Fever in a returning traveller

Try out this pathology case and test your clinical knowledge. The answers are at the bottom.

 

Questions

A 23-year-old medical student presents to his GP complaining of feeling “under the weather” for the last week. He reports not eating very much and says he often feels quite sweaty first thing in the morning. He also mentions that he came back from his elective in South Africa three weeks ago and that he had unprotected intercourse while he was abroad.

Observations:
– SpO2: 98%
– HR: 100
– Temperature 37.9
– RR: 19
– BP: 120/89

Examination:
– Throat NAD
– Maculopapular rash on left side of chest that blanches on palpation

Drug History:
– Malarone 250mg/100mg OD (Atovaquone + Proguanil)
– NKDA

Q1: What is the gold-standard investigation for the likely diagnosis in the UK & when should it be performed?

The investigation reveals the underlying diagnosis and he is referred onto secondary care for further treatment. Unfortunately, does not tolerate this treatment well and regularly misses doses.

8 months later he presents to A&E with shortness of breath and a harsh, dry cough. A sputum sample is taken and a CXR is performed as shown below:

Histology:


Nureki, Shin-ichi & Usagawa, Yuko & Watanabe, Erina & Takenaka, Ryuichi & Shigemitsu, Osamu & Abe, Takakuni & Yasuda, Norihisa & Goto, Koji & Kitano, Takaaki & Kadota, Jun-ichi. (2020). Veno-Venous Extracorporeal Membrane Oxygenation for Severe Pneumocystis jirovecii Pneumonia in an Immunocompromised Patient without HIV Infection. The Tohoku Journal of Experimental Medicine. 250. 215-221. 10.1620/tjem.250.215.

CXR:


Image 2: Case courtesy of Dr Andrew Dixon, Radiopaedia.org, rID: 9613 https://radiopaedia.org/cases/pneumocystis-pneumonia-2?lang=gb

Q2: What complication has he developed? What is the causative organism & definitive treatment?

He is successfully treated for this complication and counselled on the importance of medication adherence. However, the student insists he does not need any treatment for it and continues to not comply with the treatment regime.

Five years later he is brought to the A&E by his parents who are worried about his mental health. They report that he has become more aggressive and volatile in the last year, often shouting at them for innocuous things. They also mention that he struggles to carry plates of food & cups of tea without spilling them. As you are taking a collateral history from the parents the patient becomes irate and attempts to throw a chair at the bed manager, who escapes unhurt. He eventually calms down and is seen by the neurology registrar, who orders some urgent bloods and an MRI scan. These are shown below:

Blood Results:

MRI:

Image 3: Case courtesy of Assoc Prof Frank Gaillard, Radiopaedia.org, rID: 22071
https://radiopaedia.org/cases/progressive-multifocal-leukoencephalopathy-pml?lang=gb

Q3: What complication has he developed?

(Bonus – What is the causative organism and what are other important differentials to consider?

Answers

Reveal the answers

Answer to Question 1

He is a young male presenting with a fever & malaise two weeks after returning from South Africa where he was sexually active. The lack of respiratory symptoms makes conditions such as influenza, sinusitis and pneumonia less likely. Similarly, the lack of any GI symptoms or jaundice makes conditions such as hepatitis or gastritis from food/water poisoning unlikely. The normal throat examination excludes tonsillitis, infectious mononucleosis, and the presence of a blanching rash with no meningism excludes meningitis as a cause for his malaise. As such, this is a case of pyrexia of unknown origin in a returning traveler.

The most likely cause in this case is acute HIV infection, as the lag time from returning and developing symptoms matches the known seroconversion time for HIV (7-21 days). To support this, the maculopapular rash and sexual history are consistent with this diagnosis.

An important differential would be malaria, as he has returned from Africa and is likely to have travelled around the continent. However, we can see from his drug history that he is on malaria prophylaxis, making this an unlikely cause. Other causes of PUO in a traveler e.g. schistosomiasis, dengue, zika etc. should also be considered however given his sexual history HIV is the most likely diagnosis.

The best investigation for HIV is a 4th generation antigen-antibody (Ag-Ab) sandwich ELISA. This test looks for IgG and IgM against HIV-1 and HIV-2 and also detects the presence of the p24 antigen of HIV-1, however it only gives a single positive result (i.e., you could be either Ab or Ag positive or positive for both). It should be performed 4 weeks post-infection and if negative a second test should be repeated at 12 weeks.

Answer to Question 2

CXR
– Diffuse bilateral opacification extending through multiple lobes – this should raise suspicion for an atypical form of pneumonia (most ‘common’ pneumonias e.g. streptococcus pneumoniae give patchy consolidation confined to 1-2 lobes on the same side)
– Presence of air bronchograms – indicates consolidation (i.e. fluid/inflammatory material in the alveoli itself)
– A few cystic lesions e.g. in RUZ and LMZ
– No effusion

Sputum sample
– This is a silver stain (Grocott) which is very good at showing fungi
– The stain shows lots of cystic organisms staining black
– This is consistent with an infection by pneumocystis jiroveci

Diagnosis: Pneumocystis pneumonia (PCP)

Treatment: Co-trimoxazole (sulfamethoxazole + trimethoprim)

Answer to Question 3

Bloods
– Leukopenia
– Severely reduced CD4 count – marker of HIV activity
– No acute infection with EBV or CMV
– Likely a problem with the toxoplasmosis sample/lab reagents

MRI
– This is a T2-weighted MRI (CSF white, white matter darker than grey matter)
– Very good sequence for assessing demyelination
– Severe demyelination in R parieto-temporal region extending into the insula

Diagnosis: This is consistent with progressive multifocal leukoencephalopathy (PML), which is caused by an infection by the JC virus.

Other important differentials would be:
– AIDS-dementia complex – this is difficult to separate from PML, and only the presence of JC virus on CSF PCR can confirm the former diagnosis. Also tend to get global damage to the cortex.

– Primary CNS lymphoma: unlikely given that he is EBV negative, and it presents as a homogenous discreet mass on MRI

– Toxoplasmosis: Toxoplasmosis usually presents with pyrexia + malaise and there is usually a history of feline exposure. It also demonstrates classical ring-enhancement on T1+c MRI

– Cryptococcus meningitis: Unlikely due to the time course (an entire year) and lack of infective & meningitis symptoms

To get more information about the conditions mentioned in this case including diagnosis and management, have a look at our free neurology notes on In2Med. Written by medical students, we have pitched them just at the right level to help you ace your exams.

Dr Amol Joshi
University of Cambridge

About The Author

This case is written by Dr Amol Joshi who has an interest in writing medical puzzles.