membrane involvement is almost nonexistent and the blistering is more
superficial, the course of pemphigus foliaceus is typically less severe than
that of pemphigus vulgaris; however, this is not always the case. Therapy is
directed toward decreasing the antibody formation. Immunosuppressants are the mainstay of therapy,
and combinations are occasionally required to get the disease under control.
Oral corticosteroids are typically the first medications used, along with a
steroid-sparing agent. Azathioprine, mycophenolate mofetil, cyclophosphamide,
and rituximab have all been used with varying success. Intravenous
immunoglobulin (IVIG) has also been used. Use of the non-immunosuppressive
agents, tetracycline and nicotinamide, has shown variable success. The same can
be said of hydroxychloroquine. The treatment of pemphigus foliaceus requires chronic therapy, because
this is a chronically relapsing and remitting disease. Supportive care is
required to avoid excessive trauma and friction to the skin, which can induce
blistering. Bacterial superinfection needs to be treated promptly.
Therapy for
fogo selvagem is similar in many respects. The use of mosquito and fly control
measures may be of help in the endemic regions, because these insects are
believed to be the vectors of transmission to susceptible humans.
