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The wrong button; a serendipitous diagnosis.
The wrong button; a serendipitous diagnosis.

The wrong button; a serendipitous diagnosis.

The wrong button; a serendipitous diagnosis.

By Dr Lam Muk


When the electronic medical records showed a newly admitted 18-year-old with fever, my first reaction was to yell at the screen: ‘Why would a teenager show up at an accident and emergency department for fever? Surely he would recover better at home!’

After reading the record, I realised things may not be as straightforward as I had initially thought. The patient was an 18-year-old boy who had enjoyed good past health. However, his laboratory report indicated otherwise, showing a low platelet count, deranged liver function, low sodium and high lactate dehydrogenase. The low platelet count suggested a severe infection, whilst the deranged liver function and electrolyte disturbance suggested an infective invasion that went beyond one single organ. Lactate dehydrogenase is a component of cells that is released when cells break down and die. High lactate dehydrogenase translated as the death of a lot of cells. Were those dead cells good cells being attacked by viruses? Or bad cells turning into cancers? Or sick newborn cells bred by a sick bone marrow?

The patient looked even worse than his medical record suggested. His respiratory and heart rate were both rapid. He had a pair of chapped lips signifying dehydration. Fortunately, he was still able to give me a history despite his weak voice.


I ordered a battery of blood tests looking for antibodies to Rickettsia, Dengue fever, Leptospira, Hantaan virus, Chlamydia, and sent a urine sample for Legionella.


He was a locally born, urban-dwelling Pakistani student. Neither he nor his family had travelled aboard recently. He was not a hiker and was unaware of any recent insect stings.

He had diarrhoea, a dry cough, and a headache. There was no rash. Physical examination revealed a big liver and spleen, which is a hallmark of both blood cancers and infections. There were no palpable lymph nodes. Nothing to suggest lymphoma.

I went back to the computer and came up with a plan to pin down the culprit. In addition to the traditional horticulture of putting a specimen into a Petri dish to see what grows, the laboratory now has some craftier ways of hunting down a specific pathogen, such as looking for antibodies (a protein produced by the body to combat a specific pathogen) or antigens (an element in the pathogen that triggers the body’s immune system).

The patient’s infection was so severe and widespread that I needed to think about some rarer diseases. I ordered a battery of blood tests looking for antibodies to Rickettsia, Dengue fever, Leptospira, Hantaan virus, Chlamydia, and sent a urine sample for Legionella, as all of these infections could cause deranged liver function and low sodium.

Another issue was the low platelet count. Severe infection can consume platelets, and an enlarged spleen can be a sign that the spleen is hoarding platelets, taking them out of the bloodstream. Another possibility was a deficiency in vitamin B12 and folate, the raw materials needed to manufacture platelets, so I checked both of these too.

After two days of antibiotics, the patient had deteriorated to the point of requiring oxygen. Infection can cause respiratory failure and a fast heart rate, as can pulmonary embolism. When a blood clot forms somewhere in the body, it can move to the blood vessels in the lungs. As the vessels in the lungs run narrower and narrower, the clot meets more and more resistance and eventually comes to a halt. Such a clogged vessel prevents gas exchange in the alveoli, reducing the delivery of oxygen to the body and leading to respiratory failure. My patient’s deteriorating signs pointed to this as a possibility, especially as he was not Han Chinese (thought to be at lower risk of pulmonary embolism) and was obese.

Fortunately, the CT images did not show pulmonary embolism, but I had a hidden agenda: I had ordered CT scans to check not only for pulmonary embolism, but also for signs of blood cancers. The scanner sliced my patient from head to abdomen and stopped when it reached the distended liver and spleen, showing enlarged lymph nodes around the aorta. Would they shrink or enlarge further? Only time would tell.

Mindful that a general medical ward was not the place for an 18-year-old multi-organ failure patient to stay, I called the ICU. The on-call doctor promptly returned my call, ‘We think this patient might have HLH. Please do a bone marrow biopsy and then consult a haematologist to see if immunosuppressant is warranted.’

‘H… H what?’ I was dumbfounded.

‘Just that, you know that H, H….’ His voice faded away, transforming into a vague yelling ‘what’s the name again’ amidst the background noise at the other end of the phone. Then he returned: ‘Hemophagocytic lymphohistiocytosis.’

I had heard of this condition 5 years earlier during my paediatrics rotation. It results from lymphocytes and macrophages in the body becoming overactive and releasing too many cytokines, causing widespread inflammation. It is often hereditary and more commonly seen in children. My 18- year-old patient could be seen as being at the upper limit of childhood, but seemed too old to be presenting with symptoms of a hereditary disease for the first time.

‘Why?’ I asked doubtfully.

‘Well, he has a high triglycerides level.’

‘I agreed that 6.7 was high for triglycerides, but at the same time, he was obese.’

Normal triglyceride levels are around 1. I had measured the patient’s triglycerides together with his cholesterol and fasting blood sugar, mindful that patients with diabetes and metabolic syndrome are prone to more severe infections.

‘He also has a sky-high ferritin level.’

When did he have his ferritin checked? — A vague suspicion flashed across my mind. I clicked into his electronic record. There I found his iron profile result. His serum iron was normal, but his ferritin had skyrocketed to over 10000.

Serum iron and ferritin are used in the manufacture of red blood cells. Serum iron is iron that is bound to proteins in the blood (you can view it as the liquid asset for manufacturing red blood cells), whereas ferritin is stored in the liver and immune system as a reserve supply. As ferritin is stored in the immune system, inflammation and infection naturally cause it to rise. One of the features of hemophagocytic lymphohistiocytosis is a high ferritin level.

By now it was 11am on a Saturday morning. Our laboratory worked 5.5 days a week and only received urgent blood samples after 1pm. Non-urgent samples including bone marrow biopsy specimens were left until the following week. However, not until the diagnosis of HLH was confirmed could I start the patient on medications; not until medications were given might the patient’s condition stop deteriorating.

I rang the on-call pathologist immediately, wildly exaggerating the imminent death of my patient and claiming that she was the only one who could save us. After extracting from my mouth the reasons for suspecting HLH, she sighed and asked, ‘Are you aware that today is a Saturday?’


I thanked her profusely whilst once again valuing the power of silence.


‘Yes I am.’

‘Before I look at the bone marrow biopsy slides, the laboratory staff need to stain them. Which means that technicians who should be going home in 2 hours will have to do overtime. Are you aware of this?’ I fell silent for a few crucial seconds.

‘….OK.’ I heard her sighing another time, ‘After you do the biopsy, send it to the lab before 1 pm. I will try to publish the report before 6 pm. No guarantees though.’

I thanked her profusely whilst once again valuing the power of silence.

Bone marrow biopsy

I proceeded quickly with the bone marrow biopsy. It is similar to drilling a well. First you use a fine needle to probe your way into one side of the patient’s upper buttock, and when you feel the pelvis,


The patient began screaming as soon as the needle punctured his skin. I suspected that this procedure would be more painful for him as he was obese and the fatter you are, the longer the needle needs to travel before it reaches its bony target. As soon as I felt the pelvic bone, I injected some local anaesthesia, before switching to an approximately 1cm wide bone marrow biopsy needle.

‘Oh shot!’

the patient exclaimed, in reality using local slang which, for reasons of decorum, I am unwilling to translate literally. ‘That’s right keep it going! Foul language is exactly what you need!’ While navigating and wriggling the biopsy needle, I tried to cheer him up by recalling a study that showed foul language helped to relieve pain. ‘Good boy! Keep it up!’ Apparently, he was none too pleased with my efforts. He answered angrily and scornfully ‘Of course I know that I am a good boy!’

I’ve always used this line to give encouragement to my patients during invasive procedures. Adult patients usually do not take the time to respond, whilst older, demented patients may be unable to do so. This young man, at an age where he did not want to be handled as a child, was the only one rebutting me seriously.

After finishing the procedure, I ran down nine flights of stairs and delivered the specimen to the laboratory before the 1pm deadline. Arriving back on the ward, I found the patient’s mother and aunt (who spoke English and acted as the translator) at his bedside. They were tearful and asked if they could visit daily. I refused due to the ongoing COVID-19 pandemic. The aunt asked for a daily 10-minute-visit and I refused due to the ongoing pandemic. The aunt asked for a daily 5-minute-visit and I refused due to ongoing pandemic. At last, she resorted to religion, ‘His mum needs to stand by his bedside and pray every day. That’s the only way God (pointing to the ceiling) can listen.’

To avoid turning this into a religious discrimination issue, I chose to ignore it. I blankly refused her request as ‘Hong Kong is a secular society’. Retrospectively, I could have found another premise; human lives are like the flickering of thumbs in front of God’s eternality, boundless territories are like the drop of a bucket, and the mere dozens of kilometers between you and your son’s bed is definitely within the error range of God’s GPS.


So the diagnosis came out of carelessness. That must have been God’s will!


After dispatching his family, I went back to the computer and clicked open his medical record. It was then that the penny dropped: Iron, vitamin B12 and folate are all needed to make red blood cells. On my self-edited user interface for ordering investigations (we order investigations by computer rather than hand-written forms in Hong Kong public hospitals), they were grouped together under the anemia workup. Whenever my patients were anemic, I just clicked them all. This patient was not anemic but he had a low platelet count. When I clicked vitamin B12 and folate, I must have clicked the iron profile subconsciously.

So the diagnosis came out of carelessness. That must have been God’s will!

Before I was able to gloat, the printer spat out a paper. ‘Bingo!’ Antibodies for Oriental tsutsugamushi were found in the patient’s blood, suggesting scrub typhus, an infection transmitted by chiggers. Fortunately, I had already started the patient on doxycycline at the suggestion of a senior doctor. Or was it fortune at all; after all, we had exhausted all available treatments. There was no more we could do apart from supportive treatment, and the rest was left to God’s hands.

 Chiggers (laval mites) that spread Scrub Typhus

Eschar at the site of a chigger bite.

By this time, it was 2pm and my shift had come to an end. Concerned that the patient might deteriorate, I rang the on-call-doctor to hand over her the case. By coincidence, the senior doctor who had earlier suggested prescribing doxycycline was with her at the time, so he also participated in the handover.

‘I told you to look for eschars. Have you found any?’ was the first question the senior doctor asked when he saw me. Eschars are areas of dead skin tissue that eventually slough off from healthy skin after an injury.

‘I found two skin lesions that look like eschars, but he insisted they were merely abrasions rather than insect bites.’

I walked towards the bedside while talking, drew the curtains, and asked the patient to take off his pyjama bottoms. I pointed to his right thigh and said, ‘Is this an eschar?’

‘No it isn’t.’ said the senior doctor, shaking his head.

I then pointed to his left shin, ‘This too looks like an eschar.’

‘You are right, it is.’ The senior doctor’s eyes started to shine.

The patient rebutted, ‘I got this abrasion during a fall. I don’t remember being bitten by an insect.’ However, it is not uncommon for people to be unaware of an insect bite. Nimble insects would slip away before being caught biting, leaving the dumb ones to get swatted to death.

The senior doctor pressed on with his inquires, ‘Have you been hiking recently?’

‘No,’ the patient and I answered simultaneously.

‘So how did the fall happen?’

‘It was during a football game.’

‘Were you playing football on a concrete or grass pitch?’


‘That’s right.’ The senior doctor turned his head and explained to us, ‘The grass on football pitches is shorter, so the eschar is often found at the shin. Once one of my patients went hiking in the mountains, and slipped into the shrubs to urinate during the night. An eschar appeared in his inguinal region.’

Amazed, we all whipped out our phones and took photos of the patient’s shin; an oval, thumb-nail-sized eschar that was sooty dark, ragged with white scaling, with an erythematous rim. It does not look like a typical abrasion. Up until then, I had understood that chiggers, the transmitters for typhus, lived only in rural areas. Now I learned that they could live in parks as well.

At this point, I felt remorse. Had I not mistakenly clicked the blood iron profile in my user interface, the ICU would not have suspected hemophagocytic lymphohistiocytosis, the patient would not have been subjected to a needless and painful bone marrow biopsy, and the laboratory staff would not have had to work overtime.

I almost called the on-call pathologist to let her know she could go home because we had our answer. However, fearing that the patient could still deteriorate and wondering what would happen if I needed to consult the ICU again without the promised pathology report, I settled for apologising only to myself and went home.


The comprehensive diagnosis was reached serendipitously. Should it be counted as bad luck or good? To this day, I am not really sure.


By the time I was back at work the following Monday, the patient had improved significantly and there was no need for ICU admission. However, the bone marrow biopsy report had come through at 6pm on the Saturday and showed hemophagocytosis. This meant that the whilst the bone marrow, the kindergarten for blood cells, was producing new red blood cells and platelets, the macrophages were engulfing them in a manner akin to how a first born infant white shark consumes his younger siblings. Horrible!

So, the ICU was right after all. The patient did indeed have hemophagocytic lymphohistiocytosis, but it was not genetic. Rather, it was a secondary condition triggered by typhus. Antibiotics for the typhus, instead of immunosuppressants, were all we needed for treatment.

Back to square one. By inadvertently clicking the button for blood iron profile on my user interface, the patient had suffered the torture of a bone marrow biopsy, the laboratory technicians had worked overtime, and the comprehensive diagnosis was reached serendipitously. Should it be counted as bad luck or good? To this day, I am not really sure.

By this stage, the patient was well enough to be demanding that we discharge him and neither myself nor his aunt could dissuade him. When he was signing the document of ‘discharge with acknowledgement to medical advice’, something caught my eye.

‘Is this a rash?’

‘Oh?’ The patient flapped his hands around a few times in confusion, ‘I hadn’t noticed that.’

Not just on his hands. Along his feet and shins was a dense, rosy-colored grainy rash. Another hallmark of the typhus had finally appeared. Justice delayed is justice denied, but rash delayed is still a perfect rash! I let him go only after I took as many photos as I could.

He had recovered completely by the time I saw him two weeks later. I hope for his sake that he does not stop playing football after this unpleasant experience. To this day, the one outstanding question for me is whether his high triglycerides were due to hemophagocytic lymphohistiocytosis or the mere fact that he was fat!

Dr Muk Lam graduated from HKUMed in 2016. She is currently working as a medical resident in a public hospital in Hong Kong.