Journal of Internal Medicine 2000; 247: 407±409
CASE REPORT
Could attacks of abdominal pain in cases of acute intermittent
porphyria be due to intestinal angina?
F. LITHNER
From the Department of Medicine, University Hospital, UmeaÊ, Sweden
Abstract. Lithner F (Department of Medicine,
University Hospital, UmeaÊ, Sweden). Could attacks
of abdominal pain in cases of acute intermittent
porphyria be due to intestinal angina? J Intern Med
2000; 247: 407±409.
Abdominal pain is by far the most serious symptom
in attacks of acute intermittent porphyria. Its cause
is unknown. This case study suggests visceral
ischaemia as a possible cause of the abdominal
Introduction
In attacks of acute intermittent porphyria, the
initial, most prominent single symptom, with regard
to frequency, severity and need for medical relief, is
the abdominal pain. The cause of abdominal pain in
acute intermittent porphyria attacks, is not known
and has received remarkably little attention in the
literature, being most often described only as a result
of autonomic neuropathy, but without clinical
evidence. Disturbances in smooth muscle function
have also been suggested as a cause, i.e. autonomic
disturbances [1, 2]. However, the pathological
anatomy displays serious damage to the ganglia of
the autonomic system, particularly in the abdominal
viscera [3].
A case report is presented here in order to discuss
whether intestinal angina might be a cause of the
abdominal pain of acute intermittent porphyria.
Case report
A woman suffered her first attack of acute inter-
# 2000 Blackwell Science Ltd
pain. A 31-year-old woman with recurrent bouts
died during an attack; the autopsy revealed a 20-cm
necrotic gangrene in the ileum. A protracted
intestinal vasospasm could have been the immediate
cause of death. It is discussed whether intestinal
angina could be the cause of the abdominal pain in
acute intermittent porphyria.
Keywords: abdominal pain, acute intermittent
porphyria, intestinal gangrene.
mittent porphyria at the age of 19 years. The
diagnosis was established on the basis of a low
erythrocyte concentration of porphobilinogen dea-
minase, and high concentrations of urinary d-
aminolaevulin acid and urinary porphobilinogen
(PBG). Acute intermittent porphyria was verified by
DNA mutation E250Q of porphobilinogen deami-
nase which was previously known in her family.
Apart from the attacks, the patient had been
healthy, her blood pressure was in the normal
range and she smoked only occasionally. She had
settled employment as a tour leader for a travel
agency.
At the age of 26 years her menstruation cycle
became irregular and ceased altogether for 2 years.
The attacks became more severe; morphine, glucose
and haemarginate had scarcely any effect on her
pain after she had been hospitalized about 50 times
at the local hospital; she was then referred to UmeaÊ
for treatment with gonadotropinagonist. By this
stage, she had been on the sick-list for 2 years.
When she arrived, her urinary d-aminolaevulin acid
and PBG values were high: 512 mmol/L (n , 11)
407
408 F. LITHNER
and 584 mmol/L (n , 45), respectively. She had a
slightly depressed serum magnesium concentration
(0.66 mmol L21, n = 0.70±1.00) which was com-
pensated for.
The patient was clinically diagnosed as having
polycystic ovary syndrome, based on irregular
menstruations during the last 3 years, increased
hirsutism and acne. The diagnosis was confirmed by
ultrasound, increased serum androstenediane and
an abnormal luteinizing hormone/follicle-stimu-
lating hormone (LH/FSH) quotient. The gonadotro-
pinagonist buserelin had beneficial effect and her
health improved; the attacks continued but with less
pain and she could return to her work.
At the age of 31 years she came to the local
hospital with severe abdominal pains. At first, an
intestinal infection was suspected but could not be
verified and a severe acute intermittent porphyria
attack was then suspected. However, the pains were
not alleviated by the treatment and there were more
severe electrolyte disturbances such as low sodium,
potassium and albumin levels. On day 8 there was a
pronounced lactacidaemia in spite of good oxygena-
tion and good peripheral warmth; her blood
pressure was low. The same day, she was resusci-
tated twice from cardiac arrest but succumbed to a
new cardiac arrest the next day.
The autopsy revealed a black, necrotic, 20 cm-
long part of the ileum. Blood-like fluid was found in
the stomach and intestines, but no ulcerations. In
the frontal cerebral lobe and in the stomach there
were small haemorrhagic formations. Cystic ovaries
were found bilaterally. There were no other remark-
able findings, either gross or microscopical. There
were no signs of demyelination in peripheral nerves
or in the brain.
Discussion
The autopsy of the patient revealed an intestinal
gangrene, most probably due to infarction. Intest-
inal infarctions are usually caused by atherosclerosis
with thrombosis or embolism in elderly patients.
However, this patient was young and there were no
signs of atherosclerosis or embolism at the autopsy.
Her acute intermittent porphyria was severe, prob-
ably due to the disturbed hormone balance and in
turn to her polycystic ovary syndrome.
Polycystic ovary syndrome has been reported
previously to be associated with diabetes, lipid
# 2000 Blackwell Science Ltd Journal of Internal Medicine 247: 407±409
abnormalities, and other cardiovascular risk factors.
However, in a long-term national follow-up study of
the mortality of 786 women with polycystic ovary
syndrome, mortality from circulatory disease in the
women was not markedly higher than average,
compared with the national rate. It is conceivable
that women with polycystic ovary syndrome are
protected from circulatory disease by the action of
unopposed oestrogen secreted during anovulatory
cycles and indeed none of the patients suffered from
intestinal gangrene [4]. These factors speak against
polycystic ovary syndrome as being a risk factor for
intestinal gangrene.
The cause of the intestinal gangrene in this case
could have been vasospasm, which has been
discussed for more than 70 years in the literature
and is regarded as telling evidence of protracted
vasospasm during attacks in patients with acute
intermittent porphyria causing vascular disease [5].
WaldenstroÈm stated 60 years ago that the renal
disease and hypertension in acute porphyria are
caused by arteriospasm [6].
There are many reports of cardiac and ophthal-
mological symptoms during attacks of acute inter-
mittent porphyria, suggesting arterial and arteriolar
spasm as the cause [5±12]. That a vascular spasm
with resultant ischaemia might underlie the cerebral
dysfunction in acute intermittent porphyria has
been suggested by several investigators over the
years. The hypothesis is based on the morphology
(autopsy, magnetic resonance imaging) of cerebral
abnormalities consistent with ischaemic brain le-
sions (6, 13±15). The lesions referred to develop
quite suddenly, often concomitantly in different
organs and a functional vascular disturbance is
suggested [5]. These facts lend further support to a
vascular, ischaemic mechanism being responsible
for the present case.
It may be that vasospasm can cause intestinal
angina during an acute intermittent porphyria
attack and can account for at least part of the
abdominal pain. A recent case report described a
patient who, during an acute intermittent porphyria
attack, had a small bowel infarction [16]. This is in
agreement with the suggestion in the present study
that abdominal pain in acute intermittent porphyria
attacks could be due to intestinal angina. To my
knowledge, there are no other similar reports
published.
There are two possible mechanisms for porphyrin
 CASE REPORT: ACUTE INTERMITTENT PORPHYRIA
metabolism as the cause of vasospasm. Firstly,
during an acute attack, the increased prevalence of
hypertension (HT) and renal lesions in patients with
manifest acute intermittent porphyria has been
suggested as being due to the presence of excessive
amounts of porphyrin metabolites causing cytotoxic
or vasospastic renal vascular lesions, thereby raising
the blood pressure during the attack as well as
causing chronic HT [8]. Secondly, increased urinary
excretion of catecholamines and temporary HT
occurs during an attack, probably caused by
stimulation of the sympathetic nervous system
[17±20]; the catecholamines concentration may
then increase 10-fold [17]. These factors may
precipitate a protracted vasospasm, lasting long
enough to cause vascular lesions.
However, we need more evidence of the intestinal
angina obtained by noninvasive or invasive exam-
inations in order to study the functioning of the
arterial and visceral circulation during attacks in
patients of acute intermittent porphyria.
In my opinion, the treatment of severe abdominal
pain during an acute intermittent porphyria attack
is currently unsatisfactory. Morphine is only a
partial help. Other analgesics, as well as b-blockers
or phenothiazines, have only marginal effects on the
pain. Treatment with infusions of glucose or heme is
a logical and most often effective treatment for
attacks and consequently also for the pain. How-
ever, clinical improvement will itself not be felt until
some 2 to 6 days after administration of glucose
[21] or haeme [22]. In other words, we need a better
analgesic remedy for the acute attack, which means,
primarily, research into the mechanism of the
abdominal pain in an acute intermittent porphyria
attack. It is conceivable that vasodilators should be
included in the treatment of acute attacks. More
efficient vasodilative drugs such as doxazosin could
be of value for the long-term treatment of hyperten-
sive acute intermittent porphyria patients suscepti-
ble to attacks.
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Received 15 June 1999; accepted 28 October 1999.
Correspondence: Dr F. Lithner, Department of Medicine, University
Hospital, S-90185 UmeaÊ, Sweden (fax: + 46 90 135620; e-mail:
Folke.Lithner@medicin.umu.se).