A NEW VARIANT OF ENDEMIC PEMPHIGUS
FOLIACEUS IN EL BAGRE, COLOMBIA SOUTH AMERICA
ANA MARIA ABREU VELEZ
C O N F L I C T O F I N T E R E S T: N O N E .
WHAT IS ENDEMIC PEMPHIGUS FOLIACEUS?
 Pemphigus foliaceus is an autoimmune skin disease
mediated by autoantibodies against mainly against
desmoglein 1 (Dsg1).
 The endemic form is thought to have an environmental
cause.
 Normal subjects living in an endemic area have
antibodies against (Dsg1).
ENDEMIC PEMPHIGUS FOLIACEUS
Endemic foci of fogo selvagem (FS) are almost
exclusively located in rural areas of Brazil. People
of many races and ethnic groups are affected,
including Brazilians of Portuguese, Spanish,
German, African, and Japanese descent who live
in the endemic areas.
The incidence of FS decreases dramatically as a
region becomes urbanized..
ENDEMIC PEMPHIGUS FOLIACEUS
 These findings support the concept that the production
of antibodies against desmoglein 1 is initiated by
exposure to an unknown environmental agent.
 There are two forms of pemphigus foliaceus: a none
endemic form, first described in Paris in 1844, that
occurs throughout the world, and FS (endemic form),
that was first reported in Brazil around 1903. Other
endemic foci have been reported in Colombia, Peru,
Venezuela, Salvador, and Tunisia.
ENDEMIC VERSUS NON-ENDEMIC PEMPHIGUS
 The endemic and none endemic forms of the disease
are clinically, histologically, and immunologically similar,
but several features are unique to the endemic form,
such as the geographic, temporal, and familial
clustering of cases, the higher frequency of cases
among children and young adults than among older
persons, and an association with certain HLADR alleles.
A NEW VARIANT IN EL BAGRE, COLOMBIA, AKA PEMPHIGUS ABREUMANU THAT CLINICALLY RESEMBLES SENEAR-USHER SYNDROME
 Fogo selvagem, most frequently resembles pemphigus
foliaceus (PF). It primarily affects children and young
adults, with the highest incidence rates occurring in the
10 - 30-year-old age group.
 The incidence in men and women appear to be similar.
Furthermore, Brazilian cases tend to be clustered in
specific families residing in rural areas, especially in
workers for road construction and agriculture.
GEOGRAPHIC LOCALIZATION
ENDEMIC AREA
THE SENEAR USHER FORM LIKE LUPUS
SOME CLINICAL FORMS
SOME ATYPICAL CLINICAL LESIONS
ENVIROMENT
TESTING FOR AUTOANTIGENS USING A
BACULOVIRUS EXPRESSION SYSTEM
IMMUNOPRECIPITATION
IMMUNOBLOTTING USING DIFFERENT
CELLS EXTRACTS
EXIKFAAAXREGED
IMMUNOBLOTTING USING ECL
DEVELOPMENT OF AN ELISA USING COW SNOUTS
SEQUENCE ANALYSIS BY MASS SPECTROSCOPY
We obtained 9 pg. of the 48kDa band (PF antigen) from 14 cow snouts.
Although the 48 and the 45 kDa bands comigrate closely, we only excised
the 48kDa since it co-migrate with the radiolabelled antigen. This band
was subjected to N-terminal protein sequence analysis. An N-terminus
sequence EXIKFAAAXREGED
1.2
0.8
0.4
OD
492 nm (Linear scale
from 0.0 to 1.4 units)
COMPARING FS AND EL BAGRE-EPF AUTOANTIBODIES
USING TWO ELISAS
Cut-off value
0.0
CPF FS NHS PE BP PV SLE EPF DEA
GROUPS OF DONORS
DETECTION OF AUTOPANTIBODIES USING TWO
DIFFERENT ELISAS
1.5
1.0
(r2=0.92)
0.5
OD
492nm (Linear scale
from 0.0 to 1.4 units )
ASSESSMENT BETWEEN CLINICAL
DISEASE ACTIVITY FOR SKIN AND OD
492 READINGS
0.0
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Skin surface compromised and dosage of
steroid hormones in patients with endemic
pemphigus foliaceus from El Bagre
DIF AND IIF ON
MONKEY
ESOPHAGUS
HISTOLOGICAL PATTERNS
SUMMARY: EYES, MEIBOMIAN GLANDS, TARSAL MUSCLE,
CONJUNCTIVA, PACINIAN CORPUSCLE, OPTIC NERVE
(LEPTOMENINGES)
EYES, MEIBOMIAN GLANDS, TARSAL MUSCLE, CONJUNCTIVA,
PACINIAN CORPUSCLE OPTIC NERVE (LEPTOMENINGES)
Newtonian secretion
EYES, MEIBOMIAN GLANDS, TARSAL MUSCLE, CONJUNCTIVA,
PACINIAN CORPUSCLE, OPTIC NERVE (LEPTOMENINGES)
Pacinian
corpuscle
IN OUR STUDY OF EL BAGRE-EPF
PATIENTS, THE PRESENCE OF HARDYWEMBERG LINKAGE DISEQUILIBRIA
OF STRS FROM HLA II FAVORS THE
LOCUS D6S291 FOR DISEASE
SUSCEPTIBILITY, AND SUGGESTS A
PROTECTIVE ROLE FOR LOCI D6S1019
AND D6S439 IN OUR CONTROLS.
ASSOCIATED SHORT TAMDEM REPEATS (STRS)
SOME OCULAR FINDINGS
PACINIAN
CORPUSCLES
EYE FINDINGS
Meibomian glands ductus
Tarsal muscle
EYE FINDINGS
Meibomian glands
CONFOCAL MICROSCOPY OF A NERVE
CONFOCAL MICROSCOPY OF THE HEART
EYE FINDINGS
Skin BMZ and ICS
Meibomian glands
BMZ: Basement membrane zone, ICS, Intercellular stain between keratinocytes.
OCULAR FINDINGS
Newtonian secretion
Sweat glands lipofuscin
PACINIAN CORPUSCLE
OCULAR FINDINGS
Eyelid BMZ and ICS
Muscle bundles
OCULAR FINDINGS
Meibomian glands
OCULAR FINDINGS
AUTOREACTIVITY TO MECHANORECEPTORS
AUTOREACTIVITY TO MECHANORECEPTORS
AUTOREACTIVITY TO MECHANORECEPTORS
AUTOREACTIVITY TO NERVES
AUTOREACTIVITY TO NERVES
AUTOREACTIVITY TO NERVES
AUTOREACTIVITY TO NERVES
AUTOREACTIVITY TO NERVES
PALMS
PALMS
AUTOREACTIVITY
TO SWEAT GLANDS
AUTOREACTIVITY TO SWEAT GLANDS
INDIRECT IIF KIDNEY
INDIRECT IMMUNOFLUORESCENCE ON
KIDNEY
INDIRECT IMUNOFLUORESENCE (IIF) ON KIDNEY
IIF ON
KIDNEY
HEART REACTIVITY
ELECTRON MICROSCOPY
ELECTRON MICROSCOPY
Trypsinize Bovine Epidermal Tissue
Purify on Con A Column
Patient serum linked to
Protein A-Sepharose column
Purify on Immunoaffinity
Column
Purify by SDS-PAGE