Page 132 - The Netter Collection of Medical Illustrations - Integumentary System_ Volume 4 ( PDFDrive )

Plate 4-47 Integumentary System

MAST CELL DEGRANULATION BLOCKERS

MAST CELL DISEASE
(Continued) A. Antigen reacts with antibody (IgE)

on membrane of mast cells, which
Histology: The histological features depend on the respond by secreting pharmacological
mediators.
form of mast cell disease. Most biopsy specimens show
an excessive number of mast cells, typically surrounding
the cutaneous vasculature. These mast cells are best Mast cell degranulation effects
appreciated with special staining techniques. The Leder Vagus Mast cell degranulation
(chloracetate esterase) stain, the Giemsa stain, and the nerve blockers
toluidine blue stain are the most commonly used special
stains to help highlight the cutaneous mast cells. CD117
immunostaining also stains mast cells.
Pathogenesis: Darier’s sign is caused by direct release Histamine
of histamine and other inflammatory mediators from
the excessive collection of mast cells within the affected Mucous gland
skin. On direct stimulation such as scratching or hypersecretion SRS-A
rubbing, the mast cells automatically release the con- (slow-reacting
tents of their granules. These granules contain hista- Smooth muscle substance
mine and other vasoactive substances that cause edema, contraction of anaphylaxis)
redness, and pruritus. Increased capillary
Mast cell disease is caused by a mutation in the KIT permeability and ECF-A
gene. KIT is a protooncogene that encodes a protein inflammatory reaction (eosinophil
called stem cell factor receptor (SCFR). SCFR is a chemotactic factor
transmembrane protein tyrosine kinase protein. This Eosinophil attraction of anaphylaxis)
receptor is prominent in two skin cell types, mast cells
and melanocytes. It is also present on a host of other
primitive hematological cell types. Stem cell factor is B. End-organ (airway) response compounded by nonspecific Prostaglandins
also known by various other names, including KIT reactions (ciliostasis, particle retention, and cell injury)
ligand, CD117, Steel factor, and mast cell growth ? Serotonin
factor. It is the molecule that binds to the transmem-
brane SCFR and acts to promote the reproduction of ? Kinins
mast cells. The activating mutation of SCFR seen in
mast cell disease causes an upregulation of signaling via
this pathway and an uncontrolled proliferation of mast Cromolyn Nedocromil
cells. The continuous activation of the stem cell factor
allows for prolonged survival of mast cells, which also
contributes to their increased number. Numerous
mutations of KIT have been described, and it is believed
that the different mutations play a role in the varied
clinical expression of the disease. The most common
mutation is a D816V mutation that is caused by replace-
ment of the normal aspartic acid at the 816 position
with a valine amino acid.
Treatment: Cutaneous mast cell disease in children
is often self-limited and resolves spontaneously with
time. Therapy with antihistamines may help decrease
the pruritus and provide symptomatic relief until the and many other stimuli that differ from individual to 585-nm pulsed dye laser to decrease the redness and
condition resolves on its own. The most important individual. telangiectases for cosmetic purposes. Some success has
aspect for children with cutaneous mast cell disease, Antihistamines are the mainstay of therapy. The leu- been achieved in treating systemic disease with the
especially urticaria pigmentosa, is to avoid agents or kotriene inhibitors are also used as adjunctive therapy tyrosine kinase inhibitor, imatinib. Depending on the
physical insults that may cause massive degranulation to the antihistamines. Cromolyn is a mast cell stabilizer symptoms and the body systems involved, systemic che-
of mast cells. These triggers include medications such that is not absorbed through the gastrointestinal tract. motherapy may be warranted to decrease the mast cell
as anesthetics, narcotics, polymyxin B, and many others. Its use is limited to treatment of coexisting diarrhea load. These agents rarely put patients into long-term
Physical triggers include extremes of temperature, vig- caused by mast cell disease of the gut. Telangiectasia remission, and the response is transient. At this point,
orous exercise, repeated rubbing of the involved skin, macularis eruptiva perstans has been treated with the there is no cure for mast cell disease.

118 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS