Australasian Journal of Dermatology (2004) 45, 58–63
CAS E REPORT
Periodic painful purpura: Fact or factitious?
Yin Y Vun and James Muir
Mater Misericordiae Hospital, Brisbane, Queensland, Australia
SUM MARY
A 60-year-old woman with multiple psychosocial
issues presented with a history of spontaneous painful
bruising on her left upper arm. Extensive investi-
gations did not reveal any abnormality apart from an
elevated activated partial thromboplastin time as a
result of factor XII deficiency. An autoerythrocyte
sensitization test reproduced the tender bruises on her
back. Our patient reported relief of pain with promet-
hazine injections. She was subsequently referred to the
psychiatric team for ongoing assessment and manage-
ment. Having an awareness of this rare condition will
assist in the prevention of unnecessary investigation of
such cases and will allow the early referral of patients
for appropriate psychological counselling.
Key words: autoerythrocyte sensitization syndrome,
factor XII deficiency, Gardner–Diamond syndrome,
painful bruising syndrome, psychogenic purpura,
purpura factitia, spontaneous bruising.
INTRODUCTION
Autoerythrocyte sensitization syndrome (AES) is an uncom-
mon bruising disorder affecting predominantly women with
emotional instability.1,2 It is characterized by recurrent crops
of painful bruising, usually at times of emotional stress. 1,2
The autoerythrocyte sensitization test may be used to
support the diagnosis of AES.3 We present a patient with
characteristic features of this syndrome, who had a positive
autoerythrocyte sensitization test.
CASE REPORT
A 60-year-old woman presented with a 9-month history of
painful bruising on the left upper arm. She denied any
Correspondence: Dr Yin Vun, Dermatology Department, Mater
Misericordiae Hospital, Stanley St, South Brisbane, QLD 4101,
Australia. Email: yinvun@ausdoctors.net
Yin Y Vun, MB BS. James Muir, FACD.
Presented at the Annual Scientific Meeting of the Australasian
College of Dermatologists, Brisbane, May 2003.
Submitted 17 July 2003; accepted 16 October 2003.
antecedent trauma or self-harm. The onset of bruising was
often preceded by pain in the affected area. The pain was
severe enough to wake her up on multiple occasions. As
a result, she had been receiving intramuscular tramadol
injections up to twice weekly on the buttocks from her
local doctor. Other bruises resulting from trauma were
asymptomatic.
The bruises later extended to involve her lateral thighs. At
this stage, the family doctor ceased the tramadol injections
due to concerns of dependency and commenced her on
intramuscular promethazine. This reportedly provided more
effective relief for her pain.
Multiple investigations had been carried out by other
specialists before her presentation to dermatology out-
patients. Haematological investigations revealed a prolonged
activated partial thromboplastin time of 52 s (25–42 s) as a
result of factor XII deficiency. Factor XII deficiency is not
known to cause a bleeding or bruising tendency. On the
contrary, there have been some reports of association with
thromboembolic events, and possibly recurrent miscarri-
ages.4,5 Other investigations, as outlined in Table 1, were
unremarkable. Imaging studies including computed tomo-
graphy, ultrasound and bone scans of her left arm were all
normal. Biopsy of a bruise on her left upper arm revealed
moderate amounts of pigment-laden macrophages in a
perivascular distribution within the deep dermis and sub-
cutis regions, which stained positive for iron (Fig. 1). This is
consistent with purpura.
Apart from menorrhagia, the patient had no other
prior history of excessive bleeding or bruising else-
where. There had been no haemostatic complications
with previous surgical procedures. Significant past medical
history included left-sided breast carcinoma, bilateral
mastectomy, hypertension, postoperative pulmonary
embolism, recurrent miscarriages, depression resulting
in a suicide attempt, anxiety and panic attacks. In addition,
there was a history of vague paraesthesia in the right
forearm, fibromyalgia, irritable bowel syndrome and
recurrent migraines.
Her medications included diazepam, amitriptyline, cypro-
heptadine hydrochloride, carbamazepine, metoprolol, epro-
sartan, promethazine and nitrazepam.
Multiple psychosocial stressors were present in the per-
sonal history. These included two failed marriages, alleged
domestic violence and childhood sexual abuse. She revealed
that the onset of bruising occurred around a time of conflict
with her son. Collateral history also revealed abnormal
 Periodic painful purpura 59

illness behaviour suggestive of Munchausen by proxy syn- haematocrit. Both the patient and control were blinded to the
drome. procedure.
On examination, there were three exquisitely tender
bruises on the left upper arm. They measured 11  3 cm,
1  1.5 cm and 2.5  2 cm each (Fig. 2). There was no indur-
ation, erythema or warmth. The severity of pain was
disproportionate to what was seen clinically. Her baseline
observations were all within normal limits except for an
elevated blood pressure of 160/80 mmHg. She was afebrile.
No other evidence of excessive bruising or bleeding was
found on examination. There was no lymphadenopathy.
The characteristic clinical picture of this patient lead us to
believe that she had AES. We proceeded to perform the
autoerythrocyte sensitization test, to which the patient
consented enthusiastically. Peripheral blood samples were
collected into sterile tubes containing citrate phosphate
dextrose solution-1 as anticoagulant from both the patient
and a control. The samples were centrifuged to isolate the
erythrocytes, which were rinsed twice with normal saline.
The erythrocytes were then mixed with normal saline to 70%

Figure 1 Biopsy of left arm showing pigment-laden macrophages. Figure 2 Bruises on left upper arm.

Table 1 Results of investigations

Investigation Results Reference range

Full blood count Normal –

Activated partial thromboplastin time 52.1 25–42 s
Prothrombin time 14.5 11–16 s
Fibrinogen 5.1 1.5–4.0 g/L
Platelets 260 150–400  109/L
Factors VIII, IX, XI Normal –
Factor XII 0.36 0.5–1.5 U/mL
Platelet function 120 Collagen/adrenaline closure time
(platelet function analysis-100) 85–165 s
Factor VIII studies, including Von Willebrand factor Normal –
Complement factor C3 1.30 0.9–2.0 g/L
Complement factor C4 0.22 0.15–0.45 g/L
Electrophoresis Normal pattern –
Cryoglobulin None detected –
Direct antiglobulin test negative –
Antinuclear antibodies negative –
Double-stranded DNA antibodies <5 <7 IU/mL
Lupus anticoagulant Negative –
Anticardiolipin immunoglobulin G 3 <8 U/mL
Mid-stream urine Normal –
60 YY Vun and J Muir

Using a 25G needle, 0.1 mL of each solution was injected DISCUSSION

intradermally onto the patient’s mid-back, along with 0.1 mL
Autoerythrocyte sensitization syndrome was first described
of normal saline, similar to the procedure carried out by
by Gardner and Diamond in 1955, who hypothesized that
Gardner and Diamond.3 This caused an immediate painless
these patients have an abnormal reaction to their own
bruising on the autologous red cell injection site only,
extravasated red cells.3 It mainly affects women, with
measuring 1.4 cm in diameter (Fig. 3). Over the next
reported cases ranging from 14 to 66 years old.1,2,6–10 The
2 days, the patient complained of severe pain over the
clinical picture is one of recurring, spontaneous bruising,
red cell injection site and of feeling generally unwell
often precipitated by emotional stress.6 They most commonly
(Figs 4 and 5). Unfortunately, she was unable to present
occur on the extremities, rarely on the back.2 Patients
for follow up on day 3. The bruising and symptoms gradually
characteristically describe paraesthesia or pain before the
faded from day 4. A non-tender, brown haemosiderotic
onset of cutaneous signs.7 The area becomes progressively
discoloration remained on the red cell injection site
erythematous, oedematous, warm and painful, before
1 week later. In contrast, only a mild asymptomatic purpuric
developing into an ecchymosis that lasts from 5 to 7 days.2,7
reaction developed on the control red cell injection site
The lesions vary in size from 1 to 2 cm in diameter to areas
at 30 min, which gradually faded over a week (Figs 6,7;
covering an entire limb.9 The onset of AES can be preceded
Table 2).
by surgical procedures or other forms of trauma. There was
In view of the above results and clinical picture, a diag-
even a case report in which copper from an intrauterine
nosis of AES was made. The patient was referred to the pain
device caused marked exacerbation of the condition. 11 How-
clinic for pain control, and to the psychiatric team for further
ever, cases of spontaneous onset have been reported.1,2,6–8
assessment and treatment. It was found that she had a
dependent personality with some borderline and manipu-
lative traits.

Figure 5 Autoerythrocyte sensitization test: day 2 (patient).

Figure 3 Autoerythrocyte sensitization test: immediate reaction

(patient).

Figure 4 Autoerythrocyte sensitization test: day 1 (patient). Figure 6 Autoerythrocyte sensitization test: 30 min (control).
 Periodic painful purpura 61

The autoerythrocyte sensitization test has been used to
support a diagnosis of AES.3 Positive responses have been
reported at haematocrit concentrations ranging from 20
to 50%.3,7,8 In a study involving 81 patients, all controls
developed painless, non-tender and non-inflammatory
lesions measuring 3.1 cm2, while 18 of 27 patients with
AES developed typical painful lesions within an hour.10
Various agents have been found to reproduce the painful
bruises (Table 3).6,12 In one reported case, the only com-
ponent of red cell membrane that consistently produced a
purpuric reaction was phosphatidylserine.2 The positive
reactions to stromal erythrocyte phospholipids such as
phosphatidylserine and purified protein derivative may
explain the positive anticardiolipin antibodies found in a
reported case of AES.13 It was proposed that low levels of
anticardiolipin antibodies could be linked to the variable
neurological symptoms found in AES.13 In our case, the
patient had negative anticardiolipin antibodies, but a
history of pulmonary embolism and recurrent miscarriages.
Autoerythrocyte sensitization syndrome is not known to be
associated with thrombotic phenomena or recurrent mis-
carriages. Other autoimmune diseases have been reported in
Figure 7 Autoerythrocyte sensitization test: day 1 (control).
association with AES.6,13,14 However, these were isolated case
reports and are unlikely to be of any significance.
A further study involving 71 AES patients revealed that
these patients often had multiple somatic complaints and
past surgical procedures (Table 4).9 This is consistent with
the past history of irritable bowel syndrome, fibromyalgia,
paraesthesia and recurrent migraines in our patient.
However, the most consistent association found in these
patients is that of emotional instability.6,9,10 They are thought
to express their emotional problems physically by developing
bruises through hysterical or psychophysiological mechan-
isms.1,10,15
The original theory as proposed by Gardner and Diamond
is now no longer widely accepted. The variability of results
in AES patients, depending on the site of injection, negative
Prausnitz–Kustner tests, a threshold of 20% haematocrit
required to produce a response and reports of lesions
influenced by hypnotic suggestion are against a hyper-
sensitivity reaction to red blood cells. 7,9,10
The differential diagnoses of recurrent bruising in the
absence of haematological abnormalities include purpura
factitia, purpura simplex and DNA autosensitivity. It is often
very difficult to differentiate between AES and purpura
factitia. In purpura factitia, there is usually no ‘premonition’
before the development of lesions. The results of skin-
sensitivity tests tend to follow the patient’s perception of
their doctor’s expectations, and be positive only if the
injected areas are accessible to them. 16 Patients with AES are
rarely free of lesions and continue to get lesions under
plaster casts, while self-inflicted lesions improve.1,15,17
Therefore, it may be necessary to place patients under close
observation following intradermal injections. We feel it is
unlikely that our patient had interfered with the injection
sites, as she was blinded and would have found the sites
difficult to access. Patients with DNA autosensitivity have
similar purpuric lesions, but tend to have associated bullae
and pustules.1,12
Various treatments have been tried for AES, with limited
success. These are summarized in Table 5.1,7–10,13,15,18 Our
patient reported relief of pain with antihistamine injections.
However, she claimed that promethazine was only effective
if given intramuscularly and not orally. In most cases,

Table 2 Results of autoerythrocyte sensitization test

Immediate 30 min 24 hours 48 hours 7 days

Patient
Erythrocytes Purpura (cm) 1.4 1.7 4.2 3.2 2.2
Induration ++ + + + –
Pain/tenderness – – ++ ++ –
Saline Purpura – – – – –
Induration + – – – –
Pain/tenderness – – – – –
Control
Erythrocytes Purpura (cm) – 0.5 1.0 0.8 0.6
Induration – – – – –
Pain/tenderness – – – – –
Saline Purpura – – – – –
Induration – – – – –
Pain/tenderness – – – – –
62 YY Vun and J Muir

Table 3 Agents associated with positive intradermal response emotional stress.6,7,9 No deaths have been recorded from
AES or its complications.7
Copper In conclusion, it is important for medical practitioners to
Erythrocyte stroma
Haemoglobin
recognize this syndrome to allow prompt referral for psycho-
Histamine logical counselling. Delay in diagnosis will perpetuate
Phosphatidylserine patient anxiety and encourage abnormal illness behaviour.
Platelets There have been no studies relating to the impact on the
Pregnandiol quality of life of these patients. However, as illustrated by
Purified protein derivative
our case, most become preoccupied with their symptoms,
Serotonin
Tyramine resulting in much functional impairment.

Table 4 Commonly associated complaints in autoerythrocyte

ACKNOWLEDGEMENTS
sensitization syndrome
The authors would like to thank Dr Davin Lim for his
Neurological symptoms assistance with the autoerythrocyte sensitization test, as well
Headaches as suggestions and advice on this article. Many thanks to the
Transient paresis haematology laboratory at the Mater Misericordiae Hospital
Paraesthesia for their technical assistance with the autoerythrocyte
Syncopal episodes
sensitization test, and to Dr George Middleton and Mr Greg
Ocular symptoms
Blurred vision Boulay for their contributions to the histological photo-
Diplopia graphs.
Haemorrhagic manifestations
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