INFECTION
Case 19: Three Days of Fever
History
A 24-year-old man presents to his general practitioner (GP) with a fever. This has been pres-
ent on and off for 3 days. On the first day he felt a little shaky, but by the third day he felt very
unwell with the fever and had a feeling of intense cold with generalized shaking at the same
time. He felt very sweaty. The whole episode lasted for 2.5 h, and he felt drained and unwell
afterwards. He had lost his appetite.
There is a previous history of hepatitis 4 years earlier, and he had glandular fever at the age of
18 years. He smokes 15–20 cigarettes each day and occasionally smokes marijuana. He denies
any intravenous drug abuse. He drinks around 14 units of alcohol each week. He has taken
no other medication except for malaria prophylaxis. He denies any homosexual contacts. He
has had a number of heterosexual contacts each year but says that all had been with protected
intercourse. He had returned from Nigeria 3 weeks earlier and was finishing off his prophy-
lactic malaria regime. He had been in Nigeria for 6 weeks as part of his job working for an oil
company and had no illnesses while he was there.
Examination
He looks unwell. His pulse is 94/min; blood pressure is 118/72 mmHg. There are no heart
murmurs. There are no abnormalities to find in the respiratory system. In the abdomen there
is some tenderness in the left upper quadrant. There are no enlarged lymph nodes.
INVESTIGATIONS
Normal
Haemoglobin 11.1 g/dL 13.7–17.7 g/dL
Mean corpuscular volume (MCV) 97 fL 80–99 fL
White cell count 9.4 × 109/L 3.9–10.6 × 109/L
Neutrophils 6.3 × 109/L 1.8–7.7 × 109/L
Lymphocytes 2.9 × 109/L 1.0–4.8 × 109/L
Platelets 112 × 109/L 150–440 × 109/L
Sodium 134 mmol/L 135–145 mmol/L
Potassium 4.8 mmol/L 3.5–5.0 mmol/L
Urea 4.2 mmol/L 2.5–6.7 mmol/L
Creatinine 74 μmol/L 70–120 μmol/L
Alkaline phosphatase 76 IU/L 30–300 IU/L
Alanine aminotransferase 33 IU/L 5–35 IU/L
Gamma-glutamyl transpeptidase 42 IU/L 11–51 IU/L
Bilirubin 28 mmol/L 3–17 mmol/L
Glucose 4.5 mmol/L 4.0–6.0 mmol/L
Urine: no protein; no blood; no sugar
Questions
• What abnormalities are likely to be present in the blood film?
• What is the most likely diagnosis?
• What would be the appropriate management?
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100 Cases in Clinical Medicine
ANSWER 19
There is a raised bilirubin with normal liver enzymes, a mild anaemia with a high normal
mean corpuscular volume and a low platelet count. This makes haemolytic anaemia likely.
The recent travel to Nigeria raises the possibility of an illness acquired there. The common-
est such illness causing a fever in the weeks after return is malaria. The incubation period is
usually 12–14 days. Longer incubation periods occur in semi-immune individuals and per-
sons taking inadequate malaria prophylaxis.The mild haemolytic anaemia with a low platelet
count would be typical findings. Slight enlargement of liver and spleen may occur after a few
days in nonimmune patients with malaria.
The diagnosis should be confirmed by appropriate expert examination of a blood film.
The most important feature in this 24-year-old man is the fever with what sound like rig-
ors. He has no other specific symptoms. He looks unwell, with tachycardia and some ten-
derness in the left upper quadrant that could be related to splenic enlargement. Malaria
prophylaxis is often not taken regularly. Even when it is, it does not provide complete
protection against malaria, which should always be suspected in circumstances such
as those described here. The risk might be assessed further by finding which parts of
Nigeria he spent his time in and whether he remembered mosquito bites. Measures to
avoid mosquito bites such as nets, insect repellants and suitable clothing are an impor-
tant part of prevention.
He has no history of intravenous drug abuse or recent risky sexual contact to suggest HIV
infection, although this could not be ruled out. HIV seroconversion can produce a feverish
illness but not usually as severe as this. Later in HIV infection an AIDS-related illness would
often be associated with a low total lymphocyte count, but this is normal in his case. Other
acute viral or bacterial infections are possible but are less likely to explain the abnormal
results of some investigations.
The diagnostic test for malaria is staining of a peripheral blood film with a Wright or
Giemsa stain. In this case it showed that around 1 per cent of red cells contained parasites.
Treatment depends on the likely resistance pattern in the area visited, and up-to-date advice
can be obtained by telephone from microbiology departments or tropical disease hospitals.
Falciparum malaria is usually treated with quinine sulphate because of widespread resis-
tance to chloroquine. A single dose of Fansidar (pyrimethamine and sulfadoxine) is given at
the end of the quinine course for final eradication of parasites. However, there is increasing
resistance to quinine, and artemesinin derivatives are increasingly becoming the first-line
treatment for falciparum malaria. In severe cases hyponatraemia and hypoglycaemia may
occur, and the sodium here is marginally low. Most of the severe complications are associ-
ated with Plasmodium falciparum malaria. They include cerebral malaria, lung involvement,
severe haemolysis and acute renal failure.
KEY POINTS
• No prophylactic regime is certain to prevent malaria.
• A traveller returning from a malaria endemic region who develops a fever has
malaria until proven otherwise.
• Treatment should be guided by advice from tropical disease centres.
• If the malaria species is unknown or the infection mixed, treat as falciparum malaria.
52
Case 20: Fevers and Malaise
Case 20: Fevers and Malaise
History
A 54-year-old woman has had diabetes for 40 years controlled on insulin. She also had hyper-
tension treated with amlodipine. Her renal function gradually deteriorated and 18 months
earlier she had a deceased donor renal transplant. She had three episodes of rejection treated
with increases in her immunosuppression. She had been taking co-trimoxazole but this was
discontinued at 12 months post transplant.
She arrived with a fever and malaise which had been present for 5–6 days. She also com-
plained of a non-productive cough for the same period.
Examination
On examination her temperature was 38°C, blood pressure was 132/82, pulse 86/min, respiratory
rate was 20/min, saturation 96%. No abnormalities were found in the cardiovascular or respira-
tory system. There was no tenderness over the transplanted kidney and no lymphadenopathy.
INVESTIGATIONS
Normal
Haemoglobin 12.8 g/dL 13.3–17.7 g/dL
Mean corpuscular volume (MCV) 89 fL 80–99 fL
White cell count 8.2 × 109/L 3.9–10.6 × 109/L
Neutrophils 7.6 × 109/L 1.8–7.7 × 109/L
Lymphocytes 0.2 × 109/L 0.6–4.8 × 109/L
Monocytes 0.2 × 109/L 0.6–1.0 × 109/L
Platelets 221 × 109/L 150–440 × 109/L
Sodium 134 mmol/L 135–145 mmol/L
Potassium 4.3 mmol/L 3.5–5.0 mmol/L
Urea 7.2 mmol/L 2.5–6.7 mmol/L
Creatinine 141 μmol/L 70–120 μmol/L
Bilirubin 16 mmol/L 3–17 mmol/L
Alanine transaminase 29 IU/L 5–35 IU/L
Gamma-glutamyl transaminase 53 IU/L 11–51 IU/L
Alkaline phosphatase 251 IU/L 30–300 IU/L
Urinalysis: no protein; no blood
Chest X-ray normal
She was treated with paracetamol and asked to return if there was any deterioration. Three
days later she returned with an increase in her fever and cough and a new problem of shortness
of breath. On examination her temperature was 38.8°C, blood pressure was 122/78, pulse 90/
min, respiratory rate was 26/min, saturation 92%.
Questions
• What is the most likely diagnosis?
• How would you investigate and manage this patient?
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100 Cases in Clinical Medicine
ANSWER 20
Fever in a patient who has had a transplant is most often related to a common pathogen, but the
presence of immunosuppression raises the possibility of an opportunistic infection. The possibil-
ity is higher here because of the increased immunosuppression related to the episodes of rejection.
The symptoms of dry cough and shortness of breath point to a respiratory focus of the infec-
tion. Although there was nothing to find on examination of the respiratory system other
than the increased respiratory rate and the original chest X-ray was normal, the decrease in
oxygen saturation confirms a significant problem with gas exchange in the lung.
The combination of a fever and dry cough with no respiratory signs and increasing hypoxia
suggests a diagnosis of Pneumocystis jiroveci pneumonia. The chest X-ray may appear normal
in the early stages before an increase in diffuse shadowing, with an alveolar filling pattern
most marked in the mid and lower zones, often sparing the costophrenic angles (Figure 20.1).
This patient was taking co-trimoxazole as prophylaxis against pneumocystis but this was
stopped because of a rash increasing the risk of infection.
The first investigation here should be a chest X-ray. Even if sputum is being produced, Pneumocystis
jiroveci cannot usually be found in the sputum and needs a technique such as sputum induction
with hypertonic saline or bronchoscopy with alveolar lavage to sample alveolar contents.
Pneumocystis jiroveci is a fungus previously called Pneumocystis carinii. It occurs commonly
in the environment but does not cause infection in the absence of immunosuppression.
Samples from induced sputum or alveolar lavage are stained with a silver stain, periodic acid
Schiff or by immunofluorescence.
Treatment is usually with high dose co-trimoxazole but the previous rash in this patient
means that alternative treatments such as dapsone and trimethoprim or clindamycin and
primaquine rather than the more toxic alternative of intravenous pentamidine are required.
Prednisolone is often used initially in treatment in cases with significant hypoxia.
Figure 20.1 Chest X-ray.
Key Points
• Pneumocystis jiroveci is a widespread organism but only causes disease in immuno-
suppressed patients.
• Dry cough, fever and breathlessness are common symptoms with tachypnoea and
significant hypoxia.
• Diagnosis usually requires sampling of alveolar contents by lavage or sputum induction.
54
Case 21: Tiredness
Case 21: Tiredness
History
A 55-year-old man presents to his general practitioner (GP), complaining of lack of energy. He
has become increasingly tired over the past 18 months. He works as a solicitor and describes
episodes when he has fallen asleep in his office. He is unable to stay awake after 9:30 pm and
sleeps through until 7:30 am. He finds it difficult to concentrate at work and has stopped
playing his weekly game of tennis. He had an episode of depression 10 years ago related to
the break-up of his first marriage. He has no current personal problems. He has had no other
major illnesses. His brother developed type 1 diabetes mellitus at the age of 13. On direct
questioning, he has noticed that he has become more constipated but denies any abdominal
pain or rectal bleeding. He has put on 8 kg in weight over the past year.
Examination
On examination he is overweight. His facial skin is dry and scaly. His pulse is 56/min, regular,
and blood pressure is 146/88 mmHg. Examination of his cardiovascular, respiratory and abdom-
inal systems is unremarkable. Neurological examination showed a little proximal weakness.
INVESTIGATIONS
Normal
Haemoglobin 11.8 g/dL 13.3–17.7 g/dL
Mean corpuscular volume (MCV) 96 fL 80–99 fL
White cell count 4.3 × 109/L 3.9–10.6 × 109/L
Platelets 154 × 109/L 150–440 × 109/L
Sodium 140 mmol/L 135–145 mmol/L
Potassium 4.4 mmol/L 3.5–5.0 mmol/L
Urea 6.4 mmol/L 2.5–6.7 mmol
Creatinine 125 μmol/L 70–120 μmol/L
Glucose 4.7 mmol/L 4.0–6.0 mmol/L
Calcium 2.48 mmol/L 2.12–2.65 mmol/L
Phosphate 1.20 mmol/L 0.8–1.45 mmol/L
Cholesterol 6.4 mmol/L 3.9–6.0 mmol/L
Triglycerides 1.4 mmol/L 0.55–1.90 mmol/L
Urinalysis: nothing abnormal detected (NAD)
Questions
• What is the likely diagnosis?
• How would you further examine, investigate and manage this patient?
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100 Cases in Clinical Medicine
ANSWER 21
Fatigue is a very common symptom of both physical and mental illness. The differential
diagnosis is extensive and includes cancer, depression, anaemia, renal failure and endocrine
diseases. In this case the main differential diagnoses are depression and hypothyroidism.
He has a history of depression but currently has no obvious triggers for a further episode of
depression. He is not waking early in the morning or having difficulty getting to sleep, which
are common biological symptoms of severe depression. There are a number of clues in this
case to the diagnosis of hypothyroidism. Insidious onset of fatigue, difficulty concentrating,
increased somnolence, constipation and weight gain are features of hypothyroidism. As in
this case there may be a family or past medical history of other autoimmune diseases such
as type 1 diabetes mellitus, vitiligo or Addison’s disease. Hypothyroidism typically pres-
ents in the fifth or sixth decade and is about five times more common in women than men.
Obstructive sleep apnoea is associated with hypothyroidism and may contribute to daytime
sleepiness and fatigue.
On examination the facial appearances and bradycardia are consistent with the diagnosis.
Characteristically, patients with overt hypothyroidism have dry, scaly, cold and thickened
skin. There may be a malar flush against the background of the pale facial appearance (‘straw-
berries-and-cream appearance’). Scalp hair is usually brittle and sparse, and there may be
thinning of the lateral third of the eyebrows. Bradycardia may occur, and the apex beat may
be difficult to locate because of the presence of a pericardial effusion. A classic sign of hypo-
thyroidism is the delayed relaxation phase of the ankle jerk. Other neurological syndromes
that may occur in association with hypothyroidism include carpal tunnel syndrome, proxi-
mal muscle weakness, a cerebellar syndrome or polyneuritis. Patients may present with psy-
chiatric illnesses, including psychoses (‘myxoedema madness’).
Clues to the diagnosis in the investigations are the mild normochromic, normocytic anae-
mia, marginally raised creatinine, and hypercholesterolaemia. The anaemia of hypothyroid-
ism is typically normochromic, normocytic or macrocytic; microcytic anaemia may occur
if there is menorrhagia. A macrocytic anaemia may represent undiagnosed vitamin B12 defi-
ciency. Renal blood flow is reduced in hypothyroidism, and this can cause the creatinine to
be slightly above the normal range.
The most severe cases of hypothyroidism present with myxoedema coma, with bradycardia,
reduced respiratory rate and severe hypothermia. Typically, shivering is absent.
In this case the thyroid function tests showed thyroid-stimulating hormone (TSH), 73 mU/L
(normal range <6 mU/L); free thyroxine (T4), 3 pmol/L (normal range 9–22 pmol/L). The high
TSH indicates primary hypothyroidism rather than hypopituitarism. The commonest cause
of hypothyroidism is autoimmune thyroiditis, and the patient should have thyroid autoanti-
bodies assayed.
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Case 21: Tiredness
! Causes of hypothyroidism
• Panhypopituitarism
• Autoimmune thyroiditis
• Postthyroidectomy
• Postradioiodine treatment for thyrotoxicosis
• Drugs for treatment of hyperthyroidism: carbimazole, propylthiouracil
• Amiodarone, lithium
• Dietary iodine deficiency
• Inherited enzyme defects
Treatment is with T4 at a maintenance dose of 75–200 μg/day. Response is measured clini-
cally and biochemically by the return of TSH to the normal range. Elderly patients or those
with coronary heart disease should be started cautiously on T4 because of the risk of precipi-
tating myocardial ischaemia.
KEY POINTS
• Hypothyroidism should be considered in the differential diagnosis of any patient
presenting with fatigue.
• A neurological examination should be part of the routine assessment of all such
patients.
• Clinical symptoms of hypothyroidism are usually non-specific.
• Hypothyroidism may present in unusual ways, such as psychoses or decreased con-
sciousness level.
• Autoimmune thyroiditis is the commonest cause of hypothyroidism.
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