Tuesday, 29 December 2009

End of Year Greeting

Dear Bloggers

It has been six weeks since I last updated this blog for which I am eternally sorry :-)

I hope that you have all been enjoying the end of year celebrations though.

For me, life has been rather hectic but I can assure you that I will be updating the blog with new cases and interesting matters on a more regular basis --- at least, as much as I can do in 2010.

I would like to thank you all for visiting my blog over the years and I ask that you continue to do so -- from time to time. Remember, if you have a question or comment, you can always drop me a line via the blog.

I wish you all a happy, healthy and prosperous 2010.

Tuesday, 17 November 2009

Answers to the November 'Spot Case'

Dear Bloggers

Thank you for waiting for the answers to the November short case which involved no history, but the sole use of observational skills.

Without further ado, here are the answers to the following questions:

Question 1: Please carefully examine the patient's arm (first photo). What physical signs can be seen here?

When we look at the picture we are immediately drawn to the skin abnormality which is diffuse, purplish and irregular. It is in fact some mild bruising rather than a melanoma, although the latter is indeed a good thought. However, this is in part, a pseudo- 'red herring'. It draws you away from the significant abnormality which is coiling of the hairs. Such a change is consistent with vitamin C deficiency (scurvy). One could indeed argue that the bruising is also caused by a vitamin C deficiency although there is not the typical peri-follicular hemorrhage that one sometimes sees in this condition.

If one increases the magnification of the picture (done by clicking on the picture) it soon becomes clear that there are whitish plug-like structures at some of the hair follicle bases which may represent lice infection.

Question 2: Please carefully examine the second photo. What physical signs can be seen here?

This photo tells a lot of information. The patient is unshaven which may signify he has not been looking after himself very well. The other clue to this is his dentition, which is very poor. There is also evidence of gingivitis, which supports the idea of poor dentition, but which may also be seen in vitamin C deficiency.

Question 3: Which ONE cause can link the main abnormalities seen below?

Vitamin C deficiency (scurvy) links both pictures.

Question 4: What is the most appropriate test(s) and subsequent treatment?

Vitamin C levels can be measured, but based on the examination findings, it would be reasonable to commence vitamin C replenishment therapy before the results are available.

The fact that this patient has a high probability of vitamin C deficiency, it should also alert the physician to consider other vitamin deficiencies and hence, replenishment of multi-vitamins would be an additional step in his treatment. The patient would also need general improvements in nutrition.

One has to also consider separate consults to dermatology, especially if there is a concern about melanoma and lice, and the dental surgeons and hygienists for optimising oral care. Lice eradication therapy would also be appropriate once confirmed by microscopic examination.

One should also consider the socioeconomic situation of the patient as well. If this patient has vitamin deficiency, possible malnutrition, and skin infestation, then he may require social help e.g. a carer for bathing and meals-on-wheels service, in addition to economic support if he has insufficient funds to cover the services required.

Both Professor Stein and Professor Dhaliwal correctly answered this month's case. Their comments are as follows:

Prof Stein:

Quesiton # 1 Problems in skin image:
1. 1) pigmented lesion of melenoma with irregular borders and 2 + different colors.And diffuse hyperkeratosis-like lesions
02)globules with tear drop forms and ? budding form suggest coiled hairs (looking like scurvy), doubt follicilitis (not looking like scurvy), yeast or parasite on skin

Question # 2
2. Front of oral cavity/lips: chronic gingivitis, candida gingivitis as seen in HIV pts, necrotizing gingivitis(trench mouth) also seen in HIV pts, and chronic periodonitis from Vit C deficiency (coiled hairs & hyperkeratosis), severe malnutrition causing necroziting periodonitis

3 & 4 For 1/1 link is CA melenoma>skin Bx; For 1/02 HIV test, ? vit C assay; For 2 xray teeth, dental consult, derm consult. Rx Vit C, multi-vit, general nutritional improvements

Prof Dhaliwal

Question 1: Please carefully examine the patient's arm (first photo). What physical signs can be seen here?

This is a wonderful exercise that asks two things of the clinician 1) observation/detection and 2) interpretation; success in #2 is intimately tied to #1. Stated otherwise, we cannot simply solve a problem (e.g., as in a presented case); we must detect and define the problem first.

The picture of the arm has a number of findings – although I cannot say with certainty which ones are decidedly abnormal. There is a dark pigmented macule that has some if not all of the ABCD characteristics of melanoma (http://www.melanomafoundation.org/prevention/abcd.htm) . One must always respect melanoma’s devastating metastatic potential when a second site of the body is being evaluated in the setting of a suspicious pigmented lesion. An alternative explanation for this skin finding would be a seborrheic keratosis, which is far more common, although typically favoring the trunk over the extremities.

The skin also seems to have punctuate yellow colored scale or buildup that is distributed throughout the skin. I regrettably don’t possess a large differential diagnosis for this finding, although things that come to mind include an exudation of excess lipid, a simple normal variant in skin pigmentation, or the accumulation of sebaceous material if regularly bathing has not been possible.

There are approximately 5-10 cystic appearing structures mostly in the middle portion of the photo. Although it is hard to tell whether they are attached to the hair shafts, I think they are at least compatible with lice. I’m hesitant to make this interpretation however, because tropism for the arm hair (in comparison to the head) would be atypical.

Finally, some of the hairs are linear, but there are a number of coiled hairs.

Question 2: Please carefully examine the second photo. What physical signs can be seen here?

This is a man, perhaps at least 30, inferred by some visible skin wrinkling, which smoking and sunexposure can accelerate. Otherwise, the external structures appear normal.

The left lower central incisor and the left lower lateral incisor are slightly discolored. The former has a grey hue, the latter, a ruddy off white appearance. Smoking may have caused a generally yellowing of the teeth. The gingival tissue associated with the lateral incisor appears to be inflamed, which may reflect a periodontal infection.

Question 3: Which ONE cause can link the main abnormalities seen below?

Since I do not recognize the dental abnormality outright, I have considered systemic diseases which may originate from periodontal disease (e.g., endocarditis) or can present as periodontal problems (drug effects like phenytoin, infiltrative processes such as leukemia, or connective tissue disturbances such as scurvy).

Given the previous observation of coiled hairs, a question I raised about hygiene (implying socioeconomic difficulties that could impair or radically modify access to food), I will hazard a guess of scurvy (vitamin C deficiency). Neither perifollicular hemorrhages nor gingival bleeding are seen however.

Question 4: What is the most appropriate test(s) and subsequent treatment?

In the case of scurvy, the diagnostic test is a serum ascorbic acid level and the treatment is the restoration of a proper diet.

Vitamin C (Ascorbic Acid) Deficiency

In developed countries the major groups affected by vitamin C deficiency include the severely malnourished, drug and alcohol misusers and the poor. In the UK, it is typically seen in the impoverished 'tea and toast' elderly.

Vitamin C deficiency (scurvy) can occur within just 3 months of deficiency resulting in various symptoms and signs largely due to impaired collagen production with impaired connective tissue organisation. Generalised symptoms include malaise, weakness, joint pain and / or swelling, depression, neuropathic symptoms, extremity swelling etc

Signs on examination include bruising of the skin, coiled hairs, bleeding gums, impaired wound healing, petechial hemorrhage, hyperkeratosis and Sjogren's syndrome.

The chronic gingivitis is thought to occur due to infection from oral bacteria in the gums of sufferers as a result of impaired neutrophil killing activity. Hemorrhage is a secondary phenomenon caused by infection disrupting fragile vessels within the gums.

Scurvy was described in the times of Hippocrates over 2,000 years ago! It was not until about 400 years ago that it was considered that 'fresh food' and if not available, citrus fruit, were the cure of the illness. About 250 years ago, the ever first medical trial took place by a Scottish doctor, James Lind, who treated sailors suffering with scurvy with various potential 'cures.' The sailors given vitamin C containing regimens recovered.

Take Home Message

  • When something does not look right then it is not right. This patient had coiled hairs, ecchymosis (bruising), poor dentition and gingivitis. The diagnosis of scurvy should be considered especially in the elderly with poor nutrition and socioeconomic problems.
  • When looking at clinical pictures look for the normal and the abnormal. Look at all of the anatomy rather than what you are initially drawn to, otherwise, the diagnosis may be missed entirely!
I would like to take the opportunity to thank Professor Stein and Professor Dhaliwal for their superb interpretations and correct answers to this difficult 'spot case'.

Thursday, 5 November 2009

A Short 'Spot' Case for November

Dear Bloggers

Welcome back! I hope that you have been enjoying the recent cases.

Below is an anonymised short 'spot' case whereby the physical signs provide the diagnosis.

Question 1: Please carefully examine the patient's arm (first photo). What physical signs can be seen here?

Question 2: Please carefully examine the second photo. What physical signs can be seen here?

Question 3: Which ONE cause can link the main abnormalities seen below?

Question 4: What is the most appropriate test(s) and subsequent treatment?

Results out later this month. Good Luck !!!!

p.s. a word of advice, it may not be what you first think it is!

Tuesday, 27 October 2009

An interesting rash

Dear Bloggers

This 40 year old man was mending his wall when he fell and hit his chest. He was admitted to a hospital with a pneumothorax for which a chest drain was inserted. A fever developed after several days and pus started to drain from the chest tube. MRSA was cultured from the fluid and intravenous vancomycin was commenced after discontinuing initial therapy with ceftriaxone and clindamycin.

The patient developed diarrhoea during admission for which Clostridium difficile Toxin A was found to be positive. This was considered to be due to the Clindamycin, which is an infamous cause of pseudomembranous colitis. Oral vancomycin was also commenced.

The intravenous vancomycin was continued for 14 days and the patient made an excellent recovery, with resolution of the infections and pneumothorax. However, the patient noticed a red, non-painful rash develop predominantly on the back of his calf and thigh areas.

On examination the rash was as demonstrated in the pictures below. It was palpable!

A full blood count revealed a mild eosinophilia. Platelet count and coagulation screen was normal.

Vancomycin is known to cause a leukocytoclastic vasculitis, albeit rarely. It has been proposed as a cause of drug induced Henoch Scholein Purpura either directly or through a staphylococcal glycoprotein released after bacterial breakdown.

The morphology and distribution of the rash i.e. vasculitic and on the back of the lower limbs is consistent with a possible drug induced Henoch Schonlein Purpura. HSP is uncommon in adults. However, for HSP to be diagnosed, the patient should have arthritis, GI symptoms and renal glomerular involvement with IgA deposition. These latter symptoms were absent in this patient.

Unfortunately, this rash was no biopsied especially as it began to resolve after the vancomycin was discontinued.

It is highly likely that this palpable purpura was a vasculitis, perhaps of the leukocytoclastic variety. Please see the Medline references below.

Pharmacotherapy. 2009 Jul;29(7):846-51.

Vancomycin-induced leukocytoclastic vasculitis.

Felix-Getzik E, Sylvia LM.
Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts 02115, USA. erika.felix-getzik@mcphs.edu
Vancomycin is well recognized as causing the nonallergic skin reaction known as red man syndrome; however, it is rarely suspected as causative in the setting of an immune-mediated skin reaction. We describe a 76-year-old Caucasian woman with a history of penicillin and sulfa allergies who was transferred to our medical center while receiving vancomycin for treatment of persistent methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. After admission, the patient's pacemaker was explanted; cultures from the pacemaker grew MSSA. Based on the culture data and her allergy to penicillin, vancomycin was continued. On day 4 of therapy, the patient developed a papular rash with small blisters on her distal upper extremities. Furosemide, which she was receiving intermittently to maintain fluid balance, was initially suspected as the likely cause. Furosemide was withheld; however, the rash worsened and spread to her neck and torso. Results of skin biopsy confirmed a severe leukocytoclastic, necrotizing small-cell vasculitis that met the criteria for a hypersensitivity vasculitis associated with drug therapy. Five days after discontinuation of vancomycin, the vasculitis was resolving and continued to resolve throughout the remainder of her hospitalization. Furosemide was readministered without worsening of the vasculitis. Use of the Naranjo adverse drug reaction probability scale indicated that the likelihood of vancomycin being the cause of the vasculitis was probable (score of 5). Clinicians should be aware of vancomycin as a potential cause of small-vessel vasculitis.

Braz J Infect Dis. 2002 Aug;6(4):196-200.

Uncommon vancomycin-induced side effects.

Rocha JL, Kondo W, Baptista MI, Da Cunha CA, Martins LT.
Division of Infectious Disease, Nossa Senhora das Graças Hospital, Curitiba, Paraná, Brazil. jaimeluis@b.com.br
Vancomycin has been used with increased frequency during the past 15 years and the most common toxicity with this drug is the red man syndrome . Other adverse effects include neutropenia, fever, phlebitis, nephrotoxicity, ototoxicity, thrombocytopenia, interstitial nephritis, lacrimation, linear IgA bullous dermatosis, necrotizing cutaneous vasculitis and toxic epidermal necrolysis. Only two cases of vancomycin-induced Stevens-Johnson syndrome and one case of pancytopenia have been reported in the medical literature. The treatment for both situations is based on cessation of the vancomycin therapy; in cases of Stevens-Johnson syndrome, antihistamine and/or steroid agents can be used. This article reports a case of pancytopenia and a case of erythema major associated with neutropenia.

1: Scand J Rheumatol. 1998;27(3):233-5

Henoch-Schoenlein purpura and acute interstitial nephritis after intravenous vancomycin administration in a patient with a staphylococcal infection.

Michail S, Vaiopoulos G, Nakopoulou L, Revenas C, Aroni K, Karam P, Stathakis C, Thosios T.
Department of Nephrology, Laikon General Hospital, Athens, Greece.
We describe a case of Henoch-Schoenlein purpura, associated with oliguric acute renal failure due to acute interstitial nephritis histologically proven, in a patient with a staphylococcal chest infection. The clinical syndrome appeared twice after vancomycin administration and yielded on the withdrawal of the drug. As pathogenetic mechanism we propose an anaphylactoid reaction either to vancomycin or to a staphylococcal glycoprotein released after breakdown of the microbial cells caused by vancomycin.

Wednesday, 21 October 2009

The Answers to October's Case 2009

Dear Bloggers

I hope that you have had a go at trying to work out this case. This month, Prof Matsumura (Japan) and Prof Dhaliwal (USA) have kindly contributed their expert opinions to this case. A contribution was also gratefully received from a first year Japanese resident (shown below). As a reminder, here are the original questions to the case:

Question 1: From the history, physical exam, limited laboratory and radiology data, what is your differential diagnosis?

Question 2: What emergency radiology test will you do next?

Question 3: Where is the potential origin of this problem?

Question 4: What emergency treatment(s) will you consider in this patient?

From Professor Matsumura: Thank you very much for showing me a challenging case again.

This 65-year-old lady had fever and back pain. This combination is red flag sign. Back pain is very common condition (I have had this before!). However, she had fever too. I should think infection or neoplastic diseases. Moreover, she had had history of poorly controlled diabetes mellitus and bilateral renal calculi. I think these are very important information.

Question 1: From the history, physical exam, limited laboratory and radiology data, what is your differential diagnosis?

Problem list is as follows:
#1 Back pain
#2 Fever
#3 Dysuria
#4 Poorly controlled diabetes mellitus

#5 Renal calculi

#6 History of UTI

#7 Tachycardia
#8 Low blood pressure

#9 Globular distension and tender in suprapubic area

#10 Unable to grip the examiners finger with her anus.

#11 Weakness in the lower limbs
#12 Absence of knee jerks
#13 Tender spine and muscles from L1-L5 region

#14 Psoas sign
#15 Leukocytosis

#16 Septicemia, E. coli and Klebsiella pneumoniae

#17 Gas in the soft tissue in an abdominal CT scan Differential diagnoses are as follows.

Vascular: Less likely

Infection: Emphysematous pyelonephritis, Discitis, Osteomyelitis, Epidural abscess
Neoplastic: Lymphoma, Metastatic tumor
Autoimmune: Less likely

Toxic/Metabolic: Diabetes
Trauma/Degenerative: Less likely
Iatrogenic: Less likely Idiopathic: Less likely
Congenital: Less likely

#1 Back pain, #2 Fever, #3 Dysuria, #4 DM, #5 Renal calculi, #6 History of UTI, #9 Globular distension and tender in suprapubic area.
Urinary tract infection especially pyelonephritis is suspected.

#11Weakness in the lower limbs, #13 Tender spine and muscles from L1-L5 region, #14 Psoas sign. These conditions indicate inflammation spreads to retroperitoneal area including psoas muscle.

#17 Gas in the soft tissue in an abdominal CT scan. I think emphysematous pyelonephritis is most likely.

#7 Tachycardia, #8 Low blood pressure, #15 leukocytosis, #16 Septicemia, E. coli and Klebsiella pneumoniae
These findings indicated sepsis. E. coli and Klebsiella pneumoniae are major organisms in emphysematous pyelonephritis.

#10 Unable to grip the examiners finger with her anus
Rule out cauda equina syndrome. #12 Absence of knee jerks. This patient had diabetes. She can have diabetic neuropathy.

Question 2: What emergency radiology test will you do next?
I would perform MRI of lumbar spine to exclude cauda equina syndrome, osteomyelitis, or discitis.

Question 3: Where is the potential origin of this problem?
I think urinary tract infection is likely.

Question 4: What emergency treatment(s) will you consider in this patient? If we can see typical images of emphysematous pyelonephritis, surgical resection of the involved tissue in addition to systemic antimicrobial therapy is needed.

From Dr Dhaliwal: This is a very interesting case. I have deviated from the four question format instead by “thinking aloud” as the case unfolds. My differential diagnoses are embedded throughout with diagnostic and treatment suggestions at the conclusion.

History: Fever and low back pain typically brings to mind an infectious process. The low back pain may reflect nonspecific myalgias (e.g., influenza, SBE) or can be a focus of a suppurative retroperitoneal or lumbar spine infection. The difficulty walking, standing, and urinating points to a neuraxial infection, such as epidural abscess, vertebral osteomyelitis, or discitis. Poorly controlled DM increases the susceptibility to infection in general and raises the possibility of specific complicated infections, e.g., emphysematous cystitis or pyelonephritis. The latter must be entertained with pre-existing renal calculi. She lacks the dysuria that typically accompany lower tract infection.

This is an ill patient in shock. A murmur to suggest endocarditis is not detected, but can be challenging to hear at a heart rate of 120. The tender distended suprapubic area is compatible with complicated cystitis. A pulsatile mass – which would raise suspicion of one of the most sinister fever and low back pain entities, mycotic aneurysm – is absent. The anal laxity and decreased lower extremity tone and strength collectively suggest a spinal cord syndrome, perhaps of the cauda equina variety. The areflexia is consistent with nerve root compression or early direct cord compression. Interestingly, there does not appear to be a sensory level that accompanies cord syndromes, although the sensory exam can be highly variable and subjective at times. The musculoskeletal exam appears to suggest a psoas sign of sorts, which raises the possibility of a psoas abscess, along with inflammation of any structure adjacent to the psoas.

Gram negative bacteremia suggests GI or GU pathology. Polymicrobial bacteremia should at least trigger the thought that a connection that has been established between the GI tract and the vasculature such as an aortoenteric fistula, an ingested foreign body (e.g., toothpick), or an eroding cancer. The CT finding of soft tissue gas suggests a gas-forming organisms (like E coli and Klebsiella) and is compatible with emphysematous cystitis or pyelonephritis. Mesenteric infarction or Fourneir’s gangrene could account for soft tissue gas as well, but supporting clinical features are lacking.

Conclusion: 65 year old teacher with poorly controlled DM with E Coli and Klebsiella sepsis, low abdominal/back pain, and lower extremity weakness. One pressing question is whether there is a space occupying lesion compressing her spinal cord/roots. Numerous elements of the case suggest this, and therefore I would be most interested in a lumbosarcral spinal MRI. The next question (regardless of the MRI results) would be the origin of her gram negative bacteremia. Examination of the urine (with catheter placement) and re-examination of the CT scan would be in order. Treatment pending the above studies would include vigorous fluids and IV antibiotics.

Final diagnosis:
  • Emphysematous cystitis
  • GNR bacteremia
  • Epidural abscess
Dr Kato (1st year Japanese resident) has kindly provided an answer to the case as follows:

Q1 DDx
Among DIET IN HIM, Infection is the most likely cause of the illness, b/c DM, B/C results, acute course of the symptoms etc. strongly suggest Infection. Also I would consider Neoplasm b/c it could be similar to infection even though it is less likely, given back pain day-to-day progressing and neurological exams. I don't have ideas of neurological and inflammation cause in this case b/c neurological exams show bilateral but motor-only impairments and her age.

Secondly, I think this patiet have DM neuropathy symptoms such as rectovesicle impairment but it does not explain bilateral pure motor weakness, maybe. In this case, I am confused by this bilateral proximal limb weakness, but it could be explained by infection such as abscess b/o the presence of poas signs. Anyway, DDx as follows.

#1 epidural abscess #2 discitis #3
lymphoma and other cancers #4 DM neuropathy #5 infection of the soft tissue it might cause the bacteremia.

Q2 Enhanced MRI of the lumbar spine if available soon. If not, enhanced CT is also a good choice of study.

Q3 Vertebra~Disc of L3-5

Q4 ABx covering at least GNR (especially E.coli and Klebsiella). But I consider broad ABx use until Dx is determined.

The Answers

Both Professors Matsumura and Dhaliwal's general diagnostic process was similar to my own so to save time, I shall not repeat another list of my own.
However, the history of renal calculi and diabetes mellitus are extremely important in this case. They are risk factors for infection. As has already been alluded to, fever and back pain together are a Red Flag sign and such patients need urgent investigation. Serious diagnoses such as osteomyelitis, discitis, epidural abscess and psoas abscess should be high on the differential diagnosis list.

Moreover, with the addition of neurological signs such as an inability to pass urine, weakness of proximal musculature, and inability to grip the examiners finger during rectal examination all point to a possible cord / cauda equina syndrome as both Professors have already mentioned.

Indeed, an emergency MRI of the lumbosacral region would be warranted.

When this patient was seen by another senior doctor several days after admission, the weakness of the lower limbs had progressed more distally. The patient could only move her toes and there was no movement against gravity. Interestingly, the patient still denied sensory changes in her lower limbs.
The CT scan revealed an obstructed right kidney and a normal left kidney. There was a mild 'dirty fat' sign around the right kidney and evidence of bilateral psoas abscesses with gas formation throughout the muscle plains. This gas extended deep into the erector spinae musculature. The liver, gallbladder, pancreas, and bowel all appeared normal (no toothpicks).

The infection appeared extensive throughout the lumbar area.
Emergency MRI was performed and there was no evidence spinal cord or cauda equina compression. Unfortunately, no urine analysis data was available, which in retrospect, could have been extremely useful.

The suspected diagnosis was of an emphysematous pyelonephritis.

The patient was given ceftriaxone and underwent emergency surgery which included:
  • Debridement of the erector spinae muscles; the wound was left open and examined and washed daily.
  • Insertion of drains into both psoas muscles to drain the abscesses, again with daily wash outs.
The right kidney was not specifically treated. No nerve conduction studies were performed.

After 6 weeks of intravenous antibiotics and surgical lavage therapy, the patient had improvement in well-being, in general blood parameters and became afebrile.
  • Final Diagnosis: Emphysematous Pyelonephritis (Class 3b)
Emphysematous Pyelonephritis

This is an extremely serious infection. In previously described cases, most patients have been women aged over 60 years with a history of diabetes and / or urinary tract obstruction. Usual organisms include E. coli and K. pneumoniae. Candida is also a rare cause.

Causes of urinary tract obstruction can be either papillary necrosis or less commonly, renal calculi.

The symptoms of emphysematous pyelonephritis cannot be separated from those of the more usual pyelonephritis. Patients complain of nausea, vomiting, fevers, rigors, and flank or abdominal discomfort. The onset of symptoms may occur suddenly or evolve slowly over a several weeks.

Gas can sometimes be elucidated on the plain abdominal film but CT is more sensitive and specific.

The infection is managed with intravenous antibiotics. Some cases can be successfully treated with antibiotics and percutaneous drainage of pus from the kidney with relief of the obstruction. Failing that, open surgery is required with nephrectomy.

Emphysematous pyelonephritis can be classified as follows:

  • Class 1: Gas in the collecting system only (ie, emphysematous pyelitis)
  • Class 2: Gas in the renal parenchyma without extension to the extrarenal space
  • Class 3A: Extension of gas or abscess to the perinephric space, which is defined as the area between the fibrous renal capsule and the renal fascia
  • Class 3B: Extension of gas or abscess to the pararenal space, which is defined as the space beyond the renal fascia and/or extension to adjacent tissues such as the psoas muscle
  • Class 4: Bilateral emphysematous pyelonephritis or a solitary functioning kidney with emphysematous pyelonephritis.
Arch Intern Med 2000 Mar 27;160(6):797-805.

Nevertheless, despite intensive treatment, the mortality from several studies can be between 7 to 19%. Not numbers to be ignored.

Neurological impairment
The physical examination of hypotonia, weakness and loss of reflexes is consistent with a neurological component. Despite the apparently normal MRI scan on admission, with worsening neurology post-operatively, it would be judicious to repeat the MRI scan and perform nerve conduction studies.
Although, direct muscle damage due to infection, and as part of surgical intervention, can result in weakness, particularly of the postural muscles of the spine and flexors of the thigh (psoas) in this patient, it does not account for the distal weakness or loss of reflexes alone.

It is possible that the infection resulted in nerve damage, possibly due to diffuse radiculoneuropathy. However, a cauda equina syndrome would still need to be re-excluded by repeating an MRI. The fact that the patient stated that there was no sensory deficit is intringuing. I would agree with Prof Dhaliwal that the physical examination can be subjective on occasion although I would like to add that such an exam should be done in a standardised and methodical way to ensure that all sensory modalities are checked. Diabetic neuropathy can easily be missed unless it is specifically looked for, and the patients sometimes do not even realise that they have a loss in sensation. I would invite others to comment on this point.

The fact that she had existing diabetes can indeed account for loss of reflexes which should not be forgotten.
Only with further detailed repeat neurology (in full) and repeat MRI plus nerve conduction studies can the cause and full the extent of the disease be appreciated. The cause portends the prognosis.

Learning Points from This Case
  • Don't ignore Back Pain and Fever -- together they are a Red Flag Sign -- a potential medical emergency
  • Make an assessment and consider the serious diagnoses that should not be missed e.g. abscess, discitis, osteomyelitis etc.
  • If a patient complains of leg weakness then take it seriously especially when there is a history of back pain and fever. It suggests a possible cord / cauda equina compression - a neurosurgical emergency. Do not send the patient home : urgent physical examination, lab studies and radiology (CT/MRI) are required; this is especially important with neurological impairment
  • Gas in the tissues is serious. Antibiotics, drainage of the kidney, percutaneously and urethral catheterisation to relieve obstruction are advised. Surgery may also be required depending on the extent of the disease - see the classification above.
I would like to thank Professors' Matsumura and Dhaliwal and Dr Kato for their very kind and informative contributions to this month's case.

Sunday, 11 October 2009


Dear Bloggers

This patient with inoperable gastric carcinoma was commenced on palliative chemotherapy several months before the current admission. However, there was development of intermittent fever several days after the insertion of a tunneled Hickman line. The patient was not found to be neutropaenic.

Blood cultures were taken from the peripheral veins and from the line - both grew coagulase negative staphylococci (CNS). The CNS were sensitive to minocycline and flucloxacillin (anti-staph penicillin).

The patient did not want to remain hospitalised. As the patient was otherwise well, long term oral minocycline therapy was commenced to try and eradicate the infection as an outpatient.

The patient was readmitted after several weeks with continuing fevers and rigors. There was no redness or pus around the entry site of the tunneled line. Again, cultures were positive for the same coagulase negative staphylococci from the line and peripheral veins.

Below is the nail change found in the this patient, which was symmetrical in both hands.

This blueish discolouration of the proximal nail is a rare but typical finding of long term minocycline therapy.

Please note that tetracycline antibiotics are chelators (e.g. bind iron, magnesium and calcium) and should be avoided in pregnancy (foetal harm), breast feeding women and children less than 12 years old (tooth discoloration and bone hypoplasia; BNF 57). Tetracyclines can exacerbate renal failure and should be avoided. If long term administration is desired (e.g. acne), hepatoxicity and pigmentation should be checked for every 3 months (BNF 57). If these side effects or SLE develops (very rare complication), the drug should be discontinued.

This patient was eventually treated with intravenous flucloxacillin, given via the Hickman line with resolution of the infection after 10-days of therapy. Transthoracic echocardiogram revealed no evidence of valvular vegetation.

Remember that common things are common - when you get fever and rigors in a patient with long term venous line, think of line infection as a differential diagnosis in your assessment.

However, oral antibiotic therapy is not the standard to treat such an infection. The current approach is to use IV antibiotics given via the line to try and eradicate the infection. Other methods include 'antibiotic lock' therapy by instilling antibiotic into the line under a 'hub lock' to keep the antibiotic within the line to kill the infection. More evidence is required to determine its efficacy.

Central venous catheter infections can be difficult to successfully treat by IV antibiotics even given by the line and as a consequence, there should be a low-threshold for removing it. Some advocate exchanging the old line for a new one over a guidewire but there is the obvious concern of transferring such infection onto the guidewire and then on to the new line. Moreover, there are risks of further bacteraemia and dissemination of septic emboli and such practise is generally discouraged especially when there is obvious soft tissue infection around and deep to the line.

Learning Point: Blue discolouration of the nails is not normal. Please do a chart biopsy and find out which drugs the patient has been taking.

Monday, 5 October 2009

A Case for October 2009

Dear Bloggers

A 65 year old retired lady school teacher was admitted to a hospital with a one-week history history of fever and back pain.

The back pain had started gradually over a few days and was worse on movement. Initial pain scale was 3/10 but over several days it worsened. The pain was described as sharp and there was no radiation to the lower extremities.

The fever was continuous and she had episodes when she felt very hot. She did not have a thermometer so she could not provide any home readings. However, she did admit to night sweats and shivering during the fevers.

The patient went to see her local physician who thought this was a 'common cold' with myalgia. The doctor had not formally examined the patient. Some simple anti-pyretic medication was prescribed.

Over several more days the back pain became increasingly worse reaching 10/10 and the patient found it difficult walking up stairs and standing from a crouching position. She also found it difficult to pass urine. When she was admitted to the hospital but was unable to walk, thereby requiring a wheel chair.

She denied thigh pain and joint pains. She denied frequency, dysuria, nocturia and haematuria.
There was no history of upper respiratory symptoms. She denied headache, photophobia, neck stiffness or rash. There were no other abdominal symptoms.

She had a previous medical history of poorly controlled diabetes mellitus and bilateral renal calculi diagnosed several years, the latter which were under observation. She also had a history of a urinary tract infection 8 years ago.

Medications included metformin 1 gram twice daily, aspirin 75mg daily and recent use of acetaminophen when required.

She had no relevant family or social history.

She was post-menopausal from fifteen years before. She had an otherwise previous normal menstrual history without problems. She denied any post-menopausal bleeding or abnormal discharge or pus. She was not sexually active.

There was no history of foreign travel, interaction with sick contacts or recent dental work. She had no pets and did not have any unusual hobbies. She was a non-smoker and non-drinker.

On Examination

She appeared ill. GCS 15/15. Alert.

No J A C C O L. Temp 38.4 deg C

CVS: pulse 120 min regular, BP 100/50mmHg, JVP not elevated, no heaves or thrills, normal heart sounds I + II, no 3rd/4th heart sounds. No extremity edema.

RESP: RR = 18/min, SpO2 - 98% breathing ambient room air, trachea central and no tug, expansion within normal limits, and percussion note resonant. Auscultation revealed no crackles or wheeze.

ABDO: Soft and non-0bese abdomen. Suprapubic area revealed a globular distension, tender to palpation, percussion note was dull and there were no bowel sounds in this area. No rebound or guarding. No hernial orifices were identified. No hepatosplenomegaly. Otherwise, normal bowel sounds. Rectal examination- hard stool ++, no FOB. Patient was unable to grip the examiners finger with her anus.

CNS: No focal abnormality. No neck stiffness or jolt accentuation. Kernig's sign could not be performed because of back pain. Brudziki sign was negative.


  • Tone normal upper limbs but decreased in the lower limbs.
  • Power - normal upper limbs 5/5. Proximal lower limbs muscles 3/5 especially in hip flexion and extension. Distal lower limbs were mildly weak with power 4+/5 bilaterally.
  • Reflexes - normal in the upper limbs. Knee jerks were absent and mildly present in the ankles. Babinski were bilaterally absent (no reaction).
  • Coordination - upper limbs were normal. Difficult to elicit in the lower limbs because of weakness.
  • Sensation - light touch, nociception, vibration and joint position sense were within normal limits.

Musculoskeletal exam - tender spine and muscles from L1-L5 region. Extension of the proximal limbs induced severe pain. Other muscles were non-tender.

Lab Data - revealed a leukocytosis but otherwise, liver and renal blood tests were normal. No urine analysis was available.

Blood cultures revealed E. coli and Klebsiella pneumoniae in two sets of bottles.

Radiology - An abdominal CT scan was performed which apart from other abnormalities reported of seeing gas in the soft tissue.

Question 1: From the history, physical exam, limited laboratory and radiology data, what is your differential diagnosis?

Question 2: What emergency radiology test will you do next?

Question 3: Where is the potential origin of this problem?

Question 4: What emergency treatment(s) will you consider in this patient?

Thursday, 17 September 2009

History O'History - The Wonderful World of Dermatology

Dear Bloggers

I am back with a nice dermatological short case. As usual this patient's details have been anonymised to maintain confidentiality.

This 40 year old officer worker was admitted with an uncomplicated community acquired pneumonia. Nothing unusual about that you might think. However, the admitting doctor noticed the unusual skin rash on the patient's legs (only one shown here!). The patient had noticed this just recently and was unaware of the cause.

The patient was diagnosed with iron deficiency anaemia (IDA) several years ago of unknown aetiology. She was also known to have atopic eczema.
The doctor thought the rash was livedo reticularis and was rightly concerned that the patient might have an underlying connective tissue disease e.g. SLE (resulting in immune suppression) or perhaps an unusual hyperviscosity syndrome.

Her admission blood tests revealed an Hb of 5.9 and MCV 72. Iron and ferritin were low and TIBC was high. Blood smear confirmed the diagnosis of IDA. The cause of iron deficiency was unknown at the time of admission and the doctors were planning on doing a full 'work-up' to elucidate the cause.

When reviewed by a senior doctor, the rash did not look entirely typical for livedo reticularis which has a more telangiectatic appearance. This aside, there were flexural areas with lichenification consistent with atopic eczema.

Despite querying the patient, she could not identify the cause of the new rash. Nevertheless, the senior doctor asked a focused question below:

"Have you been putting anything hot on your legs recently e.g. hot water bottles, or sitting near a heater?"

"Yes. My office has been really cold. I have been sitting very close with my legs to my electric heater"

From this information alone the diagnosis, far from being livedo reticularis, was instead the famous and little remembered
erythema ab igne or otherwise known as erythema calorica. This is a reticulated skin reaction due to repeated heat exposure and can appear very similar to livedo reticularis. Livedo is usually more symmetrical and telangiectatic rather than erythema ab igne which is pigmented and forms dependent upon the extent and location of exposure to heat.

It is typically seen in the elderly (usually women) who sit too close to the open home fire / electric heater with their lower limbs exposed, or with hot water bottles placed on their limbs, abdomen or back. With central heating having become the norm in the UK, this condition is now rarely seen. Other people affected can be bakers or those that carry hot coals. It has also been cited as a useful marker in patients with chronic pancreatitis as the warmth helps the abdominal pain !

Please see some examples below:
Please note the differences in the presentation between darker and lighter skinned persons. Nevertheless, the 'sun burst' pattern appears to be the persistent characteristic finding here.
In such patients, hypothyroidism should be ruled out. Moreover, in view that this patient presented in late summer when the outside daytime temperature was over 27 degrees Celsius, one has to wonder if the chronic anaemia had something to do with the feeling of coldness in her legs! Remember that cold hands and feet are a symptom of anaemia!

Sometimes such interesting problems arise and using your observational skills, the right questions can be asked to build up the day-to-day life of the patient. Such problems might then point to an overall cause. Remember that patients do not know what you want to hear. You have to ask the right questions to get the answers. No 'pan-man' CT scan will give the answer here. Simple communication with the patient and using 'Sherlock Holme' skills of deduction can win the day.

In this case, further history revealed that the patient was eating just one meal a day without red meat or a good source of iron. She consumed a high amount of carbohydrate e.g. bread. Despite the high possibility of nutritional deficiency from decreased intake (and Fe loss in a regularly menstruating woman) being the likely cause of iron deficiency anaemia in this case, GI loss should be excluded in addition to causes of malabsorption e.g. celiac disease.

Diagnoses In This Case:

1) Uncomplicated community acquired pneumonia
2) Erythema ab igne

3) Chronic iron deficiency anaemia - Common things are common - likely from poor nutritional intake and menstruation.
4) Atopic eczema

For the investigation and treatment of Fe-deficiency anaemia, please see any standard EBM textbook. For a good dermatology text, I would recommend Rook's Textbook of Dermatology.

Tuesday, 25 August 2009

A vision of the not so distant future

Dear Bloggers

I wanted to share my thoughts with you about how I envision the world of medical information technology will become in the next 10 to 20 years.

At present, we either write or type our medical notes. How quaint indeed. Humans have been using some form of paper for thousands of years. Papyrus was one of the earliest forms of writing material and before that, the Greeks wrote on tablets. We may indeed be going full circle in the electronic age with the tablet handheld. As you know, I love electronic gadgetry and although great inventions have been produced thus far, they are still in their infancy of development. Tablet computing is not a new thing but the size, capacity, user interface and general usability has been suboptimal for the needs of the modern physician. That may all be changing. There are rumours (and photos) indicating that Apple may be releasing a new tablet computer for next year!

I envision the day that a ward round at the bedside will involve voice recognition of the patient and the doctor by a hand held computer thereby giving a virtual transcript of the interview. With some artificial intelligence and fuzzy logic thrown in for good measure, the device could then organise the data into a structured format for the medical interview. It could then automatically list the previous medical history, social history etc, as the patient tells their story. Moreover, the computer could access the national database e.g. new UK system, to reveal the patient records in an instant.

Physical examination findings could either be recorded by the doctor through dictating the findings or by pressing selected boxes for positive or negative findings. Physical signs could then be added as a photographs or video from the built in camera.

By determining the history and hence, a list of symptoms, and the physical findings, the computer could then cross reference these symptoms and signs to a diagnostic database and provide options to the doctor for the mostly likely diagnoses and potential investigative and therapeutic options. If the doctor needs to brush up on some medical facts, the diagnoses could then be cross referenced to an EBM site such as UpToDate. Sounds like Star Trek right! Well, if you are a Trekky, in the original series, they came up with the 'mobile phone' device, memory cards, and video calls etc. Science fiction is tomorrows reality.

Such a system could provide a seamless, typing-less and paperless system that SPEEDS up patient care at the bedside rather than chaining the doctor to the PC work station or a pen and paper at the nursing desk.

With wifi being the standard technology being built in to the newest of devices, using an internal internet system (intranet) for use of secure information transfer with links to outside sites for cross referencing for diagnostic purposes, this would provide a state of the art system for patient care. PACS could also be utilised as could the ordering and checking of laboratory tests - these are already becoming a reality.

There is a new system coming to fruition that can provide fast transcription of dictations, for example, via the iPhone. However, there has been much criticism of late that such transcriptions rather than done by computer ( as advertised ) , are actually transcribed by people in centres based in other countries. This kind of technology , if it actually exists / works, is interesting but would be too slow for a ward round based system especially as sensitive information would be discussed and this should be kept confidential. Any system which could use dictation, transcription and to organise data would probably have to use artificial intelligence.

Computer technology has moved in leaps and bounds. Chips are getting smaller all the time, capacity is growing all the time and power consumption is decreasing and with the potential for new forms of batteries being produced that can charge instantly, and with such charging being across the air via magnetic waves or through direct contact without wall plugs. I can remember the large desktop computers that took minutes to boot up and crashed if you had too many programmes running simultaneously. The ZX spectrum comes endearingly to mind......Now we have laptops with consistency and reliability, fast multi-tasking and user interfaces that finally can be used with ease.

If we can get to the point when machines can have innate intelligence to be able to help humans in an intuitive and predictive way, then the above vision can become a reality.

But are we too far from that situation right now?

The best PDA around at the moment is the iPhone. Yes, I come back to this ingenious device. It has 3G and Wifi access, a camera and a pleasing user interface. It will not be too far off when specific medical software will be produced that will allow medical notes to be kept which can utilise the camera feature and will allow updating of such information on to a medical intranet database system. The iPhone can already utilise PACS data! It already has a dedicated UpToDate site and Skyscape has a multitude of medical books available which can cross reference to other books within the software package. All it takes is a little bit of cooperation and integration of the software packages to produce a system close to that I have described above.

Technology can set us free from the keyboard and paper. But, it has to be the right kind of technology. Many hospitals have the computer based patient notes, also referred to as Denshi Kalte. In my opinion, because data is kept sequestered in different areas of the database system (rather than fully integrated) with a poor implementation of the user interface, it can take a long time to enter information and to retrieve it. In fact, it can be slower and more labour intensive than using paper. Technology was supposed to be made to improve efficiency to make our lives easier, but the current medical software does not appear to achieve this objective. I can remember seeing 30 ward patients in a morning on my own and having written thorough paper notes for all of them. I can't see how the current situation with Denshi Kalte will allow anything near to that speed of input as compared to paper. Perhaps the next generation of computing will change that.....

With a portable computer in hand and the right software I think that we can get close to the idea above and set the doctors free to deal with patients rather than having to deal with the frustrations of copy and paste, trawling through old notes to find the needle in the haystack and where to find the histology report, that got put in the difficult to find tab system.

Things can only get better, but we must be prepared to change our technology to do so, but to change it in the right way.

Have a good week.

Kirk Out !

Wednesday, 19 August 2009

Answer to August 2009 Case

Dear Bloggers

Thanks for waiting for the answers to this exciting case.

I would like to apologise for the typing error with the PNS exam which should have been like this


+/- ++ n/a n/a
Bicep +/- ++ n/a n/a
+/- ++ n/a n/a
Knee n/a n/a +/- +/-
n/a n/a +/- +/-

RUL = Right Upper Limb
LUL = Left Upper Limb
RLL = Right Lower Limb
LLL = Left Lower Limb

This month Prof Alan Lefor (Surgeon, USA) and Professor Gerald Stein (Rheumatologist, USA) have kindly answered the case. Their comments follow on below:

Professor Lefor

Question 1: From the history and examination, please make an appropriate problem list. Problem List:

1. History of LOC with urinary incontinence 2. Changes in bowel habits (loose stool, black stool) 3. Neurology symptoms (double vision, dizzy, tingling, reflexes asymmetric) 4. Hx of adrenal tumor 5. PAF 6. Hx of previous Htn 7. Abnormal physical exam with axillary nodes, hypotension and tachycardia

Question 2: Please provide a differential diagnosis (es).

It would be nice to tie all of this together in one package, which may be possible, but there are other possibilities with multiple diagnoses.
1. GI tumor with brain mets, anemia 2. Other primary tumor (e.g. melanoma) with GI, brain involvement 3. GI bleeding from a non-malignancy and significant anemia 4. New onset seizures from tumor or from metabolic disturbance 5. Metastatic adrenal tumor (someone should get the details of this tumor from old records, it is essential).

Question 3: What would you immediately do for this patient?

Immediate actions:
1. Complete the physical exam with a stool guaiac test 2. IV fluid resuscitation with catheter placement to follow urine output 3. If her anemia is significant, given her LOC, tachycardia and hypotension, then transfusion is indicated.

Question 4: What tests would you perform and why?

1. I think the stool guaiac will probably be positive. She needs a colonoscopy. If that is negative then upper endoscopy especially if an NG tube shows bloody drainage 2. She has enough neurological symptoms to mandate a CT of the head for ischemic damage or mets as a cause 3. I would check a CBC (?anemia) and electrolytes (?cause of seizures, etc) 4. If all of this is uninformative, especially the endoscopy, then the axillary lymph nodes should be biopsied in the search for a primary tumor.

Question 5: What other bedside physical examination test(s) could provide additional information to aid your diagnosis?

1. Stool guaiac
2. Fundoscopy looking for signs of increased intracerebral pressure 3. Pass NG tube to R/O upper GI bleeding

Professor Stein Question 1: From the history and examination, please make an appropriate problem list.

1. Transient Loss of Consciousness with urinary incontenence need duration
2. Loose BLACK stools

3. Parathesias LUE, diplopia (Cr N 6), proptosis L eye, LUE & LLE ??? DTR
4.Adrenal tumor>-ectomy
5. HTN

6. PAF
7. 2 anti plat Rx + NSAID
8. Anemia

9. Lymphadenopathy

10. Hypotension

11. Tachycardia

Question 2: Please provide a differential diagnosis (es).

1. R/O GI bleed/hypovolemia/hypotension
2. R/O Subdural hematoma 3. R/O Midbrain or Brain stem infarct 4. R/O Brain emboli [PAF] 5. R/O arrythmia 6. R/O AMI & PE 7. R/O DM/Addison???s 8. R/O causes of hyperuricemia: renal, lymphoma 9. R/O seizure

Question 3: What would you immediately do for this patient?

1. Fluid resuscitation-hourly urine output 2. Capillary Glucose 3. STOP anti plat & NSAID Rx

Question 4: What tests would you perform and why?

Stool & NG fluid occult blood; if + EGD/colonoscopy,
ECG for PAT/hidden flutter CBC, electrolytes, Blood glucose, BUN/creat, cardiac markers, D-dimer, cortisol, Chest xp, Brain CT Cardiac, ECHO, EEG-later if needed

Question 5: What other bedside physical examination test(s) could provide additional information to aid your diagnosis?

Stool occult blood, Fundoscopy, Ausculate neck for carotid bruits and Bilat upper limb BP???s/pulses

Thank you to Professors Lefor and Stein for such excellent answers. I will now reveal the case answer below!

Question 1: From the history and examination, please make an appropriate problem list.

Problem List
  1. Loss of Consciousness
  2. Dizziness on standing
  3. Urinary incontinence
  4. Loose stools
  5. Pins and Needles of the left arm
  6. Double vision
  7. Right adrenalectomy
  8. Paroxysmal AF
  9. Hyperuricaemia
  10. Disopyramide / Aspirin / Voltarol / Allopurinol / Ranitidine/ Lactulose / Senna
  11. Large, rubbery, smooth, multifocal lymphadenopathy
  12. Tachycardia
  13. Hypotension
  14. Rectal Examination - Black stool
  15. Proptosis of Left Eye
  16. Abduction Palsy of Left Eye
  17. Left arm relative Hyper-reflexia

Question 2: Please provide a differential diagnosis (es).

In the under 50s it is often desirable to try and use Okham's Razor to bring all elements of the problem list together to try and make one unifying diagnosis. However, in the over 50s although Okham's Razor can still be used, Hickham's Dictum is perhaps more relevant. This means that patients are allowed to have as many diagnoses as '...they well please' ! :-) This was described by Hickham in the 1950's when it was said that patients are statistically more likely to have several distinct illnesses / diseases then one rare disease (re Okham), which logically becomes more likely as the patient ages.

Hence, when looking at this case, it should be considered that there are multiple diseases rather than one. Let's first consider why the patient collapsed.

The fact that the patient experienced dizziness on standing, has vital signs consistent with shock (when the patient is usually hypertensive) and has a rectal examination consistent with malaena (despite the patient saying no to this) makes an upper GI bleed the most likely cause of the collapse. The cause of such bleeding is the combination of Aspirin and NSAID despite the use of Ranitidine (H2-blocker). H2-blockers are not as effective as PPI medication and even the latter cannot always prevent GI bleeding.
However, one should also consider other causes:
  • Infection - sepsis can result in collapse from shock. Remember that sepsis can cause DIC with low platelets and a coagulopathy. This can result in GI bleeding too. The fact that the patient was unconscious should alert us to intracerebral infection such as acute bacterial meningitis. Of course, other bacterial infections can cause septic shock e.g. gram negative UTI, GI infection
  • Endocrine - remember that this patient has had a previous adrenalectomy and may therefore be relatively hypoadrenal. Hence, under a period of stress of any cause, hypoadrenalism can result with collapse (from hypotension), loss of consciousness / confusion (hypoglycaemia) etc. One might also observe a rise in the K+ and a low Na+ level. One should also consider thyroid disease e.g. thyrotoxicosis, which is a precipitator of AF.
  • Trauma - no evidence to support this but the patient is taking anti-platelet agents so minimal head trauma could conceivably cause intracranial bleeding.
  • Inflammatory (connective tissue disease) - no evidence to support this
  • Neoplastic - see later. Gastric Ca with bleeding (possibly metastatic to brain), metastatic adrenal tumour -> cerebral mets ->seizure
  • Haematovascular - SAH, intracerebral bleeding/infarction, subdural, extra-dural bleeding (less likely due to the PNS exam)
  • Metabolic - Hyponatraemia, Hypoglycaemia, Hypercalcaemia
  • Cardiovascular - cardiac dysrhythmia e.g. underlying worsening of PAF, other dysrhythmia induced by the disopyramide (!!!Remember that Class I drugs are also arrythmogenic!!!), Pulmonary embolism (always on the differential diagnosis list for collapse!) Vascular: Hypovolaemia / Sepsis / bleeding
  • CNS - Seizure (as a result of metastatic tumour / metabolic / electrolyte / structural / vascular abnormalities)
The second set of problems we must assess are the cause of the tingling left arm with hyper-reflexia, diplpopia and proptosis with a impairment of abduction of the left eye. The lymphadenopathy may also be relevant here along with the hyperuricaemia. Although the CNS manifestations are physically presenting on the same side of the body, the fact that there is proptosis of the left eye strongly suggests a space occupying lesion in the left orbit. The hyper-reflexia of the left arm with tingling suggests a right sided cerebral lesions possibly affecting the sensory (post-central) cortex. Hence, the intracranial lesions are on different sides suggesting a multifocal pattern!

The fact that there are lymph nodes makes one consider the possibilities of:
  • Infection e.g. Tb
  • Neoplasia e.g. Ca stomach, lymphoma
  • Connective tissue disease
  • Granulomatous disease e.g. sarcoid
The raised uric acid might simply be 'idiopathic' perhaps related to her diet or alcohol consumption (which we are not told about). On the other hand, high turnover of cells might suggest the presence of a tumour e.g. lymphoma (as suggested by Professor Stein)

However, the description of 'smooth and rubbery' usually points towards the idea of a lymphoma as the cause. If there are indeed multifocal intracranial space occupying lesions, common things should be considered first e.g. malignancy (metastatic disease), intracerebral lymphoma, tuberculosis, etc. Hence, the differential diagnoses on admission have been separated into the causes of collapses and the causes these odd neurological symptoms and signs with some of the causes certainly over-lapping.

Question 3: What would you immediately do for this patient ? & Question 4: What tests would you perform and why?

  • This patient has shock vital signs and she requires volume resuscitation and glucocorticoid therapy until such time that hypoadrenalism has been ruled out.
  • In view of the malaena, it is advisable to cross match 6 units of blood for possible transfusion immediately or to use later if the patient bleeds more extensively. Large bore venous lines should be placed in each antebranchial fossa of the upper limbs for the purpose of rapid fluid transfusion.
  • In order to guide fluid status, it is often advisable to place a central venous line to maintain the CVP at 8-12cmH2o and place a urinary Foley catheter to ensure adequate urinary output e.g. >30ml urine/hour. In Japan, CV pressure is estimated using echo measurements of IVC compliance that can estimate whether the CV pressure is raised or decreased. Remember that both methods are fraught with inaccuracy and hence, repeated physical examination is ALSO required to gauge when fluid rehydration is inadequate, adequate or excessive.
  • Venous glucose should be checked and if in any doubt, 50ml 50% glucose should be given to treat for hypoglycaemia. Remember that peripheral and CNS glucose have a poor correlation. Hence, even if the peripheral glucose is normal, the CNS glucose can be low!
  • Blood, sputum and urine culture should be obtained to investigate causes of sepsis. Remember that ranitidine and allopurinol drugs can affect the haemopoietic system causing immune dysfunction. If in doubt about the focus of infection, please treat accordingly with antimicrobial agents until infection has been fully excluded by negative cultures or another definitive diagnosis has been established.
  • This patient should have basic laboratory data checked to establish haematological or biochemical abnormalites (as discussed) and a chest Xray which could be a clue for the cause of cerebral lesions e.g. cancer, Tb
  • To investigate upper GI bleeding, an NG tube can be passed to aspirate blood. A negative test does not exclude GI bleeding but supports it if it positive. There is not evidence that passing an NG tube makes variceal and non-variceal bleeding any worse and it can be helpful diagnostically to know if there is fresh active bleeding. Once haemodynamically stabilised (and not before!) an EGD (gastroscopy) can be performed to look for a cause of possible upper GI bleeding. Intravenous PPI should be given e.g. omeprazole 80mg stat, followed by continuous infusion for 72 hours. Consider tranexamic acid which also reduces GI bleeding. Assess patient's Rockall score for potential of rebleeding AFTER the gastroscopy. This will help to know if the patient requires a 'bleeder bed' -- high input care on a GI ward.
  • Remember, never do procedures on an unstable patient. Moving the patient to the GI room could prove catastrophic with a 'bleed out' on the way. Better if you can take the gastroscopy machinery to the patient!
  • Once stabilised, this patient will need a CT head scan to look for SOLs, edema, bleeding, etc. If normal, a lumbar puncture would be very reasonable to exclude meningitis / bleeding. Remember, you have already given the antibiotic to cover infection. CSF can remain positive for up to 4 hours after injection of intravenous antibiotic. Even if the CSF is visibly negative for organisms, PCR can be performed.
  • Lymph node biopsy should be performed as soon as possible to look for the underlying cause e.g. lymphoma.
  • Remember to check the ECG and if there is still concern, a 24 hour Holter ECG can be performed. The disopyramide might need to be stopped until the cause of the collapse can be fully elucidated.
  • Checking of cardiac enzymes (e.g. CK-MB, Troponin I/T) and D-Dimer should be performed. The fact that there may be underlying sepsis or malignancy can give a false + D-Dimer result and hence, as part of the work-up, a cardiac echo may be required. If the pressures are normal, then a life threatening pulmonary embolism (PE) can be ruled out whereas if they are elevated, proceeding to Spiral CT would be necessary. An Echo would also be useful to exclude large intra-cardiac clot that could give rise to cerebral emboli resulting in stroke and collapse.
  • The fact that the collapse was unwitnessed and the patient has multi-focal neurological signs warrants an EEG to look for a focus of seizure. The patient might require intravenous medication -- remember though, disopyramide and pheytoin (the usually IV drug for seizures) are both Class I drugs. Phenytoin induces liver enzyme induction and can reduce the effective levels of disopyramide.

Question 5: What other bedside physical examination test(s) could provide additional information to aid your diagnosis?

  • If the patient has an intra-orbital SOL, performing fundoscopy might reveal raised pressure which may be visualised as papilloedema.
  • Comfirming the black stool as malaena with the Guaiac test would be supportive of GI haemorrhage.
  • As mentioned above, an NG tube could be passed to look for upper GI bleeding.

Comments on the Case

Below are the CT pictures that confirm the physical examination findings. Please note the multiple SOLs were considered BEFORE the CT head scan was done. Proptosis and gaze palsy with axillary lymphadenopathy should suggest the possibility of an intra-orbital tumour, as was suspected in this case. Cerebral edema from an SOL was additionally suspected as part of the differential diagnosis. There needed to be careful consideration of using high dose dexamethasone given the possibility of it affecting the GI bleeding by impairing ulcer healing.

The scan shows two mass lesions - one in the left lateral orbit (as suspected) and one in the right cerebrum with edema.

Admission laboratory data was as follows:

Hb 11.o, WCC 8.2, HCT 32.6, MCV 80.1, Plts 135, INR 1.3 Na 132, K 5.3, BUN 60.2, Creat 1.3, Ca 8.7, Glu 160, LDH 290. Normal liver function tests. Albumin 2.8, Total protein 5.9

As can be seen above, the BUN/Creat ratio is 46.3 (hence, more than 20) suggesting an upper GI source of the bleeding. Note the Na 132 and K 5.3 which might signify hypoadrenalism (remember the loss of aldosterone leads to accumulation of K and failure to absorb Na in the kidney). Even though the Hb is 11.0, a normal female Hb level is from 11.5 to 16.o and hence, this patient does have an anaemia. Moreover, the MCV is more than 80 but for the local laboratory measurement it is low! Remember to ALWAYS refer to your own lab's normal range otherwise the microcytic anemia can easily be missed !

The stool examination was +/+ for blood.

As a consequence, the patient underwent a gastroscopy and a large acute gastric ulcer was present (see below) and treated accordingly.

Despite the other mentioned possibilities of sepsis and hypo-adrenalism, unfortunately, these were not followed up by the attending team. The chest x-ray below reveals bulky perihilar areas, which given this case, is suspicious of hilar lymphadenopathy.

Lymph node biopsy revealed Diffuse Large B Cell Lymphoma. Diagnoses in this case:
  1. Acute Upper GI Bleed (iatrogenic) from Aspirin and NSAIDs causing collapse and shock
  2. Diffuse Large B Cell Lymphoma (multifocal e.g. intracranial, axillary) ? possible seizure due to intracerebral SOL with edema.
  3. Possible hypoadrenalism
Take Home Message

  • When patients are admitted with loss of conscious, unless there is a reliable witness to the events, search for more than just one cause especially in the elderly.
  • In loss of consciousness, perform a rectal examination to look for bleeding. Failure to do so may miss GI bleeding!
  • In loss of consciousness, perform a full neurological examination if the patient recovers consciousness. Even if unconscious, the GCS/JCS can be performed in addition to pupillary size, corneal reflex, fundoscopy, caloric test, tendon reflexes and Babinski reflex as common examples. In this case, only after asking specific questions did the patient offer up the neurological symptoms and only after a repeat examination did the abnormal neurology come to light. It had been otherwise missed. Hence, you need to have a high suspicion of neurological disease and actively ask additional questions rather than passively relying just on what the patient wants to tell you! Remember, patients don't write the textbooks and they don't know what you want to know (unless they are medical professional themselves!)
  • Remember that resuscitation of the patient must be done first before considering moving them to have a gastroscopy, a CT or going for surgery etc.
  • Correct all that can be corrected. This patient's INR was 1.3. That is abnormal. Giving vitamin K will not work to resolve the coagulopathy acutely. It takes several hours to have an effect by which time your patient could have bled out. The quickest treatment is giving factor replacement e.g. factor concentrate (II, VII, IX, X) if warfarin has been used, or Fresh Frozen Plasma (FFP). Even if it is justly slightly abnormal means that it is NOT normal and should be corrected. Don't take risks with your patients. Treat them how you would like to be treated given you being in the same situation.
  • If hypoadrenalism is suspected, perform a rapid ACTH test and start appropriate dose steroids e.g. hydrocortisone 100mg iv every 6 hours. Do Not Wait for the results as it can take several days to the detriment of the patient!
Thank you for your consideration.

Many thanks to Prof Lefor and Prof Stein for providing their expert opinions on this month's case.

Thanks to Dr MM, Drs Y, A, Y & U.