Formaldehyde induced urticarial vasculitis in male medical student, age
40, Michael Pellizzari, Gillian Marshman, Flinders U., Australasian J.
Dermatol. 2007 Aug: Murray 2007.08.29
http://groups.yahoo.com/group/aspartameNM/message/1468

" A complete recovery occurred only after strict elimination of all
exposure to formaldehyde, both occupationally and in the home
environment, was achieved. "


Rich Murray comments: This clinical case report is similar to that by
Donald V. Belsito in 2003 November:

" A 60-year-old Caucasian woman presented with a 6-month history of
eyelid dermatitis...

By strictly avoiding formaldehyde and all formaldehyde releasers for the
next 3 weeks, she improved only slightly.

Her problem, however, was subsequently solved when a local pharmacist
advised her to avoid aspartame.

She had begun using an aspartame-based artificial sweetener 5 months
prior to the onset of her dermatitis. [ 12 months of low-level aspartame
use until stopping. ]

Within 1 week of discontinuing the aspartame, her eyelid dermatitis
resolved completely and has not recurred over 18 months without specific
treatment....

Our patient was consuming an average of 80 mg (1.13 mg/kg) of aspartame
daily, well below the levels previously studied."

[ A packet of tabletop sweetener gives 37 mg aspartame, while a 12 oz
diet soda gives 200 mg aspartame. An aspartame reactor can have
immediate strong symtoms from an under-the-tongue wafer with 4 mg
aspartame. ]


www.blackwell-synergy.com/doi/abs/10.1111/j.1440-0960.2007.00374.x?cookieSet=1&j\
ournalCode=ajd

[ full text $ 56 ]

Australas J Dermatol. 2007 Aug; 48(3): 174-7.
Formaldehyde-induced urticarial vasculitis.
Michael Pellizzari, pell0029@...,
Gillian Marshman, gillian.marshman@...,
School of Medicine, Flinders University,
Bedford Park, South Australia, Australia.
Flinders Medical Centre, Bedford Park,
South Australia, Australia

A 40-year-old male medical student presented with urticarial vasculitis
secondary to occupational formaldehyde exposure.

Serum sickness and delayed pressure urticaria also featured prominently
during his illness.

Initial symptom control was achieved with
oral prednisolone (25 mg/day tapered to zero over 2 weeks)
and oral antihistamine therapy
(fexofenadine 180 mg once daily,
promethazine 20 mg once daily,
ranitidine 150 mg twice daily);
however, subsequent exposures to formaldehyde produced transient symptom
flares that broke through the prednisolone cover.

A complete recovery occurred only after strict elimination of all
exposure to formaldehyde, both occupationally and in the home
environment, was achieved. PMID: 17680969

Michael Pellizzari, School of Medicine,
Flinders University, 7 Vardon Street,
Seacombe Gardens, SA 5047, Australia.
Email: pell0029@...

Michael Pellizzari, MBA. Gillian Marshman, FACD.
F-HSA formaldehyde–human serum albumin

http://som.flinders.edu.au/FUSA/Medicine/1997/Staff.html
Gillian Marshman
BM, BS(Flinders), FACD
Lecturer in Medicine

http://som.flinders.edu.au/FUSA/Medicine/annrep99.pdf

DERMATOLOGY GROUP

CLINICAL STAFF
Dr Gillian MARSHMAN, BM, BS(Flinders), FACD
Dr Christopher DUGUID, MB, BS(Adel),DObsRACOG, FACD
Dr Lynette GORDON, MB, BS(Adel), FACD
Dr Yu-Chuan LEE, MB,BS(Adel), FACD

ADVANCED TRAINEE
Dr Harji KAUR, MB, BS(Delhi)
Dr Sally BALL, BM,BS (Flinders)

RESEARCH STAFF
Ms Michelle GRIMBALDESTON, BA, BTh(Hons) (Proceeding to PhD)
The core activity of the Dermatology Unit remains one of clinical
service with very busy general outpatient sessions and specialised
clinics now on a regular basis.
Combined clinics with Immunology and Paediatrics are well established
and very successful.
The role of the intern in managing patients in the outpatient setting
has been further consolidated and has proved a popular and instructional
time for those junior staff involved.
It is gratifying that many students who undertake the elective in
dermatology return to do the intern job with obvious enjoyment.
The Dermatology Day unit plays an important role in patient care and
education and nursing further education.
The Psoriasis Support Group meets periodically in this venue.
GP up-skilling places have been over-subscribed during 1999 and many
GP’s gained better understanding of dermatological diseases and their
treatment through this program.
The ongoing GP symposia held with the Southern Division again have been
very well attended and accredited.
Patch testing facilities and expertise have been consolidated and the
contact dermatitis clinic is well established.

RESEARCH
The Unit collaborated in a multi-centre blinded randomised trial
comparing the efficacy of 2 potent topical steroids in the treatment of
psoriasis.
This provided further recognition of FMC Dermatology as a centre of
excellence for the running of such trials and has led to our early
involvement in future studies.
Collaboration with the Flinders University photo-biology basic science
team is continuing with the study of the predictive value of cutaneous
mast cell numbers and function in BCC development.

A second study on suppression of the cutaneous immune system in
psoriasis is underway.
The photo-dermatoses clinic will commence early in 2000, with
mono-chromator testing, providing only the second such facility in
Australia.

Publications:
1. Gordon LA.
Compositae dermatitis.
Australasian J Dermatology 1999; 40: 123-130.

2. Lee Y-C, Gordon LA and Gordon DL.
Epoxy resin allergy from microscopy immersion oil.
Australasian J Dermatology 1999; 40: 228-229.
Senior Visiting Specialist, Dermatology Unit
Flinders Medical Centre
////////////////////////////////////////////////////////////


http://groups.yahoo.com/group/aspartameNM/message/1067
eyelid contact dermatitis by formaldehyde from aspartame,
AM Hill & DV Belsito, Nov 2003: Murray 2004.03.30 [150 KB]

[ Extracts ]

"A 60-year-old Caucasian woman presented with a 6-month history of
eyelid dermatitis...

By strictly avoiding formaldehyde and all formaldehyde releasers for the
next 3 weeks, she improved only slightly.

Her problem, however, was subsequently solved when a local pharmacist
advised her to avoid aspartame.

She had begun using an aspartame-based artificial sweetener 5 months
prior to the onset of her dermatitis. [ 12 months of low-level aspartame
use until stopping. ]

Within 1 week of discontinuing the aspartame, her eyelid dermatitis
resolved completely and has not recurred over 18 months without specific
treatment....

Our patient was consuming an average of 80 mg (1.13 mg/kg) of aspartame
daily, well below the levels previously studied."

[ A packet of tabletop sweetener gives 37 mg aspartame, while a 12 oz
diet soda gives 200 mg aspartame. An aspartame reactor can have
immediate strong symtoms from an under-the-tongue wafer with 4 mg
aspartame. (Appendix A, for comments, abstracts, and links.) ]

Contact Dermatitis. 2003 Nov; 49(5): 258-9.
Systemic contact dermatitis of the eyelids caused by formaldehyde
derived from aspartame?
Hill AM, Belsito DV. DBelsito@...,
Division of Dermatology, University of Kansas Medical Center, 3901
Rainbow Blvd., Kansas City, KS 66160, USA. PMID: 14996049

A. Michele Hill and Donald V. Belsito
Division of Dermatology, University of Kansas Medical Center
3901 Rainbow Blvd., Kansas City, KS 66160, USA [ (Appendix B, for more
abstracts by Donald V. Belsito, selections, and institutions) ]

Key Words: allergic contact dermatitis; aspartame; eyelids;
formaldehyde; systemic contact dermatitis.

Formaldehyde is a common and ubiquitous contact allergen.
Sources of exposure include hair and skin care products, cosmetics,
topical medications, permanent press clothing, cleaning agents,
disinfectants, paper and even smoke. [ Also, new buildings, mobile
homes, furniture, carpets, drapes, particleboard, medical facilities,
methanol, aspartame, dimethyl dicarbonate, dark wines and liquors ]

Sensitization is reported in between 2.2 and 9.6% of patients patch
tested (1,2).
[ (Appendix C, for abstracts on rates of formaldehyde sensitivity in
control groups, as a possible first estimate of the impact of widespread
exposure to aspartame since 1981.) ]

Case Report

A 60-year-old Caucasian woman presented with a 6-month history of eyelid
dermatitis.
A corticosteroid-containing opthalmologic ointment improved but did not
clear the rash.
She failed to improve when she discontinued the use of all eyelid
cosmetics and nail polishes for 2 months.
She had had a facial dermatitis in 1995, for which she had been patch
tested and found to be allergic to formaldehyde,
quaternium-15 and fragrances.
She had also had incidental, non-relevant reactions to
neomycin and ethylenediamine.
Her dermatitis had resolved with a change to formaldehyde-,
quaternium-15 and fragrance-free facial and nail cosmetics.

There was no personal or family history of atopy or psoriasis.
Her only oral medication was celecoxib that she had taken for years
prior to the onset of her blepharitis.
She had also taken multivitamins, calcium and flaxseed oil for many years.
She worked as a homemaker and library volunteer. [ It is relevant as to
whether she had the standard urban diet with high protein and animal
fats, meats, milk products, some inorganic fruits and vegetables, high
sugars, and processed foods. Mercury dental amalgams and mercury
contaminated fish could also play a role. Was her water fluoridated or
otherwise contaminated? Were there toxic mold exposures in her
environment? Was she exposed to pesticides in her area? ]

Her eyelid dermatitis was kept clear with tacrolimus 0.03% ointment X2
daily.
She underwent patch testing to the North American Contact Dermatitis
Group standard tray, the University of Kansas' supplemental standard
tray, and to her cosmetics, cleansers, skin and hair care products and
topical medications.
She had relevant positive reactions at days 2 and 4 to formaldehyde
(++), quaternium-15 (++), diazolidinyl urea (+), DMDM hydantoin (+) and
imidazolidinyl urea (++), her hair care products and cleansers
containing multiple sources of these allergens.

She was extensively instructed in avoidance of formaldehyde and
formaldehyde releasers, as well as that of her multiple, currently
non-relevant allergens, including fragrance, benzalkonium chloride,
neomycin, bacitracin, p-phenylenediamine and black rubber mix. [ As a
medical layman, I'm disturbed to see all these chemicals that I know
nothing about. ]

By strictly avoiding formaldehyde and all formaldehyde releasers for the
next 3 weeks, she improved only slightly.

Her problem, however, was subsequently solved when a local pharmacist
advised her to avoid aspartame.

She had begun using an aspartame-based artificial sweetener 5 months
prior to the onset of her dermatitis. [ 12 months of low-level aspartame
use until stopping. Aspartame reactors discover this possibiliy usually
from the Net, alternative medicine providers, media, nurses, friends,
and pharmacists, rarely from physicians. ]

Within 1 week of discontinuing the aspartame, her eyelid dermatitis
resolved completely and has not recurred over 18 months without specific
treatment.
[ This quick healing response is typical of cases of low-level use with
few symptoms. Long-term heavy users , above 2 L, about 6 12-oz cans
daily for years, often have severe craving and withdrawal symptoms for
weeks, with gradual recovery for months. H. J. Roberts, MD has
summarized over 1200 cases. (Appendix H) Three recent case reports are
added here. (Appendix I) ]

Unfortunately, she refused to undergo rechallenge with the sweetener.
[ This is usually the case. Commonly, there is inadvertent reexposure,
with immediate painful symptoms, even with low doses. ]

Discussion

The artificical sweetener, aspartame, is consumed by 54% of adults in
the USA (3).

It has been reported to cause dry eyes and difficulty in wearing contact
lenses (3) but never allergic contact dermatitis. [ Reference (3) is
given in full here. (Appendix H) Roberts H J. Dry eyes from use of
aspartame (Nutrasweet): Associated insights concerning the Sjogren
syndrome. The Townsend Letter for Doctors, January 1994. Appendix H also
quotes several cases of eyelid dermatitis from his review of 1200 cases
in Aspartame Disease: An Ignored Epidemic (2001). ]

Aspartame, an L-aspartyl-L-phynylalanine methyl ester, is hydrolysed in
the intestine to phenylalanine (50%), aspartic acid (40%) and aspartaic
acid methyl ester (10%).

The methyl ester is then converted to methyl alcohol (methanol) and
carried by the portal vein to the liver.

Methanol is there oxidized to formaldehyde that is converted into formic
acid (formate) by alcohol dehydrogenase, aldehyde dehydrogenase and the
microsomal oxidase pathway.

This occurs not only in the liver, but also in other organs containing
high levels of these enzymes, including the eye (4,5).

Formaldehyde binds proteins and nucleic acids, forming adducts difficult
to eliminate via metabolism.

Trocho et al. (6) demonstrated the formation of formaldehyde adducts
with DNA and proteins after administration of 20 mg/kg 14C-labelled
aspartame to rats, concluding that these adducts were responsible for
functional alterations of proteins and for DNA mutations leading to
autoimmunity, cell death or malignant transformation. [ (Appendix E)
gives links, comments, and quotes for the debate on the key Trocho study. ]

In contrast to Trocho et al. (6), McMartin et al. (7) studied
formaldehyde levels after large doses (3,000 mg/kg) of 14C-labelled
methanol and 14C-labelled formaldehyde in monkeys, which unlike rats are
sensitive to the toxicities of methanol.

No increased formaldehyde derived from methanol was found.

High levels of formic acid were found in all monkeys that were given
methanol or formaldehyde.

[ (Appendix F) reviews the major studies. Oppermann et al (1973, 1976)
found that 30% of the methanol from aspartame fed to monkeys remained in
body tissues, indubitably as toxic products of formaldehyde and formic acid.
They did not test methanol product retention in humans.
McMartin et al (1979) reported significant formaldehyde retention in the
midbrain of one monkey from oral aspartame, and substantial formic acid
in liver, kidney, optic nerve, cerebrum, and midbrain in two other monkeys.
It is clear that his formaldehyde assays were too insensitive to give
valid measurements.
There has been a dearth of relevant primate and human studies ever since. ]

Based on the work of McMartin and al. (7), Tephly (8) concluded that the
radioactive carbon from methanol, which was found in DNA and protein by
Trocho et al., was due to the normal physiologic flow of single-carbon
units through the folate pathway.

Stegink et al. (9) have shown that doses of 100 mg/kg or greater of
aspartame are required to increase methanol blood levels (and thus,
presumable formaldehyde formic acid levels) above control.

This would be equivalent to consuming 35 cans of diet beverage at one
sitting for a 70 kg person. [ This is a typical aspartame industry PR
ploy, well designed to plant the impression that only absurdly huge
amounts of diet soda might supply damaging amounts of methanol-derived
formaldehyde and formic acid toxic residuals in body tissues, thus
reducing methanol blood levels. So, it is a classic red herring tactic
to focus on methanol blood levels.

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans) is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

[ http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall ]

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and leading to
vision and eye problems, and even seizures. In many cases there is
addiction. Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.
(Appendixes D, E, F, G, H, I, J) ]

Leon et al. (10) studied doses of 75 mg/kg of aspartame daily for 24
weeks and found no change in blood or urine methanol levels and no
symptoms of methanol toxicity.

The dose used in Leon's study is 25 times the 90th percentile daily
consumption of aspartame (11). [ Appendix E gives an abstract by Davoli
(1986), using a properly sensitive assay, that proved a temporary rise
in blood methanol levels in humans from a single aspartame dose. Trocho
pointed out that formaldehyde adducts are persistent and thus
cumulative. It is reasonable to state that with long-term chronic
formaldehyde exposure, it may take a long time to both accumulate
adducts and develop markedly increased sensitivity and a series of
complex symptoms . Adequate studies would have to test substantial
exposures over a year or longer with large numbers of vulnerable types
of people and record all symptoms. ]

Our patient was consuming an average of 80 mg (1.13 mg/kg) of aspartame
daily, well below the levels previously studied.
[ A packet of tabletop sweetener gives 37 mg aspartame, while a 12 oz
diet soda gives 200 mg aspartame. An aspartame reactor can have
immediate strong symtoms from an under-the-tongue wafer with 4 mg
aspartame. (Appendix A, for comments, abstracts, and links.) ]

However, it is possible that the eye, with its high level of metabolic
activity, could be affected by methanol (and subsequently formaldehyde)
released from these low levels of aspartame and respond as a localized
target organ to minute amounts of her known allergen, formaldehyde, or
its metabolite, formate.

It is also possible that the amplifying effects of cell-mediated
immunity might detect trace amounts of a chemical not identified by more
standard assays, such as blood or urine levels. [ (Appendix D gives
Thrasher's data about immune system reactions from long-term, low-level
formaldehyde exposure, while Martin Pall gives a complex general theory,
specifically discussing formaldehyde as a major trigger.)

http://www.drthrasher.org/formaldehyde_1990.html full text Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223. "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with
long-term formaldehyde inhalation." PMID: 2400243

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame: Martin L. Pall:
Murray: 2002.12.09

FASEB J 2002 Sep; 16(11): 1407-17.
NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and
organic solvents as the mechanism of chemical sensitivity in multiple
chemical sensitivity.
Pall ML. PMID: 12205032 [ 162 references, received 1.3.2 ]
School of Molecular Biosciences, Washington State University,
Pullman, Washington 99164-4660, USA. martin_pall@... ]

Such a hypothesis might explain why her dermatitis was limited to the
eyelids and give clinical support to Trocho's theory of formaldehyde
adducts.

Unfortunately, without rechallenging her with aspartame, we cannot test
this hypothesis.

Nonetheless, her long-lasting remission following discontinuation of
aspartame intake suggests that its breakdown to formaldehyde may have
been a possible mechanism for her prior blepharitis.

References

1. Christophersen J, Menne' T, Tanghoj P, Andersen K E, Brandrup F.
Clinical patch test data evaluated by multivariate analysis.
Contact Dermatitis 1989: 21: 291-299.

2. Fransway AF, Schmitz N A.
The problem of preservation in the 1990s.
II. Formaldehyde and formaldehyde-releasing biocides: incidences of
cross-reactivity and the significance of the positive response to
formaldehyde.
Am J Contact Dermat. 1991: 2: 78-88.

3. Roberts H J. Dry eyes from use of aspatame (Nutrasweet):
Associated insights concerning the Sjogren syndrome.
The Townsend Letter for Doctors, January 1994.[full text in Appendix H]

4. Murray T G, Burton T C, Rajani C, Lewandowski M F,
Burke J M, Eells J T.
Methanol poisoning: A rodent model with structural and functional
evidence for reinal involvement.
Arch Opthalmol 1991: 109: 1012-1016.

5. Eells J T.
Methanol-induced visual toxicity in the rat.
J. Pharmacol Exp Ther 1991: 257: 56-63.

6. Trocho C., Pardo R, Fafecas I, Virgili J, Remesar X,
Fernandez-Lopez, J A.
Formaldehyde derived from dietary aspartame binds to tissue components
in vivo.
Life Sci 1998 1988: 63: 337-349. [ abstract and quotes in Appendix E )

7. McMartin K E, Mrtin-Amat G, Noker P E, Tephly T R.
Lack of a role for formaldehyde in methanol poisoning in the monkey.
Biochem Pharmacol 1979: 28: 645-649. [ abstract, quotes, discussion,
related studies in Appendix F ]

8. Tephly T R: Comments on the purported generation of formaldehyde from
the sweetener aspartame.
Life Sci 1999: 65: 157-160. [ letter, usually not peer-reviewed,
abstract in Appendix E ]

9. Stegink L D, Brummel M C, McMartin-Amat G., Filer L J, Baker G L,
Tephly T R.
Blood methanol concentrations in normal adult subjects administered
abuse doses of aspatame.
J Toxicol Environ Health 1981: 7: 281-290.

10. Leon A S, Hunninghake D B, Bell C, Rassin D K, Tephly T R.
Safety of long-term large doses of aspartame.
Arch Intern Med 1989: 149: 2318-2324.

11. Tschanz C., Butachko H, Stargel W, Kotsonis F N (eds).
The Clinical Evaluation of a Food Additive: Assessment of Aspartame
Boca Raton: CRC Press, 1996.
////////////////////////////////////////////////////////////


http://groups.yahoo.com/group/aspartameNM/message/1464
13 mainstream research studies in 24 months showing aspartame
toxicity, also 3 relevant studies on methanol and formaldehyde: Murray
2007.08.17

http://groups.yahoo.com/group/aspartameNM/message/1467
4 cases of aspartame-induced thrombocytopenia [ very low platelets in
blood ], HJ Roberts MD, Letter in Southern Medical Journal 2007 May:
100(5); 543: Murray 2007.08.25
This cogent clinical warning adds to the other 13 mainstream studies
in the last 24 months that justify prudent concerns
about aspartame toxicity.

http://groups.yahoo.com/group/aspartameNM/message/1455
FEMA slow to safety test Katrina toxic trailers, Charles Babington,
Associated Press -- 1 ppm formaldehyde in air is about half the daily
dose from 3 cans aspartame diet soda and ten times the 1999 EPA alarm
level for drinking water: Murray 2007.07.23


http://groups.yahoo.com/group/aspartameNM/message/1457
aspartame bans, tis more an avalanche than a trend...: Rich Murray
2007.08.17

So far, USA print and broadcast media are deaf, blind, and dumb,
regarding recent major bans of aspartame and MSG in the UK and EU.

The EU Parliament voted July 12 to ban artificial sweeteners
in newly born and infant foods.

On May 15 four huge UK supermarket chains announced bans
of aspartame and MSG, food dyes, and many additives
to protect kids from ADHD --
Sainsbury, Tesco, Marks & Spencer, and ASDA, a unit of WalMart.

May 31: Coca-Cola and the much larger Cargill Inc.,
after years of secret development, with 24 patents,
will soon sell rebiana (stevia) in drinks and food
in the many nations where it is approved as a sweetener --
for decades a major sweetener in Japan, China, Korea, Taiwan,
Thailand, Malasia, Saint Kitts, Nevis,
Brazil, Peru, Paraguay, Uruguay, and Israel,
and an approved supplement in USA, Australia, and Canada,
according to Wikipedia.


http://groups.yahoo.com/group/aspartameNM/message/1454
recent research and news re aspartame and stevia: Murray 2007.08.16

"Of course, everyone chooses, as a natural priority,
to actively find, quickly share, and positively act
upon the facts about healthy and safe food, drink,
and environment."

Rich Murray, MA Room For All rmforall@...
505-501-2298 1943 Otowi Road, Santa Fe, New Mexico 87505

http://groups.yahoo.com/group/aspartameNM/messages
group with 82 members, 1,468 posts in a public,
searchable archive http://RMForAll.blogspot.com


http://groups.yahoo.com/group/aspartameNM/message/1395
Aspartame Controversy, in Wikipedia democratic
encyclopedia, 72 references (including AspartameNM # 864
and 1173 by Murray, brief fair summary of much more research:
Murray 2007.01.01

http://groups.yahoo.com/group/aspartameNM/message/1453
Souring on fake sugar (aspartame), Jennifer Couzin,
Science 2007.07.06: 4 page letter to FDA from 12 eminent
USA toxicologists re two Ramazzini Foundation
cancer studies 2007.06.25: Murray 2007.07.18

http://groups.yahoo.com/group/aspartameNMmessage/1451
Artificial sweeteners (aspartame, sucralose) and coloring
agents will be banned from use in newly-born and baby foods,
the European Parliament decided: Latvia ban in schools 2006:
Murray 2007.07.12

http://groups.yahoo.com/group/aspartameNMmessage/1437
stevia to be approved and cyclamates limited by
Food Standards Australia New Zealand:
JMC Geuns critiques of two recent stevia studies by Nunes:
Murray 2007.05.29

http://groups.yahoo.com/group/aspartameNM/message/1427
more from The Independent, UK, Martin Hickman, re ASDA
(unit of Wal-Mart Stores) and Marks & Spencer ban of
aspartame, MSG, artificial chemical additives and dyes
to prevent ADHD in kids: urray 2007.05.16
http://news.independent.co.uk/uk/health_medical/article2548747.ece

http://groups.yahoo.com/group/aspartameNM/message/1426
ASDA (unit of Wal-Mart Stores WMT.N) and Marks & Spencer
will join Tesco and also Sainsbury to ban and limit
aspartame, MSG, artificial flavors dyes preservatives additives,
trans fats, salt "nasties" to protect kids from ADHD:
leading UK media: Murray 2007.05.15

http://groups.yahoo.com/group/aspartameNM/message/1438
Coca-Cola and Cargill Inc., after years of development,
with 24 patents, will soon sell rebiana (stevia)
in drinks and foods: Murray 2007.05.31

www.ncbi.nlm.nih.gov/sites/entrez search PubMed
////////////////////////////////////////////////////////////


www.emedicine.com/derm/topic449.htm

Urticarial Vasculitis
Last Updated: March 16, 2007

Synonyms and related keywords: normocomplementemic urticarial
vasculitis, hypocomplementemic urticarial vasculitis, wheals, hives,
allergic reaction, hypersensitivity reaction, systemic lupus
erythematosus, SLE, connective tissue disease, connective-tissue
disease, vasculitis

AUTHOR INFORMATION
Author: Darius Mehregan, MD, Clinical Assistant Professor, Department of
Dermatology, Wayne State University of Michigan

Coauthor(s): Iltefat Hamzavi, MD, Staff Physician, Department of
Dermatology, Wayne State University School of Medicine, Michigan

Darius Mehregan, MD, is a member of the following medical societies:
American Academy of Dermatology, American Medical Association, and
American Society of Dermatopathology

Editor(s): Gregory J Raugi, MD, PhD, Professor, Department of Internal
Medicine, Division of Dermatology, University of Washington at Seattle;
Chief, Dermatology Section, Primary and Specialty Care Service, Veterans
Administration Medical Center of Seattle; Richard P Vinson, MD,
Assistant Clinical Professor, Department of Dermatology, Texas Tech
University School of Medicine; Consulting Staff, Mountain View
Dermatology, PA; Jeffrey P Callen, MD, Chief, Division of Dermatology,
Professor of Medicine (Dermatology), Department of Internal Medicine,
University of Louisville School of Medicine; Joel M Gelfand, MD, MSCE,
Medical Director, Clinical Studies Unit, Assistant Professor, Department
of Dermatology, Associate Scholar, Center for Clinical Epidemiology and
Biostatistics, University of Pennsylvania; and Dirk M Elston, MD,
Director, Department of Dermatology, Geisinger Medical Center

INTRODUCTION Section 2 of 11

Background: Urticarial vasculitis is an eruption of erythematous wheals
that clinically resemble urticaria but histologically show changes of
leukocytoclastic vasculitis. Urticarial vasculitis may be divided into
normocomplementemic and hypocomplementemic variants. Both subsets can be
associated with systemic symptoms (eg, angioedema, arthralgias,
abdominal or chest pain, fever, pulmonary disease, renal disease,
episcleritis, uveitis). The hypocomplementemic form more often is
associated with systemic symptoms and has been linked to
connective-tissue disease (ie, systemic lupus erythematosus [SLE]).

Pathophysiology: The pathophysiology of urticarial vasculitis is similar
to other forms of cutaneous small vessel leukocytoclastic vasculitis.
Urticarial vasculitis is a type III hypersensitivity reaction in which
antigen-antibody complexes are deposited in the vascular lumina. This
reaction results in complement activation and chemotaxis of neutrophils.
These cells release various proteolytic enzymes, such as collagenase and
elastase, resulting in damage to the vascular lumina. Some authors have
speculated that eosinophils may be involved in the early stages of the
vasculitic lesions. Patients with hypocomplementemic urticarial
vasculitis are more likely to show autoantibodies to C1q and vascular
endothelial cells. The presence of antineutrophilic cytoplasmic
antibodies is rare.

Frequency:

* In the US: The exact frequency is not known in the United States
or worldwide.

* Internationally: Previous studies varied in their definitions of
the condition. However, when a study in the United Kingdom used
consistent criteria restricted to patients diagnosed with vasculitis by
biopsy and with urticarial lesions of more than 3 months duration, 2.1%
of 1310 patients with urticaria were found to have urticarial vasculitis.

Mortality/Morbidity: Urticarial vasculitis carries a good prognosis,
with most occurrences resolving in months to years. Urticarial
vasculitis associated with hypocomplementemia is associated with a
greater incidence of coexisting disease (ie, angioedema,
connective-tissue disease [primarily SLE], chronic obstructive pulmonary
disease). Mortality is rare.

Sex: Male-to-female ratio is 1:2.

Age: The median age of involvement is 43 years with a range of 15-90
years. While this is primarily a disease of middle-aged adults, it can
be seen in persons of any age.

CLINICAL Section 3 of 11

History:

* Patients present with an urticarial eruption, often accompanied
by a painful or burning sensation.

o Lesions are generalized wheals or erythematous plaques,
occasionally with central clearing, lasting for more than 24 hours in a
fixed location (in contrast to urticaria, which resolves in minutes to
hours or migrates continually). Petechiae may be noted within the
lesions, and they may resolve with ecchymoses or postinflammatory
hyperpigmentation.

o Patients may have photosensitivity, lymphadenopathy,
arthralgia, angioedema, fever, abdominal pain, dyspnea, and pleural and
pericardial effusions.

* The primary causes of urticarial vasculitis are as follows:

o Drug induced, such as ACE inhibitors, penicillin,
sulfonamides, fluoxetine, and thiazides

o Rheumatic disease, such as SLE and Sjögren syndrome:
Urticarial vasculitis has also been reported with immunoglobulin A and
immunoglobulin M monoclonal gammopathies, mixed cryoglobulins, and
hematologic and solid malignancies.

o Viral disease, such as hepatitis B, hepatitis C, and
infectious mononucleosis

* Most cases of urticarial vasculitis are idiopathic.

* Urticarial vasculitis is divided into hypocomplementemic and
normocomplementemic categories.

o Hypocomplementemia often is associated with a systemic
condition, such as SLE (in which >50% of patients have
hypocomplementemia). In addition, as many as 71% of patients with
hypocomplementemic urticarial vasculitis have a positive antinuclear
antibody titer but do not fulfill the American Rheumatism Association
criteria for SLE.

o Some authors have suggested evaluation of
hypocomplementemic urticarial vasculitis for immunoglobulin G antibodies
to C1q. Individuals with these antibodies have a higher incidence of
angioedema, ocular inflammation, glomerulonephritis, and obstructive
pulmonary disease.

o Normocomplementemic vasculitis can be associated with
connective-tissue disease but at a much lower rate.

Physical: Lesions initially appear as erythematous wheals (see Image 1).
As the lesions progress, purpura may develop. Often, the lesions resolve
with postinflammatory pigmentation. Annular or targetoid lesions may be
observed.

Causes: The etiology of urticarial vasculitis has not been elucidated.
Associated conditions are listed in History.
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