Aplastic anaemia presenting with features of raised intracranial pressure.

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Aplastic anaemia presenting
with features of raised
intracranial pressure
Aditi MohlaOlugbemisola OworuColin Hutchinson
J R Soc Med 2006;99:315–316
Anaemia is a commonly encountered medical condition
although retinopathy due to aplastic anaemia is not
commonly seen.
CASE HISTORY
A 23-year-old male presented with a 1-week history of
bilateral blurred vision, worse in the left eye. It was
associated with frontal and temporal headache made worse
by coughing. There was no preceding trauma or blood loss,
he was on no medication and was not exposed to noxious
chemicals or irradiation. He was not diabetic nor
hypertensive. Prior to developing blurred vision, he had
coryzal-like symptoms for 2 days but no myalgia, rash or
joint pains. His maternal uncle died of a blood disorder and
his maternal cousin has acute lymphoid leukaemia.
On examination, he was non obese but looked pale. He
was haemodynamically stable with a heart rate of 82 beats/
min and a blood pressure of 150/56mmHg. Visual acuity
was 6/18 (right eye) and 6/60 (left eye). Anterior
segments of both eyes were normal with no pupillary
defect. Fundoscopy showed bilateral grossly swollen optic
discs with scattered retinal haemorrhages more marked in
the posterior pole and gross macular oedema in the left eye
(Figure 1a,b).
A computerized tomography scan and magnetic
resonance imaging of head and orbit showed no evidence
of raised intracranial pressure, i.e. no space occupying
lesion and normal ventricles. There were no meningeal
infiltrations and optic nerves were normal. There were no
features to suggest cerebral venous thrombosis.
Blood tests, including serum glucose, angiotensin
converting enzyme, antineutrophilic cytoplasmic antibodies,
syphilitic serology, anti-mitochondrial antibody, electro-
lytes and urea, folate and vitamin B12were normal.
Full blood count revealed severe pancytopenia with
haemoglobin of 5.8g/dL, white cell count of 2.7?109/L,
platelet count of 15?109/L and mean corpuscular volume
of 109.8fl. Blood film showed aplastic anaemia confirmed
by a bone marrow biopsy.
He had packed cells and platelet transfusions initially and
this was repeated due to insufficient endogenous haemopoi-
esis. He was subsequently commenced on antilymphocyte
globulin and cyclosporin. As his haemoglobin improved, so
did the retinopathy and visual acuity.
Ten months later, his haemoglobin stabilized at 15g/dL
with immunosuppressive treatment alone. The retinopathy
had almost completely resolved with only a residual deep
blotch haemorrhage at the left macula. His visual acuity was
6/5 right eye and 6/6 left eye.
COMMENT
Retinopathy associated with gastrointestinal haemorrhage
and resolving following correction of the anaemia, was first
reported by Ulrich in 1883.1The manifestations of anaemic
retinopathy are non-specific. Ophthalmic features include
GRAND ROUND
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Eye Department, Huddersfield Royal Infirmary, Lindley,
Huddersfield HD3 3EA, UK
Correspondence to: Olugbemisola Oworu
E-mail: gbemsol@hotmail.com
(a)
(b)
Figure 1 Findus picture at presentation: there are multiple
superficial flame-shaped haemorrhages and areas of deep blotch
haemorrhages in both (a) right eye and (b) left eye. (This figure can
be seen in colour online)

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retinal haemorrhages, exudates, disc pallor, optic atrophy,
neuritis, retinal detachment and papilloedema.1
The features of anaemic retinopathy seem to be
universal, irrespective of the cause of the anaemia. The
retinopathy also seems to resolve once the anaemia is
corrected, as shown in the patient presented. It is widely
believed that anaemia causes diminished capillary oxygena-
tion, which increases the vessel wall permeability resulting
in extravasation of blood products.2There seems to be a
direct correlation between the degree of anaemia and the
severity of the retinopathy.
Aplastic anaemia is a life threatening condition. It
usually presents with anaemia, bleeding and infection. It can
be inherited but it is more commonly acquired. The ocular
findings include cotton wool spots, nerve fibre layer or
preretinal haemorrhages, vitreous haemorrhages and optic
disc oedema.
Mansour et al. reported ocular findings in 18 patients
with aplastic anaemia.3In their report, the patients were
known to be anaemic prior to the development of the
retinopathy.
In our case, the patient certainly had disc oedema and
nerve fibre layer haemorrhages with gross macular oedema,
all of which resolved once the anaemia was corrected.
Some patients with aplastic anaemia also develop
pseudotumour cerebi which may require treatment geared
towards lowering the raised intracranial pressure.4–6It has
been suggested that papilloedema associated with aplastic
anaemia could be due to increased intracranial pressure
from anaemia-induced cerebral hypoxia.7
The presentation in this patient initially was suggestive
of raised intracranial pressure. We feel it is important that
clinicians are made aware of this unusual presentation and
that this case might hopefully help direct treatment to the
underlying cause.
REFERENCES
1 Weiss L. Anaemic retinopathy. Pennsylvania Med 1966;69:35–6
2 Koh A. Anaemia—more than meets the eye. Singapore Med J 1998;39:
222
3 Mansour AM, Salti HI, Han DP et al. Ocular findings in aplastic
anaemia. Ophthalmologic 2000;214:399–402
4 Biousse V, Rucker JC, Vignal C, Crassard I, Katz BJ, Newman NJ.
Anaemia and papilledema. Am J Ophthalmol 2003;135:437–46
5 Nazir SA, Siatkowski RM. Pseudotumor cerebri in idiopathic aplastic
anemia. J Am Assoc Pediatr Ophthalmol Strabismus 2003;7:71–4
6 Jeng MR, Rieman M, Bhakta M, Helton K, Wang WC. Pseudotumor
cerebri in two adolescents with acquired aplastic anemia. J Pediatr
Hematol Oncol 2002;24:765–8
7 Lubeck MJ. Papilloedema caused by iron deficiency anaemia. Trans Am
Acad Ophthalmol 1959;63:306
Severe ischaemic
cardiomyopathy associated
with khat chewing
Sagar Saha Clare Dollery
J R Soc Med 2006;99:316–318
Legal chewing of khat leaves is prevalent in East African
migrants to the UK; however severe cardiac ischaemia and
liver damage can result.
Khat also known as qat or chat is the fresh leaves of
Catha edulis. It is a shrub grown in East Africa and the
Arabian Peninsula where khat chewing is common with
open legal trade. Around 20 million people use khat in
these countries and its use has spread to the immigrant
communities across Europe and America. The 2001 census
records 44 000 Somalis in the UK and estimates of 95 000
were made in 2003. On chewing, khat leaves release
amphetamine-like constituents; cathinone and cathin and
other alkaloids (cathulidins). Khat is currently legal in the
UK though cathinone and cathin are controlled drugs
(Misuse of Drugs Act 1971). Khat is illegal in the USA,
Canada, Norway and Sweden.
CASE HISTORY
A 33-year-old East African man presented with acute onset
chest pain. He smoked (15 pack years), but had no other
coronary risk factors (cholesterol 4.8 mmol/L). The
patient had been chewing khat almost constantly for 2–3
days, but denied a regular habit; no reason for this change in
behaviour was given. He took no medication and did not
use illegal drugs.
His electrocardiogram (ECG) showed acute anterior
myocardial infarction. After thrombolysis with rt-PA his
pain resolved but the ECG showed no signs of reperfusion.
Calcium channel antagonists were given intravenously for
possible vasospasm. Troponin T at 12 h was 10.11 mg/L
(normal range 50.01) indicating myocardial infarction.
Transthoracic echocardiogram showed anteroseptal and
apical akinesis with a moderately impaired left ventricle.
The patient refused coronary angiography and received
medical therapy of aspirin, an angiotensin converting
enzyme inhibitor, a b-blocker and a statin.
The patient failed to attend for follow up having stated
that he relied on his faith for his health. He returned 27
months later with shortness of breath at rest and
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The Heart Hospital, London W1G 8PH, UK
Correspondence to: Dr Sagar Saha
E-mail: sagsaha@hotmail.com

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intermittent chest pain. In the interim, he had continued
daily khat chewing. He was short of breath at rest,
tachycardic, normotensive, and had a pansystolic murmur.
He had signs of biventricular failure. Electrocardiogram
showed his previous myocardial infarction without acute
changes. Troponin T was 0.09 mg/L. Echocardiography
revealed severely impaired biventricular function (ejection
fraction of 15%, normal range 65–80%).
Coronary angiography showed a 6 cm stenosis in the left
anterior descending coronary artery and filling defects
consistent with thrombus. The other coronary arteries were
normal (Figure 1a). A dobutamine stress echocardiogram
revealed no symptoms or electrocardiogram changes at peak
stress and failed to show significant contractile reserve or
viability suggesting an established infarct with no salvageable
myocardium. In view of the negative stress echocardiogram,
coronary intervention was not attempted and the patient
was discharged on perindopril, carvedilol, frusemide,
clopidogrel, simvastatin and spironolactone.
One month later, he returned with worsening chest pain
and shortness of breath having stopped taking all his
medications. He was hypotensive (104/64 mmHg), his
jugular venous pulse was elevated and his electrocardiogram
was unchanged despite a Troponin T of 1.83 mg/L. The
patient had impaired liver function from admission, which
continued to deteriorate with peak alanine transaminase of
626 IU/L. Ultrasound showed an enlarged liver with
reduced echogenicity consistent with acute hepatitis. A
hepatitis screen was negative (B and C, autoantibodies) as
was an HIV test. The patient’s left ventricle had
deteriorated and echocardiography showed an extensive
mural thrombus in the apex of his severely impaired left
ventricle (Figure 1b). He was anticoagulated with warfarin
and intravenous diuretics were required to treat fluid
overload. An implantable cardioverter defibrillator was not
attempted at this admission due to the risk of embolism
from the left ventricle thrombus. Ultimately, the patient
was discharged on maximal medical therapy after a 6-week
stay to stabilize his severe biventricular failure.
COMMENT
Khat contains alkaloids cathulidins and cathinone which
mediate its sympathomimetic effects.1These release
serotonin and dopamine in the central nervous system and
noradrenaline from peripheral sympathetic neurones.1
Cathinone has a similar action to amphetamine and cocaine
causing an elevation in blood pressure and heart rate
proportional to blood levels which peak 1.5–3.5 h after
chewing.2Myocardial oxygen demand increases followed by
catecholamine-mediated platelet aggregation and coronary
vasospasm.3We describe a case of severe ischaemic
cardiomyopathy due to khat-related myocardial infarction.
A case-control study in the Yemen comparing 100
patients with acute myocardial infarction to 100 age- and
sex-matched controls showed a 39-fold increased myocar-
dial infarction risk in heavy khat chewers. In a multivariate
analysis the relative risk of myocardial infarction associated
with khat was 5.0 (confidence interval 1.9–13.1).4Our
patient’s unusually sustained khat use for 2–3 days without
sleep probably caused his extensive infarction.
No published guidelines exist for the optimal manage-
ment of khat-induced coronary ischaemia; however,
extrapolation from cocaine-associated myocardial infarction
supports use of benzodiazepines, calcium channel blockers and
nitrates with coronary intervention if these are unsuccessful .5
To date, khat-associated human hepatotoxicty is
unknown; but rabbit studies implicate long-term high dose
khat use in chronic hepatic inflammation and porto-portal
fibrosis with associated liver dysfunction.6Our patient’s
hepatitis was is probably due to right heart failure and
possible direct khat toxicity (it did not respond to
withdrawal of statin or proton pump inhibitor).
Khat also causes gingivitis and tooth loss and may
increase oesophageal cancer risk.7Case reports implicate
khat usage in memory impairment, depression and
psychoses.7The World Health Organization classifies khat
as causing psychological, but not physical dependence.7
The practice of chewing khat leaves has been a part of
the culture in areas of East Africa and the Arabian Peninsula
since the 7th century. In these regions, khat is traded openly
and is used socially across a range of age and class groups,
particularly as alcohol is not permitted in Islam. It also has
religious association and has been described as an aid to
religious devotion and prayer. Migrants from these regions
see khat chewing as integral to retaining their cultural and
social identity. However, approval is not universal and
varies with gender, region and generation; there is an
awareness of the harmful effects on health and productiv-
ity.8This differing of opinion was reflected in a survey by
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Figure 1 (a) Coronary angiogram showing 6 cm stenosis in the
left anterior descending artery (arrows) filled with clot.
(b) Transthoracic echocardiogram (parasternal long axis view)
showing a large apical left ventricle clot (arrows)
(a)(b)

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Nacro, a government drugs charity. This showed that in the
UK, although 50% of Somali men regularly use khat and
35% of the 553 Somalis interviewed regarded it as
important to cultural identity, 49% wanted to see it
criminalized.9The legal status of khat is currently under
Home Office review. Although the harmful effects of
chronic khat usage have been widely reported, the cultural
effects of a ban on an immigrant minority need to be
considered.
Our patient demonstrates its adverse effects on multiple
organ systems including, not only the severe cardiovascular
consequences of long-term khat use, but also its possible
hepatotoxicity. Increased medical awareness of khat’s
availability and use by urban migrant populations in the
UK is needed to allow prompt treatment of coronary
ischaemia, particularly in young male khat chewers with few
other risk factors for coronary disease.
Acknowledgments We would like to acknowledge Dr
Malcolm Walker’s contribution to this patient’s care and
preparation of this report.
Competing interests None.
REFERENCES
1 Kalix P. A comparison of the catecholamine releasing effect of the khat
alkaloids (7)-cathinone and (+)-norpseudoephidrine. Drug Alcohol
Depend 1983;11:395–401
2 Halket JM, Karasu Z, Murray-Lyon IM. Plasma cathinone levels
following chewing khat leaves. J Ethnoparmacol 1995;49:111–13
3 Al-Motarreb AL, Broadly KJ. Coronary and aortic vasoconstriction by
cathinone, the active constituent of khat. Auton Autacoid Pharmacol 2003;
23:319–26
4 Al-Motarreb AL, Briancon S, Al-Jaber N, et al. Khat chewing is a risk
factor for acute myocardial infarction: a case control study. Br J Clin
Pharmacol 2005;59:574–81
5 Braunwald E, Antman E, Beasley J, et al. ACC/AHA 2002 guideline
update for the management of patients with unstable angina and non-ST-
segment elevation infarction. J Am Coll Cardiol 2002;40:1366–74
6 Al-Habori M, Al-Aghbari A, Al-Mamary M, et al. Toxicological
evaluation of Catha edulis leaves: a long term feeding experiment in
animals. J Ethnopharmacol 2002;83:209–17
7 Houghton P. Khat—a growing concern in the UK. Pharmaceutical J
2004;272:163–5
8 8. Stevenson M, Fitzgerald J, Banwell C. Chewing as a social act:
cultural displacement and khat consumption in the East African
communities of Melbourne. Drug Alcohol Rev 1996;15:73–82
9 Patel SL, Murray R. Khat chewing amongst Somalis in four English
cities. [http://www.homeoffice.gov.uk/rds/pdfs05/r266.pdf]
Oesophageal lichen planus:
a missed diagnosis
Abdul R Mohammed1
Paul Sherwood2
J R Soc Med 2006;99:318–320
Lichen planus is a chronic inflammatory mucocutaneous
disease of unknown aetiology with no racial predisposition,
although there is a considerable variation in its incidence.
Involvement of oesophagus is considered to be extremely
rare; the diagnosis is often not made until complications
occur. An epidemiological study of 584 patients with oral
lichen planus showed oesophageal involvement in only six
patients, clearly showing a rare prevalence. The incidence
of this disease in dermatology clinics is 1.4%, compared to
3% in oral medicine clinics. We describe a 69-year-old
woman whopresentedwith
odynophagia due to oesophageal lichen planus. This case
is very unusual in that she had skin involvement 28 years
before and had no recurrence.
a 2-year history of
CASE HISTORY
A 69-year-old retired midwife was referred to the
gastroenterology clinic by her general practitioner with a
2-year history of progressive odynophagia. It occurred
especially if she ate bulky foods such as bread and potatoes.
She was only able to eat extremely slowly and occasionally
had choking episodes. Antacids were ineffective, and
lansoprazole caused intolerable colic and diarrhoea.
Eighteen months previously she had a normal barium
swallow and fibreoptic laryngoscopy. She had suffered
extensive lichen planus of the skin in 1977 for which she
received treatment for 3 months, and had complete
remission within a few months. She had no further skin
involvement. Subsequently, she had oral lichen planus
diagnosed by her dentist 4 years previously, which subsided
without treatment. She was not on any regular medications
when the referral was made to us. Interestingly, her sister
had been diagnosed with lichen planus of the skin a few
weeks before. An outpatient gastroscopy was organized.
During gastroscopy a lacy network of white lines was
visible in the oesophagus representing Wickham’s striae of
lichen planus (Figure 1). The upper third of oesophagus felt
tight and ‘gripped’ the scope. The lower oesophagus looked
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1Senior SHO in Internal Medicine;2Consultant Gastroenterologist, Northampton
General Hospital, Northampton NN1 5BD, UK
Correspondence to: Dr Abdul R Mohammed, Specialist Registrar, Department of
Gastroenterology, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK
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normal except that she had a small (<5 cm) sliding hiatus
hernia. Oesophageal candidiasis was considered as a
possibility, but the appearances were not typical of this
diagnosis and there were no risk factors for it. Multiple
upper oesophageal biopsies were taken, but, to our dismay
at this stage, the histopathologist reported that the features
were consistent with reflux oesophagitis and that there were
no features to suggest lichen planus or candida infection. As
per the histopathology report, the patient was put on
esomeprazole 40mg once daily. She was followed up 4 weeks
later and reported that her symptoms were worse than
before. A repeat gastroscopy performed 9 weeks later whilst
she was taking esomeprazole revealed the same macroscopic
findings as before. Multiple biopsies were again taken from
upper oesophagus and the histology showed patchy basal
degeneration of squamous epithelium. There was also
evidence of dense infiltration of lymphocytes with an
occasional Civatte body within squamous epithelium, features
consistent with oesophageal lichen planus. Subsequently she
has been put on oral prednisolone 40mg per day for 2 weeks,
reducing by 5mg per fortnight. She is currently taking 5mg
per day and reports 85% improvement in odynophagia.
DISCUSSION
Lichen planus is a chronic inflammatory mucosal disease of
unknown aetiology affecting skin, mouth or genitals. Its
association with HLA-BW 16, B8, and DR1 suggests the
possibility of genetic predisposition.1It is characterized by
shiny, violaceous, flat-topped polygonal papules which
retain the skin lines, and which vary in size from pinpoint to
a centimetre or more across.2White lines, known as
Wickham’s striae may traverse the surface of the papules.
Linear lesions often appear along scratch marks or in scars
(Koebner phenomenon). Skin lesions may be disfiguring, and
involvement of the oral mucosa or genital mucosa in severe
cases can be debilitating. While most cases of lichen planus are
idiopathic, some may be caused by the ingestion of certain
medications (e.g., gold, antimalarial agents, penicillamine,
thiazides, beta blockers, nonsteroidal anti-inflammatory drugs,
quinidine and angiotensin-converting enzyme inhibitors) or
linked to hepatitis C virus infection.3Diabetes mellitus is a
possible associated disease of oral lichen planus4and
candidiasis may also coexist in some patients.
The well-known histopathological features of lichen
planus are compact orthokeratosis, wedge shaped hyper-
granulosis, vacuolar alteration of the basal layer, necrotic
keratinocytes (so-called Civatte bodies) and a dense band-
like infiltrate composed mostly of lymphocytes.5Not all of
these features must be present to establish the diagnosis of
lichen planus.
Oesophageal lichen planus is said to be often
unrecognized and underestimated.6It should always be
evaluated for in patients with mucocutaneous involvement.
The overwhelming clinical presentation is dysphagia; but
reflux-type symptoms, or retrosternal pain, can also be
associated. Delay in diagnosis may lead to serial dilations of
oesophageal strictures that, without simultaneous medical
treatment, may lead to koebenerization of lichen planus and
worsening of the stricture. Patients can lose significant
weight and become dehydrated secondary to stenosis.
Squamous cell cancer developing on mouth lesions is
uncommon, but is a potential danger, especially with
ulcerated lesions.2No case has yet been reported in
oesophageal lichen planus. After the initial diagnosis of
oesophageal lichen planus is made, systemic steroids are
often needed to quell the inflammation. A variety of steroid
sparing agents have been used successfully, including
azathioprine, cyclosporine and etretinate.7Most patients
with symptomatic disease initially respond to immunosup-
pressant therapy, but recurrent stenosis, in spite of
treatment, is common and repeated endoscopic dilatations
are necessary in the long run.8
Recognition of oesophageal lichen planus is critical for
several reasons. Misinterpretation of the histological
features as secondary to reflux disease or as simply a non-
specific reaction can lead to delay in the diagnosis and the
continuation or worsening of the symptoms.7It outlines the
importance of a proper history and full examination to look
for any potential extra oral manifestations of lichen planus.
Although no case of carcinoma developing in the setting of
oesophageal lichen planus has been reported, some authors
think such patients should be followed endoscopically, even
prospectively evaluated, for this possibility.9
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Figure 1 Endoscopic view of oesophageal lichen planus