Dermatology

Clinical records Patient 1 A 6-month-old infant presented with eczema in January 2006 and was initially treated with antiseptic bath oil, emollients and topical corticosteroid ointments. The infant presented again 3 weeks later with a 7–10-day history of groin and axillary desquamation. Brown hyperpigmentation and superficial brown desquamation were notable around the nappy area. Erythematous areas were noted in the skin folds (Figure A). The infant’s mother reported using an antiseptic bath oil (containing 6% benzalkonium chloride, 2% triclosan, and 55.8% light liquid paraffin) up to three times a day in his bath. Emollient cream and low potency topical corticosteroid ointment had been applied to the nappy and axillary areas. The emollient cream and a high potency topical corticosteroid ointment had been applied to other unaffected areas. Cessation of the antiseptic bath oil was recommended. The patient continued to use corticosteroid ointments, plain emollient bath oil, and 50% white soft paraffin with 50% liquid paraffin. Use of the emollient cream was later recommenced without problems. Patient 2 A 7-year-old girl with moderate eczema developed a flare around her neck in February 2006. She had previously been educated on the use of bath oil in wet wraps and cool compresses for treating flares, and had started using the same antiseptic bath oil as Patient 1 (at the concentration recommended by the manufacturer for use as a rinse) in cool compresses. Eleven days after starting use of the cool compresses, she presented with a painful, weeping raw neck, upper chest (Figure B), back, and cubital fossae, requiring opioid analgesia and admission to hospital. Her reddened weepy areas settled with cessation of the antiseptic bath oil, and use of plain bath oil, topical corticosteroid ointment, oral corticosteroid, and regular moisturising with 50% liquid paraffin and 50% white soft paraffin. Patient 3 A 14-year-old girl with previously mild eczema presented in November 2006 with a flare affecting her cubital fossae. She was advised to use an antiseptic bath oil (containing 6% benzalkonium chloride, 2% triclosan, and 52.5% light liquid paraffin), emollients and potent topical corticosteroid ointment, and was given advice on using wet wraps to settle the affected areas. Over a 10-day period, the patient’s eczema settled. She then acutely developed large bullae bilaterally in the cubital fossae, in a sharp “cut-off” distribution (Figure C). She could not fully extend her elbows due to the pain, and was admitted to hospital. Acute contact dermatitis was diagnosed, and use of the antiseptic bath oil was ceased. Her symptoms settled with the use of oral corticosteroid, frequent moisturising with 50% liquid paraffin and 50% white soft paraffin, and potent topical corticosteroid ointment. Photographs of each patient at time of discharge, clockwise from below left: A: Patient 1 — a 6-month-old infant with contact dermatitis from frequent bathing with antiseptic bath oil. B: Patient 2 — a 7-year-old girl with contact dermatitis on her neck from using antiseptic bath oil in cool compresses. C: Patient 3 — a 14-year-old girl with contact dermatitis on the cubital fossa from using antiseptic bath oil in wet wraps. These three children all presented with acute contact dermatitis from use of antiseptic bath oil. The distribution of the reaction in each case suggested that cumulative irritant contact dermatitis was the likely cause. However, in all of these cases the reaction did not develop immediately, so allergic contact dermatitis was also a possible cause. Patch testing for an allergic cause was not undertaken in these children, as it was felt that this would not alter management in their acute care. Ingredients in the two antiseptic bath oils used by these patients include benzalkonium chloride (6%), triclosan (2%), and paraffin. Direct contact with triclosan in formulated products has only rarely been associated with skin irritation or sensitisation in humans.1 Allergic contact dermatitis to benzalkonium chloride is also rare.2 Benzalkonium is a known strong cutaneous irritant and is reported to be corrosive to mucous membrane at a concentration of 10%.3 For Patient 1, the antiseptic bath oil was frequently being applied to his skin in the bathwater and not rinsed off. We believe that secondary occlusion to the groin (and axilla) by skin folds and the close fit of his nappy contributed to ongoing irritation. Prolonged contact with another bath oil with the same active ingredients in the same concentration has previously been reported to cause irritant dermatitis.3 Lessons from practice Consider a diagnosis of acute contact dermatitis if brown hyperpigmentation and superficial desquamation complicate eczema, particularly if the patient is using an antiseptic bath oil. Use antiseptic bath oils in a diluted concentration, not exceeding the manufacturer’s instructions. If antiseptic bath oil is used, rinse off after use. Use only plain bath oils for cool compresses and wet wraps. It remains unclear whether the frequent application of cool compresses to the softer skin of the neck of Patient 2 resulted in irritant contact dermatitis, or whether true allergy developed. Similar eruptions have been described in reaction to standard concentrations of bath oil, as well as to concentrations greater than the manufacturer’s recommendations.3-6 However, the distribution in this case suggested irritant contact dermatitis. The older child, Patient 3, stated that she had had marked initial improvement after starting use of the bath oil. Her mother thought that after this improvement there may have been a decrease in vigilance in measuring the concentration of the oil, as well as possible prolonged exposure time, which probably resulted in the subsequent acute burn seen in Figure C. A case has been previously described where an increased concentration of the same antiseptic bath oil caused subcorneal pustular dermatitis, with some features resembling a chemical burn, and restriction of movement.6 It is notable that, in all three cases, the thinner skin folds were preferentially affected. This has been previously described, when total body application of antiseptic bath oil to a 27-year-old man resulted in diffuse swelling of his penis and scrotum only.5 In view of the increasing frequency of use of these products, and the subsequent increase in incidence of contact dermatitis as a result (personal observation), we suggest that clinicians, nurses and pharmacists should be aware of the potential for this complication to occur. Using the appropriate concentration of antiseptic bath oils should be emphasised. We recommend that antiseptic bath oils be used only for rinse-off type applications, and, if used in the bath, we suggest rinsing after bathing. Furthermore, we strongly suggest that only plain bath oils should be used as part of a cool compress or wet wrap regimen.

Mignon Moyle MB BS, BAppSci(AdvClinNsg) · Elizabeth J Moore RN, PgDipACN(Paed), MN · George A Varigos MB BS, PhD, FACD

A 75-year-old woman had a 2-year history of severe onycholysis and chloronychia (olive green discolouration) of most of her fingernails (Figure). Fungal infection had been excluded by microscopy and culture of nail scrapings. Some nails had superficial ridges and pits, as well as translucent orange-brown discolouration of the nail beds (the “oil drop” sign). This, along with a well defined, red, scaly plaque over her right elbow, led to a diagnosis of limited plaque psoriasis. The green discolouration was a classic sign of a secondary bacterial infection caused by Pseudomonas aeruginosa. Treatment was to consist of vinegar soaks (10 parts water and 1 part white vinegar applied topically for 5–10 minutes twice daily for 5 days) for the Pseudomonas infection, followed by a course of dexamethasone iontophoresis to treat the psoriatic onycholysis. (In the latter process, the fingers are held in contact with a dexamethasone solution and a low electrical current stimulates the transdermal migration of dexamethasone ions into the nail beds.) The “oil drop” sign is seen on the index fingernail. The fifth fingernail, without onycholysis and secondary infection, appears ridged and pitted.

Shinichiro Sakata MB BS · Anne Howard MB BS, FACD

A 50-year-old woman presented to her dermatologist in 1999 with a 6-month history of recurrent pruritic scaly plaques on the abdomen, arms and hairline. The rash, which was presumed to be seborrhoeic dermatitis, improved after treatment with systemic prednisolone. No skin biopsies were taken at the time. In 2004, she developed a leonine facies (Box, A), widespread erythroderma, alopecia, generalised peripheral lymphadenopathy, hyperkeratosis of the palms, and bilateral swollen pinnae with otorrhoea (Box, B). Punch biopsies revealed Pautrier microabscesses containing atypical CD4+ lymphocytes. A peripheral blood film showed Sézary cells, confirming Sézary syndrome. The patient’s condition deteriorated despite treatment with methotrexate, prednisone, bexarotene, interferon, psoralen and ultraviolet A, as well as extracorporeal photopheresis. Radical palliative radiotherapy to the head and neck improved her leonine facies and otitis externa (Box, C). The patient died in 2006, 8 years after initial presentation. Sézary syndrome is a rare, aggressive, cutaneous T-cell lymphoma characterised by widespread erythroderma, atypical peripheral lymphocytes (Sézary cells) and lymphadenopathy. Cutaneous T-cell lymphomas typically present as indolent cutaneous eruptions and are often misdiagnosed at initial presentation, as the skin lesions mimic common dermatological disorders such as eczema or psoriasis. A: Leonine facies. B: Oedematous right pinna. C: Left pinna after radiotherapy.

David R Waterhouse MB ChB · Subhaschandra Shetty MB BS, MS(ENT) · Jeremy S Gathercole MRCS, LRCP, FRACS · Christopher J Seeley MB ChB, FRACS

A woman presenting with recurrent purpura fulminans was eventually found to have inflammatory bowel disease. We suggest the inflammatory state resulted in a deficiency of functional protein C. Clinical recordFirst admissionA 28-year-old woman presented to hospital with a 1-week history of diarrhoea (three soft, non-bloody stools daily), 2 days of vomiting, and a 12-hour history of a purpuric truncal rash. Five years previously, she had experienced a 1-month diarrhoeal illness, managed as an outpatient. At that time, the full blood count and erythrocyte sedimentation rate were within the normal range. Faecal microscopy had shown scanty leukocytes. Colonoscopy was scheduled; however, the symptoms disappeared and investigation did not proceed. The patient subsequently suffered from mild, intermittent diarrhoea. Her uncle had a history of inflammatory bowel disease, although the patient was not aware of this when she first presented to us. On presentation, her vital signs were normal. There was mild right upper quadrant abdominal tenderness, and multiple large, purpuric lesions over the trunk. Blood tests suggested a systemic inflammatory response and mild disseminated intravascular coagulation (Box 1). Faecal microscopy was positive for leukocytes and erythrocytes. The differential diagnosis was broad, and included systemic infection (such as meningococcaemia), Henoch Schönlein purpura, the antiphospholipid syndrome, thrombotic thrombocytopenic purpura, and purpura fulminans associated with protein C deficiency. Ceftriaxone and enoxaparin were commenced as empirical treatment for infection and/or purpura fulminans. Over the next day, the skin lesions became larger and confluent, with new lesions on the legs and perineum. A morphine infusion was required for analgesia. Four units of fresh frozen plasma were infused for suspected protein C deficiency, while awaiting laboratory test results. These confirmed a slightly reduced functional protein C level (63%). This was considered most likely an acquired deficiency, as seen in inflammatory states. Further fresh frozen plasma or protein C replacement was regarded as unnecessary. Additional tests for prothrombotic (Box 1) and autoimmune diseases (antinuclear, extractable nuclear antigen, and double-stranded DNA antibodies) revealed no abnormality. Thrombocytopenic purpura was excluded by the finding of a normal haptoglobin level. There was no significant bacterial growth from blood, urine or faeces. Ceftriaxone was ceased on Day 3. Purpura fulminans was confirmed on skin biopsy by the finding of dermal venous and capillary thrombosis, without evidence of vasculitis (Box 2). There was no further progression in the number or size of the skin lesions. However, on Day 5, the lesions formed bullae and ulcerated (Box 3). Metronidazole and dicloxacillin were added to treat secondary infection of the ulcers. The morphine infusion was ceased on Day 14, and oral oxycodone was substituted. The results of blood tests taken on Day 22 (Box 1) reflected an ongoing intense systemic inflammatory response. At the time of discharge on Day 23, the patient continued to pass three soft stools daily and had multiple ulcers over the trunk and perineum, which required daily nursing care for wound management. The discharge diagnosis was purpura fulminans, possibly precipitated by an enteric infection. After dischargeBy Day 36 of the illness, the diarrhoea had resolved. However, the patient remained fatigued, and the blood tests (Box 1) indicated persistent systemic inflammation and rising serum liver enzyme concentrations. Abdominal ultrasound was normal. The liver abnormalities were considered secondary to the oxycodone. Over the ensuing weeks, the analgesia was reduced and stopped, the blood parameters normalised, and the patient returned to her normal level of function. The skin lesions had healed by Week 15, but left significant scarring. Twenty-five weeks following the onset of the illness, the patient re-presented as an outpatient with a 1-week history of diarrhoea (six watery stools daily). There was one mouth ulcer, but no new skin lesions. A faecal specimen showed only erythrocytes. The erythrocyte sedimentation rate, C-reactive protein, and platelets were slightly elevated (Box 1). The symptoms and abnormal blood parameters resolved completely over the following week. Referral was made for colonoscopy to investigate for inflammatory bowel disease. Second admissionThe patient presented again, 46 weeks after her original hospitalisation, with a 1-week history of bloody diarrhoea and colicky abdominal pain. The colonoscopy was due the following week. Her vital signs were normal. She had left lower quadrant tenderness. Laboratory tests indicated inflammation and mild coagulation abnormalities (Box 1). She was admitted to hospital. Over the next 24 hours, a purpuric rash consistent with purpura fulminans developed on her abdomen, sacrum and vulva (Box 4). Colonoscopy revealed widespread inflammation involving the entire colon, with multiple deep ulcers, but relative rectal sparing. The histology showed active chronic pancolitis, most suggestive of ulcerative colitis (Box 5). The consensus diagnosis was inflammatory bowel disease (colitis, unspecified). Methylprednisolone 60 mg intravenously was administered daily for 1 week. The skin lesions regressed, without ulceration, and the diarrhoea ceased. She was discharged on a reducing dose of prednisolone. Five months after ceasing prednisolone, she has remained asymptomatic. DiscussionPurpura fulminans is an uncommon condition characterised by rapidly progressive dermal vascular thrombosis leading to haemorrhagic necrosis of the skin, which may extend to the muscle and bone, resulting in severe scarring.1,2 It has been described in three settings: (1) hereditary or acquired abnormalities in the protein C anticoagulant pathway; (2) infections, especially meningococcaemia; and (3) idiopathic.3 Purpura fulminans is associated with high mortality and morbidity rates, reflecting the seriousness of the underlying disease, such as bacterial sepsis, and the complications of tissue necrosis, such as secondary infection and limb loss.4,5 Therapy should be primarily aimed at treating the underlying cause and providing supportive care. Surgical intervention such as fasciotomy, skin grafting and amputation may be required.2,4,6 However, because of its rarity, there are few data to support specific treatments for purpura fulminans. Fresh frozen plasma is recommended for idiopathic purpura fulminans or protein C or S deficiencies.1,2,7 Idiopathic purpura fulminans has also been reported to respond to heparin.2 Protein C replacement has been most widely used for purpura fulminans as a result of severe sepsis or congenital protein C deficiency.2,5,7,8 The use of corticosteroids in treating purpura fulminans remains controversial.1,5 There has been one other report of purpura fulminans associated with ulcerative colitis, involving a 60-year-old man who was deficient in protein S, protein C and antithrombin III.9 There was no improvement with heparin or methylprednisolone. Fresh frozen plasma was administered and he underwent total colectomy. No further skin lesions developed, but he died as a consequence of nosocomial infections. In retrospect, our patient had symptoms of inflammatory bowel disease for several years. Purpura fulminans, a rare manifestation of inflammatory bowel disease, had dominated the initial clinical presentation, distracting clinicians from the underlying condition. We believe that a possible pathophysiological explanation for this case is that the inflammation associated with the colitis led to a deficiency in protein C, thus precipitating purpura fulminans. Methylprednisolone appeared most effective in halting the progression of purpura fulminans, although this may have been secondary to treatment of the colitis, rather than of the purpura fulminans per se. What remains to be seen is whether future exacerbations of her colitis will be associated with recurrent purpura fulminans. 1 Results of laboratory tests Test, unit (reference range) First admission Recovery period Recurrent symptoms Second admission Day 1 Day 2 Day 22 Day 36 Week 15 Week 25 Week 46 Haemoglobin, g/L (115–160) 129 123 84 93 126 122 126 White cell count, 109/L (4–11) 5.4 4.8 7.9 8.5 8.0 9.1 11.6 Platelet count, 109/L (150–400) 150 56 888 948 395 510 414 ESR, mm/h (1–20) — 16 106 112 14 44 36 Total bilirubin, μmol/L (2–20) 15 10 4 7 2 6 12 ALT, U/L (< 55) 52 29 7 67 16 31 51 ALP, U/L (20–110) 204 209 157 1039 99 108 129 GGT, U/L (12–43) 34 48 48 293 56 33 50 Albumin, g/L (33–50) 34 31 24 30 42 39 42 C-reactive protein, mg/L (0–10) — 197 97 31 <5 25 239 Haptoglobin, g/L (0.6–2.7) — 2.1 — — — — 2.9 Prothrombin time, s (9–15) 17 18 15 — — — 17 APTT, s (23–34) 31 33 40 — — — 32 Fibrinogen, g/L (1.5–4.0) 4.6 2.9 4.4 — — — 5.9 XDP, mg/L (0–0.19) 3.24 4.30 0.22 — — — 0.75 Functional protein C (70%–130%) — 63% — — — — 65% Free protein S Ag (50%–130%) — 106% — — — — 116% Antithrombin III (70%–145%) — 95% — — — — 63% Lupus anticoagulant, factor V Leiden, and prothrombin mutations — Not detected — — — — — ACA IgG (< 8) — 2 — — — — — Bold indicates abnormal results. — = not measured. ACA = anti-cardiolipin antibody. ALP = serum alkaline phosphatase level. ALT = serum alanine transaminase level. APTT = activated partial thromboplastin time. ESR = erythrocyte sedimentation rate. GGT = serum γ-glutamyl transferase level. XDP = cross-linked fibrin degradation products. 2 Skin lesions: histopathology A: Thrombosis of venules and capillaries is visible in both superficial and deep dermis (arrows) with intact overlying epidermis (haematoxylin and eosin [H&E]; ×50). B: Higher power view of thrombosed venule showing some apoptotic debris (arrows) but no inflammation (H&E; ×200). 3 Skin lesions: first hospital admission Three bullous lesions (arrows) involving the abdomen, with mild surrounding erythema and diffuse purpura. The largest lesion involves the umbilicus. 4 Skin lesions: second hospital admission Within 24 hours of presentation, multiple purpuric lesions developed over the patient’s abdomen and perineum. Two of these early lesions (black arrows) can be seen adjacent to the large scar involving the umbilicus and three smaller scars (white arrows) from the previous episode. 5 Colonic mucosa: histopathology A: There was some crypt shortening and architectural distortion, and the lamina propria contained a brisk mixed inflammatory infiltrate, which extended into the submucosa (haematoxylin and eosin [H&E]; ×100). B: Eosinophils and neutrophils were prominent in the lamina propria, and there was patchy cryptitis (arrow) (H&E; ×400).

Karina J Kennedy MB BS · Sarah Walker MB BS, BSc(Hons) · Paul Pavli MB BS(Hons), PhD, FRACP · Lavinia Hallam BSc(Hons), FRCPath, FRCPA · Chris Hemmings BHB, MB ChB, FRCPA

To the Editor: Primary care skin cancer clinics continue to receive negative publicity. We have previously reported on the workload profile of one network of clinics.1 We report here the profile of clinical activity of the four MoleScan skin cancer clinics situated on the Sunshine Coast, Queensland. Between them, these clinics have been open for a total of 22 years, ranging from 2 years to nearly 9 years of operation. MoleScan is a service company with clinics across Australia. Doctors are employed as subcontractors and are provided with digital dermascopes. The clinics do not have dedicated day surgery facilities, and surgical procedures are conducted in the consulting rooms (http://www.molescan.com.au). Using Medicare Benefits Schedule item number billing data (as previously reported1), we calculated the number of consultations, biopsies, excised lesions (benign, non-melanoma skin cancers [NMSCs] and melanoma), surgical repairs, non-surgical treatment of skin cancers, and non-surgical treatment of other skin lesions. We also estimated the number needed to treat (NNT), defined as the number of benign lesions removed per melanoma. There were 98 276 consultations at the four clinics during the 22 years of operation (Box). In all, 14 982 skin cancers were treated: 395 melanomas and 7468 NMSCs by surgical excision, and 7119 NMSCs by non-surgical methods. The estimated NNT was 22.5. Of the 16 962 lesions excised, 11% (1812) were repaired by a skin flap, 68% (1226) of which were simple flaps. Our previous report, on a different network of clinics,1 showed a different pattern of surgical repairs: 33% (2651) of the 8055 lesions excised were repaired by a skin flap, 45% (1187) of which were simple flaps. Clearly, the clinical practices of these two clinic networks vary. Another area of apparent difference between the two clinic groups is the NNT — 22.5 reported here, compared with 28.6 from the other network.1 The lower NNT in these MoleScan clinics may result from the use of digital dermoscopy, but this requires further study. These early findings from our analyses of MoleScan data highlight the dangers of generalising about the activities of primary care skin cancer clinics from one dataset. Workload profiles of different clinical services may vary markedly, and the widely expressed concern about large numbers of inappropriate surgical repairs may not be warranted. Activities billed at four MoleScan skin cancer clinics on the Sunshine Coast, Queensland, over a total of 22 years of operation * Eyelid, nose, ear, lip, neck, hand, digit or genitals.

Deborah A Askew · David Wilkinson · Gordon L Patrick

There is now an inexpensive first-line approach for diagnosing pigmented skin lesions Over the past decade, the number of published reports on new technologies for diagnosing primary melanoma and other pigmented lesions of the skin has grown exponentially. However, there is still confusion about the relative merits of the various technologies and in which patient setting they are best used. The technologies discussed here are dermoscopy (also known as surface microscopy, epiluminescence microscopy, or dermatoscopy) and its digital modifications. In dermoscopy, hand-held magnification devices (usually × 10 magnification), together with either application of liquid at the skin–microscope interface or the use of cross-polarising filters that require no liquid, allow the visualisation of morphological features not seen with the naked eye. This increases the accuracy of diagnosis for virtually all pigmented skin lesions, including melanoma.1,2 In a meta-analysis of 13 studies comparing dermoscopy with the naked-eye examination, the mean sensitivity for the diagnosis of melanoma (percentage of melanomas correctly diagnosed) increased by 19%, and the mean specificity (percentage of non-melanomas correctly diagnosed) increased by 6.2%.3 While this analysis suggested that dermoscopy did not markedly increase specificity, other studies have shown it to have a dramatic effect on reducing biopsy rates. In a clinical trial of dermatologists randomly allocated to either naked-eye examination or naked-eye examination plus dermoscopy, there was a 42% reduction in the number of patients referred for biopsy in the dermoscopy arm of the trial.4 This trial followed the observation that, for dermatologists trained in the use of dermoscopy, there was a significant reduction in the benign to malignant ratio of excised melanocytic lesions — from 18 : 1 (pre-dermoscopy era) to 4 : 1 (post-dermoscopy era).5 The impact of dermoscopy has also been assessed in general practice. In a study of the diagnosis of melanoma using dermoscopy by Australian general practitioners, my colleagues and I reported a 39% improvement in sensitivity. No improvement was noted in specificity.6 Our finding has been reproduced in a recent clinical trial of primary care providers in Europe.7 The major endpoint of the trial was the result of re-evaluation by two participating specialists of lesions identified as suspicious. The percentage of suspicious lesions correctly detected (sensitivity) increased by 46% in the dermoscopy group. Again, the specificity remained unchanged. Furthermore, there was a significant improvement in the identification of malignant lesions by the dermoscopy group (although the trial lacked adequate power to detect differences in melanoma diagnosis). Since 2000, there has been an increasing interest in digital dermoscopy sequential imaging.1,2 Digital (computerised) dermoscopy monitoring devices take digital dermoscopy images and allow tiling on the computer screen for comparing change in melanocytic lesions over time. Such devices are used in two clinical settings. First, short-term digital monitoring over a 3-month period is used to monitor suspicious melanocytic lesions lacking features of melanoma on dermoscopy. Patients may present with changing common or mildly atypical naevi, or atypical naevi without an accompanying history of no change in their appearance. In contrast, patients with multiple atypical naevi are monitored for periods of 6–12 months (long-term monitoring). Both these monitoring techniques have been shown to detect dermoscopically featureless melanoma.2 In a large series of 91 melanomas detected by sequential digital monitoring in Australia and Europe, more than half of the lesions were in situ and all were less than 1 mm thick, indicating the safety of monitoring lesions over time.8 Recently, the impact of digital dermoscopy was demonstrated in a cohort of patients at high risk of primary melanoma; 34% of melanomas detected lacked dermoscopic features of melanoma and were exclusively detected by sequential digital dermoscopy monitoring.9 With the realisation that melanoma is a relatively uncommon presentation in general practice and may be suboptimally diagnosed even in a specialist setting, automated diagnostic instruments have been developed that require no diagnostic input by the operator. While many are commercially available, such devices are at various stages of development, so that attempting to compare their impact on diagnosis with that of any other technology in the field is difficult.2 Nevertheless, comparisons can be made of the various instruments by contrasting ideal requirements, as outlined elsewhere.10 While it is difficult to draw robust conclusions about the impact of such instruments in the absence of supporting clinical studies, such studies are being performed and their results are eagerly awaited. In summary, dermoscopy has been shown to improve both the sensitivity and specificity of the diagnosis of melanoma by specialists and to improve the sensitivity of melanoma diagnosis by GPs. As it is an inexpensive technique, it should be recommended to all clinicians as a first-line approach for diagnosing pigmented skin lesions. Sequential digital dermoscopy monitoring devices are readily available and are restricted to diagnosing melanocytic lesions (naevi and melanoma). They have been shown to allow the detection of dermoscopically featureless melanoma in any patient presentation, but, to date, studies have only been performed in a specialist setting. Such devices are more expensive and may currently be beyond the reach of general practice. Nevertheless, a clinical trial on the impact of dermoscopy and sequential digital dermoscopy monitoring on excision rates or patient referrals for biopsy by Australian GPs is due to be completed at the end of this year.

Scott W Menzies MB BS, PhD

Eczema is common, occurring in 15%–20% of infants and young children. For some infants it can be a severe chronic illness with a major impact on the child’s general health and on the family. A minority of children will continue to have eczema as adults. The exact cause of eczema is not clear, but precipitating or aggravating factors may include food allergens (most commonly, egg) or environmental allergens/irritants, climatic conditions, stress and genetic predisposition. Management of eczema consists of education; avoidance of triggers and allergens; liberal use of emollients or topical steroids to control inflammation; use of antihistamines to reduce itch; and treatment of infection if present. Treatment with systemic agents may be required in severe cases, but must be supervised by an immunologist. Urticaria (“hives”) may affect up to a quarter of people at some time in their lives. Acute urticaria is more common in children, while chronic urticaria is more common in adults. Chronic urticaria is not life-threatening, but the associated pruritus and unsightly weals can cause patients much distress and significantly affect their daily lives. Angioedema coexists with urticaria in about 50% of patients. It typically affects the lips, eyelids, palms, soles and genitalia. Management of urticaria is through education; avoidance of triggers and allergens (where relevant); use of antihistamines to reduce itch; and short-term use of corticosteroids when antihistamine therapy is ineffective. Referral is indicated for patients with resistant disease.

Constance H Katelaris MB BS, PhD, FRACP · Jane E Peake MB BS, FRACP

To the Editor: We read with alarm the skin cancer clinic profile published recently in the Journal.1 This article publicly states what has been privately suggested for some time — that doctors in skin cancer clinics provide a service no better than the average Australian general practitioner. Surely, if these doctors are calling themselves skin cancer “experts”, the aim of their practice should be to reduce the skin biopsy rate. This is obviously not the case. They report a consultation to biopsy ratio of 1.79. Thus, 56% of all their consultations result in a skin biopsy. The biopsy to treatment ratio of 3.1 is also very high. In addition, they report that only 32% of all biopsies yield a non-melanoma skin cancer. This figure indicates either no additional diagnostic ability on the part of the skin cancer clinic doctors compared with the average Australian GP (who, according to a recent retrospective study, can clinically diagnose a basal cell carcinoma 34% of the time2) or an effort to maximise income. Similarly, the article describes a number needed to treat (NNT) of 28.6. This means that for every 29 benign lesions excised and sent for histological examination to exclude melanoma, only one melanoma is detected. The authors concede that this figure is equivalent to that observed in mainstream general practice. We therefore question the motives of doctors at these clinics in presenting themselves as skin cancer “experts”. However, perhaps the greatest indicator of their seeming intent to maximise financial gain can be demonstrated by an analysis of skin flap item numbers. The article indicates that the total number of excisions was 8055, of which 116 were melanomas and 4709 were non-melanoma skin cancers (ie, 4825 cancers were excised). If one assumes that a suspicious or benign mole biopsy is never closed with a skin flap repair (standard clinical practice), then, of the 4825 skin cancers excised, 2651 (55%) were closed with a flap procedure, and of these, 55% were either “complicated” or “site-specific” flap repairs. There were only 111 skin grafts performed out of the 4825 cancers excised (2.3%). Thus, more than half of the skin cancers excised were closed with a flap repair! Moreover, more than half of the flaps used were “complicated” or “site-specific” flaps, with 24 flaps performed for every skin graft! Surely, no one can argue that these figures are reasonable or consistent with good clinical practice. In comparison, current Australian Medicare data indicate that dermatologists and specialist surgeons close large skin cancer excisions (lesions > 2 cm on the trunk [item number 31290]) with skin flaps at rates of 15% and 17%, respectively (Andrew Miller, Australian Medical Association Skin Representative Group, personal communication). Large lesions normally require a higher skin flap closure rate than smaller lesions. Hence, a flap repair rate of 55% — for lesions of all sizes and sites — reported by the skin cancer clinic doctors is all the more extraordinary. We believe that the above suggests that many skin cancer clinic practitioners are more concerned with maximising income than improving patient care.

Alvin L K Chia · Stephen Shumack

In reply: Our previous publications1,2 should calm Chia and Shumack’s “alarm”. We have urged for the development of education, standards, accreditation, research and audit for skin cancer clinics.1 Over the past 12 months, the Skin Cancer Society of Australia has been formed (http://www.skincancersociety.com.au), standards have been developed, a process of skin cancer practice accreditation has been established, and a masters-level degree in primary care skin cancer medicine has been created (http://www.som.uq.edu.au/skincancer/masters.htm). Our results described activities of a single network of skin cancer clinics.2 They should not be viewed as a benchmark, and caution must be exercised in making any generalisations from them. They are simply the first such data to be presented for public scrutiny. It will be important to see results from other skin cancer clinics. Regarding flap repairs, we were unable to confirm the findings alluded to by Chia and Shumack based on a personal communication. However, we are currently undertaking a detailed analysis of relevant Medicare Benefits Schedule data for general practitioners and specialists and we look forward to presenting this for rigorous peer review and publication shortly. Skin cancer medicine is an established component of primary care. Whether this occurs in mainstream general practice, “special interest services” or skin cancer clinics, the same standards apply to all.

David Wilkinson · Deborah A Askew

Clinical records The details of four patients treated at the Head and Neck Unit, Princess Alexandra Hospital, Brisbane, over a 1-year period are summarised in the table. All four patients presented with progressive trigeminal or facial nerve palsies following excision of cutaneous lesions from the head and neck. Patient Age (years) Sex Presentation History of cutaneous head and neck malignancy Specialties involved Delay in diagnosis Investigations Final diagnosis Management Patient 1 40 male 3 years’ progressive paraesthesia of the left upper lip and cheek Nasal tip lesion removed with cryotherapy: no histology available General practice, dermatology, otolaryngology 3 years MRI PNS (SCC) along V2 Intracranial/skull base surgery with postoperative radiotherapy Patient 2 41 male 8 months’ progressive left cheek paraesthesia, jaw pain and trismus Excision of a left lower lip SCC 2 years previously: histology showed small nerve PNS, so postoperative radiotherapy given General practice, maxillofacial, neurology, otolaryngology 6 months MRI (showed hyperintensity of the left masseter consistent with denervation changes) Masseteric muscle biopsy PNS (SCC) along V2 and V3 extending to the pons Palliative radiotherapy Patient 3 67 female 2.5 years’ progressive left facial nerve palsy Extensive facial SCCs, including an aggressive recurrent right cheek SCC treated with radical excision and radiotherapy Neurology, ophthalmology, otolaryngology 2.5 years MRI PNS (SCC) along VII and V2 Intracranial/skull base surgery with postoperative radiotherapy Patient 4 72 female 5 months’ progressive left facial nerve palsy and left forehead and cheek paraesthesia Two skin lesions excised from the right (contralateral to nerve palsies) nasolabial sulcus 20 years previously: no histology available Otolaryngology 5 months Initial MRI (Box 1) reported as “normal”, although on retrospective review PNS was seen. Subsequent MRI (Box 2) showed extension of the tumour to the pons. PNS (melanoma) along V2 and V3 extending to the pons Palliative care MRI = magnetic resonance imaging. PNS = perineural spread. SCC = squamous cell carcinoma. V2 = maxillary division of trigeminal nerve. V3 = mandibular division of trigeminal nerve. VII = facial nerve. The incidence of non-melanotic head and neck skin cancers in Queensland is among the highest in the world.1 Perineural spread (PNS) from these lesions involves either small nerves, identified at pathological examination (incidental), or large nerves, presenting clinically as cranial nerve palsies. Basal cell carcinoma is the more common skin cancer, but incidental PNS is most frequently associated with squamous cell carcinoma.2 In 32 out of 34 patients over a 5-year period, isolated major nerve PNS was due to squamous cell carcinoma (unpublished data). PNS from melanoma and microcystic adnexal carcinoma has also been described.3,4 Because many clinicians are not familiar with PNS involving large cranial nerves, the diagnosis can easily be missed or delayed. The disease is associated with high treatment morbidity and poor prognosis once clinical or radiological evidence becomes apparent, with a 5-year survival rate of 20%–30%.5 Early detection of PNS in large cranial nerves is essential, as the condition is often unsalvageable once the tumour has spread through the skull base. The facial and trigeminal nerves are most commonly affected,6 although forehead tumours can gain access to the orbit via the ophthalmic nerve.7 Symptoms of trigeminal nerve infiltration include formication, dysaethesia, paraesthesia, numbness and pain (often severe and “electric shock-like” in nature).8 Slowly progressive facial nerve palsy may represent seventh cranial nerve infiltration or infiltration within the parotid, whereas diplopia and visual impairment indicate advanced orbital disease. These symptoms can mimic other diagnoses, such as Bell’s palsy or trigeminal neuralgia, but almost always manifest as slowly progressive and irreversible palsies. Close follow-up of patients to ensure resolution of symptoms is mandatory. The four patients we have described illustrate delays between clinical presentation and diagnosis. These delays could have been avoided by establishing the link between unresolving cranial nerve palsies and excision of cutaneous lesions from the head and neck. Patients 2 and 3 had a history of aggressive squamous cell carcinoma of the face treated with radical excision and postoperative radiotherapy. Advanced, recurrent skin squamous cell carcinomas have a higher incidence of PNS, particularly when located close to a cranial nerve, and should alert the clinician to the possibility of neural metastasis.9 Tumour size before excision, postoperative defect size, subclinical extension and Moh’s micrographic surgery levels are significantly larger in patients with PNS than in patients without PNS.10 PNS can be subtle and missed on initial pathology but, because of the propensity for local recurrence, most specialist multidisciplinary units that deal with skin cancer will recommend adjuvant radiotherapy, particularly if the lesion is excised from the trigeminal nerve distribution. In Patients 1 and 4, no histology was available. Small skin lesions are often treated with cryotherapy or curettage, resulting in no pathological report. However, these lesions may still have a propensity for PNS, so their excision should be elicited in the history. In Patient 4, the skin lesions were excised from the side of the face contralateral to the cranial nerve palsies and were unlikely to represent the primary disease. Nevertheless, this case illustrates that patients with a history of cutaneous lesions from any site on the head and neck are at risk of developing PNS. These cases also illustrate that the interval between excision of a lesion and presentation of PNS can be long.11 Clinicians should hold a high index of suspicion even if the interval is several years. A further source of delay is that patients are seen by a variety of clinicians before diagnosis. Cross-referral for second opinions is common, resulting in further delay. Patients 1–3 illustrate how the unfamiliarity of clinicians with the disease process resulted in patients seeking opinions from several specialties before definitive diagnosis. In addition, investigations may be performed to exclude a different pathology or misinterpreted because the clinician is unaware of the phenomenon, resulting in further delay. In Patients 2 and 4, initial imaging revealed changes compatible with PNS, but these were not recognised, either because the radiologist was not familiar with the entity or because the referring clinician may not have raised the possibility of PNS. In Patient 2, the hyperintensity of the masseter muscle on magnetic resonance imaging (MRI) led the clinician to suspect a primary muscular disorder, instead of the correct interpretation of denervation changes from trigeminal nerve involvement. The patient underwent an unnecessary muscle biopsy. Earlier detection may have resulted in Patients 2 and 4 being treated with curative intent instead of palliative care. High resolution MRI is the investigation of choice, and may identify the earliest changes of PNS. However, disease may not be radiologically apparent until it has reached the orbit, cranial fossa or the skull base foramina. Computed tomography (CT) identifies the disease at a late stage when the tumour has eroded adjacent bony margins. MRI has the added advantage of defining the relationship of the perineural tumour to important anatomical landmarks such as the cavernous internal carotid artery; this is important when planning a resection or biopsy. However, subtle changes on MRI may be missed even by experienced radiologists and, given a strong clinical suspicion with normal imaging, nerve biopsies should be performed. Presently, positron emission tomograph (PET) scanning has no role to play in the staging of PNS. Delayed diagnosis of major cranial nerve PNS may result in devastating outcomes for patients, so early detection is crucial. Patients who present with slowly progressive cranial nerve palsies with a history of head and neck cutaneous malignancies should be investigated for PNS with a high index of suspicion. We recommend that all patients who undergo excision of high risk skin malignancies should be advised to seek a medical opinion if they develop facial numbness or weakness in subsequent years. 1 Coronal T2-weighted MRI images of Patient 4 These images were reported as “normal”, although retrospective review shows perineural spread of melanoma with thickening and nodularity along the left V2 (A), V3 (B) and the trigeminal ganglion (C). MRI = magnetic resonance imaging. 2 Contrast-enhanced T1-weighted MRI images of Patient 4 The images show perineural spread of melanoma with perineural thickening and enhancement along the left V2 (A), V3 (B), the trigeminal ganglion (C) and the trigeminal nerve as it exits the pons (D). MRI = magnetic resonance imaging.

Giles C Warner MSc, MD, FRCS · Mitesh Gandhi MRCP(UK), FRCR, FRANZCR · Benidict Panizza MB BS, MBA, FRACS

Acute generalised exanthematous pustulosis (AGEP) is a clinical reaction pattern that is induced, in over 90% of cases, by systemic drugs (most frequently antibacterial drugs). This is the first reported case of AGEP caused by the herbal remedy Ginkgo biloba. Clinical recordA 45-year-old man developed a symmetrical maculopapular eruption on his limbs. Within 2 days, the rash generalised to involve the face. Disseminated non-follicular small pustules on erythematous skin were predominant (Box 1). The palms, soles and mucous membranes were spared. His body temperature was 38.8°C. The rash had developed 48 hours after starting oral Ginkgo biloba treatment for tinnitus (Ginkgo biloba was the only ingredient listed on the medication). The patient denied previously taking Ginkgo biloba and was not on any other medication. He reported no previous adverse drug reactions and no history of psoriasis. Blood tests returned the following results: C-reactive protein 135 mg/L (reference range [RR], < 12 mg/L); white blood cells 17.2 × 109/L (RR, 4.0–11.0 × 109/L); neutrophils 15.8 × 109/L (RR, 2.0–7.5 × 109/L); and eosinophils 0.79 × 109/L (RR, 0.04–0.40 × 109/L). A skin biopsy showed neutrophil-containing spongiotic pustules in the epidermis and a mixed cellular infiltrate with oedema in the papillary dermis, consistent with acute generalised exanthematous pustulosis (Box 2). The rash cleared within 10 days after withdrawal of Ginkgo biloba. The patient refused a follow-up cutaneous patch test. DiscussionAcute generalised exanthematous pustulosis (AGEP) is considered to be a clinical reaction pattern, induced, in over 90% of cases, by systemic drugs. It is a rare presentation of an adverse drug reaction most frequently triggered by antibacterial drugs. AGEP can be difficult to distinguish from other pustular dermatoses. To my knowledge, this is the first reported case of AGEP caused by the herbal remedy Ginkgo biloba. Ginkgo fruits and seeds have been used in traditional Chinese medicine for millennia, mostly to treat asthma and chilblains. The flavonoids and terpene lactones from the ginkgo leaf, which today is used for medicinal purposes, are associated with diverse pharmacological actions. In clinical practice, ginkgo is mostly used to treat memory impairment,1,2 dementia,3 tinnitus4 and intermittent claudication.5 In some European countries, ginkgo is registered for these indications; in the United States, it is marketed as a dietary supplement. In-vitro and in-vivo studies suggest that ginkgo has antioedemic, antihypoxic, antioxidant, metabolic, antiplatelet, haemorrhagic, microcirculatory and free-radical-scavenging actions.6,7 Reported adverse skin reactions to Ginkgo biloba include contact dermatitis and diffuse morbilliform eruption. The primary allergens from the ginkgo leaf appear to be ginkgolic acids. Ginkgolic acid molecules have similar side-chains to the catechols of the poison ivy group and are suspected of displaying some cross-allergenicity.8 Allergic contact dermatitis to the Rhus antigen present in the ginkgo fruit seeds has been extensively documented.8,9 This raises the question of whether or not ginkgolic acids could evoke a systemic reaction if taken orally. Systemic contact dermatitis can develop from oral challenge after contact sensitisation with other allergens.10 The criteria for diagnosis of AGEP are defined by the EuroSCAR score.11 Features of the condition include acute onset of small, sterile, non-follicular pustules on erythematous skin beginning in intertriginous areas or on the face; systemic signs, with fever over 38°C (in a typical course, an acute rash appears within 1–2 days and resolves by skin desquamation within 4–10 days after discontinuation of the causative agent); and neutrophilia, in the setting of a consistent histological pattern.11 The patient described here had a classic drug-induced AGEP with typical morphology, course and histology and a validation score of 12 points (the range for definite AGEP is 8–12).11 Ginkgo biloba treatment is commonly recommended by non-medical practitioners. With the rise of complementary and alternative medicine, there may be an increase in frequency and type of adverse reactions to this treatment. 1 Disseminated small pustules on erythematous skin 2 Histological section of skin biopsy The section shows neutrophil-containing spongiotic pustules (black arrow) in the epidermis and a mixed cellular infiltrate with oedema (clear arrow) in the papillary dermis (haematoxylin–eosin stain, original magnification &times 100).

Robert S Pennisi MPhil, FRACGP, DPD

Noel McK Bennett Infectious Diseases Physician, Victorian Department of Human Services, 14A Marquis Street, Ashburton, VIC 3147. bennettnATbigpond.net.au To the Editor: In a recent issue of the Journal, Chew et al described a woman from Vietnam with skin nodules that, on histological examination, showed lobular panniculitis with granulomatous inflammation.1 No mycobacteria were visible and a polymerase chain reaction test for Mycobacterium tuberculosis was negative. Two months after starting quadruple antituberculous therapy (including rifampicin), her lesions had resolved. Erythema induratum (ostensibly due to hypersensitivity to M. tuberculosis) was diagnosed, despite the absence of evidence of tuberculosis. Other possible diagnoses were considered, but leprosy was not mentioned. In regions of Australia where leprosy is not endemic, the disease is frequently overlooked.2 Birrell3 described a man from Malta with recurring skin lumps. Biopsy showed panniculitis with giant cells, and the man was initially misdiagnosed as having “Weber–Christian syndrome” or “relapsing febrile non-suppurative nodular panniculitis”. Soon after, another Maltese patient presented similarly. This time, leprosy was suggested, and a biopsy revealed the presence of Mycobacterium leprae.4 Re-examination of slides from the first case showed similar organisms, confirming leprosy.5 The patients described by Chew et al and Birrell had migrated from countries in which leprosy was endemic, and biopsies revealed granulomatous panniculitis. Weber–Christian syndrome and erythema induratum are rare, ill-defined conditions with confused aetiologies, and both lack a specific diagnostic test. Therefore, cases of leprosy can be easily misdiagnosed as one of these conditions. That the biopsy in this patient did not show visible M. leprae is against a diagnosis of leprosy. But in my experience, even in lepromatous (multibacillary) disease, occasionally a skin smear of a lesion or (more rarely) a biopsy specimen may fail to reveal bacilli. Of course, this would be likely if the patient had received specific treatment for leprosy previously. Respectfully, I suggest that Chew et al should attempt to exclude lepromatous leprosy in their patient by looking for possible missed stigmata of leprosy, enquiring whether she has ever been treated for leprosy, asking whether any close acquaintances have had the infection or a chronic skin condition, and following up the patient in the long term.

Noel McK Bennett

James B Muir Dermatologist, Southeast Dermatology, 1202 Creek Road, Carina Heights, QLD 4152. arnoldmuirAToptusnet.com.au To the Editor: One of the Journal’s recent Lessons from Practice illustrates common errors in the approach to dermatological conditions.1 As in all areas of medicine, an accurate diagnosis is crucial to the management of any skin disease. This is especially so if a medical practitioner institutes treatments, such as oral steroids, that have considerable potential for causing morbidity. The lessons I would draw from the case of erythema induratum described are as follows. If you suspect an unusual presentation of a common condition, perform investigations to confirm your suspicions. Although erythema nodosum classically occurs on the anterior lower leg, lesions above the knee may occasionally be seen. To make a diagnosis, investigations need to be appropriate. The battery of blood tests ordered in the case described would not have shed light on the pathological process occurring in the skin. There is a reluctance among the general medical community to perform skin biopsies. These procedures cause little morbidity, have a high diagnostic yield, and should be within the skill set of any medical graduate. Concern over causing a scar is often cited as a reason for not doing a biopsy. But, in my experience, patients are rarely worried about such a prospect. Missing the diagnosis is surely of much greater concern. Taking a simple biopsy, including fat, at the initial presentation would have saved the patient in question a lot of trouble and risk. If there is no response to your treatment, it may well be that the initial diagnosis was incorrect. For example, it is common to see “steroid-resistant eczema” that is actually intraepidermal carcinoma. Erythema nodosum will usually show at least some response to non-steroidal anti-inflammatory treatment. Lack of response to a treatment that usually works should lead to a re-evaluation of the diagnosis. Systemic steroids should not be used for a dermatological condition without a firm diagnosis. Firstly, they can suppress many of the clinical and histological changes that allow a diagnosis to be made. Appropriate investigations need to be done before starting steroids. Secondly, a drug like prednisolone may well make matters worse, especially if, as here, there is an infectious aetiology. Patients from areas in which tuberculosis is endemic should have this condition excluded before being given systemic steroids. A lack of obvious exposure to or symptoms of tuberculosis is not unusual in patients from such areas who are subsequently shown to harbour this infection. The authors state that, as erythema induratum can resolve with corticosteroid treatment, this can lead to an erroneous diagnosis of erythema nodosum. Using response to treatment as a quasi-diagnostic test is dangerous indeed. Steroids will cause many conditions associated with significant inflammation to improve or even appear to resolve. But this does not mean that there is no infectious or malignant aetiology.

James B Muir

Gary Y Chew,* Christopher Henderson,† John W Quin‡ * Registrar, ‡ Director of Clinical Immunology, Department of Immunology, Liverpool Hospital, Bigge Park Centre, PO Box 103, Liverpool, NSW 2170; † Anatomical Pathologist, South Western Sydney Area Health Service, Liverpool, NSW. john.quinATswsahs.nsw.gov.au In reply: We thank Bennett and Muir for their pertinent comments. Our patient did not have any history or clinical evidence of lepromatous leprosy. The skin biopsy did not reveal any dermal granulomatous involvement, and there were definitely no organisms seen on an auramine stain of the biopsy specimen. Subcutaneous involvement in leprosy is uncommon except in erythema nodosum leprosum or as a neurotropic phenomenon. When present, it tends to be a neutrophil-rich hypersensitivity necrotising vasculitis — no features of which were seen in this case. Neither the woman’s partner nor child had a chronic skin condition or clinical history of leprosy or tuberculosis. Furthermore, the patient has been followed up for 12 months, with no recurrence of the rash. We agree with Muir that an accurate diagnosis is crucial to managing any skin disease and that there were many lessons to be gathered from this case apart from the five points we listed. It is our usual practice not to begin definitive treatment until we have examined a skin biopsy of any suspicious lesion and made a diagnosis. As this patient was very concerned about getting a scar, we did not perform a skin biopsy initially, but informed her that we may need to do so if the condition did not respond to treatment. We agree that patients from areas where tuberculosis is endemic should have tuberculosis excluded before instituting systemic steroid treatment. In this case, the patient was given a chest x-ray by the appropriate authorities before her migration to Australia. She has not returned to Vietnam since then. Furthermore, the patient had failed a trial of a non-steroidal anti-inflammatory drug and found the lesions cosmetically distressing. Consequently corticosteroids were instituted.

Gary Y Chew · Christopher Henderson · John W Quin

Russell Stitz,* Michael R Kidd,† Liz M Kenny,‡ Anne M Howard§ * President, Royal Australasian College of Surgeons, Spring Street, Melbourne, VIC 3000; † President, Royal Australian College of General Practitioners, Melbourne, VIC; ‡ President, Royal Australian and New Zealand College of Radiologists, Sydney, NSW; § President, Australasian College of Dermatologists, Sydney, NSW. college.presidentATsurgeons.org To the Editor: The MJA is to be congratulated on promoting the debate related to the significant increase in the number of “skin clinics”.1 Standards are important in both the maintenance of the facilities and the formal training of the practitioners undertaking the assessment and care of patients. The four medical Colleges actively involved in treating skin conditions, who have their training programs accredited by the Australian Medical Council and their selection and assessment processes authorised by the Australian Competition and Consumer Commission, are the Royal Australian College of General Practitioners (RACGP), the Royal Australian and New Zealand College of Radiologists (Faculty of Radiation Oncology), the Royal Australasian College of Surgeons (RACS), and the Australasian College of Dermatologists. The Colleges already have established standards for accreditation of facilities (eg, Guidelines and standards for day surgery in Australia <http://www.surgeons.org/Content/NavigationMenu/FellowshipandStandards/ AustraliaDaySurgeryCouncil/Guidelines_and_Stand.htm>, or the RACGP Standards for general practice <http://www.racgp.org.au/document.asp?id=17623>) and have well established programs for training medical practitioners in the treatment of skin conditions. The Colleges base these programs on high standard “holistic” care that is not influenced by entrepreneurial medicine. Our Colleges encourage the development of improved training programs at all times. It is important that we maximise the benefit of the structures and standards that currently exist. Our Colleges have already begun discussion about the ways we can build on our work to date. Our members, and the Australian public, expect specialist medical Colleges to take a lead in ensuring the quality of health care, and we will continue to do so.

Russell Stitz · Michael R Kidd · Liz M Kenny · Anne M Howard

Objective: To describe the workload profile in a network of Australian skin cancer clinics.Design and setting: Analysis of billing data for the first 6 months of 2005 in a primary-care skin cancer clinic network, consisting of seven clinics and staffed by 20 doctors, located in the Northern Territory, Queensland and New South Wales.Main outcome measures: Consultation to biopsy ratio (CBR); biopsy to treatment ratio (BTR); number of benign naevi excised per melanoma (number needed to treat [NNT]).Results: Of 69 780 billed activities, 34 622 (49.6%) were consultations, 19 358 (27.7%) biopsies, 8055 (11.5%) surgical excisions, 2804 (4.0%) additional surgical repairs, 1613 (2.3%) non-surgical treatments of cancers and 3328 (4.8%) treatments of premalignant or non-malignant lesions. A total of 6438 cancers were treated (116 melanomas by excision, 4709 non-melanoma skin cancers [NMSCs] by excision, and 1613 NMSCs non-surgically); 5251 (65.2%) surgical wounds were repaired by direct suture, 2651 (32.9%) by a flap (of which 44.8% were simple flaps), 42 (0.5%) by wedge excision and 111 (1.4%) by grafts. The CBR was 1.79, the BTR was 3.1 and the NNT was 28.6.Conclusions: In this network of Australian skin cancer clinics, one in three biopsies identified a skin cancer (BTR, 3.1), and about 29 benign lesions were excised per melanoma (NNT, 28.6). The estimated NNT was similar to that reported previously in general practice. More data are needed on health outcomes, including effectiveness of treatment and surgical repair.

David Wilkinson MB ChB, DSc, FRACGP · Deborah A Askew BAppSci, MHlthSci, PhD · Anthony Dixon MB BS, FACRRM

The number of skin cancer clinics functioning within Australia’s primary care environment is increasing rapidly, and significant concerns have been raised about the type and quality of work done by some doctors in some clinics. Mainstream general practice is threatened by perceived fragmentation, and specialist practice in dermatology and plastic surgery is threatened by encroachment into their domains of practice. We propose an agenda of training, standards, accreditation, audit and research to ensure that skin cancer clinics provide optimal health outcomes for patients.

David Wilkinson MB ChB, FRACGP, DSc · Scott Kitchener MB BS, DrPH, FAFPHM · Peter Bourne MB BS · Anthony Dixon MB BS, FACRRM

Research shows that a large proportion of shade structures provide insufficient protection against the sun’s ultraviolet light. Shade creation guidelines need to be updated. Community organisations such as child care centres and schools that need to provide effective shade are hindered by cost and building regulations. The protective function of shade structures is more important than their aesthetic appeal.

David J Turnbull PhD · Alfio V Parisi PhD

Clinical record A 29-year-old Vietnamese woman who had migrated to Australia 5 years previously was referred with a 2-month history of erythematous painful nodules on her thighs and left buttock, the largest of which measured 3 cm × 4 cm. There was no history of recent infections or previous exposure to tuberculosis. She denied any symptoms of inflammatory bowel disease, vasculitis or connective tissue disease. Examination disclosed no abnormalities such as lymphadenopathy, hepatosplenomegaly or synovitis. A chest x-ray was normal. Blood tests showed a total white cell count of 7.3 × 109/L, haemoglobin level of 133 g/L, platelet count of 295 × 109/L and an erythrocyte sedimentation rate of 11 mm/h. No antinuclear antibodies or antineutrophil cytoplasmic antibodies were detected. Liver and thyroid function tests and coagulation studies were all normal. A working diagnosis of erythema nodosum was made, and the patient was commenced on naproxen. When treatment with naproxen was unsuccessful after 4 weeks, she was commenced on 45 mg (1 mg/kg) of prednisolone daily. As she showed only a partial response to prednisolone, a deep incisional biopsy of a lesion was performed. It revealed a granulomatous lobular panniculitis with necrosis (Box), consistent with erythema induratum (EI). There were no visible mycobacteria or fungi on staining. A subsequent Mantoux test was strongly positive, while a polymerase chain reaction test for Mycobacterium tuberculosis DNA performed on the paraffin-embedded tissue was negative. The patient was commenced on a 6-month course of quadruple antituberculous directly observed therapy, consisting of rifampicin, isoniazid, pyrazinamide and ethambutol, together with pyridoxine, while the prednisolone dose was quickly tapered and ceased. Within 2 months, the cutaneous lesions had resolved, and had not recurred a month after the completion of antituberculous therapy. Bazin1 first described erythema induratum (EI) in 1861 to illustrate chronic, painful, violaceous, indurated and occasionally ulcerative nodules that occurred predominantly on the lower limbs of patients (mainly women) with tuberculin hypersensitivity. Its appearance can easily be confused with erythema nodosum, polyarteritis nodosa or perniosis. The diagnosis of EI could easily have been missed, as the cutaneous lesions were similar to those characteristic of erythema nodosum. In addition, there was a partial response to corticosteroids. A diagnosis of EI is based on cutaneous characteristics, a positive Mantoux test, evidence of tuberculosis and histological findings.2 The diagnosis of EI in this patient was established with three of the four criteria. Furthermore, the patient responded clinically to antituberculous therapy. The negative polymerase chain reaction (PCR) result is not surprising. In other studies, only 56%–88% of patients previously diagnosed with cutaneous tuberculosis had a positive PCR result using the IS6110 primer.2,3 Schneider et al4 found a positive PCR result in only 5 of 20 patients with EI. Shimizu et al5 failed to isolate Mycobacterium tuberculosis by either culturing cutaneous EI tissue or inoculating the tissue into guinea pigs. The association of EI with tuberculosis is still a matter of debate. Some have considered EI to be a type III or type IV hypersensitivity reaction to M. tuberculosis antigens.6 This may explain the patient’s partial response to corticosteroids. Lessons from practice Erythema induratum (EI) can easily be mistaken for erythema nodosum, perniosis or cutaneous polyarteritis nodosa. The failure to detect Mycobacterium tuberculosis on microscopy or by a polymerase chain reaction test on the biopsy specimen does not exclude the diagnosis. EI lesions can resolve with corticosteroid therapy, which may lead to a misdiagnosis of erythema nodosum. EI should be treated with antituberculous therapy. Histological section of subcutaneous tissue from one of the nodules The lower-power image shows florid inflammatory changes involving fat lobules (L) with thickening of lobular septa (S), consistent with a florid, predominantly lobular, panniculitis. The higher-power image (inset) shows a classical combination of granulomatous inflammation (G) and eosinophilic granular fat necrosis (N).

Gary Y J Chew MB BS, BSc(Med) · John W Quin PhD, FRACP, FRCPA · Christopher Henderson MB BS, FRCPA

A 76-year-old woman presented for a routine skin check in late spring. On examination, she was noted to have a marked purpuric rash involving her lower legs (Figure A). The rash was accompanied by a slight burning sensation. The patient had played golf the day before. A skin biopsy revealed limited changes suggestive of leukocytoclastic vasculitis (Figure B). The rash resolved over 3 days. As the patient was concerned about herbicides causing the rash, she was subsequently patch-tested to an extensive panel of contact allergens, but all tests were negative. In our experience, an erythematous-to-purpuric rash occurring on the legs and ankles of older people is not uncommon after prolonged exercise, such as golfing or hiking, in hot weather. It usually resolves within a week. Surprisingly, there have been very few published reports of this type of rash occurring. We recently reported a case series of 17 other patients,1 and suggested that the condition — a benign variant of cutaneous vasculitis, for which a combination of exercise, heat and stasis appears to be the most significant cause — be known as “golfer’s vasculitis”. However, a colleague who practises in Florida and who is familiar with the condition refers to it as “Disneyworld leg”! A: Purpuric rash on skin of lower leg. B: Skin biopsy of lower leg showing a perivascular infiltrate of predominantly lymphocytes with occasional eosinophils, endothelial swelling and some extravasated red blood cells.

Rosemary L Nixon FACD, FAFOM · Jacinta M Opie MB BS, DRANZCOG · Robert I Kelly MB BS, FACD

To the Editor: The interesting case report by Currie and colleagues describes a variable cutaneous eruption of uncertain aetiology in a cluster of methadone-dependent patients.1 The rash was described as including pruritic, exanthematous, purpuric and eventually desquamative components, and typically as involving the trunk and extremities, particularly palms and soles. Secondary syphilis classically presents in a similar fashion, but no mention was made as to whether this had been excluded by serological testing. Indeed, the histology of the rash (perivascular inflammation, including plasma cell infiltrate, progressing to endarteritis) is similar to that seen in skin biopsies from methadone patients with secondary syphilis. However, an allergic or toxic cause appears to be implicated, in view of previous, well documented reports of hallucinogenic or other drug-related vasculitis published by ourselves2 and others.3-5

Vernon J Heazlewood

To the Editor: As a Victorian always on the lookout for something new, I read with interest the report by Currie and colleagues of a syndromic rash in patients attending methadone clinics in New South Wales.1 From the title I expected to read about a rash occurring as part of a syndrome, yet no group of concurrent symptoms was described. In fact, there was a long list with each patient of negative findings. I also had trouble deciding whether the four patients described indeed had the same rash. While the “lumpers” among us may consider it pedantic to split “rash” into more than one category, some doctors make an occupation of it quite successfully. For example, Patient 1 had petechiae and purpura, but no erythema and no involvement of the palms and soles. No photo, but nevertheless a nice description of vasculitis — common among intravenous drug users. Patient 2 had, from the look of the photo, a toxic erythema that resolved with desquamation of the palms and soles. No petechiae or purpura. Therefore, must be a different rash to Patient 1. Patient 3 is described as having “ a prominent purpuric rash involving both lower limbs”. However, the photo shows a macular erythema with some associated purpura that looks almost certainly to be an incidental manifestation of dependency. Difficult to say from a photo, as touch is so important in the diagnosis of true purpura. Of course, a 2 mm punch biopsy of the skin could resolve this almost instantly. Again, it is not clear whether this rash is similar to that seen in either Patient 1 or Patient 2. Patient 4 is described as having a red and itchy rash (erythematous and pruritic), but, from the photograph, we can clearly see that the rash is urticarial. This raises the possibility of urticaria, or urticarial vasculitis, or even erythema multiforme. Again, a skin biopsy would be very useful. The severe palmar peeling almost seems incongruous, but it does give me faith that buried in this report there might actually be a new desquamating rash associated with methadone use. In summary, I am still not clear whether the four patients described had the same rash, but I concur with the authors that several of these patients might warrant specialist assessment. Let’s hope they get it.

Rodney D Sinclair

In reply: The purpose of our report1 was to alert the wider medical community to the recent outbreak of a “syndrome” (“a group of symptoms and signs, which, when considered together, are known or presumed to characterise a disease or lesion”2) that included the development of various forms of rash in patients taking methadone syrup. Our report included four cases illustrating the different types of rash encountered to date. From October 2004, over 400 cases were reported from methadone clinics in New South Wales, although very few new cases have been reported since February 2005, presumably reflecting the success of preventive measures instituted by the NSW Health department. To date, the cause of this methadone-associated syndrome has not been elucidated. Skin biopsies of rash lesions have been performed in a number of our patients. All have shown chronic perivascular inflammation, with most demonstrating hyperkeratosis. A small number of patients have had a true leukocytoclastic vasculitis. As Heazlewood has commented, both secondary syphilis and illicit drugs such as amphetamines and cocaine have been reported to cause vasculitic rashes. However, none of the more than 50 patients in whom we have performed syphilis serological testing has had positive results, and few of our affected methadone patients have had urine drug-test results positive for amphetamine or cocaine use. We therefore believe that the syndrome we have described remains specific to the patients’ current use of methadone syrup. We are unaware of a rash that is “an incidental manifestation of dependency”, as suggested by Sinclair, but we would assure him that specialists from a wide variety of fields, including dermatology, immunology, immunopathology, infectious diseases, addiction medicine and epidemiology, have all been involved in the assessment and treatment of patients with this syndrome, and in the wider investigation of its pathogenesis.

Jon N Currie · Lisa Snell · Elizabeth M Benson

An elderly man attending a dermatology outpatient clinic for an unrelated skin complaint proudly insisted on demonstrating his simple do-it-yourself (DIY) solution to a deformity of his great toenails (pincer nail) that he had endured for many years. As he slipped off his socks, a number of medical students observing the consultation turned ashen (see Figures). Pincer nails are a transverse overcurvature of the nail, commonly caused either by degenerative osteoarthritis of the distal interphalangeal joints or by ill-fitting shoes. Less commonly, they may be associated with subungual tumours or ingestion of β-blockers. Treatment options for pincer nail usually include bracing (with steel or plastic devices that exert countertension on the nail), surgery to ablate the lateral horns of the nail matrix, or permanent removal of the nail either chemically or surgically.1 Our patient found that, by inserting a stainless steel screw through the free edge of each of his overgrown and overcurved great toenails and into a small broad nut, he was able to satisfactorily correct his deformity by making a series of tightening adjustments over a period of months. Our patient’s novel approach, which is quite unlike that of usual bracing devices, exerted countertension on the ventral aspect of the free edge of the nail. Korean authors have recently described a similar technique using custom-fitted aluminium splints. These are bound with cyanoacrylate adhesive to the ventral nail plate after separating the affected great toenail longitudinally using CO2 laser vaporisation.2 Our patient’s device might begin to create some discomfort as the nail grows longer, requiring repositioning (proximally) to maintain the effect on moulding nail growth, although these considerations were not discussed in the brief consultation with our patient!

Alex Chamberlain MB BS · Annika Smith · Adrian Mar FACD

We report an outbreak of a “rash” syndrome in patients attending methadone clinics in New South Wales. It presents with a pruritic, exanthematous or purpuric rash involving the trunk, limbs, palms and soles, which develops over a week and proceeds in most patients to desquamation (mainly of palms and soles) persisting for 3–4 weeks. Mucosae are not involved, and patients are generally systemically well. To date, the rash has affected 22% of 316 patients attending one methadone clinic in western Sydney, as well as patients in clinics elsewhere in Sydney and rural NSW. The aetiology is as yet unknown. We report an outbreak of a “rash” syndrome in patients attending a number of methadone clinics across New South Wales during October and November 2004. The syndrome first came to our attention when, over a week, two patients presented to a methadone clinic in western Sydney and three to the Westmead Hospital emergency department with a distinctive rash. Subsequent enquiries and patient surveillance revealed that 70 of 316 patients (22%) at the methadone clinic had developed a similar “rash” syndrome in October and November. All were prescribed methadone syrup. Clusters of patients have also been increasingly reported at other methadone clinics across metropolitan Sydney and some regional and rural areas in NSW. To date, informal communication with interstate methadone clinics has identified small numbers of patients with the “rash” syndrome outside NSW. In the first western Sydney case reliably identified by history, symptoms developed in August 2004. The principal features of the “rash” syndrome are a pruritic, exanthematous or purpuric rash that typically develops over 2 to 4 days on the hands, feet, trunk and lower limbs and persists for up to 7 days. It is usually followed by a desquamative phase that particularly involves the hands and feet and lasts up to 3 to 4 weeks. Some patients develop only the desquamative phase. The condition appears relatively benign, with few, if any, systemic symptoms, although the palms and soles of the feet can become painful with pressure after desquamation. In several patients, the rapidly developing purpuric nature of the presenting rash raised initial concern about meningococcal disease or a systemic vasculitic syndrome sufficient to warrant referral for specialist assessment. We describe four illustrative cases. Clinical recordsPatient 1A man aged in his 30s presented to a hospital emergency department with a 3-day history of a petechial and purpuric rash. He was an intravenous drug user who had been in a methadone treatment program for 7 years. He intermittently injected his oral methadone intravenously, most recently 24 hours before onset of the rash. This initially involved the lower limbs, but spread over 24 hours to affect the buttocks, lower back and abdomen. Associated but relatively mild symptoms included malaise and nausea for a week before rash onset, followed by sore throat, myalgia, ankle arthralgia, abdominal and chest pain and vomiting. At presentation, the patient was afebrile. Blood pressure was 120/60 mmHg, and pulse 70 bpm. A sparse petechial and purpuric rash was present on lower limbs, feet, buttocks and lower abdomen. There was no pedal oedema, joint effusion or tenderness. There were no abnormalities on respiratory and cardiovascular examination, no clinical evidence of endocarditis, no lymphadenopathy, and mucosae were normal. The right upper abdominal quadrant was tender, but the liver and spleen were not enlarged, and no renal masses were palpable. Investigations were uninformative (Box 1). Inpatient progress was unremarkable, and, 10 days after presentation, all symptoms had resolved, despite ongoing oral and intravenous methadone use. Patient 2A middle-aged man presented with a 2-day history of an erythematous, pruritic rash over his trunk and limbs which was now beginning to desquamate. He was also an intravenous drug user in a methadone treatment program. In addition to taking prescribed oral methadone, he intermittently injected both methadone and stimulants, such as amphetamine, intravenously. There was no history of fever, oropharyngeal, genital, eye or systemic symptoms. On examination, he was afebrile, looked well and had a generalised exanthem, with erythema and significant desquamation of soles and palms (Box 2, A and B). There were no oral, mucosal or eye signs, and no lymphadenopathy or hepatosplenomegaly. Results of investigations were unremarkable (Box 1). He was treated for 2 days with oral prednisolone and an antihistamine, and then discharged. The rash settled over a week, although he continued to have desquamation of the soles and palms 2 weeks later. Patient 3A young man who was an intravenous drug user in a methadone treatment program presented to the same hospital with a 2-day history of a purpuric lower-limb rash. In addition to taking prescribed oral methadone, he intermittently injected both heroin and methadone intravenously. Five days before presentation, he developed bilateral calf pain and generalised myalgia. He was initially seen at another hospital, where he was treated with broad-spectrum intravenous antibiotics for presumed sepsis. He discharged himself after 24 hours and was admitted to our hospital about 12 hours later because of his concern about the rash. On admission, he was afebrile, with blood pressure of 115/65 mmHg and pulse of 75 bpm. He had a prominent purpuric rash involving both lower limbs (Box 2C), with sparse lesions on both forearms. Mucosae were normal, and there was no meningism, lymphadenopathy, hepatosplenomegaly, joint swelling or tenderness, no abnormalities on respiratory and cardiac examination, and no stigmata of endocarditis. Results of investigations were once again unremarkable (Box 1). The patient remained well despite the rash and was discharged from hospital 24 hours after admission. Patient 4A young woman who was an intravenous drug user in a methadone treatment program presented to the methadone clinic with a 4-day history of an erythematous, pruritic rash over her trunk, limbs and hands. Other than oral methadone, she was taking no drugs and was otherwise well. Examination revealed an extensive exanthem over her trunk, hands and legs. She had no fever, and blood pressure was normal. She was reviewed a week later and still had an extensive generalised erythematous exanthem, as well as finger and palm desquamation (Box 2, D and E). Results of investigations were unremarkable (Box 1). DiscussionThe aetiology of this “rash” syndrome is yet to be elucidated. Currently, it appears to be restricted to people using methadone syrup, with no reports of rash in over 100 patients in western Sydney prescribed buprenorphine for treatment of opioid dependence, nor among non-methadone-using family members of patients with the rash, nor among healthcare workers in contact with these patients. To date, all patients with the “rash” syndrome who have been assessed for hepatitis C exposure are seropositive, but not all are viraemic. Some patients with the “rash” syndrome smoke cannabis and intermittently inject methadone or other drugs. However, these characteristics are not universal among affected patients, nor more frequent than in unaffected patients on the methadone program, among whom they are also common. Similarly, the use of prescription or complementary medicines does not seem to be associated with the “rash” syndrome. Similar rashes and associated desquamation are common in staphylococcal and streptococcal toxin-induced illnesses, such as toxic shock syndrome and scalded skin syndrome,1-3 and in some viral illnesses, such as parvovirus infection and measles.4 However, the patients in the current outbreak did not give a history of bacterial or viral illness, and family members not taking methadone do not appear to have developed the syndrome. HIV antibody testing has been performed in some affected patients and has been negative. Throat swabs taken in some patients have grown only normal respiratory flora. Markers of streptococcal infection, such as antideoxyribonuclease B antibodies and anti-streptolysin O titre, are positive in some but not all patients. Skin biopsy performed in a number of patients has failed to help define the aetiology of the rash. Histological examination often shows focal and mild spongiosis with superficial perivascular chronic inflammation, while direct immunofluorescence examination shows deposition of IgM and complement 3 in dermal capillaries. These findings are consistent with an immunological reaction in the skin, but do not clarify whether it is the primary cause of the rash or a secondary phenomenon. A hypersensitivity reaction to a contaminant in the methadone syrup could present with such a picture. The fact that, to date, all the patients identified in western Sydney had been taking methadone syrup from a single manufacturer raises the possibility of batch contamination; however, batches are distributed nationally, so more widespread involvement would probably be expected if this was the basis of the syndrome. In addition, examination of the methadone syrup has failed to detect any contamination. The possibility of alternative sources of contamination, such as methadone storage or delivery devices, remains to be explored. We believe it is important for physicians to be aware of this newly emerging syndrome, both to assist with more accurate delineation of its epidemiology and pathogenesis, and to permit more effective investigation and treatment of affected patients. State public health units and the Therapeutic Goods Administration are investigating this outbreak to try to determine the cause of this new syndrome. 1 Results of investigations in four patients with rash Investigations Reference range Patient 1 Patient 2 Patient 3 Patient 4 Full blood count and film Normal; platelet aggregates on film Normal apart from WBC 10.8 x 109/L; occasional reactive lymphocytes Normal Normal, apart from Hb 107 g/L Haemoglobin (Hb) (g/L) 115–161 White blood cell count (WBC) (x 109/L) 3.7–9.5 ESR (mm/h) 0–15 4 11 5 38 C-reactive protein (mg/L) 0–11 20 27 22 15 Liver function tests Normal Abnormal Abnormal Normal γ-Glutamyltransferase (U/L) 8–43 47 48 Alanine aminotransferase (U/L) 10–47 88 157 Aspartate aminotransferase (U/L) 12–45 104 154 ANA, ANCA, ENAs, rheumatoid factor, complement C3 and C4 Normal nd Normal nd Cryoglobulins Absent nd Detected nd Prothrombin time (s) 11–18 Normal Normal Normal nd APTT (s) 25–36 Normal 39 Normal nd Hepatitis C virus IgG-positive; undetectable viral load (< 600 IU/mL) IgG-positive; viral load not assessed IgG-positive; viral load > 850 000 IU/mL IgG-positive; refused viral load assay HIV antibody Negative nd nd nd Urinalysis Trace protein (39 mg/24 h); no casts/red cells Normal Normal nd Blood culture Negative Negative Negative nd Throat swab Nd Normal flora nd nd Electrocardiogram Normal nd nd nd Chest x-ray Normal Normal Normal nd Echocardiogram Transthoracic normal; transoesophageal not tolerated by patient nd nd nd ESR = erythrocyte sedimentation rate. nd = not done. ANA = antinuclear antibody. ANCA = antineutrophil cytoplasmic antibody. ENAs = extractable nuclear antigen antibodies. APTT = activated partial thromboplastin time. 2 Features of the rash in four patients ↑A. Generalised exanthem on trunk and limbs in Patient 2. ↑B. Palm desquamation in Patient 2. ↑C. Purpuric rash involving lower limbs, with areas of confluence on the lower calf in Patient 3. ↓D. Extensive erythematous exanthem over trunk and limbs in Patient 4. ↑E. Palm desquamation in Patient 4.

Jon N Currie FRACP, FAChAM · Jimmy Chien BMed · Lisa Snell RN · Margaret Cluff RN · Karen Scrivener RN · Lucinda Wallman PhD, FRACP, FRCPA · Elizabeth M Benson FRACP, FRCPA