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CASE 77: HEADACHE AND BLURRED VISION
A 45 year-old woman presents to the emergency department with a 4-day history of head-
ache and blurred vision. She denies having photophobia, fever, or rash. She is not on any
regular medications and has no past medical history. She recalls that the symptoms started 5
days after she received her second dose of the COVID-19 vaccination (ChAdOx1-S [recom-
binant] AstraZeneca vaccine).
Examination
On examination, she has no fever, and her cardiorespiratory observations are within normal
limits. Her blood results are shown here.
INVESTIGATIONS
•
Haemoglobin 125
•
White cell count 13
•
Platelets 43
QUESTIONS
1.
What is the differential diagnosis?
2. What further tests would you arrange?
3. What would be your next management step? Are there any special consider-
ations in this case?
DOI: 10.1201/9781003242697-80
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ANSWERS
With a recent history of the COVID-19 vaccination, one must consider vaccine-induced
thrombosis presenting with cerebral venous sinus thrombosis (CVST). If excluded, then the
headache could be a side eect from the recent vaccination or related to abnormalities in
blood pressure or visual acuity.
Further investigations should include blood pressure measurement and CT venogram of
the brain to exclude thrombosis. The patient’s platelet count is low, which is suggestive of
vaccine-induced immune thrombocytopenia and thrombosis (VITT). VITT may also be
called vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) or thrombotic
thrombocytopenic syndrome (TTS).
If VITT is confirmed, then one should also request a coagulation screen, including Clauss
fibrinogen assay, D-dimer measurement, and a blood film, to confirm true thrombocytope-
nia. To confirm the diagnosis, an enzyme-linked immunosorbent assay (ELISA) for platelet
factor 4 antibodies is useful. To complete the assessment, a detailed assessment of vision by
an optometrist is also required
In this case, the CT venogram did confirm a CVST. Given the history, this is very likely a
vaccination-induced event. The rate of this complication is low. However, it did receive sig-
nificant attention from the public and media during the height of the COVID-19 pandemic.
Other possible causes of thrombocytopenia with thrombosis other than VITT include
antiphospholipid syndrome, cancer, heparin-induced thrombocytopenia, and thrombotic
thrombocytopenic purpura (TTP).
Management would include anticoagulation. However, the challenge here is that the platelets are
already low, which would increase the risk of bleeding as a complication from anticoagulation.
A possible consideration would be to reduce the dose, for example, to give 50% of the treatment
dose. However, for VITT, current guidelines would still recommend full-dose anticoagulation,
using a non-heparin-based anticoagulation, for example, direct oral anticoagulants (DOACs),
unless platelets are less than 30 × 109/L. If platelets are lower than 30 × 109/L, the following
alternative anticoagulation strategies may reduce the risk of bleeding: either reduced dose of arg-
atroban or a therapeutic dose of argatroban with platelet transfusion.
Also, if fibrinogen is low, replacement therapy with fibrinogen concentrate or cryoprecipitate
to maintain a level of fibrinogen of at least 1.5 g/L should be given.
Despite this episode of thrombosis, current evidence would still support that this patient
should still receive a booster dose with a messenger RNA (mR NA) vaccine, provided at least
12 weeks have elapsed from the implicated dose.
KEY POINTS
•
VITT should be considered in the differential diagnosis in any patient presenting
with a compatible history and a recent vaccination.
•
When presenting with low platelets and thrombosis, it is important to exclude
antiphospholipid syndrome, heparin-induced thrombocytopenia and TTP.
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CASE 78: LOWER BACK PAIN
During a routine review in the clinic, a patient reports worsening of her chronic lower back
pain. She is 76 years old and completed chemotherapy for multiple myeloma 6 months ago.
Her past medical history includes asthma and degenerative spinal disease. Her presenting
paraprotein before treatment was IgG kappa with 45 g/L. After treatment, this was only
2 g/L with normalisation of haemoglobin and creatinine levels.
Examination
On examination, she has no neurological signs. Two days before this latest consultation her
blood tests were done with the results shown below.
INVESTIGATIONS
Haemoglobin 130 g/L
White cell count 6
Platelet count 180
Serum protein electrophoresis: IgG kappa 3 g/L
QUESTIONS
1.
What is the differential diagnosis?
2. What further tests would you arrange?
3. What would be your next management step?
DOI: 10.1201/9781003242697-81
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ANSWERS
The lower back pain could be secondary to the known degenerative changes, especially
as the patient’s haemoglobin level remains normal and her paraprotein level remains low.
However, the creatinine level has increased, which is a matter of concern in a patient with
multiple myeloma.
Further tests should include MRI of the lower spine and light chain analysis. In this patient
the MRI scan shows a large mass of 4 × 5 cm infiltrating the cauda equina. The serum free
light chains (SFLC) analysis reveals a kappa light chain level of 2000 mg/L, with lambda
light chain level of 60 mg/L and a ratio of kappa:lambda of 333.
This mass is likely a plasmacytoma that is causing the worsening of back pain with abnormal
production of light chains. The patient is fortunate that she does not have neurological signs
or symptoms, and it is therefore important to have a high level of suspicion in patients with
myeloma and back pain. Light chain production is usually balanced between kappa and
lambda with normal reference ranges:
•
Kappa light chains: 3.3–19.4 mg/L
•
Lambda light chains: 5.7–26.3 mg/L
•
Normal kappa-to-lambda ratio: 0.26–1.65
However, when the ratio is significantly abnormal—for example, kappa light chains are more
than seven times the level of the lambda ones—then this represents clonal production. In the
case of this patient, there has been a light chain ‘escape’, with the monoclonal band (IgG,
which has both heavy and light chains) remaining low; however, there is significant abnormal
production of light chains.
In terms of management, this patient has a medical emergency, and she needs admission to
hospital with a discussion with the neurosurgical team. If no surgical intervention is indicated
for her cauda equina compression, then she should be referred to the clinical oncology team
for radiotherapy to the plasmacytoma to prevent further progression and damage to the
spine. Whilst waiting for the above, she should be started on dexamethasone, which helps to
provide some initial control of the disease. After radiotherapy, further chemotherapy will still
need to be given with close monitoring of the patient and the light chain levels.
KEY POINTS
•
Lower back pain in a patient with a history of plasma cell myeloma must be care-
fully assessed, as it could represent a relapse of the condition.
•
A stable paraprotein level does not necessarily exclude a relapse of myeloma.
•
Imaging and SFLC analysis must be arranged to complete the assessment in a
patient with myeloma.
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MICROBIOLOGY
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CASE 79: FLU-LIKE ILLNESS AFTER FOREIGN
TRAVEL
A 38-year-old man presents to his local sexual health clinic for a check-up after a one-time
heterosexual encounter with a new partner while he was away on a business trip in the Far
East 4 weeks ago. He does not report any genitourinary symptoms at present or in the previ-
ous weeks. On direct questioning, he recalls that he was feeling “generally unwell” last week
and ascribed it to the flu. He has no active medical problems and takes no medications.
Examination
General, systemic, and urogenital examinations are unremarkable.
INVESTIGATIONS
•
FBC, U+E, LFT: Normal
•
Urethral swab: Negative for gonorrhoea
•
Chlamydia urine PCR: Negative
•
Syphilis, hepatitis B and hepatitis C serology: Negative
•
HIV p24 Ag: Positive, confirmed on second sample
•
HIV serology: Negative
QUESTIONS
1.
Explain why the patient has HIV despite the absence of positive serology.
2. Discuss the pathogenesis of the immunodeficiency arising from HIV infection.
3. Describe the natural history of HIV infection. What is the difference between HIV
and acquired immunodeficiency syndrome (AIDS)?
4. What further HIV-specific investigations should be performed at this stage?
5. What prophylactic measures can be taken against opportunistic infections in
HIV-infected individuals?
DOI: 10.1201/9781003242697-83
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ANSWERS
Human immunodeficiency virus (HIV) is a retrovirus that has infected more than 30 million
people worldwide. The laboratory diagnosis of HIV can be made genomically (detection of
viral nucleic acid by polymerase chain reaction [PCR]), serologically (detection of antigens or
antibodies by enzyme-linked immunosorbent assay [ELISA]), or immunologically (through
detection of a low CD4 cell count). Here, the presence of the capsid protein (p24) of HIV has
been confirmed but no anti-HIV antibodies have been detected. This is because the serologic
response to HIV infection may take a minimum of 4–8 weeks to develop (even as long as
6 months in some cases—the ‘window period’).
The primary target of HIV is the immune system, and the virus predominantly infects CD4
T cells (helper T cells), as well as other immune cells such as macrophages and dendritic cells.
In a subversive manner, latent infection of these cells is released when the immune system is
activated—inflammatory cytokines lead to activation of NFκB, which binds the promoters
of various target cytokine genes as well as sequences of the HIV genome, leading to activa-
tion of proviral DNA. When new virions bud o, cell lysis is induced (up to 2 billion CD4 T
cells may be killed in this way each day). Aside from the quantitative impact on T cells, HIV
also produces qualitative defects in T-cell function, with reduced proliferation in response to
antigenic stimulation and a general reduction in T
H
1 responses, leading to a deficit in cell-
mediated immunity. It should be appreciated that CD4 T cells act as a “master regulator” of
the adaptive immune response (e.g., through activating B cells and antibody production), and
hence the virus indirectly causes a defect in the entire immune system.
The interplay between the virus and the immune system governs the clinical course of HIV
infection, and typically, there are three phases to infection:
1. Acute retroviral syndrome: This is the primary response of an immunocompetent
individual to HIV and is characterised by a flu-like illness 3–6 weeks after exposure
(seen in this case).
2. Middle chronic phase: The virus is latent and the immune system is largely intact.
It may be asymptomatic or characterised by generalised lymphadenopathy.
3. Full-blown AIDS: In this final phase, there is a dramatic increase in the viral load
with breakdown of host defences and appearance of serious opportunistic infec-
tions, secondary neoplasms, and neurologic disease (‘AIDS-defining illnesses’—e.g.,
Pneumocystis, toxoplasmosis and mycobacterial infection, Kaposi’s sarcoma, and pri-
mary central nervous system [CNS] lymphoma).
As the diagnosis of HIV has been confirmed, the specific antiretroviral investigations that
need to be performed include obtaining a CD4 T-cell count and the HIV viral load (detec-
tion of viral RNA by real-time PCR). There is typically an inverse relationship between the
two, with the latter governing the rate of decline of the former, which predicts the susceptibil-
ity of the host to opportunistic infection. Other tests required at this stage include serologic
tests for toxoplasma and cytomegalovirus (CMV ), a tuberculin skin test (given the potential
of reactivation or infection of tuberculosis [TB] in an immunodeficient host), an ECG (for
baseline purposes prior to initiating any antiretroviral therapy), and a chest radiograph (as
several HIV-related infections may produce lung disease).
Certain prophylactic measures can be taken against opportunistic infections if the patient
has a high susceptibility (governed by CD4 T-cell count). For example, trimethoprim-
sulphamethoxazole (Septrin) can be used to prevent Pneumocystis carinii pneumonia (if CD4
count is <200) and toxoplasmosis (if CD4 count is <100). Similarly, azithromycin can be used
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Case 79: Flu-like Illness after Foreign Travel
237
as mycobacterial prophylaxis in individuals with a CD4 count of 50 or less, while prolonged
anti-tuberculous treatment is merited in any HIV-positive patient with a positive tuberculin
test. Patients should also receive streptococcal, influenza and hepatitis B vaccines, regardless
of CD4 count.
KEY POINTS
•
Antibody responses to HIV may take a few weeks to become detectable, so cau-
tion should be observed when interpreting serology in the immediate period after
potential viral transmission.
•
HIV mainly infects CD4 T cells, producing both qualitative and quantitative defects
in their function.
•
There are three phases to HIV infection, starting with an acute retroviral syndrome,
moving on to a middle latent phase, and progressing to full-blown AIDS.
•
Prophylaxis against opportunistic infection is used, depending on the CD4 T-cell
count.
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