Iron Overload In Veterans

Iron Overload In Veterans

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Instrument No.71 of 1994



Statement of Principles

concerning

PORPHYRIA CUTANEA TARDA

ICD CODE: 277.1

Veterans' Entitlements Act 1986
subsection 196B(2)


1. Being of the view that there is sound medical-scientific evidence
that indicates that porphyria cutanea tarda and death from porphyria
cutanea tarda can be related to operational service rendered by
veterans, peacekeeping service rendered by members of Peacekeeping
forces and hazardous service rendered by members of the Forces, the
Repatriation Medical Authority determines, under subsection 196B(2) of
the Veterans' Entitlements Act 1986, that the factors that must as a
minimum exist before it can be said that a reasonable hypothesis has
been raised connecting porphyria cutanea tarda or death from porphyria
cutanea tarda with the circumstances of that service, are:


(a) being exposed to herbicides in Vietnam before the clinical onset
of porphyria cutanea tarda; or


(b) decanting, mixing, applying, or ingesting polychlorinated aromatic
hydrocarbons before the clinical onset of porphyria cutanea tarda; or


(c) having psychoactive substance abuse or dependence involving
alcohol before the clinical onset of porphyria cutanea tarda; or


(d) having active viral hepatitis before the clinical onset of
porphyria cutanea tarda; or


(e) having HIV-1 infection before the clinical onset of porphyria
cutanea tarda; or


(f) having skin exposed to sunlight before the clinical worsening of
porphyria cutanea tarda; or


(g) inability to obtain appropriate clinical management for porphyria
cutanea tarda.


2. Subject to clause 3 (below) at least one of the factors set out in
paragraphs 1(a) to (g) must be related to any service rendered by a
person.


3. The factors set out in paragraphs 1(f) and (g) apply only where:


(a) the person's porphyria cutanea tarda was contracted prior to a
period, or part of a period, of service to which the factor is
related; and


(b) the relationship suggested between the porphyria cutanea tarda and
the particular service of a person is a relationship set out in
paragraph 8(1)(e), 9(1)(e), 70(5)(d), or 70(5A)(d) of the Act.


4. For the purposes of this Statement of Principles:


"active viral hepatitis" means infection with Hepatitis A, B, C, D, or
E with signs or symptoms or pathological tests indicating active
inflammation of the liver, attracting ICD code 70;


"being exposed to herbicides in Vietnam" may be said to have occurred
only if the person had:


(a) rendered more than 30 days service on land in Vietnam; or


(b) regularly eaten fish, fish products, crustaceans, shellfish, or
meat from Vietnam; or


(c) regularly eaten food cooked with water from Vietnam discoloured by
sediment, or regularly drunk water from Vietnam discoloured by
sediment; or


(d) regularly inhaled dust in a defoliated area in Vietnam or
regularly inhaled herbicide fog in Vietnam; or


(e) sprayed or decanted herbicides in Vietnam as an occupational
requirement;


"HIV-1 infection" means serological evidence of infection with human
Immunodeficiency Virus Type 1, attracting an ICD code in the range 42
to 44 (inclusive);


"ICD code" means a number assigned to a particular kind of injury or
disease in the tenth edition of the International Classification of
Diseases 9th Revision, effective date of 1 October 1993, copyrighted
by the US Commission on Professional and Hospital Activities, and
having the Library of Congress number 77-94472;


"polychlorinated aromatic hydrocarbons" means chemical compounds
containing a benzene ring and multiple chlorine atoms;


"porphyria cutanea tarda" means a disease with abnormalities of
porphyrin metabolism with dermatological manifestations, attracting an
ICD code of 277.1;


"psychoactive substance abuse or dependence" means a maladaptive
pattern of use, attracting an ICD code of 303 or 304, that is
indicated by either:


(a) continued use of the substance despite knowledge of having a
persistent or recurrent social, occupational, psychological or
physical problem that is caused or exacerbated by use of the
substance; or


(b) recurrent use of the substance when use is physically hazardous
(for example, driving while intoxicated).




Dated this day of 1994




The Common Seal of the )

Repatriation Medical Authority )

was affixed to this instrument )

in the presence of: )






KEN DONALD

CHAIRMAN
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<<snip>>
ascorbate suppresses hepatic URO accumulation at low, but not high
hepatic iron levels
<<snip>>

Effect of iron and ascorbate on uroporphyria in ascorbate-requiring
mice as a model for porphyria cutanea tarda.
Gorman N, Zaharia A, Trask HS, Szakacs JG, Jacobs NJ, Jacobs JM,
Balestra D, Sinclair JF, Sinclair PR
Hepatology. 2006 Dec 22; 45(1): 187-194


Excess hepatic iron is known to enhance both porphyria cutanea tarda
(PCT) and experimental uroporphyria. Since previous studies have
suggested a role for ascorbate (AA) in suppressing uroporphyria in
AA-requiring rats (in the absence of excess iron), the present study
investigated whether AA could suppress uroporphyria produced by
excess
hepatic iron. Hepatic URO accumulation was produced in AA-requiring
Gulo(-/-) mice by treatment with 3,3',4,4',5-pentachlorbiphenyl, an
inducer of CYP1A2, and 5-aminolevulinic acid. Mice were administered
either sufficient AA (1000 ppm) in the drinking water to maintain
near
normal hepatic AA levels or a lower intake (75 ppm) that resulted in
70
% lower hepatic AA levels. The higher AA intake suppressed hepatic
URO
accumulation in the absence of administered iron, but not when iron
dextran (300-500 mg Fe/kg) was administered. This effect of iron was
not due to hepatic AA depletion since hepatic AA content was not
decreased. The effect of iron to prevent AA suppression of hepatic
URO
accumulation was not observed until a high hepatic iron threshold was
exceeded. At both low and high AA intakes, hepatic malondialdehyde
(MDA), an indicator of oxidative stress, was increased three-fold by
high doses of iron dextran. MDA was considerably increased even at
low
iron dextran doses, but without any increase in URO accumulation. The
level of hepatic CYP1A2 was unaffected by either AA intake.
Conclusion:
In this mouse model of PCT, AA suppresses hepatic URO accumulation at
low, but not high hepatic iron levels. These results may have
implications for the management of PCT. (HEPATOLOGY
2007;45:187-194.).


Abstract · PubMed FullText · SFX · GS Clip Export InterDB ·
Terms Related · Graph Tag · Scopus · Cites 10.1002/hep.21474

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[High-dose vitamin therapy as prophylaxis against porphyria cutanea
uremica.]
Wimmershoff F, Gardlo K, Bolsen K, Ruzicka T, Fritsch C
Hautarzt. 2006 Mar ; 57(3): 228-36


50 patients with chronic renal failure undergoing hemodialysis with
or
without porphyria cutanea tarda (PCT)-like skin changes were
investigated. The total porphyrin amount in erythrocytes, plasma and
dialysate and the distribution of porphyrin metabolites in plasma and
dialysate were measured. In plasma, the group of patients with skin
changes (referred as PCU = porphyria cutanea uremica) showed
significantly increased uroporphyrin levels as compared to the
non-symptomatic group. In addition, significant differences
concerning
the ratio uro-/coproporphyrin in plasma were shown: non-symptomatic
patients with 0.87, as opposed to the PCU group with 3.7.
Considerable
differences between the level of vitamin ingestion were identified
between the groups. Patients with PCU took distinctly less vitamins
C,
E and B than patients without symptoms.

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Ann Dermatol Venereol. 2003 Jan;130(1 Pt 1):37-9. Links
[Successful treatment of haemodialysis-related porphyria cutanea
tarda
with deferoxamine][Article in French]
Pitche P, Corrin E, Wolkenstein P, Revuz J, Bagot M.
Service de Dermatologie, CHU Henri Mondor, 51, avenue du Marechal de
Lattre de Tassigny, 94010 Creteil.

BACKGROUND: End-stage renal failure and long-term hemodialysis
treatment promote porphyria cutanea tarda. Iron overload is often
associated with this disease and is thought to play a role in its
pathogenesis. We report a case of hemodialysis related-porphyria
cutanea tarda improved by deferoxamine. CASE REPORT: A 45-year-old
man,
with end-stage renal failure and who had received hemodialysis
treatment since 1993, presented a several months-history of blisters
of
the face and the dorsum of the hands. Laboratory analysis showed:
hemoglobin 10 g/dl; a moderate hepatic cytolysis; ferritin 195 ng/l.
HIV, HBV, HCV serologies were negative. Porphyries analyses showed a
porphyria cutanea tarda pattern. The cutaneous histology was non
specific; direct immunofluorescence was negative. The patient
received
deferoxamine (40 mg/kg intravenously every week for 6 weeks) which
led
to dramatic improvement of the symptoms. DISCUSSION: Several
treatments
are proposed in the management of dialysis-related porphyria cutanea
tarda. This case confirms that deferoxamine can induce rapid and
prolonged remission.


PMID: 12605155 [PubMed - indexed for MEDLINE]



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