The treatment of vitiligo with Ammi Majus Linn. A preliminary note


Sidi, E.; Bourgeois, G.Vardin, J.

Journal of Investigative Dermatology 18(5): 391-395

1952


Ammi Majus Linn is a yearly umbelliferous plant closely related to the plant Ammi Visnaga, from which it can be differentiated only with difficulty with the naked eye. Ammi Majus Linn is well known in Egypt where it is found abundantly in the Nile delta, but it has also been grown in French soil. Since the 13th century the Egyptians have used a powder prepared from the fruit of this plant for the treatment of leukodermas. However, the powder of Ammi Majus Linn, just like that of Ammi Visnaga, provoked such undesirable manifestations as headache, nausea, vomiting, diarrhea, gastric burning and, when given in very strong doses, even nephritis and coma. In 1947, I. R. Fahmy and H. Abu-Shady (1) undertook to extract the active principle of this plant. They were able to isolate two crystalline bitter substances, close to the furocourmarines, namely Ammoidin (G 41180 4 with a melting point of 148°) and Ammidin (melting point 98°). They also assayed the toxic dose on toads and found it to be 400 mg per kg weight for Ammoidin and 800 mg per kg weight for Ammidin.

THE
TREATMENT
OF
VITILIGO
WITH
AMMI
MAJUS
LINN*
A
PRELIMINARY
NOTE
EDWIN
SIDI,
M.D.
AND
J.
BOURGEOIS-GAVARDIN,
M.D.
Paris,
France
At
the
suggestion
of
our
Egyptian
colleagues
we
have
used
an
extract
of
the
plant
Ammi
Majus
Linn
in
the
treatment
of
cases
of
vitiligo
on
the
service
of
Dr.
Arnault
Tzanck
at
the
Hospital
St.
Louis
in
Paris.
Ammi
Majus
Linn
is
a
yearly
umbelliferous
plant
closely
related
to
the
plant
Ammi
Visnaga,
from
which
it
can
be
differentiated
only
with
difficulty
with
the
naked
eye.
Ammi
Majus
Linn
is
well
known
in
Egypt
where
it
is
found
abundantly
in
the
Nile
delta,
but
it
has
also
been
grown
in
French
soil.
Since
the
13th
century
the
Egyptians
have
used
a
powder
prepared
from
the
fruit
of
this
plant
for
the
treatment
of
leukodermas.
However,
the
pow-
der
of
Ammi
Majus
Linn,
just
like
that
of
Ammi
Visnaga,
provoked
such
undesirable
mani-
festations
as
headache,
nausea,
vomiting,
diarrhea,
gastric
burning
and,
when
given
in
very
strong
doses,
even
nephritis
and
coma.
In
1947,
I.
R.
Fahmy
and
H.
Abu
-Shady
(1)
undertook
to
extract
the
active
principle
of
this
plant.
They
were
able
to
isolate
two
crystalline
bitter
substances,
close
to
the
furo-
courmarines,
namely
Ammoidin
(G
4
11
8
0
4
with
a
melting
point
of
148°)
and
Ammidin
(melting
point
98°).
They
also
assayed
the
toxic
dose
on
toads
and
found
it
to
be
400
mg
per
kg
weight
for
Ammoidin
and
800
mg
per
kg
weight
for
Ammidin.
EXPERIMENTAL
Experimentation
with
these
substances
was
started
in
1949
in
Egypt
by
El
Mofti,
A.
Abdel
Malek
and
Hassan
Hefnaoui
(2).
In
April
1951,
we
began
treatment
with
Ammi
Majus
Linn,
in
six
patients
with
vitiligo,
fi
ve
men
and
one
woman.
Their
ages
were
from
30
to
50
years.
Three
of
these
patients
previously
had
been
treated
with
various
other
procedures
(arsenic,
gold
salts,
oil
of
berga-
mot
plus
ultraviolet
lamp
light,
p-aminobenzoic
acid,
vitamins
B
and
C)
with-
out
any
noticeable
effect.
Two
of
these
patients
presented
lesions
distributed
over
many
parts
of
the
body,
while
four
presented
less
numerous
areas
which
were
principally
located
on
the
face,
neck,
forearms,
and
hands.
Serologic
tests
for
syphilis,
determinations
of
the
basal
metabolic
rate
and
blood
counts
were
done
in
all
patients
before
start
of
the
treatment
and
failed
to
show
abnormal
results.
Ammi
Majus
Linn
can
be
used
(a)
by
oral
administration,
(b)
by
local
topical
application
at
the
affected
sites
followed
by
sun
or
ultraviolet
lamp
exposure,
or,
(c)
by
a
combination
of
(a)
and
(b).
Three
of
our
patients
were
subjected
to
the
combined
treatment,
two
only
to
topical
treatment
and
one
to
treatment
by
mouth
for
5
months
and
from
then
on
to
the
combined
treatment.
The
local
treatment
consisted
of
light
swabbing
of
the
skin
with
an
alcoholic
solution
containing
Ammoidin
71
mg
and
Ammidin
21
mg
per
milliliter.
It
was
carried
out
in
our
patients
2
or
3
times
per
week
followed
by
ultraviolet
lamp
*
Received
for
publication
November
14,
1951.
391
392
THE
JOURNAL
OF
INVESTIGATIVE
DERMATOLOGY
irradiation
during
the
fi
rst
weeks
and
then
sun
exposures
when
this
became
feasible
in
May.
The
length
of
exposure
to
the
ultraviolet
lamp
was
a
sub
-
erythema
dose
as
determined
in
every
patient
in
preliminary
tests;
the
usual
starting
dose
was
2
to
3
minutes
at
80
cm
distance.
The
healthy
adjoining
zones
were
covered
with
a
10%
alcoholic
solution
of
p-aminobenzoic
acid
and
did
not
participate
in
the
reaction.
Despite
these
precautions
all
the
patients,
after
the
fi
rst
exposures,
developed
in
the
irradiated
zones
bullous
reactions
of
more
or
less
severe
but
constant
degree
similar
to
burns.
These
burns
were
treated
with
boric
acid
compresses
and
Dali-
bour
cream,
and
after
10
days
we
were
able
to
resume
the
local
treatment.
16-1,
1
41
-
-vr,
1
1W11111
1
-
y
.
FIG.
1.
Vitiligo
of
15
years'
duration,
previously
treated
with
many
different
procedure
without
any
benefit.
Treatment
with
Ammi
Majus
Linn
by
external
application
and
by
mouth
produced
a
minimal
result
during
the
fi
rst
two
months
and
from
then
on
a
quicker
and
more
significant
improvement.
On
the
body
the
plaques
are
in
the
process
of
repig-
mentation,
except
for
the
scrotum
where
the
vitiligo
areas
have
not
changed.
The
internal
treatment
consisted
of
ingestion
of
tablets
containing
Ammoidin
10
mg
and
Ammidin
5
mg
starting
with
1
tablet
per
day
and
gradually
increasing
to
4
tablets
daily
at
the
end
of
two
weeks,
if
there
were
no
signs
of
intolerance.
The
daily
dose
of
4
tablets
was
exceeded
only
in
one
of
our
patients.
Two
of
the
four
patients
who
received
the
internal
treatment
complained
of
nervousness
and
insomnia,
and
one
of
these
also
had
nausea
and
gastric
burning.
In
these
patients
the
medication
was
interrupted
for
8
days
and
was
then
re-
sumed
and
was
well
tolerated:
In
one
patient
the
weaker
dose
of
2
tablets
per
day
and
in
the
other
patient
4
tablets
per
day
on
2
out
of
every
3
days.
One
of
the
four
patients
even
stated
that
there
was
an
improvement
in
his
general
condition.
Blood
counts
done
after
the
treatment
were
normal.
In
two
of
the
three
patients
who
received
the
combined
treatment
strongly
pigmented
islands
with
a
follicle
opening
in
the
center
appeared
in
the
leukodermic
plaques
21
days
after
start
of
the
treatment
(Figs.
1
and
2).
In
the
third
pa-
tient,
the
fi
rst
areas
of
pigmentation
were
not
seen
until
after
3
months.
In
the
two
patients
who
received
the
local
treatment
only,
the
fi
rst
areas
of
TREATMENT
OF
VITILIGO
WITH
AMMI
MAJUS
LINN
393
pigmentation
appeared
15
days
after
healing
of
the
burns
i.e.,
about
a
month
after
the
start
of
the
treatment.
In
distinction
to
the
patients
described
above,
only
the
areas
to
which
the
solution
had
been
applied
became
repigmented.
I
44
44.'
.1
0
A
B
Fro.
2.
A.
after
the
start
of
repigmentation;
new
areas
with
pigment
in
the
vitiligo
areas
on
the
dorsa
of
the
hands;
B.
after
4
months
of
treatment;
the
patches
on
the
dorsa
of
the
hands
have
continued
to
improve,
while
the
distal
ends
of
the
fi
ngers
remain
unchanged.
Finally
the
sixth
patient,
who
took
4
to
6
tablets
per
day
for
5
months
(i.e.,
since
March)
without
any
side
effects
but
also
without
any
evidence
of
repig-
mentation,
noticed
a
sudden
start
of
repigmentation
in
August
after
only
two
local
applications
with
subsequent
exposure
to
the
sun
(Fig.
3).
Although
not
all
the
plaques
were
exposed
to
the
sun
and
though
the
sun
exposures
were
entirely
interrupted
for
one
month,
the
repigmentation
has
become
generalized
and
has
progressed
rapidly,
394
THE
JOURNAL
OF
INVESTIGATIVE
DERMATOLOGY
In
three
of
our
patients,
a
generalized
pruritus
in
all
the
plaques
preceded
the
onset
of
the
repigmentation.
7
,
FIG.
3.
A.
after
4
months
of
internal
treatment:
no
change;
B.
two
local
applications
followed
by
sun
exposures
have
brought
on
almost
complete
repigmentation
of
the
perioral
areas
of
vitiligo.
DISCUSSION
The
repigmentation
appeared
in
all
patients
as
pigmented
minute
macules
with hair
follicles
in
their
center.
These
macules
were
distributed
over
the
leuko-
dermic
plaques
and
increased
progressively
in
size
until
they
joined,
forming
larger
islands.
This
was
particularly
distinct
in
the
lesions
on
the
trunk
and
on
the
extremities.
On
the
face
the
repigmentation
developed
more
rapidly
and
appeared
to
be
progressing
more
from
the
periphery
towards
the
center.
Some
of
our
patients,
who
have
now
been
under
treatment
for
5
months
and
in
whom
the
face
is
entirely
repigmented,
still
present
on
the
trunk,
the
legs
and
especially
TREATMENT
OF
VITILIGO
WITH
AMMI
MAJUS
LINN
395
on
the
feet,
plaques
which
merely
show
spotty
repigmentation.
The
areas
of
vitiligo
which
have
developed
most
recently
appear
to
be
the
ones
which
respond
best
to
treatment.
As
a
matter
of
fact,
the
genital
region
which,
in
some,
was
the
fi
rst
region
to
become
involved
has
not
responded
to
this
treatment
in
any
of
our
patients.
The
repigmentation
does
not
seem
to
occur
simultaneously
in
all
the
plaques
of
vitiligo;
rather,
we
have
seen
it
to
develop
successively
in
different
body
regions
but
usually
simultaneously
in
symmetrically
situated
regions
of
the
body.
The
newly
pigmented
sites
are
always
significantly
darker
in
color
than
in
the
normal
surrounding
skin.
But
this
hyperpigmentation
fades
out
very
quickly,
and
then
the
previously
depigmented
skin
takes
on
the
same
color
as
the
sur-
rounding
skin.
In
the
hairy
areas
the
appearance
of
repigmentation
of
the
skin
is
preceded
by
restoration
of
the
hair
pigment.
Repigmentation
appeared
in
the
same
manner
in
the
areas
which
had
a
vesicular
reaction
after
sun
or
ultraviolet
exposure
as
in
those
which
did
not,
indicating
that
vesiculation
is
not
a
prerequi-
site
for
production
of
the
pigment.
The
sun
also
appears
to
have
a
more
significant
effect
than
the
ultraviolet
lamp.
Is
there
an
effect
from
the
internal
administration
of
Ammi
Majus
Linn?
It
is
very
likely,
for
in
the
patients
who
had
received
internal
treatment
we
have
seen
the
same
islands
of
repigmentation
appear
in
the
plaques
which
had
not
received
local
treatment
as
in
those
which
had.
Moreover,
certain
patients
have
told
us
that
the
ingestion
of
the
tablets
alone,
without
local
application
of
the
solution,
provoked
a
marked
erythema
of
the
lesions
after
exposure
to
the
sun;
even
the
normal
skin,
after
internal
treatment,
seemed
to
become
much
more
pigmented
after
sun
exposure
than
previously
and
tended
to
develop
more
than
the
usual
degree
of
sunburn.
Also
the
rapid
repigmentation
in
3
days
after
2
sun
exposures,
in
the
patient
who
had
fi
rst
had
5
months'
internal
therapy,
would
indicate
the
efficacy
of
the
internal
treatment.
Thus
it
appears
that
the
plant
Ammi
Majus
Linn
has
a
specific
action
in
viti-
ligo;
the
similarity
of
the
response
of
the
6
patients
cannot
be
explained
as
a
chance
fi
nding.
However,
this
investigation
has
been
carried
out
in
too
small
a
number
of
patients
to
permit
the
drawing
of
fi
nal
conclusions.
It
is
well
to
re-
member
that
none
of
our
patients
is
as
yet
completely
cured
in
all
affected
areas
and
that
one
cannot
foretell
whether
there
will
be
any
recurrences.
Two
of
our
patients
who
still
are
under
treatment
and
whose
lesions
are
in
the
process
of
repigmentation,
nevertheless
have
shown
some
new
areas
of
vitiligo.
The
mecha-
nism
of
action
of
Ammi
Majus
Linn
must
still
be
investigated.
In
any
event
the
fi
rst
results
which
we
have
observed
are
sufficiently
impressive
to
make
us
continue
our
studies.
REFERENCES
1.
FAHMY,
I.
R.
AND
ABU
-SHADY,
H.:
Ammi
Majus
Linn.
Pharmadiagnostical
study
and
isolation
of
a
crystalline
constituent,
Ammoidin.
Quart.
J.
of
Pharm.
&
Pharmacol.
20:
281-291,
1947.
2.
a.
EL
MOTT',
J.:
Royal
Egyptian
Med.
Assoc.
8:
650.
b.
HEFNAOUI,
H.:
personal
communication.
C.
ABDEL
MALEK,
A.:
personal
communication.