William Gardner
Clinical Articles iconClinical Articles

Anemia is a major health problem, with nearly 2 billion people affected globally...

A/Prof Vicki Kotsirilos AM
Podcasts iconPodcasts

Air pollution has contributed to more than 3,000 premature deaths per year in Australia, nearly x3 that of deaths from MVA

Clinical Articles iconClinical Articles
Expert/s: Healthed
Dr Lawrie Bott
Clinical Articles iconClinical Articles

Glomerular filtration rate (GFR) is the best single measure of kidney function. A subnormal GFR is an important early indicator of possible chronic kidney disease. However, it also does not identify the cause. It is also not a ‘catch all’, for example, in early diabetes mellitus, GFR will typically be normal or even increased, due to ‘hyperfiltration’. Optimal detection and risk stratification of early kidney disease also requires measurement of urine albumin, rather than just eGFR.

Expert/s: Dr Lawrie Bott
Dr Linda Calabresi
Clinical Articles iconClinical Articles

These days the first question most GPs get asked, after confirming a wanted first pregnancy is what does the woman need to take or eat, and, importantly what should she avoid. It gets tricky doesn’t it? If you avoided  everything that is said to potentially cause harm (according to the world wide web and social media) the pregnant woman will run a serious risk of malnutrition!  Much of the fear stems from the risk of contracting listeria – that surreptitious bacteria that can cause – very occasionally, severe infection in affected adults – but more importantly for the pregnant women can cause miscarriage, premature birth or stillbirth. You need some authoritative, credible information sources to fall back on when giving these vulnerable patients advice. Enter the Food Standards Australia and New Zealand website. On their website they have this fantastic resource: an information page entitled Listeria and food. Quite simply, it’s a precis of what women should and should not eat to keep them safe from this infection. To be fair this resource doesn’t help women keep the problem in perspective, as it doesn’t mention how rarely this condition affects pregnant women. But it gives very definitive advice – eat this – don’t eat that. The reality is, this could save the GP at least 15 minutes discussion time, and provide a ready reckoner for the woman negotiating the local café menu or shopping centre food halls. There is no debate, the pregnant woman, especially the first-time pregnant woman represents a very vulnerable, information-hungry demographic. Keep this site bookmarked and you won’t be sorry.   >> Access the resource here

Dr Linda Calabresi
Clinical Articles iconClinical Articles

The entity ‘mildly dysplastic naevus’ has been removed from the World Health Organisation’s classification of dysplastic naevi. Dysplastic naevi are now to be graded as ‘low grade dysplastic naevus’ (previous moderately dysplastic naevus) or ‘high grade dysplastic naevus’ (previous severely dysplastic naevus).
  • Current data suggest no further treatment is necessary for lentiginous junctional/compound naevi and dysplastic naevus with low grade dysplasia (previous mildly dysplastic and moderately dysplastic naevi) with clear histologic margins and no pigment evident clinically, unless there was a high level of prebiopsy clinical concern.
  • Re-excision with a 2-5mm clinical clearance is recommended for high grade dysplastic naevi (previous severely dysplastic naevi) with involved histologic margins.
  • There is growing evidence that observation may be reasonable for low grade dysplastic naevi (previous moderately dysplastic naevus) if they were excised with clinically clear margins/ no residual clinical pigment is observed, despite histologically involved margins. More data may be required before this is accepted into clinical practice.
  • There does not appear to be a clear consensus regarding whether high grade dysplastic (previous severely dysplastic) naevi require re-excision, if initially excised with clear margins, albeit less than 2mm.

    Dysplastic naevus: the controversy since the 1970s

    The entity of dysplastic naevus has been shrouded in controversy since first described in the 1970s.1 This appears to be due to:
    1. Interobserver differences between histopathologists in applying the previous three tier grading system for dysplasia
    2. Perceived risk of progression to melanoma, and
    3. The possibility of benign entities simulating melanoma, all of which contribute to uncertainty and variability in management.2,3
    Dysplastic naevi are benign neoplasms of melanocytes.3 Dysplasia in melanocytes may occur de novo or in association with either congenital dermal naevi or common dermal naevi. It is probable that dysplasia arising in pre-existing naevi results from successive acquisition of genetic abnormalities.3 Both common naevi and dysplastic naevi demonstrate BRAF or NRAS mutations.3 It was at one time proposed that there is a step-wise model of tumour progression from dysplastic naevi through mild, to moderate, then severe dysplasia, and finally melanoma.4 However, there is no evidence that dysplastic naevi are, in fact, common precursors of melanoma.4 In actuality, the most common naevus remnant found in association with melanoma is the common acquired naevus.4 Given the large number of dysplastic naevi, compared with the comparatively small number of melanomas arising in association with dysplastic naevi, it seems that the rate of progression from dysplastic naevus to melanoma is extremely low.4 Dysplastic naevi seen associated with melanomas have an increased incidence of TERT promoter mutations, a common early genetic event in the evolution of melanoma in situ.3 This suggests that some dysplastic naevi are an intermediate entity between benign naevus and melanoma.3 There is a lack of data examining the frequency of similar genetic alterations in non-melanoma associated dysplastic naevi; thus, although the risk of progression is very low, it is suggested that naevi with high grade dysplasia or added genetic events (e.g. TERT promoter mutation) are considered for complete excision.3 It has been suggested that dysplastic naevi represent a marker of increased risk for an individual developing melanoma.5 It is difficult to establish the risk of melanoma at a separate site in patients with dysplastic naevi, as the reported incidence of dysplastic naevi in fair-skinned individuals varies widely (between 2% and 50%).4 One study has demonstrated that only the diameter of the dysplastic naevus had a significant association with a personal history of melanoma,6 whilst another study has shown that individuals with many naevi, whether common or dysplastic, have an increased risk of developing melanoma.7 Thus it would seem that two factors are associated with an individual’s risk of developing melanoma: a large number of common or dysplastic naevi (>100) and the larger size of the naevi (>4.4mm).6 It is generally agreed that there is low interobserver agreement between pathologists when grading dysplastic naevi, particularly in those lesions exhibiting moderate atypia to early in situ melanoma.8,9 This leads to uncertainty with regard to management of these lesions, especially if there is margin involvement. In 2017, Wall et al.2 conducted a survey investigating the management of dysplastic naevi by Australian dermatologists. This survey demonstrated that, similarly to comparable studies reported within the USA and Canada, most dermatologists would re-excise a moderately or severely dysplastic naevus with involved margins.2 There is, however, variability in Australian dermatologists’ approaches to severely dysplastic naevi (clinically concerning for melanoma) which are completely excised on biopsy, with 44% re-excising with a 5mm margin, and the remainder considering no further treatment necessary.2 In addition, whilst between 5-12% of US and Canadian dermatologists re-excise mildly dysplastic naevi involving margins, that rate in Australian dermatologists is 49%.2 A consensus statement released by Kim et al.10 in 2015 identified a critical gap in knowledge with regard to management of dysplastic naevi with involved margins. This consensus statement recommended that mildly to moderately dysplastic naevi with clear histologic margins need no re-excision. If a biopsy report reveals severe dysplasia with positive margins, re-excision to achieve a 2-5mm clinical margin is recommended. The statement suggested that mildly dysplastic naevi with positive histologic margins after biopsy (and no residual pigment) may be observed, and while observation may be a reasonable option for moderately dysplastic naevi with positive histologic margins (and no clinical pigment), more data are required to make a definitive recommendation.10 A further multi-centre retrospective cohort study in 2018 by Kim et al.11 suggests that close observation is a reasonable management approach for moderately dysplastic naevi with positive histologic margins. No specific recommendations are made regarding a severely dysplastic naevus with clear margins on biopsy.  

    WHO redefines melanocytic naevi

    The World Health Organisation (WHO) released their new Classification of Skin Tumours in 2018.3 They define dysplastic naevus as ‘a subset of melanocytic naevi that are clinically atypical and characterized histologically by architectural disorder and cytological atypia, always involving their junctional component.10 Diagnostic criteria for dysplastic naevi traditionally include a division of cytoarchitectural atypia into mild, moderate and severe categories.3 Pathologists often further subdivide these categories into ‘mild to moderate’ and ‘moderate to severe’ to reflect the histological field effect often perceived in these lesions. Lentiginous junctional or compound naevi (previously labelled mildly dysplastic naevi) are not associated with increased melanoma risk/progression to melanoma, and are also common within the population.3 The WHO consensus meeting working group recommends against the continued use of the term ‘mildly dysplastic naevus’ and instead recommends the use of low grade and high grade dysplasia. So, where are we now with these new recommendations regarding the grading of dysplastic naevi, and what are the management implications? It seems that the new WHO recommendations support the view that biopsies of the previously known mildly dysplastic naevi need no further treatment, having removed the entity from their classification. It would appear that there is agreement that dysplastic naevi with high grade dysplasia (previous severely dysplastic naevi) with involved margins requires re-excision to achieve a 2-5mm clinical margin of clearance. However, there appears to be no recommendations or clear consensus regarding whether these high grade dysplastic (previous severely dysplastic) naevi require re-excision, if initially excised with clear margins, albeit less than 2mm. With regard to dysplastic naevi with low grade dysplasia (previous moderately dysplastic naevi), there is a slowly growing body of evidence to suggest that it may be reasonable for these cases to be observed if they were excised with clinically clear margins/no residual clinical pigment is observed, despite histologically involved margins. Given the current variation in clinical management of these lesions, as well as the continued lack of interobserver agreement between histopathologists when diagnosing these lesions, more data may be required before this recommendation is accepted. In conclusion, as the consensus statement by Kim et al.10 recommends, the decision to re-excise dysplastic naevi should be based on both the clinical and histologic findings. If the prebiopsy level of clinical concern is high, re-excision should be considered if the biopsy reveals positive margins, even if the level of histopathological dysplasia is low. In addition, there may be clinical scenarios warranting re-excision of a mildly, mildly-moderately/moderately dysplastic lesion (now known as lentiginous junctional/compound naevi and dysplastic naevus with low grade dysplasia respectively), including patient preference.10  


    1. Duffy K, Grossman D. The dysplastic nevus: from historical perspective to management in the modern era. J Am Acad Dermatol. 2012;67 (1): 1. E1-18. DOI: 10.1016/j.jaad.2012.03.013
    2. Wall N, De’Ambrosis B, Muir J. The management of dysplastic naevi: a survey of Australian dermatologists. Australasian Journal of Dermatology. 2017;58:304-307. DOI: 10.1111/ajd.12720
    3. Elder DE, Massi D, Scolyer RA, Willemze R, editors (2018). WHO classification of skin tumours. 4th Ed. Lyon: IARC.
    4. Busam KJ, Gerami P, Scolyer RA (2019). Pathology of Melanocytic Tumors. 1st Ed. Philadelphia: Elsevier.
    5. Elder DE. Dysplastic naevi: an update. Pathology. 2010;56(1):112-120.
    6. Xiong M, Rabkin M, Piepkorn M, Barnhill R, Argenyi Z, et al. Diameter of dysplastic naevi is a more robust bio marker of increased melanoma risk than degree of histologic dysplasia: a case-controlled study. J Am Acad Dermatol. 2014;71(6):12578.e4. DOI:
    7. Holly EA, Kelly JW, et al. Number of melanocytic nevi as a major risk factor for malignant melanoma. J Am Acad Dermatol. 1987;17:459-468. DOI:
    8. Hiscox B, Hardin MR, Orengo IF, Rosen T, Mir M, Diwan AH: Recurrence of moderately dysplastic nevi with positive histological margins. J Am Acad Dermatol . 2017;76:527530.  DOI: 10.1016/j.jaad.2016.09.009
    9. Stefanato C. The “Dysplastic Nevus” Conundrum: A look back, a peek forward. Dermatopathology. 2018;5:53-57. DOl: 
    10. Kim C, Swetter S, Curiel-Lewandrowski C, Grichnik J, Grossman D, et al. Addressing the knowledge gap in clinical recommendations for management and complete excision of clinically atypical nevi/dysplastic nevi. JAMA Dermatol. 2015;151(2):212218. DOI: 10.1001/jamadermatol.2014.2694
    11. Kim C, Berry E, Marchetti M, Swetter S, Liam G, et al. Risk of subsequent cutaneous melanoma in moderately dysplastic nevi excisional biopsies but with positive histologic margins. JAMA Dermatology. 2018;154(12):1401-1408 DOI: 10.1001/jamadermatol.2018.3359
      - General Practice Pathology is a regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.  
    Dr Brett Montgomery
    Clinical Articles iconClinical Articles

    As many mothers will know, health professionals seem ever ready to stoke up guilt with their advice. Don’t smoke. Don’t drink. Have your vaccines. Take your folate tablets. Eat a nutritious diet, but avoid soft cheese, cured meat, food that’s been long in a fridge, or (the list goes on). Avoid cats. Don’t co-sleep. Breast is best. And if other women can manage all this, why can’t you? As reported this week, Australia’s college of obstetricians (RANZCOG) has just added another task to the burgeoning to-do lists of doctors and midwives. We’re now to tell women to try to avoid cytomegalovirus (CMV). They have reasons for doing so, but as a GP and academic, I find myself sceptical.

    What is CMV, and why does it matter in pregnancy?

    CMV is a widespread virus which often causes only a mild illness. Most adults have been infected with it in the past, and are immune. But it’s different in pregnancy. If a pregnant woman is not already immune to CMV, and if she catches the virus, it can sometimes infect her fetus. And when it does, sometimes this causes problems such as hearing loss, epilepsy or developmental delay. Though previously thought to be rare, researchers now think congenital CMV is under-recognised. They estimate that one or two in every 1,000 infants may develop symptoms from being born with CMV – not rare, but uncommon. The virus is spread through fluids such as saliva, snot and urine. Child-rearing is messy; if toddlers catch CMV, it’s easy for them to pass it on to non-immune parents.

    The new guideline

    So what are women now urged to do to avoid CMV? To quote from the new RANZCOG guideline:
    • Do not share food, drinks, or utensils used by children (under the age of three years)
    • Do not put a child’s dummy/soother in your mouth
    • Avoid contact with saliva when kissing a child (“kiss on the forehead not on the lips”)
    • Thoroughly wash your hands with soap and water for 15-20 seconds especially after changing nappies or feeding a young child or wiping a young child’s nose or saliva
    • Clean toys, countertops and other surfaces that come into contact with children’s urine or saliva.
    Does that sound easy? If you think so, perhaps double-check with a friend who has young children. From my spot poll of parents, many feel that careful adherence to these rules would be unmanageable. Homes are not hospitals; interacting with our loved ones is not a sterile procedure. I can’t help but feel that we are setting mothers up to fail by introducing these standards, and thereby compounding the guilt they carry. Early parenthood is a risky time of life for mental health issues like depression. If we are to make new mothers feel guilty about such fundamental human interactions as sharing meals and kissing, won’t we intensify their stress at this vulnerable time? If mothers feel they must respond to a joyful kiss from their toddler not with reciprocation, but with admonishment – “not on the lips, darling, only the cheek” – mightn’t this affect their bonding with their child?

    What about the evidence?

    The stresses above might be worth enduring if there was good evidence that these behavioural changes made a difference. But I’m unconvinced. According to researchers who recently reviewed the world evidence, there are only three studies looking at whether hygiene and behaviour recommendations can prevent congenital CMV. The largest was a study comparing how often women in a maternity hospital picked up CMV before and after hygiene advice. Infected proportions changed from 0.42% before the advice to 0.19% afterwards. But “before-after” studies aren’t a reliable guide to cause-and-effect. The most susceptible women may just have caught CMV earlier, leaving only women at less risk left for the second phase of the study. The best study design to establish cause-and-effect is a “randomised controlled trial”, in which women are randomly allocated to receive hygiene advice or not. There are two such trials. One was tiny, and found no significant difference between the non-pregnant women it randomised to hygiene advice. Separately, they followed 14 pregnant women who were given hygiene advice, who all remained uninfected, but they weren’t randomised – there was no group of pregnant women without such advice to compare to. The bigger trial randomised 166 non-immune mothers of young children to either receive hygiene advice or not. Despite providing free soap and gloves to the hygiene group, and visiting these women every three months to monitor their behaviour, exactly 7.8% of women in each group caught CMV – no difference. Pregnant women who knew from special tests that their child was shedding CMV had a low infection rate – presumably this test result was a motivator for behaviour change. But this is evidence for the effect of testing, not of giving hygiene advice. So I can’t see convincing evidence that routine hygiene advice works – not without the addition of tests of mothers’ immunity and children’s viral status. And doing such tests is not part of the new RANZCOG guideline – indeed, it explicitly advises against routine testing.

    So what should we do?

    I’m really torn on this issue. My heart aches for the families of children severely affected by congenital CMV. They must carry a heavy burden of guilt, wondering if they could have prevented the infection. I understand their motivation to prevent further harms. I share their desire for more research on CMV prevention. But I am saddened, too, by the prospect of a generation of women taught to see their toddlers as dangerous, all in the name of preventive measures which remain unproven. What do you think? Perhaps we need a community conversation about balancing the trade-offs here: the uncertain prevention of serious but uncommon outcomes versus widespread anxiety about normal family behaviours. Meanwhile, it’s time for me to close my laptop, share a meal with my family, and, later, kiss my kids goodnight.The Conversation Brett Montgomery, Senior Lecturer in General Practice, University of Western Australia This article is republished from The Conversation under a Creative Commons license. Read the original article.
    Clinical Articles iconClinical Articles

    Cutaneous disorders are among the most common conditions presented to primary care doctors. Many are easily identifiable and may be dealt with effectively without the need for cutaneous biopsy. Nevertheless, in many instances the diagnosis is not obvious on clinical grounds. The rash may display atypical features or may not respond to therapy as predicted. In these cases, and when dealing with cutaneous tumours or worrying pigmented lesions, cutaneous biopsy with histological assessment becomes necessary. The art of cutaneous biopsy is to derive the maximum amount of information from the minimum amount of tissue, causing least discomfort to the patient. This will be achieved if due regard is given to the advantages and shortcomings of the various techniques available for biopsying cutaneous tissue, and if the pathologist is supplied with a good clinical history.

    Clinical History

    For several reasons, clinical history assists greatly in the interpretation of skin biopsies. Clinicopathological correlation is particularly important in many inflammatory cutaneous disorders. As the histological features can be very similar, clinical notes may help us to arrange a list of provisional diagnoses in order of likelihood. The key features to discuss with regard to cutaneous rashes include:
    • duration
    • distribution
    • description (macular, papular, vasculitic or vesicular)
    • drugs or other possible aetiological agents
    • provisional clinical diagnosis.
    As there is wide variation in the normal microscopic picture from different sites, the area biopsied should also be stated. For biopsies performed to distinguish between squamous cell carcinoma and keratoacanthoma, the rate of growth of the lesion is important. When sending specimens of pigmented lesions, the degree of clinical suspicion should be stated, together with any history of melanoma within the individual or within the individual’s family. Any condition associated with cutaneous disorders, such as systemic lupus erythematosus, pregnancy or bone marrow transplant, should be mentioned in the clinical notes. The clinical history should also include the type of biopsy procedure used (see below) as this determines the way we handle the specimen in the laboratory. For example, the whole of an incisional biopsy will be blocked in order to gain the maximum amount of information, whereas an excisional biopsy will be transversely sectioned in order to fully assess the lateral excision margins in the case of a tumour biopsy.

    Excision Biopsy

    This is the best technique to use for pigmented lesions and cutaneous tumours. It allows for histological assessment and diagnosis of the lesion, and assessment of surgical excision margins. If appropriate, an orientation suture can be placed at one end of the excision, e.g. the superior end of the specimen, so that if the excision is inadequate, the margin involved can be indicated on an accompanying diagram. Occasionally, excision biopsy is appropriate for inflammatory cutaneous disorders where the condition is characterised by the formation of vesicles. The best chance of removing an intact vesicle (which greatly aids diagnosis) may be through excision.

    Incision Biopsy

    With incision biopsy, a thin elliptical biopsy is taken radially through the edge of the tumour or through the edge of a macular or annular rash. Incision biopsy is superior to punch biopsy for diagnosing rashes, more tissue is displayed on histological section and scarring is often reduced. A typical incision biopsy is 5-6 mm in length and about 2 mm in width. It should be deep enough to extend into the subcutaneous adipose tissue. The biopsy should run radially from the centre or central areas of the lesion to include approximately 1 mm of normal cutaneous tissue surrounding the lesion.

    Punch Biopsy

    Punch biopsies are easier to perform and, in general, are more convenient. Nevertheless, they nearly always yield less information than an incision biopsy. For tumours, the biopsy should be taken centrally. For cutaneous eruptions, the biopsy should be taken from an area typical of the rash. In some cases, multiple biopsies may increase the amount of information. In this procedure, it is best not to include normal skin. Punch biopsies come in various sizes. As 2 mm punches often yield inadequate information for diagnosis, a 3 mm punch biopsy is the smallest that should be used.

    Shave Biopsy/Curettage

    This technique is suitable for superficially-located lesions with plaque-like clinical features, e.g. seborrhoeic keratoses. It is not an appropriate technique for nodular lesions, cutaneous rashes or melanocytic lesions.

    General comments concerning cutaneous biopsies

    Preparation of the skin surface: Be gentle when cleaning the skin surface prior to biopsy; try not to disturb any overlying scale as the keratin layers sometimes contain diagnostic information (e.g. this is where dermatophytic fungi may be seen). Let any alcohol preparation dry before collecting specimens for immunofluorescence. Local anaesthesia: Only a small amount of local anaesthetic is required for punch biopsy procedures (0.5 mL maximum). Too much local anaesthetic within the tissues can distort the histological appearances and simulate dermal oedema. Marking the lesion: It is often prudent to mark the target area for biopsy with an ink marker, as some lesions can blanch following introduction of local anaesthetic. The erythema in many lesions is due to vascular dilatation occurring as part of the inflammatory disorder. Local anaesthetic can cause vasoconstriction and diminish the erythema clinically. This may result in a poorly targeted biopsy yielding subdiagnostic histology. Depth of biopsy: It is best to continue into the subcutaneous adipose tissue so that the entire dermis is represented on histological section. This helps greatly with the categorisation of many inflammatory skin disorders and also demonstrates the deep border of any cutaneous tumour. When performing a punch biopsy, the biopsy instrument appears to ‘give’ when it penetrates the dermal connective tissue into subcutaneous adipose tissue. A similar sensation will be noticed when dissecting free an incision biopsy. Care with biopsy tissue: All too often, after biopsy tissue has been retrieved from the patient, crush artefact occurs during its transfer into formalin. Crush artefact greatly distorts the histological appearance and repeat biopsy may become necessary. Rather than grasping the biopsy tissue with non-tooth forceps, it should be transferred to the specimen container using needle tips, a skin hook or fine forceps, delicately grasping one edge of the biopsy. Fixative: Ordinary blue, 10% buffered formalin supplied with the specimen jars is suitable for nearly all cutaneous biopsies, except those submitted for microbiological culture or immunofluorescent examination. Labelling: Please label all specimen containers with the patient’s name and details, which should match those stated on the request slip. Unlabelled specimens can still be processed and interpreted if they arrive with labelled paperwork; however, the medico-legal status of any generated report is doubtful. The report will usually be generated with a ‘specimen received unlabelled’ comment attached.


    Diagnosing cutaneous conditions can be challenging. The chances of success are improved when the clinician, is armed with a variety of biopsy techniques for use in the correct clinical setting, and when the pathologist is supplied with an adequate clinical history.   - General Practice Pathology is a regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.
    Expert/s: Healthed
    Dr Alistair McGregor
    Clinical Articles iconClinical Articles

    It is estimated that up to 25,000 Australians are affected by asplenia or hyposplenism.1  Many are unaware of the fact, and its potential consequences. The spleen plays an important role in immune function, in particular the prevention of infection due to some specific organisms (Table 1).

    Infection Risk

    Infection is a relatively common occurrence in those without a functioning spleen. Overwhelming post-splenectomy infection (OPSI), occurs in up to 5% of asplenic patients and has a mortality rate of over 50%. The risk is particularly high in children aged under five, and in the first three years post-splenectomy. However, the risk is lifelong.1

    Organisms of Concern

    Table 1:     Organisms of Concern
    Agent Comment
    Streptococcus pneumoniae Accounts for >50% of severe infections. Vaccine available and recommended
    Neiserria meningitidis Vaccine available and recommended.
    Haemophilus influenza type B Vaccine available and recommended.
    Capnocytophagia species Oral flora in animals. Risk of acquisition after animal bites.
    Bordetella holmesii Newly recognised pathogen.
    Plasmodia species (Malaria) Babesia, Ehrlichia Potential risk for travellers. Seek pre-travel advice.

    Causes of Asplenia and Hyposplenism

    Asplenia maybe congenital but is more often acquired as a result of trauma or the surgical removal of the spleen due to haematological conditions, or after incidental splenic damage incurred during intra-abdominal surgery. Functional hyposplenism also confers an increased risk of infection and may occur as a result of a number of medical conditions (Table 2).   Table 2:    Medical conditions associated with hyposplenism
    Coeliac disease
    Sickle Cell disease
    Rheumatoid arthritis
    Malignant infiltration e.g. lymphoma
    Splenic infarction or radiation
    Graft versus host disease

    Detection of Asplenia and Hyposplenism

    The presence of Howell-Jolly bodies in a blood film may be a clue to the presence of unrecognised asplenia or hyposplenism.  Other investigations that may be of assistance in suspected cases are imaging studies such as ultrasound or CT.

    Prevention of Infection

    Evidence suggests it is possible to significantly decrease the incidence of infection in asplenic and or hyposplenic patients. Spleen Australia has recently demonstrated a 69% reduction in serious infections in patients on their registry.2 The key strategies utilised by Spleen Australia include; 1. Education
    • Informing patients and their families of the risk of infection, signs and symptoms of sepsis and the need to develop a management plan should these occur:
      • Importance of seeking urgent medical attention if symptomatic.
      • Maintaining a standby supply of antibiotics for emergency use.
    • Provision of advice regarding travel and other potential exposure risks e.g. animal contact.
    • Encouraging the wearing of a Medical Alert bracelet.
    2.  Provision of advice regarding appropriate antibiotic therapy (as per Therapeutic Guidelines)
    • Consider antibiotic prophylaxis, particular in first three years post-splenectomy (With either penicillin or roxithromycin).
    • Maintain a standby emergency supply of antibiotics in case of sepsis (usually Amoxil 3g).
    3.  Provision of current, detailed, practical guidelines for vaccination (As per Immunisation Handbook)
    • Pneumococcal, Meningococcal, Haemophilus influenza type B vaccines - initial course and ongoing boosters as required.
    • Annual influenza vaccine - to minimise the chance of post-influenza bacterial infection.
    Currently, persons resident in Victoria, Queensland and Tasmania are able to register with Spleen Australia and will then receive regular newsletters and reminders when vaccines are due. It is hoped that this service will be extended to other states. See for details.  

    Key Messages

    • Infection is a significant, life-long risk in asplenic and hyposplenic patients.
    • The risks can be mitigated by:
      • The early recognition of the underlying condition,
      • Comprehensive patient education,
      • Appropriate use of use of prophylactic and empirical antibiotics, and
      • Ensuring that patients receive recommended initial and ongoing vaccinations.
    Spleen Australia provides an excellent range of resources and is happy to assist in the management of these patients if required.  


    1. Spleen Australia. Welcome to Spleen Australia: a clinical service and registry for people with a non-functioning spleen. Melbourne VIC: Diabetes Australia. Available from:
    2. Arnott A, Jones P, Franklin LJ, Spelman D, Leder K, Cheng AC. A Registry for Patients With Asplenia/Hyposplenism Reduces the Risk of Infections With Encapsulated Organisms. Clin Infect Dis. 2018 Aug 1; 67(4): 557-61. Available from:
      General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.
    Dr Joyce Wu
    Clinical Articles iconClinical Articles

    Glycated haemoglobin (HbA1c) has been used for monitoring patients with established diabetes for many years but its diagnostic application is a more recent development. This article provides some background to the test, explains dual reporting of results and discusses the use of HbA1c in the diagnosis and monitoring of diabetes.

    What is HbA1c?

    Adult haemoglobin is predominantly (97% of total) HbA. HbA1c is formed when a glucose molecule non-enzymatically attaches to the N-terminal valine of the β-chain of HbA. The amount of HbA1c formed is directly proportional to the average plasma glucose concentration during the 120-day life span of the erythrocyte, with recent plasma glucose contributing more than earlier concentrations. HbA1c is therefore a reflection of the average glycaemia over roughly the preceding 6–8 weeks and has a vital role in assessing the risk of an individual developing the complications of diabetes.1

    HbA1c for the diagnosis of diabetes mellitus

    A 2012 position statement of the Australian Diabetes Society, the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists (AACB)2 contains the following:
    • HbA1c levels ≥6.5% (≥48 mmol/mol) are acceptable for diagnosing diabetes so long as the test is done in a laboratory and no conditions exist which preclude its accuracy.
    • In an asymptomatic patient with a positive result, the test should be repeated to confirm the diagnosis.
    • The existing criteria based on fasting and random glucose levels and on the oral glucose tolerance test remain valid and are the diagnostic tests of choice for gestational diabetes, type 1 diabetes and in the presence of conditions that interfere with HbA1c measurement.
    The use of HbA1c simplifies the diagnostic process and may facilitate the detection of diabetes diagnosis. The test can be performed at any time of the day, does not require special pre-test preparation, such as a diet or fasting, and is stable when collected in the appropriate specimen tube. Testing should be restricted to patients at high risk of undiagnosed diabetes and who are asymptomatic.3 If one or more symptoms suggestive of diabetes are present in a low-risk patient, blood glucose tests should be used, because patients with rapidly evolving diabetes can have normal HbA1c. HbA1c <6.5% (<48mmol/mol) indicates that diabetes is unlikely but (since the patient is high-risk) the test should be repeated in 12 months. Patients should be given appropriate lifestyle advice and other modifiable cardiovascular risk factors should be assessed.3 There is uncertainty about the use of HbA1c to diagnose prediabetes. While patients with HbA1c above normal but below 6.5% (48 mmol/mol) are more likely to develop diabetes than is suggested by their AUSDRISK score alone, they have minimal risk of developing microvascular complications. Management is the same as for those at high risk of type 2 diabetes with HbA1c within the normal range.3 HbA1c ≥6.5% (≥48 mmol/mol) should be confirmed by another test (glucose or repeat HbA1c). Repeat HbA1c should be performed on a different day but as soon as possible, before any lifestyle or pharmacological interventions are initiated.3 It is important that clinicians state clearly the indication for the test when requesting HbA1c testing, with wording such as ‘diabetes monitoring’ or ‘diabetes screening’. This will allow the correct Medicare item number and interpretative comments to be used.

    Individualisation of HbA1c treatment targets

    In monitoring patients with established diabetes, the general target is ≤7.0% (≤53 mmol/mol). Individualisation of target HbA1c, taking into account patient-specific factors, such as type of diabetes and its duration, pregnancy, diabetes medication used, existing cardiovascular disease, risk of hypoglycaemia and comorbidities, may modify the target range from ≤6.0% (≤42 mmol/mol) to ≤8.0%(≤64 mmol/mol).4

    Dual reporting of HbA1c

    There are many assays for measuring HbA1c. For many years, the NGSP in the US and other national and regional programs harmonised HbA1c methods. This allowed valid, interlaboratory comparison of results. The NGSP uses percentage (%) units. The IFCC standardised glycated haemoglobin measurement by making it traceable to an international standard.5 The IFCC uses mmol/mol (mmol HbA1c per mol total Hb). The improved specificity of IFCC-HbA1c is reflected in results which are consistently 1.5%–2.0% lower than NGSP values.1 A 2007 consensus statement from the American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), IFCC and International Diabetes Federation (IDF) was adopted and implemented by Australasian laboratories.5 It recommended that HbA1c results be reported in both IFCC units (mmol/mol) and derived NGSP units (%) to allow clinicians to become familiar with IFCC results before reporting of NGSP % units is withdrawn. Currently, there is no agreement on when dual reporting will cease and hence HbA1c results are still reported with two units.

    Conditions affecting HbA1c results

    As HbA1c is simply haemoglobin with the addition of a glucose molecule, conditions that affect red blood cells or their survival time, such as haemoglobinopathies or anaemia, will affect the HbA1c result.3 Patients with abnormal haemoglobins may form other glycated products which may form at different rates to that of normal haemoglobin. Haemolytic anaemia can reduce HbA1c by decreasing red cell survival, leading to reduction in the availability of haemoglobin for glycation. This occurs with autoimmune haemolytic anaemia, haemoglobinopathies and chronic renal failure. Any drugs that give rise to haemolytic anaemia will have the same effect. Red cell survival time is also reduced in severe liver disease, anaemia of chronic disease, vitamin B12 and folic acid deficiencies, and regular phlebotomy. Interestingly, iron deficiency anaemia can increase HbA1c by up to 2%.1 There are alternative ways of monitoring diabetes treatment in these patients, including the use of closer glucose monitoring and fructosamine testing. Any discordance between glucose and HbA1c levels should alert the clinician so that other testing options should be considered.

    Key points

    When requesting HbA1c it is vital that the clinician specify clearly the indication for the test, for example, ‘diabetes monitoring’ or ‘diabetes screening’.
    • HbA1c ≥6.5% (≥48 mmol/mol) can be used to diagnose diabetes in asymptomatic, high-risk patients. HbA1c ≥6.5% should be confirmed with glucose or another HbA1c performed on a different day but as soon as possible, before any intervention has commenced.
    • The recommended treatment target is HbA1c ≤7.0% (≤53 mmol/mol). Treatment targets may need to be individualised to between ≤6.0% (≤42 mmol/mol) to ≤8.0% (≤64 mmol/ mol), depending on patient-specific factors, such as type and duration of diabetes and risk of hypoglycaemia.
    • Currently, HbA1c is reported in both National Glycohemoglobin Standardization Program (NGSP) units (%) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) units (mmol/mol), with the aim of eventually reporting in IFCC units only.
    • A number of medical conditions affect HbA1c results and preclude its use in both monitoring and diagnosis of diabetes mellitus.


    1. Kilpatrick ES. Haemoglobin A1c in the diagnosis and monitoring of diabetes mellitus. J Clin Pathol 2008;61(9):977-982
    2. d’Emdem MC. et al. The role of HbA1c in the diagnosis of diabetes mellitus in Australia. MJA 2012;197(4):1-3
    3. d’Emdem MC. et al. Guidance concerning the use of glycated haemoglobin (HbA1c) for the diagnosis of diabetes mellitus – A position statement of the Australian Diabetes Society. MJA 2015;203(2):89-91
    4. Cheung NW. et al. Position statement of the Australian Diabetes Society: individualisation of glycated haemoglobin targets for adults with diabetes mellitus. MJA 2009;191(6):339-344
    5. Jones G. et al. Consensus Statement on the Worldwide Standardisation of the Haemoglobin A1c Measurement – An Australasian Update. The Clinical Biochemist Newsletter 2008;14-18. Available online:

    General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.
    Expert/s: Dr Joyce Wu
    Dr Paul Glendenning
    Clinical Articles iconClinical Articles

    Markers of bone turnover, measured in blood or urine, correlate with changes in the metabolic activity of bone. The rate of bone remodelling is important. With ageing, the quantum of bone removed/ resorbed and the amount replaced/ formed becomes increasingly imbalanced. Consequently, the more bone remodelling units that are active at any one time, or the greater the activity of individual units, the greater the overall rate of bone loss. Bone turnover markers are probably predictive of the rate of bone loss and could help determine the efficacy of treatment.

    Bone turnover markers:

    • May predict fracture risk independently of bone mineral density, according to some studies.
    • A drop in bone resorption is an early predictor of response to all anti-resorptive osteoporosis treatments initiated in general practice (bisphosphonates, denosumab or raloxifene), with these markers changing earlier than comparable markers of bone formation.
    • They may be predictive of later changes in bone mineral density (BMD), and can be measured before BMD changes can be evaluated.

    Which bone resorption marker?

    Markers measuring the rate of bone loss are degradation products of type 1 collagen cleaved during bone resorption. Cross-linking telopeptides of collagen can be measured by immunoassays that are specific for the beginning (N terminal- called NTX) or end (C terminal- called CTX) of type 1 collagen. While measuring urinary NTX and serum CTX provide comparable information there are some advantages of CTX over NTX. Consequently, serum CTX has been proposed as a reference method. The measurand in the CTX assay is clearly defined, allowing this 8 amino acid oligopeptide to become the reference method.
    • Most serum CTX is from osteoclastic bone resorption (indicating high specificity).
    • The assay can be performed manually or by automated methods and is only provided by one manufacturer (obviating the need for harmonisation)
    • The biological and analytical variability for CTX is well documented in the literature.

    Uses and limitations

    Serum CTX is a potentially useful test when investigating the cause of increased alkaline phosphatase, verifying compliance with osteoporosis treatment, improving persistence with that treatment or identifying occult secondary causes of osteoporosis such as apathetic hyperthyroidism or other metabolic bone disorders such as Paget’s disease. Samples collected fasting in the morning minimise intra-individual variation and requests ideally should include the reason for testing. Medicare currently provides a rebate for tests of bone resorption in patients with known bone disease taking treatment.
    1. Not all anti-resorptive treatments suppress bone resorption to the same degree. Provision of the type of anti-resorptive agent used and the duration of treatment is not only helpful for billing but allows us to report more specifically - whether the rate of bone resorption is typical or higher than expected for a particular anti-resorptive agent. For example, denosumab suppresses bone resorption earlier and to a greater degree than a bisphosphonate.
    2. Bone resorption is not predictive of future fracture risk in individuals. CTX can provide complementary information to bone mineral density in subpopulations but this measurement has not been currently adopted into fracture risk alogrithm calculators such as FRAX or the Garvan risk calculator for individuals.
    3. The measurement of serum CTX cannot be used to select treatment. This is because the baseline rate of bone remodelling is not predictive of the rate of change of bone remodelling or rate of change of bone density while on treatment.
    4. Measurement of bone formation and bone resorption do not provide additive information. While bone remodelling is a coupled process wherein bone formation and bone resorption are linked, the measurement of bone resorption or bone formation markers provide comparable information regarding the rate of bone remodelling. Measurements of both bone formation and bone resorption markers in individual patients do not help determine the degree of imbalance in bone remodelling and is therefore unnecessary. Understanding these limitations and the potential value of measuring bone remodelling markers can be useful when making decisions regarding individual patient management in those taking treatment for osteoporosis.
    Reproduced with permission from Medical Forum magazine Oct 2017 edition
    General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.
    Dr Jenny Robson
    Clinical Articles iconClinical Articles

    Identified in 1983 by Australian Nobel prize winners Marshall and Warren, H. pylori is linked to a spectrum of disease including non-ulcer dyspepsia, peptic ulcer, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Infection is estimated to be present in about 30% of adult Australians, though not uniformly distributed in the population. Prevalence is higher in immigrants, those of lower socioeconomic status and the institutionalised. It has been conventionally treated with a standard first-line triple therapy including a proton pump inhibitor (PPI), clarithromycin and amoxicillin or metronidazole administered for seven days. However, in the past decade the effectiveness of this triple therapy, although still recommended in Therapeutic Guidelines, has declined mainly due to the development of antibiotic resistance. A recent meta-analysis1 of treatment, which reviewed 15,565 studies worldwide, highlighted the geographically localised nature of resistance profiles. It concluded that one single ‘most effective’ treatment was unlikely to be identified across the world, as the treatments needed to be tailored to regional resistance profiles. The range of tests, both non-invasive and invasive, following endoscopy are outlined below.

    Pylori serology

    This detects organism-specific IgG. It requires the collection of 5 mL of serum. No special preparation of the patient is required. Antibodies may take 5–10 weeks to develop after infection and may remain positive long term. A positive result may indicate present or past infection. Epidemiologic evidence now indicates that most infections are acquired during childhood, even in developed countries, and the frequency of H. pylori infection for any age group in any locality reflects that particular cohort's rate of bacterial acquisition during childhood years.

    Urea breath test (UBT)

    The UBT requires the patient to drink 13C-labelled or 14C-labelled urea, which is converted to labelled CO2 by the urease in H. pylori. The labelled gas is measured in a breath sample. Sullivan Nicolaides Pathology currently utilises the nonradioactive 13C-labelled isotope. The test has a sensitivity of 95% and a specificity of 98%. It is generally not suitable for children under five years because of the difficulty in following test instructions. This test has an out-of-pocket fee to the patient of $60.

    Faecal antigen test

    Active H. pylori infection can be detected by identifying H. pylori–specific antigens in a stool sample with the use of monoclonal antibodies. This assay has similar sensitivity and specificity to the UBT and has no additional out-of-pocket expenses for the patient.

    Rapid urease test (CLO test)

    If endoscopy is indicated, a biopsy specimen can be placed into a CLO tube containing urea and a pH indicator. If H. pylori is present, the urease will convert the urea to ammonia, leading to a colour change in the pH indicator. This is a reliable and cheap method for identifying H. pylori infection with reported excellent sensitivity and specificity in excess of 90%. The colour change usually occurs within minutes and the clinician can record the results the same day. If the inoculated CLO tube is forwarded to the laboratory the results can be recorded in the pathology Laboratory Information System, but must be read within 72 hours of the tube being inoculated for the result to be valid.


    Histology is slightly more sensitive and specific than the rapid urease test and provides additional information on the type of gastritis, atrophy, intestinal metaplasia and malignancy. If proton pump inhibitors (PPIs) have been taken, biopsies from the gastric body in addition to the antrum can improve the diagnostic yield. The organism can be identified with conventional stains including haematoxylin and eosin and Giemsa. Immunohistochemistry increases sensitivity and specificity further and is of most use in cases of assumed low density colonisation.

    Culture and susceptibility testing

    Culturing of the organism is available for those who fail therapy. This is done from a gastric biopsy and permits testing for sensitivity to antimicrobial agents. Specialised transport media Portagerm pylori (PORT-PYL – Item 25016) is available to improve organism viability. Susceptibility guided versus empirical antibiotic treatment for H. pylori infection has been shown to be superior to empirical 7–10 day triple therapy for first line treatment. The recent meta-analysis showed that the worst-ranking treatment is standard triple therapy (proton pump inhibitor, clarithromycin and amoxycillin or metronidazole) administered for seven days. Over the past 10 years our microbiology laboratory has cultured H. pylori from 108 endoscopic biopsies and 102 patients. Most of these cultures were performed because patients had failed therapy, introducing significant sample bias. For 24% of episodes, despite the organism being cultured, it did not remain viable to complete susceptibility testing. Susceptibility results for 76 isolates that remained viable for testing indicate that antibiotic resistance (clarithromycin – 59.7%; metronidazole – 51.3%; ampicillin – 22.4%) is a significant cause of treatment failure. Ref:
    1. Li Bao-Zhu, Threapleton DE et al Comparative effectiveness and tolerance of treatments for Helicobacter pylori: systematic review and network meta-analysis. BMJ 2015;351:h4052

    General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.